The Cat: Clinical Medicine and Management

The Cat Clinical Medicine and Management Susan E. Little, DVM, DABVP (Feline Practice) Bytown Cat Hospital Ottawa, On...

Author: Susan Little DVM DABVP (Feline)

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The Cat

Clinical Medicine and Management

Susan E. Little, DVM, DABVP (Feline Practice) Bytown Cat Hospital Ottawa, Ontario, Canada

3251 Riverport Lane St. Louis, Missouri 63043

THE CAT: CLINICAL MEDICINE AND MANAGEMENT Copyright © 2012 by Saunders, an imprint of Elsevier Inc.

ISBN: 978-1-4377-0660-4

No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. International Standard Book Number: 978-1-4377-0660-4

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Section Editors

Randolph M. Baral, BVSc, MACVSc (Feline Medicine) Paddington Cat Hospital Sydney, New South Wales, Australia Feline Internal Medicine

Susan E. Little, DVM, DABVP (Feline Practice) Bytown Cat Hospital Ottawa, Ontario, Canada Fundamentals of Feline Practice Feline Internal Medicine Special Considerations for the Senior Cat Feline Reproduction and Pediatrics

Joe Bartges, BS, DVM, PhD, DACVIM, DACVN Professor of Medicine and Nutrition Acree Endowed Chair of Small Animal Research Staff Internist and Nutritionist Department of Small Animal Clinical Sciences College of Veterinary Medicine The University of Tennessee Knoxville, Tennessee Feline Nutrition

Leslie A. Lyons, PhD Professor Department of Population Health and Reproduction School of Veterinary Medicine University of California, Davis Davis, California The Feline Genome and Clinical Genetics

Brenda Griffin, DVM, MS, DACVIM Adjunct Associate Professor Department of Small Animal Clinical Sciences College of Veterinary Medicine University of Florida Gainesville, Florida Population Medicine

Margie Scherk, DVM, DABVP (Feline) Editor Journal of Feline Medicine and Surgery; CatsINK Vancouver, British Columbia, Canada Managing the Cat with Concurrent and Chronic Diseases Kersti Seksel, BVSc (Hons), MRCVS MA (Hons), FACVSc, DACVB, CMAVA, DECVBM-CA Registered Veterinary Specialist, Behavioural Medicine Sydney Animal Behaviour Service Seaforth, New South Wales, Australia Adjunct Senior Lecturer Charles Sturt University Wagga Wagga, New South Wales, Australia Feline Behavior

Melissa Kennedy, DVM, PhD, DACVM Associate Professor Director of Clinical Virology Department of Biomedical and Diagnostic Services College of Veterinary Medicine The University of Tennessee Knoxville, Tennessee Infectious Diseases and Zoonoses

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Contributors Randolph M. Baral, BVSc, MACVSc (Feline Medicine) Paddington Cat Hospital Sydney, New South Wales, Australia Approach to the Vomiting Cat Approach to the Cat with Diarrhea Diseases of the Intestines Diseases of the Exocrine Pancreas Approach to the Cat with Ascites and Diseases Affecting the Peritoneal Cavity Endocrine Pancreatic Disorders Thyroid Gland Disorders Adrenal Gland Disorders Disorders of Calcium Metabolism Lower Respiratory Tract Diseases The Thoracic Cavity Bacterial Infections

Scott A. Brown, VMD, PhD, DACVIM Josiah Meigs Distinguished Professor Department of Small Animal Medicine and Surgery College of Veterinary Medicine The University of Georgia Athens, Georgia Chronic Kidney Disease and Hypertension Jane E. Brunt, DVM Founder and Owner Cat Hospital At Towson-CHAT Baltimore, Maryland Executive Director Catalyst Council, Inc. Annapolis, Maryland The Cat-Friendly Practice Jeffrey N. Bryan, DVM, MS, PhD, DACVIM (Oncology) Associate Professor of Oncology Department of Veterinary Medicine and Surgery College of Veterinary Medicine University of Missouri Columbia, Missouri Lymphoma

Georgina Barone, DVM, DACVIM (Neurology) Veterinary Medical Center of Long Island West Islip, New York Neurology Joe Bartges, BS, DVM, PhD, DACVIM, DACVN Professor of Medicine and Nutrition Acree Endowed Chair of Small Animal Research Department of Small Animal Clinical Sciences College of Veterinary Medicine The University of Tennessee Knoxville, Tennessee The Unique Nutritional Requirements of the Cat: A Strict Carnivore Nutrition for the Normal Cat Nutritional Disorders Nutritional Management of Diseases Current Controversies in Feline Nutrition

Jenna H. Burton, DVM Assistant Professor Animal Cancer Center Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Chemotherapy for the Feline Cancer Patient Debbie Calnon, BSc, BVMS, MACVSc (Animal Behavior), CMAVA, Cert IV TAA Behaviour Counselling Service Mount Waverley, Victoria, Australia; Good Pet Behaviour Kingston, Victoria, Australia Box Hill Institute TAFE Box Hill, Victoria, Australia Behavioral History Taking

Marie-Claude Bélanger, DMV, MSc, DACVIM Associate Professor Department of Clinical Sciences Faculty of Veterinary Medicine University of Montreal St-Hyacinthe, Quebec, Canada Heart Failure and Chronic Kidney Disease

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CONTRIBUTORS

Sarah Caney, BVSc PhD DSAM (Feline), MRCVS Cat Professional Ltd. Midlothian Innovation Centre Pentlandfield, Roslin, Midlothian, United Kingdom Hyperthyroidism and Chronic Kidney Disease Kevin Choy, BVSc Resident, Oncology Department of Veterinary Clinical Sciences College of Veterinary Medicine Washington State University Pullman, Washington Lymphoma Mammary Tumors Melissa Clark, DVM Resident, Clinical Pharmacology Department of Veterinary Biosciences College of Veterinary Medicine University of Illinois at Urbana-Champaign Urbana, Illinois Monitoring Long-Term Therapy Leah A. Cohn, DVM, PhD, DACVIM Professor Department of Veterinary Medicine and Surgery College of Veterinary Medicine University of Missouri Columbia, Missouri Immune Deficiency, Stress, and Infection Immunosuppressive Drug Therapy Steve Dale, CABC Contributing Editor (pets) USA Weekend; Pet Columnist Tribune Media Services; Host National Radio Shows Black Dog Radio Productions Chicago, Illinois Kitten Socialization and Training Classes Duncan C. Ferguson, VMD, PhD, DACVIM, DACVCP Professor of Pharmacology and Head Department of Comparative Biosciences College of Veterinary Medicine University of Illinois at Urbana-Champaign Urbana, Illinois Monitoring Long-Term Therapy

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Brooke Fowler, DVM Oncology Resident Small Animal Department of Veterinary Medicine and Science College of Veterinary Medicine University of Missouri Columbia, Missouri Basic Approach to the Feline Cancer Patient Deborah S. Greco, DVM, PhD, DACVIM Senior Medical Consultant Nestle Purina Petcare New York, New York Diabetes Mellitus and Feline Lower Urinary Tract Disorders Brenda Griffin, DVM, MS, DACVIM Adjunct Associate Professor Department of Small Animal Clinical Sciences College of Veterinary Medicine University of Florida Gainesville, Florida Care and Control of Community Cats Population Wellness: Keeping Cats Physically and Behaviorally Healthy Beth Hamper, DVM, DACVN Department of Small Animal Clinical Sciences College of Veterinary Medicine The University of Tennessee Knoxville, Tennessee The Unique Nutritional Requirements of the Cat: A Strict Carnivore Nutrition for the Normal Cat Nutritional Disorders Nutritional Management of Diseases Current Controversies in Feline Nutrition Greg L. G. Harasen, DVM Animal Clinic of Regina Regina, Saskatchewan, Canada Musculoskeletal Diseases Chamisa Herrera, DVM Oncology Resident Department of Small Animal Medicine and Surgery College of Veterinary Medicine University of Missouri Columbia, Missouri Paraneoplastic Syndromes

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CONTRIBUTORS

Margarethe Hoenig, DrMedVet, PhD Professor Department of Veterinary Clinical Medicine College of Veterinary Medicine University of Illinois Urbana, Illinois Hyperthyroidism and Diabetes Mellitus Diabetes Mellitus and Obesity Jan E. Ilkiw, BVSc, PhD, DECVAA Associate Dean for Academic Programs Professor Department of Surgical and Radiological Sciences School of Veterinary Medicine University of California, Davis Davis, California Anesthesia and Perioperative Care Katherine M. James, DVM, PhD, DACVIM Veterinary Education Coordinator Veterinary Information Network Davis, California Fluid Therapy Edward Javinsky, DVM, DABVP (Canine/Feline) Veterinary Medical Consultations Ottawa, Ontario, Canada Gastrointestinal Parasites Hematology and Immune-Related Disorders Anthony S. Johnson, BS, DVM, DACVECC Assistant Clinical Professor Emergency and Critical Care Department of Veterinary Clinical Sciences School of Veterinary Medicine Purdue University West Lafayette, Indiana Fluid Therapy Melissa Kennedy, DVM, PhD, DACVM Associate Professor Director of Clinical Virology Department of Biomedical and Diagnostic Sciences College of Veterinary Medicine The University of Tennessee Knoxville, Tennessee Viral Diseases Bacterial Infections

Claudia Kirk, DVM, PhD, DACVN, DACVIM Professor of Medicine and Nutrition Department Head Department of Small Animal Clinical Sciences College of Veterinary Medicine The University of Tennessee Knoxville, Tennessee The Unique Nutritional Requirements of the Cat: A Strict Carnivore Nutrition for the Normal Cat Nutritional Disorders Nutritional Management of Diseases Current Controversies in Feline Nutrition William C. Kisseberth, DVM, PhD, DACVIM (Oncology) Associate Professor Department of Veterinary Clinical Sciences College of Veterinary Medicine The Ohio State University Columbus, Ohio Injection-Site Sarcoma Jennifer Dawn Kurushima, BS, PhD Post-Doctoral Fellow Population Health and Reproduction School of Veterinary Medicine University of California, Davis Davis, California A Short Natural History of the Cat and Its Relationship with Humans Gary Landsberg, BSc, DVM, DACVB, DECVBM-CA Veterinary Behaviorist North Toronto Animal Clinic Thornhill, Ontario, Canada; Director Veterinary Affairs CanCog Technologies, Inc. Toronto, Ontario, Canada Kitten Development Behavioral Therapeutics Michael R. Lappin, DVM, PhD, DACVIM Professor Small Animal Medicine Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado The Upper Respiratory Tract Molecular Assays Used for the Diagnosis of Feline Infectious Diseases

CONTRIBUTORS

Sidonie Lavergne, DVM, PhD Assistant Professor Comparative Biosciences College of Veterinary Medicine University of Illinois at Urbana-Champaign Urbana, Illinois Managing Adverse Drug Reactions Kristin M. Lewis, DVM Internal Medicine Resident Department of Veterinary Medicine and Surgery College of Veterinary Medicine University of Missouri Columbia, Missouri Immunosuppressive Drug Therapy Jacqueline Mary Ley, BVSc (Hons), MACVSc (Veterinary Behavior), PhD Research Assistant Psychology Monash University Melbourne, Victoria, Australia; Veterinary Behaviourist Sydney Animal Behaviour Service Sydney, New South Wales, Australia; Veterinary Behaviourist Veterinary Behavioural Medicine Melbourne Veterinary Specialist Centre Melbourne, Victoria, Australia Kitten Development Normal Behavior of Cats Behavioral Therapeutics Christine C. Lim, DVM, DACVO Assistant Clinical Professor Veterinary Clinical Sciences College of Veterinary Medicine University of Minnesota St. Paul, Minnesota Ophthalmology

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Susan E. Little, DVM, DABVP (Feline Practice) Bytown Cat Hospital Ottawa, Ontario, Canada Diseases of the Esophagus Diseases of the Stomach Endocrine Pancreatic Disorders Musculoskeletal Diseases Toxicology The Lower Urinary Tract Viral Diseases Bacterial Infections Managing the Senior Cat Evaluation of the Senior Cat with Weight Loss Male Reproduction Female Reproduction Pediatrics Katharine F. Lunn, BVMS, MS, PhD, MRCVS, DACVIM Assistant Professor Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Fluid Therapy Leslie A. Lyons, PhD Professor Department of Population Health and Reproduction School of Veterinary Medicine University of California, Davis Davis, California A Short Natural History of the Cat and Its Relationship with Humans The Feline Genome and Clinical Implications Genetics of Feline Diseases and Traits David J. Maggs, BVSc, DACVO Professor Department of Surgical and Radiological Sciences School of Veterinary Medicine University of California, Davis Davis, California Ophthalmology

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CONTRIBUTORS

Carolyn McKune, DVM, DACVA Clinical Assistant Professor Department of Large Animal Clinical Sciences College of Veterinary Medicine University of Florida Gainesville, Florida Analgesia

Bruno H. Pypendop, DrMedVet, DrVetSci, DACVA Professor Department of Surgical and Radiological Sciences School of Veterinary Medicine University of California, Davis Davis, California Anesthesia and Perioperative Care

Karen A. Moriello, DVM, DACVD Clinical Professor, Dermatology Department of Medical Sciences School of Veterinary Medicine University of Wisconsin Madison, Wisconsin Feline Skin Diseases

Jessica Quimby, DVM, DACVIM Graduate Student Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado The Upper Respiratory Tract

Daniel O. Morris, DVM, DACVD Associate Professor and Chief of Dermatology/Allergy Department of Clinical Studies School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania Human Allergies to Cats Maryanne Murphy, DVM Hill’s Fellow in Clinical Nutrition and Doctoral Student Department of Small Animal Clinical Sciences College of Veterinary Medicine The University of Tennessee Knoxville, Tennessee The Unique Nutritional Requirements of the Cat: A Strict Carnivore Nutrition for the Normal Cat Nutritional Disorders Nutritional Management of Diseases Current Controversies in Feline Nutrition John C. New, Jr., DVM, MPH, DACVPM Professor and Director of Public Health and Outreach Department of Biomedical and Diagnostic Sciences College of Veterinary Medicine The University of Tennessee Knoxville, Tennessee Feline Zoonotic Diseases and Prevention of Transmission Mark E. Peterson, DVM, DACVIM Director Department of Endocrinology and Nuclear Medicine Animal Endocrine Clinic New York, New York Thyroid Gland Disorders Adrenal Gland Disorders Pituitary Disorders

Donna Raditic, DVM, CVA Adjunct Associate Clinician Department of Animal Clinical Sciences Integrative Medicine Service College of Veterinary Medicine The University of Tennessee Knoxville, Tennessee The Unique Nutritional Requirements of the Cat: A Strict Carnivore Nutrition for the Normal Cat Nutritional Disorders Nutritional Management of Diseases Current Controversies in Feline Nutrition Alexander M. Reiter, Dipl. Tzt., Dr. med.vet., DAVDC, DEVDC Associate Professor and Chief of Dentistry and Oral Surgery Department of Clinical Sciences School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania Dental and Oral Diseases Jill A. Richardson, DVM Pharmacovigilance Veterinarian Merck Animal Health Summit, New Jersey Toxicology

CONTRIBUTORS

Mark Rishniw, BVSc, MS, PhD, DACVIM Visiting Scientist Department of Clinical Sciences College of Veterinary Medicine Cornell University Ithaca, New York; Director of Clinical Research Veterinary Information Network Davis, California Cardiovascular Diseases Sheilah Robertson, BVMS (Hons), PhD, DACVA, DECVAA, MRCVS Professor Department of Large Animal Clinical Sciences College of Veterinary Medicine University of Florida Gainesville, Florida Analgesia Palliative Medicine: Pain Assessment and Management Ilona Rodan, DVM, DABVP (Feline) Feline-Friendly Consulting Medical Director Cat Care Clinic Madison, Wisconsin Understanding the Cat and Feline-Friendly Handling Preventive Health Care for Cats Bernard E. Rollin, PhD University Distinguished Professor Department of Philosophy College of Liberal Arts Colorado State University Fort Collins, Colorado Palliative Medicine, Quality of Life, and Euthanasia Decisions Margie Scherk, DVM, DABVP (Feline) Editor Journal of Feline Medicine and Surgery; CatsINK Vancouver, British Columbia, Canada The Upper Urinary Tract Palliative Medicine, Quality of Life, and Euthanasia Decisions

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Kersti Seksel, BVSc (Hons), MRCVS MA (Hons), FACVSc, DACVB, CMAVA, DECVBM-CA Registered Veterinary Specialist, Behavioural Medicine Sydney Animal Behaviour Service Seaforth, New South Wales, Australia Adjunct Senior Lecturer Charles Sturt University Wagga Wagga, New South Wales, Australia Normal Behavior of Cats Kitten Socialization and Training Classes Behavior Problems Behavioral Therapeutics Lisa M. Singer, VMD Resident, Internal Medicine Department of Internal Medicine, Small Animal College of Veterinary Medicine Michigan State University East Lansing, Michigan Immune Deficiency, Stress, and Infection Marcy J. Souza, DVM, MPH, DABVP (Avian), DACVPM Assistant Professor Department of Biomedical and Diagnostic Sciences College of Veterinary Medicine The University of Tennessee Knoxville, Tennessee Feline Zoonotic Diseases and Prevention of Transmission Andrew H. Sparkes, BVetMed, PhD, DECVIM, MRCVS Veterinary Scientific Advisor International Society for Feline Medicine Tisbury, Wilts, United Kingdom Preventive Health Care for Cats Jennifer Stokes, DVM, DACVIM Clinical Associate Professor Department of Small Animal Clinical Sciences College of Veterinary Medicine The University of Tennessee Knoxville, Tennessee Fungal and Rickettsial Diseases Vicki Thayer, DVM, DABVP (Feline) Purrfect Practice PC Lebanon, Oregon; President Winn Feline Foundation, Inc. Hillsborough, New Jersey Deciphering the Cat: The Medical History and Physical Examination

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CONTRIBUTORS

Lauren A. Trepanier, DVM, PhD, DACVIM, DACVCP Professor Department of Medical Sciences School of Veterinary Medicine University of Wisconsin Madison, Wisconsin Guidelines and Precautions for Drug Therapy in Cats Julia Veir, DVM, PhD, DACVIM Assistant Professor, Small Animal Medicine Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Molecular Assays Used for the Diagnosis of Feline Infectious Diseases Katrina R. Viviano, DVM, PhD, DACVIM Clinical Assistant Professor Department of Medical Sciences School of Veterinary Medicine University of Wisconsin Madison, Wisconsin Therapeutics for Vomiting and Diarrhea

Angela L. Witzel, DVM, PhD, DACVN Clinical Instructor Department of Small Animal Clinical Sciences College of Veterinary Medicine The University of Tennessee Knoxville, Tennessee The Unique Nutritional Requirements of the Cat: A Strict Carnivore Nutrition for the Normal Cat Nutritional Disorders Nutritional Management of Diseases Current Controversies in Feline Nutrition Jackie M. Wypij, DVM, MS, DACVIM (Oncology) Assistant Professor Department of Veterinary Clinical Medicine College of Veterinary Medicine University of Illinois at Urbana-Champaign Urbana, Illinois Palliative Care Debra L. Zoran, DVM, MS, PhD, DACVIM-SAIM Associate Professor Chief of Medicine Department of Small Animal Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Texas A&M University College Station, Texas Diseases of the Liver Management of Concurrent Pancreatitis and Inflammatory Bowel Disease

This book would not have been possible without the support and advice of many, including my colleagues at Bytown and Merivale Cat Hospitals (Ottawa, Ontario, Canada), most especially Dr. Douglas Boeckh who made it possible for me to become a feline specialist. My long-suffering family was integral in many ways (advice on the book cover from my son Benjamin, photographs from my daughter Tori-Rose, and expert writing from my husband Dr. Edward Javinsky) and they put up with the endless and exacerbating process of editing a textbook. And, finally, it would not have been possible without over two decades of feline patients—I hope I can continue to learn from them every day.

AN OUTLINE OF FELINE MEDICINE* J. E. B. Graham† This paper is an attempt to give a broad outline of feline medicine rather than to concentrate on any particular aspect of this field. No attempt will be made to cover the virus infections since they are familiar to most veterinarians.

Preliminary Examination The following examination is the type done on any sick cat when the diagnosis is not obvious. It should require no more than ten minutes. An examination table with a slippery surface, such as stainless steel or arborite, facilitates handling. Since most cats are nervous after traveling, a few moments spent stroking their head and back to allay their suspicions is time well spent. The anus and surrounding hair are checked for tapeworm segments and a well lubricated thermometer is inserted in the rectum. Cats resist a dry thermometer more than dogs do. While waiting for the thermometer to register, an accurate history is obtained from the owner. The next step is the examination of the skin paying particular attention to external parasites, dermatitis, excessive dryness of the skin or hair, quality of the coat and excessive hair shedding. The external lymph nodes are examined and any abnormality of the subcutaneous tissue or muscular system is noted. The ears are then checked for mites, infection of the canal or excess wax production. The lips are examined for evidence of rodent ulcer, the gums and tongue are checked for evidence of ulceration, anemia, jaundice or cyanosis, the teeth are checked for tartar accumulation and loose roots, and the odor of the mouth is noted. After forward withdrawal of the tongue to see any infected spots, tumor formation, foreign body or tonsil infection, the back of the throat is checked. The character of the respirations are observed and any abnormalities noted. All quadrants of the chest are examined with a stethoscope. Abnormal heart or lung sounds are determined. (A moment with a stethoscope will also give you some privacy to collect your thoughts.) Palpation of the abdomen is easier in cats than in dogs. By palpation a pregnant uterus can be noted after the fourth week, and pyometra is readily discernable. Intestines are checked for foreign bodies, constipation, thick walls, gas pockets, tumors and enlarged lymph nodes. Kidneys are palpated for size: they are small and hard in chronic interstitial nephritis, large and painful in acute nephritis, enlarged and knobby in kidney lymphosarcoma. The wall of the bladder is thick in cystitis. The spleen is often enlarged in anemia. If the border of the liver is palpable it is pathological. *A paper presented at the Mid-Ontario Veterinary Association meeting held at Toronto on October 27, 1960. †3206 Eglinton Avenue East, Toronto, Ontario.

FIGURE FM-1 In 1961, J.E.B. Graham presented an outline of all that was currently known about feline medicine in the Canadian Veterinary Journal in 10 pages. Today, 50 years later, we have advanced in knowledge to the point that we need one hundred times that many pages devoted to feline medicine. Undoubtedly, the cat has benefited from this expansion of knowledge but the clinician has the daunting task of learning and putting it into practice. (From Graham JEB: An Outline of Feline Medicine, Can Vet J 2:8, 1961.)

Preface

As any veterinary clinician knows, it is a daunting task to work with cats! Over the years, I have found my experiences as a feline specialist humbling, but also have realized what a great learning opportunity feline medicine provides. Cats force us to be expert diagnosticians, relying more than ever on the “old school” skills of a good medical history and a thorough physical examination. Unfortunately, cats are still the “poor stepchild” in companion animal medicine, receiving less attention in research on common medical problems as well as improved diagnostic and treatment approaches than is given to their canine counterparts. It is therefore fitting that the Winn Feline Foundation has endorsed this book, as the organization has provided the research funding and support necessary to uncover an impressive amount of the information found in this text. Fortunately, we know much more about feline medicine than we did 10 or 15 years ago. This book compiles the current state of knowledge from a group of talented and wise experts. These superb clinicians and diagnosticians share insights from their many combined years of feline practice, based on available evidence whenever possible, to bring together in one volume comprehensive information on state-of-the-art diagnostic tests, treatments, and techniques. I am grateful for their generosity in sharing and their desire to pass on their knowledge. The focus of this book is first and foremost practical and concentrates on what most of us can and should accomplish in general practice. It is designed to give veterinarians information that can be used every day in an accessible format. It contains information on new topics (e.g., management of cats with chronic and concurrent diseases, feline life-stage medicine) and expanded information on emerging topics (e.g., genetics, felinefriendly practice, the importance of senior cat care, and the special needs of indoor cats). Throughout the book, algorithms, key points, and many photos are used to illustrate conditions and techniques. The book is also available electronically where the many illustrations will fully come alive.

Presenting the current state of knowledge about feline medicine in one volume presents challenges, but it has forced us to focus on the most important and clinically relevant aspects. Material is organized largely by body system to make finding information easy, and it has been kept concise and readable. In most cases, a logical “road map” for diagnosis and treatment has been provided, such as how to approach the vomiting cat or the cat with diarrhea. Common procedures, such as placing an esophagostomy tube, are described in detail with accompanying photos. Students, and those new to performing certain procedures, will find this approach invaluable. The reader will also find that some topics are covered more than once in different sections of the book. This allows different perspectives and even different points of view on important issues to be presented by experts in their areas of expertise. The foundations of feline medicine are more important than ever, and thus a full section has been devoted to updated information and techniques for handling and physical examination, the art of taking the medical history, the idiosyncrasies of cats and drug therapy, the most effective drugs and techniques for analgesia, and detailed information on fluid therapy and anesthesia for many different medical situations. Special attention is paid to reducing the barriers that prevent so many of our feline companions from receiving regular veterinary care in a ground-breaking chapter on making your practice feline-friendly. Veterinarians must continually strive to be open to learning from cats because cats do not give up their secrets easily. Clues are there for those who are willing to observe and listen. This textbook is a guide to that experience and it will enhance every veterinarian’s feline practice skills, whether a new graduate or an “old hand.” Our hope is that it will be your “go-to” reference for feline medicine, whether on your bookshelf or in electronic form. Susan E. Little, DVM, DABVP (Feline) Ottawa, Ontario, Canada

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Acknowledgments

I owe a debt of gratitude to my support team at Elsevier—Shelly Stringer, David Stein, and Heidi Pohlman—for helping a novice editor survive. My thanks also go to Dr. Anthony Winkel, whose idea this was in the first place. About the artist: The cover and section opener images were provided by photographer Mats Göran Hamnäs. Mats was born in Stockholm, Sweden, in 1947. He works as a data programmer and lives and works in southern Sweden, Helsingborg, and Malmö. Mats interests include design, art, and architecture. His intent with his feline photographs is to portray cats in their natural environment.

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Foreword

A new text in the field of feline medicine is always eagerly anticipated, especially in an era of rapidly increasing scientific knowledge and as more is learned about feline genetics and genetic diseases. An impressive group of authors have collaborated to present the latest information with the aim of improving feline health. This becomes more important as cats have longer lives and are increasingly selected to share the homes of people everywhere. The Winn Feline Foundation is a not-for-profit organization founded by The Cat Fanciers’ Association (CFA) in 1968, and it has been funding feline health studies for over 35 years. As a nonprofit foundation, Winn has funded over $3.3 million in direct research grants. Some of these projects have been basic science investigations; others have been aimed at immediate clinical impact. Examples of feline disease research supported by Winn Feline Foundation include studies that have investigated feline leukemia virus, feline immunodeficiency virus, feline infectious peritonitis, hypertrophic cardiomyopathy and other heart disorders, polycystic kidney disease and other kidney disorders, mammary and other cancers, hyperthyroidism, asthma, and inflammatory bowel disease. The Foundation also supports research into behavioral disorders. The emergence of feline genomic

research in recent years is leading to an added focus in research at the molecular level. Grants are made to researchers at the leading research universities and institutions in the United States, and increasingly to researchers around the world. Winn has been associated with some of the major breakthroughs in feline health. To name a few of these: identification of feline immunodeficiency virus, discovery of the link between taurine deficiency and dilated cardiomyopathy, development of methods to measure feline blood pressure, discovery of genes that cause several inherited diseases, and studies showing that early-age spays and neuters are safe. Winn, in partnership with the American Veterinary Medical Association (AVMA), presents an annual Excellence in Feline Research Award and an annual scholarship award to an outstanding veterinary student with a special interest in feline medicine. Winn welcomes this text as an important addition to the libraries of scientists, veterinarians, and veterinary students around the world.

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Betty White Winn Feline Foundation, Past President

C H A P T E R

1

Understanding the Cat and Feline-Friendly Handling Ilona Rodan O U T L I N E The Client’s Perspective, 2 The Veterinary Team’s Perspective, 3 The Cat’s Perspective, 3 A Better Way, 3 Understanding the Cat, 4 Cat Communication, 5

Causes of Misbehavior and Aggression at Veterinary Visits, 7 Learning in Cats, 8 Feline-Friendly Veterinary Visits, 9 Conclusion, 18

The cat has become the most popular pet in the United States, Canada, and Northern Europe, and its popularity continues to grow. Cats are fun, affectionate, beautiful, unique, and fascinating. Many people love their cats; 78% of us consider them family members.38 As much as we help cats, they help us: by protecting human health, such as by decreasing their owners’ blood pressure, reducing the probability of a second heart attack, and lessening the risk of depression or loneliness. Nevertheless, and despite the great advances in feline medicine and surgery, many of us—veterinarians, veterinary teams, and cat owners—do not understand the nature of the cat and normal feline behavior. Among other issues, a lack of understanding of how cats react to fear and pain leads to difficulty during veterinary visits and a subsequent lack of routine veterinary care.18 Compared with cat owners, dog owners take their pets to the veterinarian more often and are more likely to follow recommendations. In fact, in 2006 in the United States dog owners took their dogs to the veterinarian more than twice as often as cat owners brought their cats.18 In addition, 72% of cats were seen by a veterinarian less often than once a year, compared with 42% of dogs.18 Dog owners were also more likely than cat owners to procure vaccinations, physical examinations, and preventive dental care for their pets. In multipet households 33% of cats did not visit a veterinarian annually, compared with only 13% of dogs.18 Feline diseases

The Cat: Clinical Medicine and Management

and pain thus go undetected, client relationships are not developed, and cats may suffer a reduced quality of life and decreased longevity. This is an important issue involving feline welfare. We are all affected—our clients, the veterinary team, and the cats—by the challenges associated with feline veterinary visits. To understand the gravity of the problem and to find a solution, we must first understand several perspectives: that of the client, the veterinary team, and the cat.

THE CLIENT’S PERSPECTIVE Many cat owners encounter practical difficulties in simply getting the cat to the veterinarian, such as putting the cat into a carrier.40 Cat owners also worry that taking their cat to the veterinarian may damage the bond they have with their beloved feline. Some cat owners are embarrassed about their cat’s behavior at the veterinary hospital, and others are upset about the way the veterinarian or veterinary team handles and interacts with their cat. They have often had a negative experience with their cat at a veterinary hospital, or when their cat returns home and is treated differently by the other cat (or cats). Some clients believe that the traumatic experience is more detrimental to the cat’s health than a lack of veterinary care. 2

Copyright © 2012 by Saunders, an imprint of Elsevier Inc.

CHAPTER 1 Understanding the Cat and Feline-Friendly Handling

THE VETERINARY TEAM’S PERSPECTIVE The challenges that the veterinary team faces with difficult feline patients include potential injury, zoonotic diseases (e.g., cat-scratch disease), decreased efficiency, increased use of resources (e.g., time and staff needed to handle a single cat), and an inability to properly educate clients because of their preoccupation with their cat’s behavior or on how the clinicians handle their cat. Liability issues related to injury, zoonoses, and handling techniques are also cause for concern.30 In addition, performing a thorough physical examination or collecting laboratory samples from the cat may be difficult or impossible. Even when possible, feline stress associated with the veterinary visit may affect the results. Stress can result in the following examination abnormalities: tachycardia, bradycardia (if stress is prolonged), increased respiratory rate, dilated pupils, and hyperthermia. Some cats may evacuate anal sacs or bladder and bowel contents. The stool may be soft, blood tinged, and covered with mucus on account of colitis associated with the stressful experience. Further, diagnostic test results can be markedly abnormal in a healthy but fearful patient. Stress hyperglycemia is associated with patient struggling and can occur rapidly.32 Blood glucose levels can increase quickly and be as high as 613 mg/dL with or without glucosuria; this hyperglycemia can last for 90 to 120 minutes. Another blood chemistry abnormality is hypokalemia caused by epinephrine release.6,10 Complete blood count (CBC) changes associated with epinephrine release include platelet hypersensitivity, lymphocytosis, and neutrophilia.10 The author has seen lymphocytosis values of 8000 to 11,000 in fearful cats that have no underlying medical problems. In addition, “white-coat hypertension” can elevate the blood pressure well above 200 mm Hg (normal levels range from 104.5 to 159.3 mm Hg).16

THE CAT’S PERSPECTIVE Imagine for a moment what a cat likely thinks and feels during the clinic visit and when traveling to and from the facility. The cat’s perception differs significantly from that of the owner or the veterinarian. It is napping in a pool of sunlight when it sees its favorite person pulling out the cage that appears only when a veterinarian visit is imminent. The cat runs to hide, only to be pursued, then snatched from the safety of its hiding place. No matter how much the cat protests, it is shoved into the hated cage. The owner might be stressed, too, and might

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shout and grumble. Then comes the jostling, bumpy trip in the car, which might make the cat feel nauseated. If the cat urinates, defecates, or vomits, it must sit in the results, surrounded by the horrible stench. Even if the cat does not become sick, it may become so terrified in the car or at the clinic that it experiences increased gastrointestinal motility, leading to possible nausea, vomiting, or diarrhea. The cat might also salivate profusely because it is so nervous and uncomfortable.22 Once the cat arrives at the clinic, strangers touch it and do things that make the cat feel uncomfortable. The cat is afraid and might scratch or bite in an attempt to protect itself. Worse yet, when the cat returns home, the other cats will probably give it a hard time because it smells different. Fortunately, the veterinarian can make the experience less stressful for the cat, the owner, and the veterinary team.

A BETTER WAY Most clients cannot judge the veterinarian’s knowledge of feline medicine, but they can judge the veterinarian’s ability to work confidently, respectfully, and effectively with their cat. Having excellent surgical skills and medical knowledge is necessary but not sufficient; clients have higher needs and expectations. Clients do not care how much the veterinarian knows until they know how much the veterinarian cares—for the client as well as the cat. By respecting and understanding the cat, veterinarians can build trusting relationships among cat owners, veterinary teams, and feline patients that will result in improved feline health and well-being through regular veterinary visits. Veterinary visits will be safer—and more relaxing—for all concerned. Examinations and diagnostic testing will yield more accurate results, and the veterinary team’s job satisfaction will be enhanced while working with feline patients. Equally important, effective client education and communication can readily occur in this improved atmosphere. Finally, better practices attract new clients and feline patients, leading to more frequent veterinary visits—and the resultant better care—for cats. Fortunately, veterinary visits can be made more pleasant for all involved. This chapter describes methods to better understand cats and how they perceive the world and react as they do. Further, this chapter addresses ways in which cat communication and learning can be used to help prevent aggression and fear. In addition, this chapter provides practical information regarding techniques to get the cat to the veterinary hospital, client education, and respectful handling of all feline patients during examinations and sample collections to prevent pain and distress.

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SECTION I Fundamentals of Feline Practice

UNDERSTANDING THE CAT The History of the Cat The earliest known ancestors of the Felidae family existed 45 million years ago. The modern cat, Felis catus, is descended from Felis libyca, also known as the African wildcat or small African bush cat. Recent discoveries indicate that cats began to live among humans when agriculture began in the Fertile Crescent (modern-day Western Asia and the Middle East) approximately 10,000 years ago.8 The relationship between cats and humans likely began because it was mutually beneficial, with cats killing rodents attracted to stored grain. The earliest direct evidence of cat domestication occurred 9500 years ago, when a kitten was buried with its owner in Cyprus.39 Archaeologists found a feline molar at a site in Israel dating to roughly 9000 years ago (7000 BCE) and also discovered an ivory cat statuette estimated to be 3700 years old (1700 BCE), also in Israel. Some 3600 years ago (1,600 BCE) in Egypt, cats were worshiped and mourned at their death. Mourners shaved off their eyebrows, and cats were mummified for burial in sanctified plots, often with mummified mice added for use in the afterlife. Egyptian paintings from that time depict cats poised under chairs, sometimes collared or tethered and often eating from bowls.7 The cat population increased and spread to other countries, likely by people who prized cats’ ability to control rodent populations. The cat’s good reputation in Europe began to plummet in the late Middle Ages, when Catholic leaders declared cats to be agents of the devil and associated them with witchcraft. From approximately 1400 to 1800, vast numbers of cats were exterminated, and individuals who kept them were accused of being witches and also killed. Louis Pasteur’s discovery of microbes in the nineteenth century helped to reinstate cats to their former high regard; they were considered the cleanest of animals. By the late 1800s, the growing middle class became interested in cat shows and developing and establishing distinctive breeds, especially long-haired breeds. During the twentieth century, cats became even more cherished, often living long and comfortable lives. Other domesticated species have undergone genetic selection. For example, there are specialized breeds of dogs for hunting, herding, and guarding. However, the mutually beneficial relationship between humans and cats made such genetic selection unnecessary. As a result, domestic cats have retained many aspects of their wild predecessors. Cats are true carnivores and have amazing athletic abilities and keen senses to allow them to hunt successfully. They can sense and avoid danger, and they possess a heightened fight-or-flight response.11 Like their wild ancestors, they hide illness and pain as a protective mechanism, which adds to the mistaken impression that cats are independent and require little or no care.

Indeed, cats are social animals, but their social structure differs from that of humans and dogs. Given sufficient food resources, free-living cats will choose to live in social groups, called colonies.20,27 The social organization of the colony is based on females cooperatively nursing and raising their young.20 Within a colony, cats will choose preferred associates, or affiliates. These cats show affection toward one another by allogrooming: grooming one another, generally on the head and neck.4,5 Because the head and neck are preferred areas for physical touch, cats may become upset and even aggressive when people try to pet them in other areas. Therefore, unless a person knows an individual cat’s preferences, stroking or petting in other areas should be avoided in favor of rubbing or stroking the cat around the neck and head (e.g., under the chin). Feral cat colonies are quite insular, and strangers are generally driven away. If a new cat continues to visit the colony, it may eventually be integrated into the group, but the process requires several weeks.19 This is why gradually introducing a cat into a household with resident cats is so important. Although social, cats are solitary hunters. They catch small prey and may need to hunt as often as 20 times a day. Because cats are solitary hunters, they must maintain their physical health and avoid fights with other cats whenever possible. Much of feline communication serves to prevent altercations over food and territory, and most cats try to avoid the risks associated with active fighting.

The Cat’s Senses: How Cats Perceive the World Because perception is everything, humans can better understand and interact with the cat by understanding how it perceives the world. Cats’ perception is based on their senses, most of which are highly sensitive compared with ours. The cat’s sense of hearing is approximately four times more acute than a human’s. Cats can hear a broad range of frequencies, including ultrasound, allowing them to perceive the ultrasonic calls or chattering of rodents.11 Their movable pinnae help localize sounds. Because of their sensitive hearing, sources of stress at the clinic include ringing telephones, paging systems, and human voices, which sound uncomfortably loud even when we think we are talking in a normal tone.29 The noise from centrifuges, x-ray machines, blood pressure monitors, and other medical equipment can startle feline patients. The sounds of other cats and other animals, such as barking, whining, growling, and yowling, can also generate stress.29 Cats can see well in dim light and are very sensitive to movement, abilities that help them hunt for prey. Consequently, rapid movements, especially if unanticipated,


CAT COMMUNICATION Cats communicate with us all the time, but are we listening? Before stressors at the clinic and home can be identified, it is necessary to understand that cats perceive the world through their senses and use vocal, visual, olfactory, and tactile means to communicate. Understanding this communication system is critical in preventing altercations with other felines. As solitary hunters, cats need to maintain their physical health and fitness. Clear communication helps them avoid injury and possible threats to their survival.2,13 As a result, cats turn to fighting only as a last resort, after other attempts to communicate have failed. Being able to perceive and understand the cat’s communication signals can prevent many aggressive acts at the veterinary hospital.

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will likely heighten a cat’s responses and can lead to a more reactive patient. In other words, veterinary staff members working with cats should remember that “slow is fast, and fast is slow.” Cats have an excellent sense of smell and have 5 to 10 times more olfactory epithelium than humans.1 They also have vomeronasal organs (Jacobson’s organ) located in the roof of the mouth behind the upper incisors. The flehmen response, wherein the cat grimaces and partially opens the mouth, occurs when the vomeronasal organs detect the odors of other cats.36 Cats are also very sensitive to touch and use their whiskers to examine their environment. When aroused, they can be very sensitized and may respond aggressively even to gentle petting or stroking. In summary, multiple stressors that come from auditory, visual, olfactory, and tactile stimuli typically occur at the veterinary hospital. The accumulated stress arising from these stimuli can be greater than the sum of the stress from the individual components.29

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FIGURE 1-1 Recognizing body postures that communicate fear or aggression keeps fear from escalating to a situation that can lead to injuries to all involved. (Adapted from Bowen J, Heath S: An overview of feline social behaviour and communication: Behaviour problems in small animals: practical advice for the veterinary team, ed 1, Philadelphia, 2005, Saunders. The original figure was adapted from Leyhausen P: Cat behaviour, New York, 1979, Garland STMP Press.)

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Visual Communication Cats use a range of subtle body postures, facial expressions, and tail positions to communicate with other cats to defuse tension and avoid physical contact (Figures 1-1 and 1-2). Understanding body postures allows humans to recognize—and reward—calm behavior; if postures associated with fear are recognized in time, it is possible to keep that fear from escalating to a point at which injuries are likely (see Figures 1-1 and 1-2). Knowing how to recognize offensive and defensive behavior in cats is important because the purpose of most signaling and posturing is to avoid battle. Familiarity with feline body postures helps humans identify whether the cat intends to flee, freeze, or fight. Although most cats do not want to fight, they may bluff, making themselves look much larger in an attempt to

FIGURE 1-2 Facial signals change more quickly than body postures and provide more immediate indications of a cat’s level of fear and aggression. (Adapted from Bowen J, Heath S: An overview of feline social behaviour and communication: Behaviour problems in small animals: practical advice for the veterinary team, ed 1, 2005, Saunders Ltd. The original figure was adapted from P Leyhausen: Cat behaviour, 1979, Garland STMP Press, New York.)

scare away others.2 Figure 1-1 shows various body postures that cats use to communicate. The normal cat is in the top left corner. The cat becomes increasingly fearful in the subsequent illustrations (moving from top to bottom). The cat in the lower left-hand corner is extremely fearful but will become aggressive if no escape route is

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available.26 In the clinic a common example is a terrified cat that feels cornered and huddles in the back of a cage. As we move from left to right in the figure, the cat becomes increasingly aggressive. At first, the cat might be bluffing, but it may become aggressive if it cannot flee and continues to feel threatened. The cat in the lower right-hand corner is the most fearful and aggressive. Whereas body postures effectively signal a cat’s level of fear and aggression, even from a distance, facial signals (see Figure 1-2) change much more quickly and provide more immediate indications of a cat’s level of fear and aggression. As with Figure 1-1, as we move from top to bottom in the figure, the cat becomes increasingly fearful, and as we move from left to right, the cat becomes increasingly aggressive.26 Ears are erect when the cat is alert and focusing on a stimulus (top left corner). Ears are swiveled downward and sideways in a defensive cat (bottom left); in the aggressive cat, the ears are swiveled, displaying the inner pinnae sideways (bottom right).26 The pupils specifically are the most instructive feline signal. Slit pupils indicate the normal state (top left corner), widely dilated pupils are associated with fear and the fight-or-flight response (lower left corner), and oblong pupils signal aggression (lower right).26 Pupil size generally correlates to the intensity of the situation, as moving from top to bottom in Figure 1-2 illustrates. Cats understand these subtle differences and use them to help prevent fights. (It is important to recognize that ambient light can also affect pupil size.) Two other eye communications are very important; knowing these can help to reduce the cat’s stress levels. First, blinking is believed to signal that the cat is seeking reassurance in a tense environment. Fortunately, this behavior works for both intercat and human–cat communication.2 Blinking slowly or making “winky-eyes” in the direction of the cat can help comfort the cat. Second, because prolonged eye contact, especially from an unknown cat or human, constitutes a threat to cats, people who are not well known to the cat should not stare. Veterinary team members should be taught to blink slowly in the cat’s direction and refrain from staring to make the veterinary visit less stressful for the cat. The cat’s tail is remarkably expressive. When the tail is held up vertically or wrapped, it signals relaxed, friendly intentions. A tail held straight down or perpendicular to the ground indicates an offensive posture.26 The cat lashes the tail vigorously from side to side when very agitated, annoyed, or aroused or during conflict. If this signal is unheeded, the cat’s behavior can escalate to aggression.2

Olfactory Communication Sebaceous glands that deposit the cat’s scent are located around the lips and chin, interdigitally, and in the

perianal area. Cats leave olfactory signals by rubbing the sebaceous glands of the face on objects, other cats, and humans; scratching (to deposit scent from the interdigital glands); and spraying. Spraying is usually a normal olfactory communication among cats (although intercat conflict in a household can induce spraying). Additionally, some cats communicate through urination and middening (fecal marking). Olfactory signals play an important role in communication and social behavior. They enable hunting cats to communicate remotely, for example, by marking a territory as their own with a durable signal that lasts over a period of time.2 Strategic use of olfactory signals means that hunting cats can protect their space without needing to meet or interact physically with other cats. In veterinary hospitals the scent of unfamiliar cats, dogs, and humans can frighten and arouse feline patients. Because the cat’s sense of smell is more acute than a human’s, veterinarian staff members usually do not notice the olfactory signals left by another cat or even the scent of a cleaning solution that may be offensive to a cat. Often in an examination room that seems to be thoroughly cleaned, cats go directly to a specific area, sniff at that area, and then exhibit the flehmen response. When one cat is stressed, the feeling almost seems contagious, spreading quickly to other cats. This happens because distressed cats leave the scent of their distress, which affects the other cats. Knowing the importance of olfactory communication among cats helps the staff in the veterinary hospital. Clients can be educated to put something that smells like home—the cat’s basket, blanket, or a favorite person’s clothing (that is not freshly laundered)—in the carrier when bringing the cat to the veterinary hospital. If the cat needs to stay at the hospital for any reason, the familiar item should also stay with the cat. In addition, when reintroducing cats after a veterinary visit or introducing new cats, the client can be taught to take simple precautions such as exchanging the bedding, or wiping the “at-home” cat with a towel and then wiping the returning cat with the same towel, to help reduce stress and conflict.

Vocal and Tactile Communication Most feline vocalizations bring cats together. Cats also vocalize when communicating with humans, and they learn quickly how to make humans respond to their vocalizations for food and attention. Although cats purr when they are content, they may also purr when sick or fearful. The purr solicits contact and care. The trill and miaow are friendly greeting calls. Affiliate cats engage in allorubbing (rubbing against one another) and allogrooming, and they often lie close together.4


CAUSES OF MISBEHAVIOR AND AGGRESSION AT VETERINARY VISITS Fear is the number-one cause of misbehavior and aggression in cats at the veterinary hospital. Punishment and poor socialization often lead to fear aggression.15 Anxiety can also lead to misbehavior and aggression. It is crucial that all staff members understand the important role that fear plays in feline misbehavior and aggression. Further, giving negative labels to difficult patients (e.g., “evil” or “naughty)” can subtly influence the staff’s behavior and attitude and further harm interactions with fearful patients. Fear, defined as an emotional response that enables an animal to avoid situations and activities that could be potentially dangerous,2 commonly occurs in cats in unfamiliar environments.11 A common saying, “Cats don’t like change without their consent,” is only too apt. Having a sense of control, even if is not exerted, makes the cat more comfortable and reduces stress.21 Giving the cat some control during the veterinary visit by letting it choose a comfortable position and place to be examined will significantly reduce stress associated with veterinary visits. Box 1-1 provides a list of common causes of aggression at the veterinary hospital. The belief that dominance causes feline aggression at the veterinary hospital is a common misconception.24 Cats may experience anxiety, as well as fear, at the veterinary hospital. Anxiety is the emotional anticipation of an adverse event—which may or may not be

BOX 1-1 Common Causes of Feline Aggression in the Veterinary Hospital Fear aggression: fear of unfamiliar places or people Pain-associated aggression Anxiety or memory of a previous negative (fearful or painful) experience at the veterinary hospital Getting attention for the behavior (e.g., “poor kitty”) Play aggression Lack of socialization Forceful restraint Loud noises Unpleasant smells Fast or rushed movements toward cat Underlying medical problem (e.g., meningioma or other central nervous system problem) Petting intolerance or aggression Owner anxiety Physical punishment Redirected aggression

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real.25 A cat that has had a previous painful experience at a veterinary hospital will likely be anxious during the next visit, anticipating pain. Using analgesia to prevent or treat pain and also prevent anxiety at future veterinary visits is critical. Indeed, pain is the second most common reason for aggression in cats. Boxes 1-2 and 1-3 present some frequently underrecognized painful conditions and procedures. Cats tend to hide expressions of pain as a protective mechanism. If there is any question regarding the presence of pain, administer an analgesic and then reassess the patient’s response. Response to therapy is an appropriate and important tool in pain assessment.14 For a more detailed list and additional information about analgesia, see Chapter

BOX 1-2 Frequently Overlooked Conditions that Cause Pain Anal sac impaction and evacuation Arthritis Cancer Chin acne, severe Chronic wounds Clipper burns Congestive heart failure Constipation Corneal ulcers and other corneal diseases Dental disease Otitis (from ear mites, yeast, and bacterial infections) Pleural effusion Pruritis Pulmonary edema Spondylosis Urine scalding Vomiting

BOX 1-3 Frequently Overlooked Procedures that Cause Pain Abdominocentesis Anal sac expression Bandaging Ear cleaning Handling—even gentle handling and hard surfaces can increase pain in animals with arthritis or other conditions that are painful Intravenous catheterization Manual extraction of stool Restraint and forceful handling procedures Thoracocentesis

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6, as well as the Pain Management Guidelines developed by the American Animal Hospital Association and the American Association of Feline Practitioners.14 Prompt provision of effective analgesia will both address the pain and eliminate or reduce pain-associated aggression. Buprenorphine is an excellent analgesic and is well absorbed when given transmucosally (0.02 mg/kg).34 A prophylactic dose provides full effect within 30 minutes (although analgesia has been noted earlier), the same as that conferred by intravenous administration.33 When buprenorphine is given before painful procedures and examinations, a prolonged, stressful, terrifying session can be transformed into a relatively quick, well-tolerated experience. Buprenorphine can also be administered subcutaneously, with full effect occurring at 60 minutes. Injectable delivery is preferred for cats that do not like to have their mouths handled.

Fear Responses Because fear responses are among the more common causes of aggression, we will address them here. Any cat will try to defend itself if it feels threatened. Fearful animals engage in the fight-or-flight response. If cornered, most cats choose escape, or “flight,” over “fight.” However, if not allowed to leave, the cat will fight, which may involve biting and scratching. These are normal feline behaviors derived from predator-avoidance behaviors. The fight or flight response includes the Four Fs:

prey.4 Kittens learn quickly by observing an adult cat, generally the queen, performing a task before they attempt it. Thus, if an adult cat in the household is especially fearful at the veterinary clinic, scheduling separate appointments for the kitten is ideal. A common misconception is that cats cannot learn tricks; in fact, they enjoy the interactions of training and can learn to “sit,” “come,” and follow other commands as long as they receive positive reinforcement (Figure 1-3). In fact, employing some useful and familiar commands or tricks in the veterinary hospital, along with treats, can help cats feel more comfortable and prevent reactivity. Humans can influence what cats learn by affecting their experiences. For example, if a cat has a painful experience during its first visit to the veterinarian, it will almost certainly be fearful during subsequent visits. In contrast, if the cat learns to associate the carrier, car trip, and veterinary visit with treats and other positive experiences, it learns to enjoy everything associated with a trip to the vet. People generally focus on preventing undesired behavior rather than rewarding desired behavior. Punishment inhibits learning and increases anxiety. If the cat does not understand what is wanted or why it is being punished, it may learn to associate pain or fear with the situation; eventually, this association can lead to overt aggression.42 Verbal or physical punishment should never be used with cats.

• Freeze—the cat “freezes,” crouching and becoming immobile. This immobility usually occurs at the beginning of the trigger stimulus or when the trigger stimulus is relatively low. This behavior is common in cats at the veterinary hospital, and it frequently expedites the examination. • Flight—the cat actively avoids the trigger stimulus. For example, the cat may dart into a corner or under a chair to keep from being picked up. • Fight—the cat exhibits defensive aggression to avoid or back away from a frightening stimulus. For example, when the veterinarian reaches for a cat that is cowering at the back of a cage, the cat may become aggressive to protect itself. • Fiddle or fidget—the cat engages in a displacement activity, such as grooming, when faced with a fear-eliciting stimulus. Although the cat wishes to avoid the stimulus, it cannot do so.

LEARNING IN CATS Kittens are excellent observational learners. This characteristic likely developed as an evolutionary adaptation, because kittens learn from the queen how to kill their

FIGURE 1-3 Teaching a kitten to sit during kitten class. Sit is easy: Slowly raise a treat from close to the nose slightly over the kitten’s head. As the head goes up, the tail goes down. Softly say, “Sit” as the cat sits.


Consequently, it is important to teach team members and clients that positive reinforcement of desired behavior is the most effective way to teach a cat and unwanted behavior should be ignored or redirected to a desirable behavior. Desirable behavior is being calm, playing, purring, and accepting gentle handling. Positive reinforcement must be given within 3 seconds of the desired behavior so that the cat has no opportunity to engage in another, less desirable activity that might be inadvertently rewarded instead. At the veterinary hospital, the cat should always be rewarded with delicious treats and praise for calm behavior. Because anxiety can inhibit learning, cats with a history of anxiety at the veterinary hospital may require anxiolytic medication. Alprazolam is a short-acting benzodiazepine that takes effect rapidly. This drug can both abort and prevent anxiety or distress associated with veterinary visits. Recommended doses for alprazolam are 0.125 to 0.25 mg/kg, PO, every 12 hours. It should be given 60 minutes before the scheduled appointment. Alprazolam works well in conjunction with food treats and other rewards. Further, alprazolam can be used concurrently with tricyclic antidepressants or selective serotonin reuptake inhibitors. Although tranquilizers, such as acepromazine, have been used to prevent fear and aggression at the veterinary hospital, they do not relieve anxiety and can disinhibit aggression, resulting in a more aggressive cat.

Sensitive Period of Socialization The socialization period is the age range during which particular events are especially likely to have long-term effects on the individual’s development. In kittens the sensitive period is from 2 to 9 weeks (as a point of comparison, the sensitive period in dogs lasts until 16 weeks). Kittens that have positive handling experiences during this period are more resistant to stress, display less fear, and can learn some tasks faster than cats that are not handled.26 Early enrichment and positive exposure to a wide variety of stimuli, especially the stimuli that the cat will commonly encounter during its lifetime (e.g., car travel, veterinary visits, children, dogs, vacuum cleaners), mean the kitten (and later the cat) will perceive these experiences as comfortable, even pleasant. The veterinary team should encourage clients to expose the kitten to people of different ages and gender, under calm conditions, and reinforce the pleasant experience appropriately (e.g., using treats, toys, massage, and praise). Fortunately, the older cat can still learn, acclimate, and adapt to new experiences, although it is far easier to teach kittens during their sensitive period of socialization.

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FELINE-FRIENDLY VETERINARY VISITS The Situation Today Historically, the education of veterinarians and technicians has focused on caring for sick, poisoned, and injured cats. Over the past several decades, the importance of preventive care has been recognized. More recently, education has emphasized communication and the business of veterinary medicine. Good business decisions include good communication with team members, clients, and patients. Unfortunately, listening to, understanding, and respecting the cat often receive little consideration. The current reality is that college instructional programs for veterinary students and technician trainees focus on the dog as the primary small animal companion, both in medical care (as the lecture ends, the professor might add, “…and yes, cats get arthritis, too”) and patient handling and training. Because the primary patients that students encounter are dogs, they have little (or no) opportunity to learn appropriate handling techniques for feline patients or consider problems associated with excessive restraint. Schools typically teach technicians to overhandle cats, thus making visits unduly stressful for both feline patients and their owners.

Client Education Client education starts with the phone call, before the client (whether a repeat or first-time client) even comes to the clinic. The veterinary staff member who answers the phone should ask all clients whether they expect difficulty in transporting the cat to the veterinary hospital. The staff member should provide information as needed regarding ways that the client can help make the visit as pleasant as possible. Because most people are visual learners and the busy clinic phone line precludes spending sufficient time to educate them effectively, it is a good idea to mail or e-mail handouts or videos explaining techniques to get the cat into the carrier and accustom the cat to car rides, as well as suggesting items that should accompany the cat to the veterinary hospital. Educational resources are listed in Box 1-4.

Getting the Cat to the Veterinary Hospital The veterinary team can teach clients a simple way to make the carrier a feline haven: simply by keeping the carrier in a location that is easily accessible to the cat (Figure 1-4).22 Placing familiar clothing from a favorite person in the carrier, along with treats or toys, will entice the cat to enter on its own. Rewarding the cat for entering the carrier with treats, food, and calm praise will positively reinforce the cat’s favorable associations with

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Finally, draping a blanket or towel over the carrier helps prevent motion sickness. Carriers designed to open from the top as well as from the front make it easier to move the cat into and out of the carrier in a nonstressful manner. The ideal carrier also allows for removal of the top half, so that an especially timid cat can remain in the bottom half of the carrier during as much of the veterinary examination as possible. Hard-sided carriers can be secured by the car’s seatbelt to increase the cat’s safety and prevent jostling during the car ride.

Receiving the Cat and Client FIGURE 1-4 This kitten’s carrier is always left out next to the cat tree. The kitten has learned to use the carrier as a safe haven, which greatly reduces or eliminates fear associated with travel and veterinary visits.

BOX 1-4 Educational Resources For Veterinarians 1. American Association of Feline Practitioners Feline Behavior Guidelines: http://www.catvets.com 2. Feline Advisory Bureau: Creating a Cat Friendly Practice and Cat Friendly Practice 2, www. fabcats.org/catfriendlypractice/guides.html 3. Video: For veterinary professionals: Encourage cat visits, Ilona Rodan, http://www.catalystcouncil. org/enewsletter/february10/index.html 4. Healthy Cats for Life: http://www.healthycatsfor life.com/clinic.html

For Clients 1. Video: Tips for taking your cat to the veterinarian, Ilona Rodan, www.catalystcouncil.org/resources/ video/?Id=89

the carrier. Once the cat regularly enters the carrier at home and uses it for resting, the owner can take the cat on car rides periodically, pairing the ride with positive experiences. Edible treats, favorite toys, and a comb or brush (if the cat enjoys being groomed) can be brought along to make the trip more pleasant and less strange. Fasting the cat for at least a few hours before car travel prevents motion sickness. The fasting also increases the cat’s interest in treats both during the car ride and at the veterinary hospital, which creates a more positive experience. Spraying Feliway (Ceva Animal Health, St. Louis, Mo.), a synthetic feline pheromone that calms the cat, in the carrier 30 minutes before travel is very helpful.28

No matter how calm the reception area is, taking the cat directly to an examination room as soon as it arrives will reduce fear and anxiety caused by seeing, hearing, and smelling unfamiliar people and animals. Minimizing the waiting time is also important because most cats do not calm down as quickly as a dog might in the same circumstances.

First Veterinary Visits and Kitten Classes First veterinary visits allow the veterinary team to set up the kitten or cat for success. If first veterinary visits are pleasant, future veterinary experiences are also likely to be positive.23 Clients are more willing to bring back their cats for routine health care visits if they are not fraught with tension. Cat owners should be taught early about giving their cat positive exposure to normal feline maintenance procedures—such as claw trimming, combing, ear inspections and cleaning, and teeth brushing—so that these stimuli have little or no adverse impact during veterinary visits and home care. Clients should be encouraged to bring their kittens to the clinic between appointments for weight checks, increased socialization, and fun visits, especially during the first year of life. Kitten classes are an excellent way to teach owners how to understand cats and their needs, to provide opportunities for family members to learn how to handle kittens for home maintenance procedures (e.g., claw trimming), and to allow kittens to socialize with other kittens.37 See Chapter 11 for more information on kitten classes.

Getting the Cat Out of the Carrier Once in the examination room, the cat should be allowed to initiate contact; cats are less apprehensive if they can control their environment. While greeting the client and reviewing the cat’s history, the veterinarian should open the carrier door and allow the cat to sniff or explore the room. Tossing or quietly placing catnip or treats near the carrier can entice the cat to venture out on its own. While obtaining the history, the


veterinarian can also assess the patient from a distance without making direct eye contact—which, as previously discussed, the cat may perceive as a threat—to evaluate respiratory pattern, gait, and overall behavior. Monitoring the patient’s posturing and facial expressions and response to treats can reveal the cat’s fear level. If the cat remains wary, the veterinarian may extend an index finger toward the cat that it may smell (and ideally rub against); most cats enjoy rubbing against protruding objects. The veterinarian should not touch the cat on its head or neck as it is exiting the carrier because this often causes the cat to retreat instinctively rather than move forward. If the cat will not leave the carrier voluntarily, the top half of the carrier should be carefully removed, if possible, so that the cat can remain in the bottom half for as much of the examination as possible (Figures 1-5 and 1-6). If the cat is still fearful, the veterinarian may slowly slide a towel between the top and bottom of the carrier while the top is removed. The towel provides a safe hiding place for the cat and is in place for wrapping the towel around the cat (a feline “burrito wrap”) if needed; the towel wrap helps calm and reassure the cat (Figure 1-7). When the cat must be removed from the bottom half of the carrier, lift the cat from underneath, supporting the caudal abdomen near the hind legs. It is extremely important never to dump the cat out of the carrier. Once the cat is out of the carrier, the carrier should be placed out of sight so that the cat will not attempt to return to it.

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Finally, once the examination is finished, the cat should be returned to its carrier as soon as possible.

Handling During Examination 1. The best place to examine the cat is wherever the cat wants to be; as previously explained, this gives the cat some control over its environment. Many cats do not like examination tables because they have been punished for climbing on tables at home. An examination room with perches or shelves, benches, and a small pet scale provides a

FIGURE 1-6 Examining the cat in the bottom half of the carrier often makes it feel more secure and is easier on everyone involved.

FIGURE 1-5 If the cat doesn’t voluntarily leave the carrier, remove the top half. Ideally, have the front of the carrier facing the wall to prevent escape. (Image courtesy Yin S: Low stress handling, restraint and behavior modification of dogs & cats: techniques for developing patients who love their visits, Davis, Calif, 2009, CattleDog.)

FIGURE 1-7 The “burrito” towel wrap often makes cats feel more secure and prevents scratching of those working with the patient. The best handler should educate other staff during staff meetings and assist with new employee training.

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FIGURE 1-8 Cats often prefer to be with their people, either in their laps or sitting next to them. This cat is receiving positive reinforcement, the reward of attention, for good behavior at the veterinary hospital.

FIGURE 1-10 Some confident cats prefer to be higher up and enjoy the cat perches in this examination room.

FIGURE 1-9 Many cats like to stay in a small pet scale after being weighed. The raised sides make them feel more secure.

good selection of options (Figures 1-8 through 1-10). Many cats prefer being examined when they are on a familiar blanket or item of clothing from the carrier, which already has the cat’s scent. Often, it is easiest to have the cat stay next to the client or on the floor or a lap during the examination (Figure 1-11). Cats that like sitting on laps are often comfortable in the clinician’s lap, but it should be in a position where it is facing away from the clinician and can see the family member. Further, it may help the cat feel more secure if it can lean against the clinician’s body; otherwise, it might fear falling from the table. The following suggestions will make the examination far less stressful. • If the table must be used for the examination and collection of laboratory samples, the cat should be placed on a fleece, towel, or other soft

FIGURE 1-11 Some cats prefer to be examined on the floor. Just as children get stickers or treats when they go to the doctor, cats can receive treats or catnip.

material that already has the scent of the cat, such as the padding or favorite person’s clothing from the interior of the carrier. • Slow motions should be used instead of fast ones. • If possible, the cat should be allowed time to relax before the next part of the examination is performed. • The cat should not be stretched out; it should be held in a relaxed manner, without pulling its feet (Figure 1-12).


FIGURE 1-12 The cat should not be stretched out when being held on its side. See how the legs are held in a comfortable position, with the handler’s fingers supporting the feet gently.

2. The least restraint is always the best restraint. If the cat is positioned comfortably and handled minimally, it will be less likely to fight to get away or protect itself. Contrary to common belief, holding a cat by its scruff often makes it more aroused and fearful because it does not provide the cat with a sense of control.39 In the author’s opinion, scruffing should be reserved for queens with their young kittens; the mother cat can sense how much to scruff. The following points describe improved handling techniques. • Rather than scruffing, many cats like to be massaged on their head, behind the ears, or under the chin. Such massage can both distract and calm the cat. Acupressure is another calming technique. The three middle fingers are used to slowly massage or stroke the top of the head, and the first and fifth digits (i.e., thumb and pinkie) are used to control the cat’s head and thereby protect both examiner and cat (Figures 1-13 and 1-14). • The cat should not be stretched or extended; instead, it should be held in a relaxed manner, without pulling the feet. • The order of the examination should be modified to make it easier on the patient; it is not necessary to examine every cat starting at the head and working to the tail. In fact, performing the least stressful parts of the examination first and reserving areas that the cat does not like touched (for some, the teeth and mouth; for many arthritic cats, the feet; for cats with urinary tract problems, the abdomen) until the end of the examination will help the cat stay more relaxed. 3. Remember: “Slow is fast, and fast is slow.” Fast or abrupt movements may alarm the cat and cause it

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FIGURE 1-13 Slowly massaging the top of the head helps comfort the cat.

FIGURE 1-14 Notice how the thumb and fifth digit hold the cat’s head in place while acupressure is used to calm the cat.

to struggle, which may necessitate several holders. It is important to work slowly and confidently to make the cat comfortable. 4. Desired behavior should be rewarded with treats, catnip toys, and soft praise. Rewards help reinforce desired behavior. Unwanted behavior should be ignored or redirected. 5. The clinician should try not to loom over the cat or grab for it; these actions can increase fear in the patient. 6. Anxious cats should be distracted by engaging them in alternative behaviors that are incompatible with fearful or anxious behavior, such as playing with an interactive toy, following a laser pointer, eating treats, or rubbing on catnip. Gently petting the cat behind the ears or rubbing it under the chin can also divert its attention from the procedures being performed.

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7. Many towel-handling techniques can be used to successfully examine both fearful and fearfully aggressive cats and to collect laboratory samples.43 In addition to the previously mentioned burritowrap method (see Figure 1-7), other common towel techniques include the following: • Covering the head with a towel to eliminate visual cues that might induce stress or anxiety • Moving a towel from one side of the cat to another to examine different parts of the cat (Figure 1-15) • Gently placing a towel around the ventral neck and one front leg to keep the cat snugly wrapped, with only one front leg exposed for placing an intravenous catheter or collecting blood from the cephalic vein (Figure 1-16) 8. Prolonged (more than 2 seconds) or repeated struggling is not advised.43 If the cat struggles, the position should be changed, or toweling, sedation, or anesthesia can be used as needed. Analgesia is always recommended if the cat is in pain or might be in pain and if painful procedures are to be performed. Senior patients commonly have arthritis and may experience pain with physical manipulation, positioning for radiographs, or placement on hard surfaces. For a list of painful conditions and procedures, see the AAHA/AAFP Pain Management Guidelines14 and Boxes 1-2 and 1-3. 9. Some cats behave more calmly when visual cues are eliminated. Most cats do not need a muzzle or similar device, but for those that do, several relatively gentle options are available, such as a soft cloth or plastic muzzle that both prevents biting and greatly reduces visual cues. When the veterinarian is working away from the head, an Elizabethan collar (E-collar) or air muzzle can also protect against biting. Some veterinarians, especially in Europe, find “clipnosis,” or pinchinduced behavioral inhibition (e.g., placement of binder clips along the dorsum of the neck), helpful for restraint.31 10. Preparing all necessary equipment in advance helps reduce handling time and keeps the cat from being startled by people going in and out of the examination room. 11. Documenting in the medical record which handling methods work best for the individual patient (and those to avoid because they frighten the cat) improves future veterinary visits and decreases stress for all. When attempting to quiet or calm the cat, the clinician should refrain from making shushing sounds, which sound like hissing to the cat and may exacerbate the aroused state. 12. Clients and veterinary team members empathize with cats that are distressed. However, saying,

FIGURE 1-15 This cat is fearful and is much more comfortable with its head covered. Notice how the technician places her left hand to hold the head in place without scruffing or tight restraint.

FIGURE 1-16 This towel technique provides comfort for the cat and a safe method of handling for venipuncture or catheter placement. (Image courtesy Yin S: Low stress handling, restraint and behavior modification of dogs & cats: techniques for developing patients who love their visits, Davis, Calif, 2009, CattleDog.)

“Poor kitty” or “It’s OK” in a soothing voice may serve as an inadvertent reward for their fearfulness. The best way to help the cat be calm and less fearful is for the veterinary staff and client to remain calm.


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Handling for Laboratory Sample Collection Collecting laboratory samples from cats usually requires only minimal handling. The clinician should ensure that the patient is comfortable during sample collection by allowing the cat to remain in the most natural position possible, without stretching or holding legs tightly. A blanket or something soft for the cat to lie on, preferably an item that smells like home, should be provided. Older, arthritic, and underweight cats are especially uncomfortable on cold, hard surfaces and benefit from having soft padding underneath them. As previously discussed, cats can also be gently wrapped in a towel to help them feel more secure. Many clients prefer to watch while laboratory samples are collected. Having owners present keeps them from worrying about what is happening to their cat, often calms the cat, and furthers client education and respect for the veterinary team.

FIGURE 1-17 Blood pressure measurements from the tail work well with cats that do not like to have their feet handled. Notice that the client is distracting the cat with grooming, which is one of its favorite rewards.

Collecting Blood Samples Measuring Blood Pressure Blood pressure measurements, when indicated, should be taken before other diagnostic tests, while the patient is kept as relaxed and calm as possible to minimize “white coat” hypertension. The environment should be quiet, away from other animals, and the owner should be present if possible.3 Measuring blood pressure is usually best performed in the examination room rather than in the treatment area. The cat needs approximately 5 to 10 minutes to acclimate to a room; by the time the history is obtained and the physical examination is performed, the cat will have become accustomed to the examination room, reducing the likelihood of white-coat hypertension if blood pressure measurement is done there.3,17 The blood pressure readings can be taken from either front (antebrachium) or back (hock) legs or 1 inch from the base of the tail. The latter option is an excellent approach for arthritic cats and those cats that are more fearful when they see what is happening (Figure 1-17). If either the front or the back leg is used, the leg should not be extended excessively; instead, placing a hand gently behind the leg prevents the cat from withdrawing the leg during the procedure and keeps the cat comfortable. Blood pressure measurements should be taken wherever the cat is most comfortable, whether on a lap, in a carrier, or in some other comfortable place. The clinician should use headphones to prevent fear associated with monitor noise. In addition, using warmed gel precludes the startle response often seen with the application of cold gel. A free downloadable article, “Doppler Blood Pressure Measurement in Conscious Cats,” (http://www.catprofessional.com/free_downloads. html) is an excellent educational resource for those new to taking blood pressure measurements.

Most laboratories request a larger blood or serum sample than they actually need; it is helpful to contact the laboratory to find out how much blood is actually needed for the samples. If the laboratory will accept smaller samples, request microtainer or avian EDTA tubes so that a small blood volume is not overly diluted. Regardless of which vein is used to collect the blood sample, most patients require no more than one person to hold them during the collection; in fact, some veterinarians can collect samples from the jugular vein with no additional assistance (Figure 1-18). Many cats tolerate jugular collection very well; this collection site enables speedy collection of a large sample. Other cats prefer not seeing the sample collection and better tolerate collection from the medial saphenous or the cephalic veins; using a butterfly catheter will prevent collapse of these veins if a large blood sample is needed. For patients highly sensitive to needle pricks, lidocaine/prilocaine anesthetic cream (EMLA, AstraZeneca Pharmaceuticals) should be applied over the site at least 30 minutes before blood collection or intravenous catheterization. The site should then be covered with a bandage to prevent the cat from licking the cream. Minimal systemic absorption of lidocaine may occur in some cats, but it is substantially below toxic concentrations.9 No other adverse effects have been reported, although struggling during catheter placement was not significantly reduced with use of EMLA cream in one study compared with placebo.41 Collecting Urine Samples Urine should be collected by cystocentesis (except in rare cases). The cat should be held in as comfortable a position as possible, without extending the legs. Although most veterinarians and technicians prefer placing the cat

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A

B FIGURE 1-18 A, Blood sample being collected from the jugular vein single-handedly. B, Single-handed jugular collection (other view). (Images courtesy Dr. Jane Brunt.)

on an examination or treatment table to perform cystocentesis, the procedure can also be performed with one person holding the cat in the lap (Figure 1-19). The free downloadable article “Cystocentesis in Cats” (http:// www.catprofessional.com/free_downloads.html) is an excellent educational resource and illustrates how to perform cystocentesis with the cat in various positions.

Hospitalization Whenever possible, it is best not to hospitalize cats; being away from home leads to disruption of the social network and lack of a sense of control, both of which can create fear and stress.29 Hospitalized cats often withdraw and are inactive, leading to the misconception that the cat is not stressed. The high stress of the hospital inhibits normal behaviors such as eating, grooming, sleeping, and elimination.11 This novel environment can be espe-

FIGURE 1-19 Cats often are more comfortable being held on someone’s lap for cystocentesis.

cially stressful for senior and geriatric cats and for cats that have not been well socialized.11 If hospitalization is essential, cats should be kept in a quiet area where they do not see other cats or dogs. Protecting the hospitalized cat from the sight and noise of barking dogs and hissing or screaming cats will greatly reduce stress. This goal can be achieved by providing both a separate hospitalized cat ward (see Chapter 2) and isolation areas for cats that hiss or scream and by covering the cat’s cage with a towel or blanket to decrease the sight of hospital activities that may increase anxiety. Obviously, removing all scents of other animals or people is nearly impossible in a hospital or clinic environment. However, spraying Feliway in the cage at least 30 minutes before the patient is moved there will help calm the cat and increase food intake and grooming.12 Most veterinary clinic caging is too small for cats. Cages should be large enough so that the cat can stretch, groom, exercise, and have separate spaces for eating, sleeping, and eliminating (Figure 1-20).11 Shelves and climbing opportunities can extend the available cage space (Figure 1-21). Indeed, by providing vantage points from which the cat can monitor its surroundings and detect the approach of people and other animals, such vertical space can make the patient feel more in control of its environment.29 In addition, providing materials the cat can use to make a hiding place can greatly reduce stress. Cats will hide when they are anxious or feel threatened35; hiding is an important coping strategy in response to change in environment.13 Hiding places can be as simple as a paper bag, a cardboard box, or even a blanket or towel. Placing a blanket or padding on top of a sturdy cardboard box creates both a hiding place and perch. Comfortable bedding should be provided in both the sleeping and hiding area. Cats prefer to rest on soft surfaces and experience longer periods of normal sleep


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FIGURE 1-20 Cat condominiums with multiple shelves allow cats

FIGURE 1-22 A towel twisted into a circle provides a convenient

to choose where they wish to be.

and comfortable bed that readily allows monitoring of intravenous catheters.

FIGURE 1-21 Cages that lack perches and hiding places can be modified by the addition of a sturdy box with space for hiding and being up high or a commercially made addition that allows hiding and perching. (Image courtesy Drs. Peter and Kari Mundschenk.)

when they lie on soft bedding.11 A towel twisted into a circle (Figure 1-22) makes a good pet bed and allows visual monitoring of the status of intravenous catheters without disturbing the patient.43 Caged cats show signs of stress when the caretaking routine is unpredictable and when they have few or no human social interactions.27 Consistent feeding and cleaning times are less stressful for feline patients,29 as are consistent times for attention, grooming, and weight checks. Because cats prefer contact with familiar people, the same staff member should, whenever possible, care for a cat being hospitalized or boarded. Also, the cat owner should be encouraged to visit the cat during hospitalization.11 Removing a fearful cat from a cage can be extremely challenging because the cat perceives that its opportunity to escape is restricted.13 To reduce the fear response, the veterinarian or technician should stand to the side of

FIGURE 1-23 Standing or squatting to the side of the cage and gradually letting the cat approach or removing the cat while it remains in its basket or box is an excellent way to remove a cat from a cage.

the cage, not directly in front. From that position, the cat should be gently encouraged to approach or enter the carrier on its own (Figure 1-23). Reaching into the cage and trying to grab the cat will be counterproductive and is likely to exacerbate any fear responses.

Returning Home In most situations a cat experiences no difficulty returning home from the veterinary hospital. Two situations should be addressed with clients, however: the aroused cat and other cats in the household that may not accept the returning cat.

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An aroused cat may remain reactive for several hours or even days before it calms down.13 If a cat is still aroused when sent home, it is important to explain the situation clearly to the client so that he or she knows what to expect. Until the cat becomes calm again at home, no one should handle the cat and— equally important—everyone should ignore the aroused behavior, so as not to not reinforce or cause it to escalate. Regardless of how long the cat has been at the veterinary hospital, other cats in the household might not readily accept the returning cat because its scent will be unfamiliar.36 In most situations, keeping the returning cat in the carrier until all cats are calm, which usually takes place within a few hours, is sufficient. Clients should be reminded to ignore any hissing or screaming and reward any positive interactions. If the re-introduction still causes problems, the client should first wipe the cat (or cats) that remained in the household with a towel and then wipe the returning cat with the same towel to transfer the familiar scent to the “stranger.” In rare cases, cats will need to go through the same procedure used when introducing a new cat to a household. One approach to prevent severe problems with the return home is taking both (or all) cats to the veterinarian at the same time, even when only one has a scheduled visit. As previously discussed, spraying Feliway in the carrier (or carriers) at least 30 minutes before travel to the veterinary hospital and including familiar clothing with your scent and the scent of the other cat (or cats) in the carrier (or carriers) will reduce stress and anxiety for the cats during the visit to the clinic.

CONCLUSION Knowing how the cat perceives and communicates with its environment and other cats helps us to better comprehend the cat’s signals at the veterinary hospital. Further, recognizing that fear and pain are the most common reasons for aggression at the veterinary hospital enables us to respect and understand the cat and provide analgesia as needed. It is now widely accepted that hissing and screaming cats are fearful cats trying to communicate with us to prevent escalation to outright aggression. Understanding the cat and working calmly with the cat will improve veterinary visits and feline health care. Working confidently with this knowledge means that veterinary team members are more relaxed and better able to help clients and cats relax during veterinary visits. This knowledgeable approach will improve the cat’s (and the client’s) visit and interactions at the veterinary hospital.

References 1. Beaver B: Feline behavior: a guide for veterinarians, ed 2, St Louis, 2003, Saunders. 2. Bowen J, Heath S: An overview of feline social behaviour and communication. In Behaviour problems in small animals: practice advice for the veterinary team, Philadelphia, 2005, Saunders, p 29. 3. Brown S, Atkins C, Bagley R et al: Guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats, J Vet Intern Med 21:542, 2007. 4. Crowell-Davis S: Social behaviour, communication and development of behaviour in the cat. In Horwitz D, Mills D, Heath S, editors: BSAVA manual of canine and feline behavioural medicine, ed 1, Gloucester, 2002, British Small Animal Veterinary Association, p 21. 5. Crowell-Davis S, Curtis T, Knowles R: Social organization in the cat: a modern understanding, J Fel Med Surg 6:19, 2004. 6. DiBartola S, de Morais H: Disorders of potassium. In diBartola SP, editor: Fluid therapy in small animal practice, ed 2, Philadelphia, 2000, Saunders, p 83. 7. Driscoll CA, Clutton-Brock J, Kitchener AC et al: The taming of the cat. Genetic and archaeological findings hint that wildcats became housecats earlier—and in a different place—than previously thought, Sci Am 300:68, 2009. 8. Driscoll CA, Menotti-Raymond M, Roca AL et al: The Near Eastern origin of cat domestication, Science 317:519, 2007. 9. Fransson B, Peck K, Smith J et al: Transdermal absorption of a liposome-encapsulated formulation of lidocaine following topical administration in cats, Am J Vet Res 63:1309, 2002. 10. Greco DS: The effect of stress on the evaluation of feline patients. In August J, editor: Consultations in feline internal medicine, ed 1, Philadelphia, 1991, Saunders, p 13. 11. Griffin B, Hume KR: Recognition and management of stress in housed cats. In August J, editor: Consultations in feline internal medicine, ed 5, St Louis, 2006, Saunders, p 717. 12. Griffith C, Steigerwald E, Buffington C: Effects of a synthetic facial pheromone on behavior of cats, J Am Vet Med Assoc 217:1154, 2000. 13. Heath S: Feline aggression. In Horwitz D, Mills D, Health S, editors: BSAVA manual of canine and feline behavioural medicine, ed 1, Gloucester, 2002, p 216. 14. Hellyer P, Rodan I, Brunt J et al.: AAHA/AAFP pain management guidelines for dogs and cats, J Feline Med Surg 9:466, 2007. 15. Landsberg G, Hunthausen W, Ackerman L: Fear and phobias: Handbook of behaviour problems of the dog and cat, ed 2, Philadelphia, 2003, Saunders. 16. Lin CH, Yan CJ, Lien YH et al: Systolic blood pressure of clinically normal and conscious cats determined by an indirect Doppler method in a clinical setting, J Vet Med Sci 68:827, 2006. 17. Love L, Harvey R: Arterial blood pressure measurement: physiology, tools, and techniques, Compend Contin Educ Pract Vet 28:450, 2006. 18. Lue TW, Pantenburg DP, Crawford PM: Impact of the owner-pet and client-veterinarian bond on the care that pets receive, J Am Vet Med Assoc 232:531, 2008. 19. Macdonald DW, Apps P, Carr G: Social dynamics, nursing coalitions and infanticide among farm cats, Felis catus, Adv Ethology 28, 1987. 20. Macdonald DW, Yamaguchi N, Kerby G: Group-living in the domestic cat: its sociobiology and epidemiology. In Turner DC,Bateson P, editors: The domestic cat: the biology of its behaviour, Cambridge, 2000, Cambridge University Press, p 95. 21. McMillan F: Development of a mental wellness program for animals, J Am Vet Med Assoc 220:965, 2002. 22. Milani M: Crate training as a feline stress reliever, Feline Pract 28:8, 2000.


23. Mills D: Training and learning protocols. In Horwitz D, Mills D, editors: BSAVA manual of canine and feline behavioural medicine, ed 2, Gloucester, 2009, British Small Animal Veterinary Association, p 49. 24. Moffat K: Addressing canine and feline aggression in the veterinary clinic, Vet Clin North Am Small Anim Pract 38:983, 2008. 25. Notari L: Stress in veterinary behavioural medicine. In Horwitz D, Mills D, editors: BSAVA manual of canine and feline behavioural medicine, ed 2, Gloucester, 2009, British Small Animal Veterinary Association, p 136. 26. Overall K: Normal feline behavior: Clinical behavioral medicine for small animals, St Louis, 1997, Mosby, p 45. 27. Overall K: Recognizing and managing problem behavior in breeding catteries. In Lawler D, editor: Consultations in feline internal Medicine 3, Philadelphia, 1997, Saunders. 28. Pageat P, Gaultier E: Current research in canine and feline pheromones, Vet Clin North Am Small Anim Pract 33:187, 2003. 29. Patronek G, Sperry E: Quality of life in long-term confinement. In August J, editor: Consultations in feline internal medicine, ed 4, Philadelphia, 2001, Saunders, p 621. 30. Patronek GJ, Lacroix CA: Developing an ethic for the handling, restraint, and discipline of companion animals in veterinary practice, J Am Vet Med Assoc 218:514, 2001. 31. Pozza ME, Stella JL, Chappuis-Gagnon AC et al: Pinch-induced behavioral inhibition (“clipnosis”) in domestic cats, J Feline Med Surg 10:82, 2008. 32. Rand J, Kinnaird E, Baglioni A et al: Acute stress hyperglycemia in cats is associated with struggling and increased concentrations of lactate and norepinephrine, J Vet Intern Med 16:123, 2002.

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33. Robertson S, Lascelles B, Taylor P et al: PK-PD modeling of buprenorphine in cats: intravenous and oral transmucosal administration, J Vet Pharmacol Ther 28:453, 2005. 34. Robertson S, Taylor P, Sear J: Systemic uptake of buprenorphine by cats after oral mucosal administration, Vet Rec 152:675, 2003. 35. Rochlitz I: Recommendations for the housing of cats in the home, in catteries and animal shelters, in laboratories and in veterinary surgeries, J Feline Med Surg 1:181, 1999. 36. Rochlitz I: Basic requirements for good behavioural health and welfare in cats. In Horwitz D, Mills D, editors: BSAVA manual of canine and feline behavioural medicine, ed 2, Gloucester, 2009, British Small Animal Veterinary Association, p 35. 37. Seksel K: Preventing behavior problems in puppies and kittens, Vet Clin North Am Sm Anim Pract 38:971, 2008. 38. Taylor P, Funk C, Craighill P: Gauging family intimacy: dogs edge cats (dads trail both): Pew Research Center Report, 2006. 39. Vigne J, Guilaine J, Debue K et al: Early taming of the cat in Cyprus, Science 304:259, 2004. 40. Vogt AH, Rodan I, Brown M et al: AAFP-AAHA: Feline life stage guidelines, J Feline Med Surg 12:43, 2010. 41. Wagner K, Gibbon K, Strom T et al: Adverse effects of EMLA (lidocaine/prilocaine) cream and efficacy for the placement of jugular catheters in hospitalized cats, J Feline Med Surg 8:141, 2006. 42. Yin S: Classical conditioning: learning by association, Compend Contin Educ Pract Vet 28:472, 2006. 43. Yin S: Low stress handling, restraint, and behavior modification of dogs and cats: techniques for developing patients who love their visits, Davis, Calif, 2009, CattleDog Publishing.

C H A P T E R

2

The Cat-Friendly Practice Jane E. Brunt O U T L I N E Feline Veterinarians, 21 Foundations of a Cat-Friendly Practice, 21

Physical Features of a Cat-Friendly Practice, 21 Conclusion, 24

The need for attention to cats’ medical needs was first acknowledged by the American Association of Feline Practitioners (AAFP) in the early 1970s.1 Since that time, increasing membership and programming in AAFP and other feline-oriented veterinary organizations, coupled with growth in the cat population, has allowed the areas of feline medicine and surgery to become increasingly mainstream and available through traditional companion animal veterinary hospitals and clinics, as well as feline-exclusive veterinary facilities. The addition of board certification for feline medicine specialists through the American Board of Veterinary Practitioners (ABVP) (http://www.abvp.com/categories_feline.htm. Accessed February 7, 2010) has further elevated the field of feline veterinary medicine. An increasing number of felinespecific scientific journals and consumer publications in print and online have provided more information to diverse audiences. Efforts to increase feline scientific and market research have been undertaken by foundations such as Winn Feline Foundation,15 Morris Animal Foundation,9 and the Cornell Feline Health Center.4 Despite the increased popularity of and knowledge about cats, recent statistics have shown that veterinary expenditures are declining even while the cat population continues to grow.5 According to the American Veterinary Medical Association, the number of owned cats in the United States went from an estimated 59.1 million in 1996 to 81.7 million in 2006. Relative to veterinary care and services for dogs, cats receive far less medical care compared with dogs, and there was an 11% decline in feline veterinary visits between 2001 and 2006. In 2006 only 64% of owned cats visited the veterinarian, compared with 83% of dogs.5 Reasons for this disparity


range from the difficulty of transporting cats (e.g., putting them in a carrier) to a lack of awareness regarding cats’ basic medical needs, a failure to recognize signs of illness, and the misperception that cats are able to take care of themselves.8 In response to the decline in veterinary care for cats, in February 2008 the AAFP hosted the CATalyst Summit, which featured representatives from more than 30 independent organizations across North America, including veterinary associations, shelter and welfare groups, foundations and cat fanciers, the media, and commercial industries. At this event more than 50 people united in their concern for the health and well-being of cats vowed to change the negative ways in which cats are often perceived and portrayed (http://catalystcouncil.org/newsroom/index.aspx? Id=9; accessed February 3, 2010).3 After the summit, leaders formed the CATalyst Council and set forth a vision of a future in which “all cats are valued and well cared for as pets.”3 Several collaborative and strategic initiatives were identified and implemented, including the development and publication of Feline Life Stage Guidelines by the AAFP and American Animal Hospital Association (AAHA) for veterinary health care teams.14 These guidelines have also been made available online (http://www.catvets. com/uploads/PDF/Feline%20Life%20Stage%20 Guidelines%20Final.pdf; accessed January 25, 2010) and are referenced in other areas of this textbook. A version of these guidelines for cat owners called CATegorical Care: An Owner’s Guide to America’s #1 Companion is also available (http://www.winnfelinehealth.org/Pages/ CATegorical_Care.pdf). 20


CHAPTER 2 The Cat-Friendly Practice

FELINE VETERINARIANS Any veterinarian who treats a single cat is a feline veterinarian and as such will benefit from a greater understanding of normal feline physiology and behavior, the ways in which cats respond to external stimuli, and the idiosyncrasies of domestic cats. Recent investigations regarding stimulation of the hypothalamic–pituitary– adrenal axis show that stressors placed on any individual cat can have negative consequences and play a role in development of disease.2 This knowledge will help all veterinary health care team members to construct or modify physical and administrative features of their veterinary practices to enhance the comfort, care, and safety of cats, clients, and coworkers. By making the necessary modifications, incorporating proper handling techniques,13 and implementing ongoing feline health education, virtually every veterinary facility can become a cat-friendly practice.

FOUNDATIONS OF A CAT-FRIENDLY PRACTICE It is important to begin by engaging the entire health care team in the development of a cat-friendly practice. The framework for any new team and client communications, techniques, and physical or administrative changes can be provided in the following sequence: • Education and commitment of staff; enlistment of a point person or team • Adoption of AAFP–AAHA Feline Life Stage Guidelines14 and development of practice protocols • Scripting and role playing to communicate cats’ needs to coworkers and clients • Adherence to respectful feline handling techniques13

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time the cat arrives. In other words, the cat may be experiencing stress before it is even presented to the practice. With this understanding, the veterinary team can take the appropriate measures to mitigate this arousal or at least respond appropriately.10

Public Areas Cat owners notice certain signs that cats are welcome at veterinary hospitals. Exterior features such as signage and cat statuary create an inviting appearance. Some facilities offer a separate entrance for cats. The reception area is usually the first place at which an owner interacts with a veterinary clinic or hospital, and a warm and calming environment contributes to a comfortable atmosphere for the client and cat (Figure 2-1). Cat-specific décor portraying cats in a positive manner is far more likely to encourage the cat owner to think, “This place likes and respects cats” than a design that focuses on dogs at the expense of cats. Posters or illustrations of staring cats are not recommended insofar as cats perceive this behavior as confrontational (Figure 2-2). Elevated counters or platforms near the reception desk allow space for cat carriers to be kept away from dogs. Segregated seating, which is less likely to result in visual and auditory arousal of the feline patient by dogs, other cats, or unfamiliar clients, is preferred (Figure 2-3)12; escorting the owner and cat into an examination room as soon as possible may help prevent further arousal. Some veterinary practices have adopted “cat-only” office hours to decrease the likelihood of interaction with canine patients. Providing cat-specific educational material in the reception area will also benefit both clients and cats.

Examination Rooms Once the cat is inside the examination room, it should be allowed to come out of the carrier on its own and

PHYSICAL FEATURES OF A CAT-FRIENDLY PRACTICE Cats are more sensitive to sights, smells, and sounds, as well as touch, and arousal occurs through these senses, particularly in an unfamiliar setting. Heightened arousal subsequent to a change in routine and then travel frequently results in fear, and the normal physiologic mechanisms of fear can lead to aggression if the cat is unable to escape to a perceived safe area.13 For example, if a cat is forced into an unfamiliar carrier and transported to the veterinary hospital, the stress generated by these activities has already initiated changes in heart rate, respiration, and other effects of epinephrine release by the

FIGURE 2-1 Calming environment of reception area. Cat Care Clinic, Madison, Wis. (Image courtesy Dr. Ilona Rodan.)

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FIGURE 2-2 Reception area with cat décor. Nine Lives Cat Hospi-

FIGURE 2-4 Performing examination on scale. Cat Hospital of

tal, Sunrise, Fla. (Image courtesy Dr. Samuel Frank.)

Metairie, Metairie, La. (Image courtesy Dr. Karen Miller-Bechnel.)

FIGURE 2-3 Segregated seating to minimize visual arousal.

explore its unfamiliar surroundings; this may help dispel the cat’s anxiety. Controlling sounds, which includes voices in and around the examination room, often helps improve patient compliance. Examination tables covered with soft mats or towels increase the comfort of the patient on the table; bedding the cat has traveled with has its own scent and will help the environment seem more familiar. Many cats enjoy sitting on a tray-style pad or scale if available, and some veterinarians use these to perform the examination (Figure 2-4). Other cats prefer to sit on their owner’s lap or stay on the floor while the veterinarian comes to their perceived safe area (see Figure 1-11). Being flexible and adjusting the examination to the individual cat’s needs is critical and is addressed in Chapter 3. The beneficial effects of synthetic facial pheromone have been documented, and this product should be considered for all areas of the hospital where cats will be present.6,10

FIGURE 2-5 Treatment area adapted to cats’ smaller size. Cat Hospital of Portland, Ore. (Image courtesy Dr. Elizabeth Colleran.)

Treatment Areas Because cats are smaller than most dogs, the use of smaller tables and work areas may increase the ease of access to and handling of the feline patient. Treatment islands and peninsulas are preferred insofar as they provide space for the veterinarian, technician, and assistants to work comfortably with the patient on adjacent or opposite sides (Figure 2-5). As in the examination room, providing nonskid padding underneath the patient will help provide comfort and stability. Care should be taken not to overstimulate patients’ senses.

FIGURE 2-6 Feline patient with intravenous pump and comfort-


23

FIGURE 2-7 Many cats prefer access to a vertical space.

able bedding.

Calm and deliberate movement and treatment of unpleasant odors will minimize arousal; keeping the treatment area free of equipment that may make loud noises, such as dental tools, centrifuges, washers, and dryers, may help prevent fear caused by loud and unfamiliar sounds.

Equipment The small size of feline patients is an important consideration when selecting supplies and equipment. Insulin syringes of various U-100 sizes (e.g., 1 2 and 1 3  mL) are helpful in administering accurate doses of injectable medications, and the small needle size decreases pain. Alternatively, 1-mL tuberculin syringes with a 23- to 25-gauge needle may be used. The use of small-volume blood collection supplies (e.g., microtubes) facilitates collection of the minimum sample size needed. Other supplies, such as endotracheal tubes in various sizes from 3.5 to 5 Fr, nasoesophageal feeding tubes (human infant feeding tubes), and esophageal feeding tubes, permit nutritional support of the ill or injured feline patient. Essential equipment includes safe warming blankets or other devices; intravenous and syringe pumps (Figure 2-6); blood pressure monitoring equipment; pulse oximetry and other anesthesia-monitoring devices; non-rebreathing anesthesia circuits; 0.5-L and 1-L rebreathing bags and resuscitation devices; general and dental radiography (digital equipment decreases the time the patient is under anesthesia and eliminates processing time and errors); refractometer and glucometer; human pediatric stethoscopes; and oxygen masks or cones, cage, or other means in which to deliver oxygen in a nonfrightening manner.7 Soft muzzles to minimize visual stimulation and protect the safety of patient and

handler may be used if appropriate training has been provided and the patient permits placement.

Housing The housing of cats in veterinary hospitals follows the same principles of minimizing arousal of the senses. Having separate wards for cats and dogs is advised, and cages should be situated so that cats do not have visual contact with other patients (Figure 2-7). Areas such as an isolation room are important to separate cats suspected of having contagious diseases. Viral upper respiratory infections are most commonly disseminated by fomite transmission, and strict hygiene procedures associated with an isolation area should be implemented throughout the facility. Cats infected with feline leukemia virus and feline immunodeficiency virus that are otherwise healthy should be housed in regular cat wards, not in an isolation ward with other cats with contagious diseases. Use of nonmetal cages decreases both sound and conduction of heat away from the body. Cats seek out vertical space and benefit from being able to move to other locations. Therefore condo-style cages can minimize stress by allowing the cat to hide or “escape” (Figure 2-8). Similarly, provision of hiding areas such as boxes, covered bedding, or the cat’s own carrier with the door removed afford cats a sense of refuge while inside the cage (Figures 2-9 and 2-10).7,12 Because cats evolved as desert animals, providing an ambient temperature that is somewhat higher than the human comfort zone of approximately 21° C (70° F) and more in the range of 26° C (80° F) may be beneficial.2a At a minimum, bedding to provide insulation and allow burrowing will permit the cat to use its own body heat

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FIGURE 2-8 Cat condos allow for retreat. Cat Hospital of Portland,

FIGURE 2-10 Patient housed with familiar carrier and bedding.

Ore. (Image courtesy Dr. Elizabeth Colleran.)

FIGURE 2-9 A cardboard box provides hiding space.

for increased warmth as well as serving as a hiding area (Figure 2-11).

CONCLUSION By understanding and following the words of legendary feline veterinarian Dr. Barbara Stein (“Cats are not small dogs”), the veterinarian can ensure a cat-friendly veterinary practice regardless of the species being treated. The key to providing cat-friendly care lies in recognizing the unique nature of cats, educating team members and clients about cats’ needs, and handling and treating feline patients according to those needs. When these fundamental points are observed, the development and implementation of procedures and adaptation of a facility become instinctive, like cats themselves.

FIGURE 2-11 Tent-style plush bedding helps keep patients warm.

References 1. American Association of Feline Practitioners. About AAFP (website): http://www.catvets.com/about/index.aspx?Id=239. Accessed January 23, 2010. 2. Buffington CA, Pacak K: Increased plasma norepinephrine concentration in cats with interstitial cystitis, J Urol 165:2051, 2001. 2a. Buffington CA: Personal communication. January 19, 2010. 3. CATalyst Council, Inc. Accessed January 23, 2010 at http:// www.catalystcouncil.org. 4. Cornell Feline Health Center. College of Veterinary Medicine. Cornell University, Division W-3, Ithaca, NY 14853. Accessed January 23, 2010, at http://www.vet.cornell.edu/FHC/. 5. Flanigan J, Shepherd A, Majchrzak S et al: US pet ownership & demographics sourcebook, Schaumburg, Ill, 2007, American Veterinary Medical Association. 6. Griffith CA, Steigerwald ES, Buffington CA: Effects of a synthetic facial pheromone on behavior of cats, J Am Vet Med Assoc 217:1154, 2000. 7. Harvey A: Cat friendly practice 2. Accessed January 23, 2010, at http://fabcats.org/catfriendlypractice/cat%20friendly%2032pp. pdf.

8. Lue TW, Pantenburg DP, Crawford PM: Impact of the owner–pet and client–veterinarian bond on the care that pets receive, J Am Vet Med Assoc 232:531, 2008. 9. Morris Animal Foundation. 10200 East Girard Ave. B430, Denver, CO 80231. Accessed January 23, 2010, at http://www.morrisani malfoundation.org/. 10. Overall K, Rodan I, Beaver B et al: Feline behavior guidelines from the American Association of Feline Practitioners, J Am Vet Med Assoc 227:70, 2005. 11. Pageat P, Gaultier E: Current research in canine and feline pheromones, Vet Clin North Am Small Anim Pract 33:187, 2003.


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12. Riccomini F, Harvey A, Rudd S: Creating a feline friendly practice. Accessed January 23, 2010, at http://fabcats.org/catfriendly practice/catfriendly44pp.pdf. 13. Rodan I, Folger B: Respectful handling of cats to prevent fear and pain. American Association of Feline Practitioners Position Statement. Accessed January 23, 2010, at http://catvets.com/uploads/PDF/ Nov2009HandlingCats.pdf. 14. Vogt AH, Rodan I, Brown M et al: AAFP–AAHA: Feline life stage guidelines, J Feline Med Surg 12:43, 2010. 15. Winn Feline Foundation: Accessed January 23, 2010, at http:// www.winnfelinehealth.org/.

C H A P T E R

3

Deciphering the Cat: The Medical History and Physical Examination Vicki Thayer O U T L I N E Establishing Relationship-Centered Care, 26 The Medical History, 26

The Physical Examination, 31

Dr. Jim Richards, the late director of the Cornell Feline Health Center, said, “Cats are masters at hiding illness.”22 As veterinarians and cat lovers, clinicians must become masters at understanding and uncovering the illnesses so effectively hidden by cats. The purpose of this chapter is to assist veterinarians in developing techniques to decipher the obscure and sometimes confusing messages delivered by their feline patients. Preparing a complete medical history and performing a feline-centric physical examination are two essential tools for resolving patient issues and informing clients of the best means to keep their feline companions healthy. Above all, by working together as a unit, the veterinary health care team can deliver a consistent message: that cats benefit from routine examinations, and wellness health care, along with early disease intervention, increases the length and quality of the feline companion’s life.31 Emphasizing this message should be the goal of the veterinarian during all interactions with the client and patient.

expectations. Use of respectful and appropriate handling techniques further enhances the veterinarian’s message while minimizing the stress and anxiety many cats exhibit during veterinary visits. A model for demonstrating concern for the patient and enhancing the clinical interview through the use of distinctive, describable behaviors is well established in the field of human medicine. A similar concept in the veterinary field is called relationship-centered care.28 Studies suggest that organizing these communication skills into a pattern of behaviors or habits is integral to the process and outcomes of medical care. The “Four Habits” model quickly establishes rapport and builds trust, facilitates the effective exchange of information, demonstrates caring and concern, and increases the likelihood of compliance and positive health outcomes for the patient (Box 3-1, Figure 3-1).7

THE MEDICAL HISTORY ESTABLISHING RELATIONSHIP-CENTERED CARE

Initial Information Phase With today’s electronic media, the veterinarian can obtain relevant information for building an initial history before the kitten or cat visits the hospital. For example, many owners use e-mail and social networks to communicate their observations and concerns. Sending a history questionnaire to the client, either electronically or by regular mail, is an effective way to

All clients expect the veterinarian to care about cats and to care about their cat in particular. By using the cat’s name and referring to its sex correctly and by eliciting and acknowledging the client’s comments, the veterinarian builds on the bond between the client and cat and provides a strong foundation for meeting the client’s


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CHAPTER 3 Deciphering the Cat: The Medical History and Physical Examination

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BOX 3-1 Four Habits: Enhancing the Clinical Encounter Habit #1: Invest in the Beginning • Create rapport quickly (use eye contact and appropriate terms of address, review record). • Elicit client’s concerns (use open-ended questions and continuers). • Plan the visit (repeating concerns, checking understanding, stating what to expect).

Habit #2: Elicit the Client’s Perspective • What caused the problem from the client’s perspective? • What is the client’s main worry? • What are the client’s expectations of the visit? • What impact has the problem had for the patient and the client?

FIGURE 3-1 Relationship-centered care (e.g., taking time to discuss medication with the cat owner) aids in client compliance. (Image courtesy Dr. Debra Givin.)

Habit #3: Demonstrate Empathy • Be compassionate. • Be open to the client’s emotions. • Be aware of nonverbal expressions of emotions.

Habit #4: Invest in the End • • • •

Share results (deliver diagnostic information). Confirm understanding of shared information. Involve the client in decision making. Complete the visit (discuss treatment plan, check for adherence, provide support).

gather information for a new or extended patient medical evaluation before the scheduled visit. Furthermore, this questionnaire can be used when an owner cannot be present for the history taking and physical examination (e.g., when patients are dropped off). Having correct contact information and a method or time for follow-up ensures accurate communication at the beginning of the client–veterinarian relationship. The veterinary team can also establish an initial history when the appointment is scheduled or during client and patient check-in. Specific questionnaires can also be developed for different medical issues, such as behavior or mobility problems and cognitive dysfunction.19,23 Histories must be consistent and comprehensive. Open-ended questions requiring a definitive response rather than a simple yes or no result in the best answers. The following are examples of open-ended questions: “What was the last day you noticed a normal appetite?”; “When did you last notice a normal volume and

consistency of stool?”; “What other changes have you noticed?” The client’s initial responses can lead to more specific questions or prompts to continue (e.g., “Please describe what you have seen”; “What else?”; “Go on”) to help define a specific problem (Box 3-2).3 By repeating key information provided by the client, veterinarians demonstrate that they are paying attention and care about the client’s perspective. Additionally, a veterinarian who demonstrates the various behaviors and sounds cats make with certain conditions, such as when coughing or vomiting, can help owners better describe their cat’s signs. By videotaping signs or behaviors and sharing the video with the veterinarian over the Internet, the client can communicate a complicated or an infrequently noted problem. This is also a useful way for the veterinarian to monitor the ongoing status of a case, especially when the cat becomes highly stressed during veterinary visits and is therefore difficult to examine. A good example is a series of videos posted online about “Cricket” (http://www.youtube.com/ user/NLMACNEILL; accessed February 24, 2010). The patient had a slowly improving right tibial nerve and hock injury requiring a series of re-evaluations. Hospital visits were problematic, and video monitoring allowed effective and less stressful follow-up. Adapting the communication style depending on the client’s age group and individual preferences may be constructive. For example, some elderly clients require extra time and a sympathetic ear for their concerns. A more focused set of interview questions and additional attention to treatment compliance may be necessary to ensure understanding. On the other hand, some younger clients prefer to communicate using newer technologies and social media.

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BOX 3-2 Sample Interview Questions General

Behavior

Gait/Mobility Appetite

Vomiting or regurgitation Water Intake Urinary

Defecation

Continuers

How has your cat been doing since the last visit? When did your cat last appear normal? Are there any hair coat changes? Has your cat changed its grooming habits? Are the signs intermittent or continuous? What behavior changes have you recently noticed? How frequently does the problem occur? When does it occur? Have there been any recent changes to the environment? Are there any changes to sleep patterns? Any changes in interactions with family or other pets? Are there any changes to the level of activity? Any fearful behavior noted? Is there decreased responsiveness? Is there increased vocalization? Is there any reluctance to move or to be handled? Any weakness noted? Is there any evidence of lameness? Any swelling? Any painful areas noted? When did your cat last eat a normal meal? Is the appetite normal, increased, or decreased? What type of food is fed and how much? Any recent food changes? Is there any pain or difficulty while eating? Any reluctance to eat or food avoidance? Is there any vomiting or regurgitation? Describe the appearance of the vomitus. How often has it happened? How soon after eating? Has water intake changed? Increased or decreased? For how long? Has the amount of urine changed? Increased or decreased? Has the frequency of urination increased or decreased? For how long? Is there any straining to urinate? What color is the urine? Is there evidence of pain while trying to urinate? Any vocalizing while urinating? Has there been any urinating in odd places or outside the litter box? Have bowel movements changed in appearance (color, consistency, size, or volume)? Is there any straining to defecate? Any crying out with defecation? Is there any defecation outside the litter box? Describe any changes you have noticed. Anything else? Please go on. Please describe. Hmm?

Routine History Signalment collection is part of the initial informational stage and includes age, breed, sex, and reproductive status. There are different wellness and disease concerns for kittens (up to 6 months of age) and junior (7 months to 2 years), adult (3 to 6 years), mature (7 to 10 years), senior (11 to 14 years), and geriatric cats (15 years and older) (see Chapter 8).31 Often, other factors, such as diet, behavior, and medication history, are more significant in light of the patient’s age group. Including questions about where the cat was acquired (e.g., shelter, rescue group, found as a stray) or whether the cat previously lived in another geographic location helps define essential elements of the history.27 Cats adopted from shelters are more likely to have been exposed to infectious disease agents (e.g., feline herpesvirus).26 Veterinarians practicing in the Pacific Northwest are less likely to diagnose feline heartworm disease in a cat raised locally than in one that was recently relocated from the Gulf State region and is not on a heartworm preventive.16

An increasing number of kittens and cats adopted from shelters, as well as strays and owned cats, have been microchipped. Each new patient should be scanned, preferably with a universal microchip scanner, to confirm the presence of a microchip and document the radio-frequency identification (RFID) in the patient record. According to research, rescanning during annual examinations ensures that the microchip remains functional and has not migrated. Also, encouraging clients to keep their personal information current with their microchip registry helps reunite the client and cat in case of separation.14 Established in 2009, the American Animal Hospital Association (http:// www.petmicrochiplookup.org; accessed February 21, 2010) and Chloe Standard (http://www.checkthechip .com; accessed February 21, 2010) microchip websites are available for rapid association of a microchip number with a client’s personal information. If no microchip is present, further discussion of the benefits of microchipping or another form of visual identification is warranted.


A new kitten or patient visit is a great opportunity to discuss behavior. An unaddressed behavior problem can lead to a diminished cat–human bond and increase the cat’s risk of being relinquished to a shelter or euthanized. An initial set of behavior-based questions can help clients and veterinarians explore this issue. Some undesirable behaviors (e.g., urinating outside the litter box) may be the result of an undiagnosed medical condition. Further, a discussion of general litter-box habits is appropriate. Reviewing behavior during the kitten visits also helps the client understand the interactions required during the early (3 to 8 weeks) and late (9 to 16 weeks) socialization periods. Proper bonding early in the kitten’s life leads to fewer behavioral problems later in life (Figure 3-2).19 A complete vaccination history documenting the types and dates of vaccinations, especially those given when the client first acquired the kitten or cat, is a critical step in building a complete patient medical history. It is important to note and highlight any past adverse reactions to vaccinations and follow up with a discussion of the potential disease risks and benefits associated with an immunization program. Age, health status, and whether the cat is kept indoors or has regular outdoor access are primary risk determinants. Even cats that are kept inside should not be considered strictly indoor creatures because outdoor pathogens and parasites can be brought inside and cats may periodically escape outside. Because of this possibility, rabies immunization remains a core vaccine recommendation for cats even in communities where it is not legally required.24 Clients should be asked whether preventive drugs for heartworm, fleas, and other external and internal parasites are used; if they are, the veterinarian should note the product, dosage, and application interval in the medical record.27,31

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A cat’s retroviral status (feline leukemia virus and feline immunodeficiency virus) is also an essential part of a complete history. Retrovirus testing is performed at different times in a cat’s life, and the dates and results should be documented in the medical record. Depending on the responses and history obtained thus far, the key retrovirus risk factors (e.g., male sex, age, outdoor access) can be explored with the client to determine the need for initial testing or retesting.12 Nutrition, especially diet type and source (including treats), and daily caloric intake are other important components of a cat’s medical history. Because a dietary change can either create or resolve an acute or chronic medical condition, updating the patient’s nutritional history is an accepted and recommended practice. Further, because some clients do not know the brand, flavor, type, and amount of food consumed by their pet, persistent questioning and follow-up may be required. This issue becomes especially important when there is a significant change in the cat’s weight and body condition score (BCS) (Figure 3-3). A change in weight may also affect the prescribed dosage of a medication. For example, because prednisolone does not appear to distribute to adipose tissue, the dosage for obese cats is based on ideal or lean body weight instead of current body weight.4 Questions regarding water sources, water intake, and the amount and type of urine and feces produced by the patient can follow. Using veterinary software to track the nutritional history and maintain contact information is beneficial in the event of a pet-food recall. The significance of the 2007 melamine contamination of pet food demonstrates the value of dietary information management.5

Prior and Existing Complaints

FIGURE 3-2 Early bonding enhances the veterinary visit and the owner’s lifelong relationship with the pet. (Image courtesy Dr. Debra Givin.)

Additional history is required when the client seeks veterinary care for an existing complaint. Knowledge of current and past medications, as well as prior laboratory test results, may help clarify a medical problem or spur additional issue-oriented questions (e.g., “How did the cat respond to treatment?”; “Did anyone have difficulty giving the medication?”; “Were there any side effects, and if so, what were they?”). Three common general presenting signs are anorexia, lethargy, and a change in normal behavior (e.g., hiding). Clients regularly report one or more of these general signs when asked to describe their cat’s problems. Specific questions should be asked about the dose and frequency of administration of prescribed medications because clients sometimes make changes without consulting the veterinarian. Moreover, clients may not report the use of nonprescription medications or supplements unless questioned directly. Questions focusing on specific observations by the client before the onset of the problem and during the

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FIGURE 3-3 An example of a 9-point body condition scoring chart for the cat. (Image used by permission from Nestle Purina Petcare.)


initial phase help the conversation move from generalizations to a specific description. Responses also help the veterinarian establish a timeline for additional intervening signs. The following are examples of questions that might prompt such responses: “Was the onset acute or gradual?”; “Were the signs steady or intermittent?”; “Has the problem occurred previously, and if so, what was the response?” Evaluating the client’s answers helps the veterinarian determine the diagnosis, develop a list of possible causes, and decide on subsequent diagnostic planning. However, diagnosis can be fluid; new or different medical problems may emerge after the initial diagnosis. If so, the veterinarian may need to ask the client additional questions, further observe the patient, and re-evaluate the original diagnosis.23,27 An effective medical history summarizes the known health situation and the needs and potential problems of the patient (Box 3-3). The next step, a comprehensive physical examination, helps assemble the pieces of the puzzle.

THE PHYSICAL EXAMINATION Initial Steps History preparation is an opportune time for the patient to adjust to its surroundings. This gives the patient a

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chance to relax, thus enabling a more productive and less stress-inducing examination. Often, if given time and opportunity, cats voluntarily leave the carrier to explore (Figure 3-4). Although most patients will relax on the examination table, it is not unusual for others to find a comfortable perch elsewhere in the room. Performing the examination where the patient is most comfortable (e.g., on the floor, on a chair or bench) may be an effective tactic for the veterinarian. Further, providing familiar objects such as toys, towels, or a fleece bed can help make the cat more comfortable. Offering treats may calm the cat and entice it to leave the carrier. Spraying a towel or nearby surfaces with a synthetic feline pheromone (e.g., Feliway) or placing pheromone diffusers in the examination room may also help reduce stress.25 Conversely, some cats respond with more heightened senses if allowed to roam the room or hide under chairs or other furniture. Learning to recognize body postures associated with fear is fundamental for veterinarians and clients.25 In these situations it is better to keep the cat in the carrier and minimize wait time and anxiety. The veterinarian should carefully observe the cat’s behavior and demeanor while it is in the carrier or walking around the room. Detecting changes in gait, evidence of pain, types of respiratory patterns, or areas of asymmetry at this time can lead to additional questions for the client and specific issues to address in the

BOX 3-3 Medical History Components Signalment Locality Acquisition Environment Vaccinations Parasite Control Diet Microchip Retroviral Testing Prior Medical History Existing Complaints

Age, breed, sex, and reproductive status Disease prevalence in current and prior geographic locations Private home, shelter, stray, pet store, or breeder Primarily indoor, outdoor or both; other household pets; city, urban, or rural; possible toxin exposure; layout of home and yard History and any adverse reactions History and treatment, current and prior Canned food, dry food, or both; brand and quantity; raw food; hunting prey; treats and supplements RFID number, registry information, periodic rescanning Dates, results, and risk evaluation Illnesses, medications, adverse reactions, laboratory tests and results Last known normal state Acute or gradual onset Progression (continuous or intermittent) Duration of problem Primary problem and prevailing secondary signs Present signs (attitude, appetite, activity, weight changes, water intake, behavioral changes, urination, defecation, and gait/mobility)

Modified with permission from Sherding RG: The medical history, physical examination, and physical restraint. In Sherding RG, editor: The cat: diseases and clinical management, ed 2, Philadelphia, 1994, Saunders, p 7.

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FIGURE 3-5 Cats should be weighed on a tabletop scale during FIGURE 3-4 The cat should be allowed time to exit the carrier on

every veterinary visit. (Image courtesy Dr. Debra Givin.)

its own before the examination when possible. (Image courtesy Dr. Debra Givin.)

physical examination. Some cats may be so ill during the initial observation that an assessment must be done quickly and the patient moved to a treatment area or enclosure. It is important to minimize stress and promptly stabilize ill patients before attempting a more detailed examination.6 An effective physical examination technique follows a routine, consistent pattern but allows for some flexibility. Cats perceive the world through their senses, and their response to a new setting and unfamiliar smells in the examination room is not predictable. If the cat prefers to remain in the carrier and exhibits signs of anxiety, the carrier top should be removed and a thick towel used to cover the cat. This is often a convenient time to weigh the cat, either after removing it from the carrier or while the cat is still in the carrier (with the carrier’s weight subtracted from the total). A tabletop scale designed for small animals or human infants is the best equipment for weighing cats (Figure 3-5). The veterinarian can proceed by adjusting the towel as needed (Figure 3-6) while the cat remains in the carrier or after gently lifting and removing the cat from the carrier. Tipping the carrier and dumping the cat onto the examination table or floor is not recommended.25 As the examination continues, the veterinarian should move slowly and deliberately and speak quietly. The veterinarian should maintain physical contact with the cat by having examination tools close at hand. Losing physical contact may increase the cat’s level of anxiety and lead to difficulty in completing the examination. The undeniable fact is that cats demand time and attention. A mindset of “less is more; more is less” and “slow is fast; fast is slow” pays dividends in both efficiency and effectiveness. The care, the time, and the examination should be tailored to the patient’s needs.

FIGURE 3-6 If needed, a towel can be used during the examination. (Image courtesy Dr. Vicki Thayer.)

Starting an examination at the tip of the nose and working toward the tip of the tail is a common and effective technique for some clinicians; others, especially during the initial examination, prefer to face the cat away to minimize eye contact, which some cats may find threatening. If the cat resists, the veterinarian can modify the routine to fit the patient and resume the examination in a less sensitive area, such as the head, over the hindquarters, or the abdomen and lumbar area. It is helpful to be flexible yet thorough and adapt to the cat’s comfort level. For most patients, obtaining an accurate rectal temperature reading is possible by slowly inserting a welllubricated, quick-reading digital thermometer (Figure 3-7) while distracting the patient with treats or gentle massage of the head. If appropriate, the veterinarian can check for fecal impaction and anal tone at this time.


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FIGURE 3-7 Using a digital thermometer to take a rectal tempera-

FIGURE 3-8 Gentle pressure in the intermandibular space elevates

ture. (Image courtesy Dr. Vicki Thayer.)

the tongue, allowing discovery of linear foreign bodies. (Image courtesy Dr. Susan Little.)

Forgoing temperature measurement during wellness examinations of less tolerant but healthy patients is acceptable. Using an ear thermometer for fractious cats is a reasonable alternative, although its accuracy, especially in ill cats, has been questioned.11 It should be noted that a cat’s body temperature can exceed 103° F (39.4° C) on warm days or as a result of travel stress. According to current expert opinion, pain is considered the fourth vital sign after temperature, pulse, and respiration. Pain assessment is an essential part of every patient evaluation. Many conditions and procedures cause pain in cats, and veterinarians must remain aware of this potential and look for its signs. Because a change in behavior is the most common sign of pain, understanding a patient’s normal behavior is important in identifying changes and making an appropriate choice to intervene. Several resources to aid in this process are available to the veterinary health care team.9

As with the nose, the lips and chin are evaluated for lesions or skin changes. Next, the teeth are assessed, with any losses noted, along with oropharyngeal inflammation, periodontal disease, tooth resorption (formerly called feline odontoclastic resorptive lesions or neck lesions), and tooth fractures. The cat’s mouth should be held open to examine the roof, both fauces, and the back of the throat (Figure 3-8). Common complaints include mouth odor, difficulty chewing, or pawing at the mouth. Jaundice is often most readily appreciated on the hard palate. The veterinarian should review the entire mouth for lesions consistent with inflammation. Applying gentle pressure with a thumb in the intermandibular space and elevating the tongue allow discovery of linear foreign material or other abnormalities in the sublingual area (see Figure 3-8).27 A nonhealing inflammatory lesion requires evaluation for potential underlying neoplasia. Squamous cell carcinoma is the most common oral cancer in cats and is often seen as a mass under the tongue.18 Further, color and appearance of the mucous membranes are indicators of anemia (pale), cyanosis (blue tint), and jaundice (yellow tint). A prolonged capillary refill time raises questions regarding the patient’s tissue perfusion status. Moving on to the eyes, the veterinarian should first appraise the status of or changes in the palpebral openings, pupils, eyelids, and nictitating membranes. The veterinarian should look for evidence of exophthalmus (may indicate retrobulbar lesions), retraction of the globe (may indicate weight loss or dehydration), excessive tearing, and blepharospasm. Next, the pupils are checked to confirm that they are equal in size and equally responsive to light. The patient’s eyes should be examined for vascularization, cellular or fluid infiltrates, and ulceration in each cornea. The conjunctiva and sclera should be observed for signs of jaundice, anemia, and

The Head First, the nose is examined for any surface changes or lesions. Any lack of symmetry or the presence of discharge or an occasional foreign body, such as a blade of grass, can be more easily detected by shining a light on the nostrils. Ulcers on the nasal commissure may indicate an upper respiratory virus infection (e.g., feline calicivirus, feline herpesvirus).15 Type and color of any nasal discharge should be documented, along with whether it is unilateral or bilateral; these signs can indicate inflammation, infection, or neoplasia. Unusual sound or air movement can denote obstruction or upper airway disease. Stertorous noise (e.g., snoring or snorting) may indicate changes involving the pharynx, whereas stridor (i.e., wheezing) is localized to the laryngeal area.13

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inflammation. The iris is assessed for change in color, thinning or thickening, and hyperemia, and hyperpigmented lesions should be monitored for changes in size or appearance during subsequent examinations. Uveal lesions may be the result of trauma, infectious disease (e.g., feline infectious peritonitis, feline immunodeficiency virus infection), or neoplasia. Senile nuclear sclerosis may occur as the cat ages. Cataracts may be congenital in some breeds, most commonly Persians and British Shorthairs, or subsequent to other problems, such as trauma or anterior uveitis.1 Finally, the retina is evaluated by direct or indirect ophthalmoscopy for hemorrhage (may indicate hypertension), detachment (may indicate tumor, hypertension, or trauma), neoplasia (e.g., lymphoma), and degenerative (e.g., retinal atrophy) or inflammatory changes (e.g., toxoplasmosis).27,32 Proceeding to the ears, the surface of each pinna is examined for areas of alopecia or other skin lesions, including inflammation, ulceration, color changes, and crustiness. Each ear is checked for wounds or abscesses, especially if the cat engages in fighting, and aural hematomas. Evidence of jaundice or petechiae, if present, is typically observed in the medial lining of the pinnae. The ear canals are examined with an otoscope for changes and views of the tympanic membrane. The eardrum is normally flat and tense and the ear canal lining is generally smooth and devoid of wax or discharge. A cytologic examination of abnormal wax content or discharge can confirm preliminary diagnoses of ear mites (Otodectes cyanotis), Demodex sp., bacterial infections, or yeast overgrowth (Malassezia sp.).29 Abnormal growths or polyps may be the result of chronic inflammation or evidence of neoplasia. Pain on opening the mouth may be a sign of underlying external or middle ear disease when oral disease is not present.

The Neck and Forelimbs Examination of the neck and forelimbs begins with palpation of the submandibular lymph nodes, salivary glands, and larynx. The paratracheal region, from the caudal larynx to the thoracic inlet, is checked for an enlarged thyroid gland. The normal thyroid gland may not be palpable. Although the classic technique to examine the thyroid gland is with the cat sitting and the neck and head extended upward for palpation, other effective techniques have been described (Figure 3-9).20 The veterinarian should continue exploring the surface of the neck for lesions, changes since prior examinations, and evidence of pain. Ventroflexion of the neck may be evidence of a thiamine or potassium deficiency, polymyopathy, or polyneuropathy. Gently flexing and extending the muscles, bones, and joints of the front legs help in detecting any swelling, discomfort, or lack of mobility. This can be accomplished through simultaneous palpation of both limbs and

FIGURE 3-9 Thyroid gland palpation is an essential component of a senior cat examination. (Image courtesy Dr. Vicki Thayer.)

comparison of one limb with the other. The veterinarian should examine both front paws for the condition of the nails, nail beds, pads, and interdigital tissue while noting any unusual lesions or injury. Polydactyl and geriatric cats often have a nail that has grown into a digital pad. Nails that are split or torn completely from the nail bed can be evidence of trauma.

The Thorax and Trunk Auscultation of the heart and lungs is a critical component of a complete thoracic examination. The veterinarian should position the cat so that it is facing forward and listen for rate, rhythm, and possible murmurs, using both the bell and diaphragm of the stethoscope (Figure 3-10). Auscultation is most effective in a quiet room. It may be necessary to ask the owner not to talk during thoracic auscultation. The presence of a cardiac murmur does not always signify underlying heart disease, nor does its absence preclude structural heart disease.21 Murmurs may result from other physical states, such as anemia or the patient’s hydration status. Both sides of the thorax are auscultated to evaluate the heart from base to apex as well as along the sternum. The maximum intensity of cardiac sounds is usually from the third to fifth intercostal spaces on the left side. Loud cardiac murmurs will create palpable vibrations on the chest wall, referred to as a precordial thrill, and are experienced as a “buzzing” sensation typically at the point of maximum intensity. Gallop rhythms and other arrhythmias, such as bradycardia, are associated with forms of feline cardiomyopathy. In hyperdynamic states such as hyperthyroidism, sinus tachycardia is frequently


35

As a final step in examining the thorax and trunk, the veterinarian should palpate the ribs, trunk, dorsum, ventrum, axillae, and mammary chains for lumps, abnormal lesions, and enlarged lymph nodes. Mammary neoplasia is not uncommon in female cats, and early detection is important for improving prognosis. Mammary masses should be considered neoplastic until proven otherwise. Pectus excavatum or deformity of the xiphoid process of the sternum may be seen in younger cats. Focal lymph node enlargement signifies regional disease, usually subsequent to abscesses or skin disease, and diffuse lymphadenopathy may be the result of systemic disease, such as lymphoma.

The Abdomen FIGURE 3-10 Cardiac auscultation should be performed in a quiet examination room. (Image courtesy Dr. Vicki Thayer.)

a prominent sign. Palpating the femoral pulse while auscultating the heart may help the veterinarian detect a pulse deficit or weakness. Diminished or no femoral pulse, along with cold, pale, and weak extremities, may indicate an aortic thromboembolism. Jugular vein distention or jugular pulses may be the result of right-sided heart failure; these are observed by wetting or shaving the hair over the jugular groove.2,27 Monitoring the respiratory rate and pattern, along with thoracic auscultation, can assist in detecting the presence of an underlying cardiac or respiratory disease. The normal respiratory rate is 20 to 40 breaths per minute. However, an increased respiratory rate can also be due to excitement, fever, pain, or fear. Dyspnea, or difficult or labored breathing, is primarily an observed state and usually causes anxiety for the cat. Pulmonary edema and pleural effusion may increase the respiratory rate with noticeable inspiratory and expiratory effort and no audible airway noise. Breath sounds are usually absent ventrally when pleural fluid is present. Careful percussion of the chest can identify areas of increased air or the presence of fluid or masses. Prolonged expiration, an expiratory or abdominal push, or other increased respiratory efforts are indicators of lower airway disease caused by narrowing or obstruction of smaller airways. Lower airway disease (e.g., possible pulmonary edema or inflammatory airway disease) may produce harsh lung sounds such as inspiratory crackles and expiratory wheezes. Additional clinical signs of chronic respiratory disease may include a barrelchested appearance and decreased chest compressibility. Patients with respiratory compromise may be unable to lie down comfortably and often sit hunched with the elbows abducted.10

The veterinarian should visually evaluate the general size and appearance of the abdomen while palpating for fluid, fat, organ distention, or pain. Abdominal pain or discomfort during palpation may be due to an underlying pathology, although this type of reaction can also result from handling anxiety. Palpation is accomplished by moving front to back and from each side, using the tips of the fingers of one hand or both hands close together. Soft ballottement of the abdominal wall may indicate the presence of fluid or enable the veterinarian to detect other causes of abdominal distention. The liver is usually not palpable, but if hepatomegaly is present, the edge of the liver will be palpable past the costochondral arch. The veterinarian should note the shape of the palpable edge of the liver (e.g., sharp versus rounded edge or smooth versus irregular) because it may indicate abnormal changes. As with the liver, the stomach and pancreas are not usually palpable. An enlarged spleen may denote hematopoietic or myeloproliferative disorders involving infiltration of the splenic tissue with abnormal type and numbers of lymphocytes and mast cells. In many cats it is possible to discern both kidneys, with the left kidney being more caudal than the right. Palpation helps in the detection of changes in size (larger or smaller) or shape (smooth versus irregular). A normal urinary bladder in the posterior abdomen has a thin wall and does not elicit pain on palpation. A larger, tense, and painful bladder may indicate a possible lower urinary tract obstruction. The normal nonpregnant uterus is not palpable in cats. An enlarged uterus may be palpated as tubular structure(s) distinct from the intestinal tract and may be caused by pregnancy or uterine disease such as pyometra. A massively enlarged uterus may be due to latestage pregnancy, pyometra, hydrometra, or mucometra and can occupy most of the abdominal space. The small intestine is usually easily palpable, and the intestinal wall is typically symmetric throughout. A

36


change in wall thickness, asymmetry, distention of intestinal segments, or pain on palpation often indicates an underlying pathology. Mesenteric lymph node enlargement may be associated with these signs and may result from inflammation or neoplasia. The various sections of colon are also palpable, and a colon full of feces is typically a sign of constipation or, more significantly, obstipation. Because obesity may mask significant changes to abdominal organs, successful palpation of obese cats requires extra attention by experienced veterinarians; in some cases, it may be impossible to perform a thorough abdominal palpation.

The Hindquarters and Tail The hind legs and paws are evaluated and compared in the same manner as the front legs and paws. The veterinarian should gently flex and extend the coxofemoral, stifle, and hock joints to test for impaired mobility or pain, noting any swelling or other abnormalities. A tendency toward medial patellar luxation in one or both stifles may be detected in some younger cats. Acute lameness in cats, especially overweight cats, may be due to an anterior cruciate ligament rupture and requires testing for anterior drawer motion and noting any pain in the stifle joint. The skin, pads, and nails of the hind paws are examined for similar problems as the front, although ingrown nails are less frequent.

Starting at the base of the tail and proceeding to the tip, the veterinarian palpates for possible wounds, pain, and swelling. Sacrococcygeal dislocations or fractures caused by trauma are most often discovered at the base. Next, the anal and perineal regions are assessed for appearance and cleanliness. Extra skin folds or the inability to clean the perineum often leads to hygienic issues and dermatitis in obese patients (Figure 3-11). Evidence of tapeworm infection, Taenia taeniaeformis or Dipylidium caninum, may be found in the hair surrounding the anus. The anal glands are located at the 4 and 8 o’clock positions around the anus. Palpation of the anal glands may determine whether they need to be emptied, and anal gland abscesses are not uncommon in the cat. Cats can develop perineal hernias leading to fecal impaction. Rectal examination, when needed, may require patient sedation or general anesthesia in some cases. The vulva is normally free of discharge, even when a queen is in estrus. The veterinarian should check unneutered male kittens and cats to confirm whether both testes are located in the scrotal sacs. If it is unknown whether a male cat has been neutered or is cryptorchid, the penis should be checked for spines. The presence of penile spines indicates a source of testosterone, typically a retained testicle.

Final General Assessment

FIGURE 3-11 Perineal dermatitis is often seen in very obese patients. (Image courtesy Dr. Susan Little.)

Finally, the veterinarian examines, touches, and evaluates the skin and hair coat during the examination and discusses any issues with the client. Unusual odors may be the result of underlying problems, such as discharge from infected wounds and exposure to questionable agents (e.g., smoke, chemicals). Most cats prefer to be clean; a decreased desire to groom may reflect illness. Excessive saliva on the hair coat, especially the hair covering the lower extremities, may indicate significant oral disease. Evidence of fleas or external parasites is found by combing sections of the hair coat at any time during the exam. The veterinarian should discuss noteworthy hair mats with the client and if needed, recommend removal (Figure 3-12). Matting of the hair coat can be uncomfortable for the cat and may reflect decreased grooming resulting from obesity, especially if the mats are evident on the caudal half of the body, in areas the cat can no longer reach. The veterinarian should monitor white cats and those with white or lightly pigmented areas on or around the pinnae, eyelids, and nasal philtrum for solar dermatitis or dysplastic changes.17 Skin bumps or growths should be measured with a ruler or caliper, and these characteristics documented in the record. Alopecia, wounds, and other skin abnormalities should also


37

FIGURE 3-12 Matting of the hair can indicate decreased grooming

FIGURE 3-13 Leg index measurement (LIM) for the Feline Body

habits, often resulting from underlying medical conditions. (Image courtesy Dr. Susan Little.)

Mass Index is the length (in cm) from the middle of the patella to the dorsal tip of the calcaneal process. (Image courtesy Dr. Susan Little.)

BOX 3-4 Formula for Calculation of the Feline Body Mass Index   RCC  − LIM     Percentage body fat =  0.7062  − LIM 0.9156   Reprinted with permission from Waltham Focus, 10:32, 2000. RCC, Rib cage circumference; LIM, leg index measurement. All measurements in cm.

be noted. Alopecia over a joint may indicate pain, such as that associated with osteoarthritis. Alopecia on the ventral abdomen may indicate bladder pain. An area of fluctuant swelling with localized warmth often indicates an abscess, a common condition for cats. During the final stages of the examination, the veterinarian scores general body condition by assigning a composite rating using either a 5-point or a 9-point scale (see Figure 3-3). Weight loss or weight gain is often best understood by the owner when it is expressed as a percentage of the cat’s previous weight (e.g., the cat has gained 15% more than the previous weight recorded). Alternatively, the Feline Body Mass Index (FBMI) developed by the Waltham Center for Pet Nutrition provides an indicator of body fat content.8 This valuable measurement tool helps clinicians and researchers better define the relationship between body fat content and disease risk in cats. The formula to determine FBMI is shown in Box 3-4. The equation uses rib cage circumference and

FIGURE 3-14 Measurement of rib cage circumference (RCC) (in cm) for the Feline Body Mass Index. (Image courtesy Dr. Susan Little.)

the leg index measurement (the length of the lower hindlimb from the middle of the patella to the dorsal tip of the calcaneal process) (Figures 3-13 through 3-15). If the cat has lost weight, muscle loss or wasting is evaluated. Specifically, a loss of muscle mass over the back (e.g., prominent vertebral spinous processes) or legs (e.g., prominent scapulae) and a pendulous abdomen or a large inguinal fat pad may indicate a serious underlying medical condition. Barring emaciation or the effects of aging, gauging skin turgor by tenting the skin over the back and monitoring its return to a resting position provides a rough assessment of hydration and assists in evaluating the patient’s health status. Mild skin tenting may not occur until a cat is at least 5% dehydrated.

Rib cage circumference (cm)

60 58 56 54 52 50 48 46 44 42 40 38 36 34 32 30 28 26 24 22 20

Overweight

Normal weight

Under weight

LIM (cm)

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

FIGURE 3-15 Use of the leg index measurement (LIM; in cm) and rib cage circumference (in cm) to determine Feline Body Mass Index. (Image courtesy WALTHAM Center for Pet Nutrition.) Emotional Soap Medical variables How do you think this animal is doing?

Emotional variables

S |S

–physical appearance –body language and demeanor

–physical appearance Subjective

–interactions with the owner

What does the owner tell you about this animal and the presenting problem? What is the important medical history? What did you find on physical exam?

–body language and demeanor –interactions with the pet

What is the reason for the visit? What does your intuition tell you about this patient?

How do you think this owner is doing?

What might the owner need from you? What do you feel/ notice/suspect?

O |O Objective What are the facts?

What past experiences and knowledge can you draw on for this case?

A |A

What diagnosis can you rule in based on your collected information?

Assessment

What does your intuition tell you about this owner? What does the owner tell you about his/her feelings and relationship with this pet? What is the important emotional history? What do you find on the Family-Pet Relationship Information Form? What past experiences and knowledge can you draw on for this case? What emotional needs and supportbased services can you rule in as potentially applicable to this case?

What can you conclude from an overall synthesis of the data? What options can you recommend and offer for treatment? What is the time frame for treatment? What is the cost of treatment?

What is the treatment follow-up?

P |P Plan What treatment and support options are available to owners?

What options/resources (supportive people, finances, time) are available to this owner? What is the time frame for support? What is the cost of the recommended support services? What is the support follow-up?

FIGURE 3-16 Emotional Subjective Objective Assessment Plan.


Moderate skin tenting occurs when a cat is 6% to 8% dehydrated, and skin tenting that stays in place for a few seconds or longer indicates at least 10% dehydration. The appearance of sunken eyes or dry, tacky mucous membranes can further confirm dehydration. A neurologic assessment is best performed when the history and physical examination indicate that it is necessary. A short version of a cranial nerve exam can be achieved while evaluating the head and neck area. The final steps in a comprehensive and effective physical examination involve reviewing findings with the client and outlining treatment recommendations. A concise written “report card” for the patient is an accepted method of helping the client understand treatment recommendations. In fact, sharing examination findings, explaining treatment options, and providing a possible prognosis within a SOAP (subjective, objective assessment plan) format increases owner compliance and satisfaction with the proposed regimen.6 If a sick cat is being assessed, an Emotional SOAP technique (http:// www.aah-abv.org, see Autumn 2002 newsletter; accessed February 24, 2010) can be used concurrently with the typical SOAP format to meet the client’s emotional needs (Figure 3-16).30 In many cases, listing differentials and so-called “rule outs” in the aforementioned format may also help explain the need for further diagnostic measures such as laboratory tests as part of a minimum database.

References 1. Barnett KC, Crispin SM: Feline ophthalmology: an atlas and text, London, 2002, Saunders, p 122. 2. Bonagura J: Cardiovascular diseases. In Sherding RG, editor: The cat, diseases and clinical management, ed 2, Philadelphia, 1994, Saunders, p 819. 3. Caney S: Weight loss in the elderly cat, J Feline Med Surg 11:730, 2009. 4. Center SA: Progress in characterization and management of the feline cholangitis/cholangiohepatitis syndrome, Proc Am Assoc Feline Pract Fall Conf 1-16, 2009. 5. Ciancolo RE, Bischoff K, Ebel JG et al: Clinicopathologic, histologic, and toxicologic findings in 70 cats inadvertently exposed to pet food contaminated with melamine and cyanuric acid, J Am Vet Med Assoc 233:729, 2008. 6. Ettinger SJ: The physical examination of the dog and cat. In Ettinger S, Feldman EC, editors: Textbook of veterinary internal medicine, ed 6, St Louis, 2005, Saunders, p 2. 7. Frankel M, Stein T: Getting the most out of the clinical encounter: the four habits model, Perm J 3:79, 1999. 8. Hawthorne A, Butterwick R: The feline body mass index: a simple measure of body fat content in cats, Waltham Focus 10:32, 2000. 9. Hellyer P, Rodan I, Brunt J et al: AAHA/AAFP pain management guidelines for dogs and cats, J Am Anim Hosp Assoc 43:235, 2007. 10. Henik R, Yeager A: Bronchopulmonary diseases. In Sherding RG, editor: The cat: diseases and clinical management, ed 2, Philadelphia, 1994, Saunders, p 979. 11. Kunkle G, Nicklin C, Sullivan-Tamboe D: Comparison of body temperature in cats using a veterinary infrared thermometer and a digital rectal thermometer, J Am Anim Hosp Assn 40:42, 2004.

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12. Levy J, Crawford C, Hartmann K et al: AAFP feline retrovirus management guidelines, J Feline Med Surg 10:300, 2008. 13. Levy J, Ford R: Diseases of the upper respiratory tract. In Sherding RG, editor: The cat: diseases and clinical management, ed 2, Philadelphia, 1994, Saunders, p 947. 14. Lord L, Ingwersen W, Gray J et al: Characterization of animals with microchips entering animal shelters, J Am Vet Med Assoc 235:160, 2009. 15. Mansell J, Rees C: Cutaneous manifestations of viral disease. In August JR, editor: Consultations in feline internal medicine, ed 5, St Louis, 2006, Elsevier, p 11. 16. Nelson CT, Seward RL, McCall JW et al: 2007 guidelines for the diagnosis, treatment and prevention of heartworm (Dirofilaria immitis) infection in cats (website): www.heartwormsociety.org/ veterinary-resources/feline-guidelines.html. Accessed February 21, 2010. 17. Ogilvie GK, Moore AS: Skin tumors. In Ogilvie GK, Moore AS, editors: Feline oncology: a comprehensive guide to compassionate care, Trenton, N.J., 2001, Veterinary Learning Systems, p 412. 18. Ogilvie G, Moore A: Tumors of the alimentary tract. In Ogilvie GK, Moore AS, editors: Feline oncology: a comprehensive guide to compassionate care, Trenton, NJ, 2001, Veterinary Learning Systems, p 271. 19. Overall K, Rodan I, Beaver B et al: Feline behavior guidelines of the American Association of Feline Practitioners, J Am Vet Med Assoc 227:70, 2005. 20. Paepe D, Smets P, van Hoek I et al: Within- and between-examiner agreement for two thyroid palpation techniques in healthy and hyperthyroid cats, J Feline Med Surg 10:558, 2008. 21. Paige CF, Abbott JA, Elvinger F et al: Prevalence of cardiomyopathy in apparently healthy cats, J Am Vet Med Assoc 234:1398, 2009. 22. Pittari J, Rodan I: Senior cats: untangling the problems of these special patients, J Feline Med Surg 11:737, 2009. 23. Pittari J, Rodan I, Beekman G et al: American Association of Feline Practitioners senior care guidelines, J Feline Med Surg 11:763, 2009. 24. Richards J, Elston TH, Ford RB et al: The 2006 American Association of Feline Practitioners Feline Vaccine Advisory Panel report, J Am Vet Med Assoc 229:1405, 2006. 25. Rodan I, Folger B: Respectful handling of cats to prevent fear and pain, American Association of Feline Practitioners Position Statement: http://catvets.com/uploads/PDF/Nov2009HandlingCats. pdf. Accessed February 21, 2010. 26. Scarlett J: Controlling feline respiratory disease in animal shelters. In August JR, editor: Consultations in feline internal medicine, ed 5, St Louis, 2006, Saunders, p 735. 27. Sherding RG: The medical history, physical examination, and physical restraint. In Sherding RG, editor: The cat: diseases, and clinical management, ed 2, Philadelphia, 1994, Saunders, p 7. 28. Suchman AL: A new theoretical foundation for relationshipcentered care: complex responsive processes of relating, J Gen Intern Med (Suppl 1):S40, 2006. 29. Venker-van Haagen AJ: Diseases and surgery of the ear. In Sherding RG, editor: The cat: diseases and clinical management, ed 2, Philadelphia, 1994, Saunders, p 1999. 30. Villalobos A: Hospice “Pawspice.” In August JR, editor: Consultations in feline internal medicine, ed 6, St Louis, 2010, Saunders, p 811. 31. Vogt AH, Rodan I, Brown M et al: AAFP-AAHA: feline life stage guidelines, J Feline Med Surg 12:43, 2010. 32. Wilkie D: Diseases and surgery of the eye. In Sherding RG, editor: The cat: diseases and clinical management, ed 2, Philadelphia, 1994, Saunders, p 2011.

C H A P T E R

4

Guidelines and Precautions for Drug Therapy in Cats Lauren A. Trepanier O U T L I N E Differences in Drug Metabolism in Cats, 40 Dosage Adjustments for Renal Insufficiency, 40 Drug Therapy Considerations in Hepatic Insufficiency, 44 Therapeutic Considerations in Neonates and Kittens, 44

Therapeutic Considerations in Senior and Geriatric Cats, 45 Drug Compounding for Cats, 46 Alternative Formulations/Routes for Medicating Cats, 47 Conclusion, 49

Drug therapy in feline patients has many potential roadblocks: differences in drug metabolism between cats and other species, which make dose extrapolations difficult; a paucity of good safety and dose optimization studies in cats; the relative lack of approved drugs with associated efficacy data in cats compared with dogs; the need for reformulation of many drugs designed for larger patients; and the difficulty in administering medications to many cats.

cats are able to normally glucuronidate endogenous compounds such as thyroxine41 and bilirubin.87 Cats are also deficient in the enzyme thiopurine methyltransferase, which metabolizes thiopurine drugs such as azathioprine. The activity of this enzyme, which can be measured in red blood cells, is 80% to 85% lower in cats than in dogs.29,79,100 This may explain why cats treated with azathioprine are especially sensitive to myelosuppression,3 which is a dose-dependent side effect of this drug. Further individual variability in thiopurine methyltransferase among cats (almost tenfold) can be attributed to genetic polymorphisms in the feline gene, such that there is overlap between some “highactivity” cats and some “low-activity” dogs.45,79 However, a relationship between polymorphisms in thiopurine methyltransferase and azathioprine response has not yet been established in either cats or dogs.

DIFFERENCES IN DRUG METABOLISM IN CATS Cats have important differences in drug metabolism compared with humans and dogs, two species from which feline dosages are often extrapolated. It is well known that cats are deficient in glucuronidation of some xenobiotics; for example, UDP-glucuronosyltranferase (UGT) activity for acetaminophen is tenfold lower in cats compared with dogs and humans.20 This is due to a nonfunctional feline pseudogene for UGT1A6,21 the UGT isoform that metabolizes acetaminophen in humans. This same enzyme glucuronidates morphine and serotonin48 and contributes to the metabolism of silybin (in milk thistle).55 Glucuronidation is therefore deficient for many drugs in cats (Table 4-1). However,


DOSAGE ADJUSTMENTS FOR RENAL INSUFFICIENCY Renal insufficiency leads to decreased filtration of renally eliminated drugs and their active metabolites, as well as impaired tubular secretion of some drugs, including famotidine, ranitidine, trimethoprim, and digoxin.86 These drugs are ionized at physiologic pH and in humans 40


CHAPTER 4 Guidelines and Precautions for Drug Therapy in Cats

41

TABLE 4-1 Xenobiotic Glucuronidation Capacity in the Cat Compounds

UGT Enzyme Responsible in Humans

Glucuronidation in Cats

Clinical Consequences and Dosing in Cats

Acetaminophen

UGT1A6 (pseudogene in cats)21

Hepatic activities tenfold lower in cats compared with dogs and humans20

Acetaminophen toxicity at threefold to fourfold lower doses in cats (≥60 mg/kg) versus dogs (≥200 mg/kg)81

Morphine

UGT2B7 and others in humans

No glucuronide metabolites in dogs in vivo50 Not evaluated in cats

Elimination half-life of morphine in cats (1-1.5 h)91 is similar to that in dogs (1.2 h)50

Chloramphenicol

UGT2B715

Not directly evaluated in cats

Slightly longer elimination half-life in cats (~4-8 h) compared with dogs (1.1-5 h)71

Aspirin

Several isoforms (UGT1A6 has high affinity)49


Longer elimination half-life in cats (22 h)69 compared with dogs (5-6 h)61 Dosed fourfold less frequently in cats versus dogs

Thyroxine

UGT1A1 and others104

Thyroxine is glucuronidated in cats63

Comparable daily thyroxine dosages in dogs and cats

Carprofen

Glucuronidated in humans78

Glucuronidated in dogs78

Isoform not identified


Oral elimination half-life in cats (20 h)69 prolonged compared with dogs (8 h) (Rimadyl label) Increased susceptibility to carprofen toxicity in cats (gastrointestinal signs at 8 mg/kg in cats versus 20 mg/kg in dogs)58

require active transport in the renal tubules for elimination in the urine. Renal insufficiency is also associated with less obvious effects on drug disposition, such as decreased renal cytochrome P450 and conjugative metabolism of some drugs, impaired binding to albumin of acidic drugs (e.g., furosemide, sulfamethoxazole, and aspirin), and reduced tissue binding of digoxin.97 All these effects can lead to drug accumulation in renal insufficiency. Dosage reductions in renal insufficiency are indicated for any drug with a relatively narrow margin of safety that either is primarily eliminated by the kidneys or has an active metabolite that is eliminated by the kidneys (Table 4-2). There is little information in cats to guide dosage adjustments for renal insufficiency. In humans dose adjustments are typically made when glomerular filtration rate (GFR), as measured by creatinine clearance, drops to about 0.7 to 1.2 mL/kg/min, depending on the drug’s therapeutic index.66 Based on the demonstrated relationship between GFR and serum creatinine in cats,60 this is equivalent to serum creatinine con centrations of approximately 2.5 to 3.5 mg/dL (221 to 309 µmol/L). In the absence of specific data in cats, it is therefore reasonable to consider dosage adjustments for renally cleared drugs when the serum creatinine reaches this range. For many renally excreted drugs, a crude dose reduction can be made by multiplying the standard dose by a normal serum creatinine concentration (e.g., 1.0 mg/dL)

divided by the patient’s serum creatinine concentration. This results in less drug given at the same intervals and is based on the finding that serum creatinine is inversely related to GFR in early to moderate renal insufficiency in cats.60 For example, in a cat with a serum creatinine concentration of 2 mg/dL (twice a typical normal value of 1 mg/dL), cephalothin would be given at 10 mg/kg every 8 hours rather than 20 mg/kg every 8 hours. An alternative approach is to multiply the dosing interval (e.g., every 12 hours) by the patient’s serum creatinine concentration, divided by a normal creatinine level. This results in the same individual dose given at less frequent intervals. For example, for the same cat enrofloxacin would be given at a dosage of 5 mg/kg every 48 hours, rather than every 24 hours. Dosage adjustments using this method may be roughly accurate for serum creatinine concentrations up to 4 mg/dL (354 µmol/L), after which the relationship between creatinine concentration and GFR becomes nonlinear in cats.60 In humans dosages for renally cleared drugs in renal failure are typically 25% to 75% of the standard daily dosage.66 Ampicillin and amoxicillin are renally excreted but have wide safety margins, so dose adjustments are probably not clinically necessary. Cephalothin can cause lipid peroxidation and nephrotoxicity in animal models105 and can be nephrotoxic in combination with aminoglycosides in older human patients.105 Therefore dosage reductions of this cephalosporin may be indicated in veterinary patients with renal insufficiency.

42


TABLE 4-2 Drugs Requiring Precaution or Dosage Adjustment in Renal Insufficiency Drug

Adverse Outcome

Recommendations

Cephalothin

Possible dose-dependent nephrotoxin in humans105

Avoid or consider adjusting dosage

Aminoglycosides

Dose-dependent nephrotoxin in cats

Avoid in renal insufficiency If unavoidable, extend dosing interval Maintain hydration Monitor urine for granular casts Minimize duration of treatment

Fluoroquinolones

Dose-dependent retinotoxicity in cats

Use fluoroquinolones with wide safety margin for retinotoxicity (e.g., marbofloxacin or orbifloxacin) Extend dosing interval

Trimethoprim–sulfadiazine

Can precipitate as obstructive sulfadiazine crystals and uroliths in humans14

Use more soluble sulfamethoxazole Maintain hydration Avoid urinary acidifiers

Furosemide

Causes dehydration and hypokalemia

Avoid in renal insufficiency unless strong rationale (e.g., overt heart failure) Use careful clinical monitoring

H2 blockers

Confusion or mania in elderly human patients

Extend dosing interval or reduce individual dose

Metoclopramide

Tremors resulting from dopamine antagonism

Empiric dosage reductions (decrease constant-rate infusion daily dose by ~50%)

Enalapril

May cause renal decompensation98

Consider using benazepril, which does not accumulate in moderate renal insufficiency in cats46

Nonsteroidal antiinflammatory drugs

Gastric ulceration, renal decompensation

Substitute other analgesics whenever possible

For more expensive beta lactam derivatives, such as meropenem, dose adjustments are recommended in humans when creatinine clearance dips below 0.7 mg/ mL/kg; initial prolongation of the dosing interval is recommended.105 Aminoglycosides are dose-dependent nephrotoxins and should be avoided, whenever possible, in preexisting renal insufficiency. For patients with renal insufficiency that develop resistant gram-negative infections, other antimicrobials (e.g., fluoroquinolones, cefotetan, meropenem, ticarcillin) should be considered whenever possible. When aminoglycosides are necessary, rehydration and concurrent fluid therapy (intravenous or subcutaneous) are recommended because hypovolemia is a risk factor for aminoglycoside nephrotoxicity in humans.65 In addition, amikacin should be considered (Figure 4-1) because it is less nephrotoxic than gentamicin in human patients89 and may be less nephrotoxic in cats as well.17 The dosage of aminoglycosides is routinely adjusted for human patients with renal insufficiency. Aminoglycosides are concentration-dependent antimicrobials (i.e., bacterial kill correlates with peak concentrations, not time above the minimum inhibitory concentration), and nephrotoxicity correlates with trough, not peak, drug concentrations.74 Therefore aminoglycosides should be given at the same dose, but less frequently, in

FIGURE 4-1 Aminoglycosides should be avoided whenever possible in cats with renal insufficiency. Administration of subcutaneous or intravenous fluids, avoidance of concurrent nonsteroidal antiinflammatory or furosemide therapy, and monitoring urine sediments daily for granular casts may decrease the risk of dose-dependent nephrotoxicity.

renal insufficiency.92 For example, for a cat with a serum creatinine concentration of 2 mg/dL, amikacin or gentamicin would be dosed every 48 hours instead of every 24 hours, assuming that no alternative antimicrobials were available.


In humans aminoglycoside drug dosages are adjusted to keep trough plasma drug concentrations below 2 µg/ mL.36 Measurement of trough drug concentrations is ideal in patients with underlying renal insufficiency; however, rapid turnaround of serum drug concentrations is necessary for therapeutic drug monitoring to be useful in real-time clinical decision making. One practical monitoring alternative is to examine daily fresh urine sediments for granular casts, which can be seen days before azotemia develops.82 Granular casts indicate renal proximal tubular damage and if observed suggest that the drug should be discontinued, unless the infection is life threatening. Toxicity in cats is lessened if aminoglycoside therapy can be limited to 5 days or less, whenever possible.38 Aminoglycosides are contraindicated in combination with furosemide1 or a nonsteroidal antiinflammatory drug (NSAID),65 both of which can exacerbate nephrotoxicity. Fluoroquinolones, like aminoglycosides, are renally cleared. Although they do not cause cartilage toxicity in growing kittens at the label dosage, they do cause dosedependent retinal toxicity in cats.101 Therefore dosage adjustments for fluoroquinolones may be important in cats with renal insufficiency, although this has not been directly evaluated. Dosage adjustments may be particularly important for enrofloxacin, which appears to be more retinotoxic in cats (retinal lesions at four times the label dosage) compared with other veterinary fluoroquinolones (orbifloxacin, retinal lesions at 18 times the label dose; marbofloxacin, no retinal lesions at 20 times the label dose).101 Although the optimal method for dose adjustment is not established in cats, extending the dosing interval may be most appropriate,23 insofar as fluoroquinolones are also concentration-dependent antimicrobials. Potentiated sulfonamides should also be used with caution in azotemic patients, owing to decreased renal clearance and decreased protein binding. Dosage reductions for the human generic drug, trimethoprim– sulfamethoxazole, are recommended in human patients.96 Dose reductions may be even more important for trimethoprim–sulfadiazine (found in Tribrissen) because sulfadiazine is reported to cause hematuria, urolithiasis, and even acute renal failure in humans.14 This is due to the relative insolubility of sulfadiazine, which can precipitate as drug crystals in the renal tubules, especially at high concentrations or in acid urine.66 Although comparable studies in feline patients are not available, this author recommends rehydration and discontinuation of urinary acidifiers before the use of trimethoprim– sulfadiazine in cats. Furosemide is renally cleared and can cause significant dehydration and hypokalemia, which can lead to further renal decompensation. Furosemide should not be used in cats with underlying renal insufficiency unless there is a good rationale (e.g., fulminant

43

congestive heart failure). Cats treated with furosemide should be monitored closely for dehydration, hypokalemia, and worsened azotemia, with routine evaluation of skin turgor, body weight, body condition score, packed cell volume and total protein values, serum potassium levels, and renal indices at each recheck. Histamine 2 (H2)–blocker antacids such as cimetidine, ranitidine, and famotidine are cleared by the kidneys, and dosage reductions are recommended for human patients with renal insufficiency.62 H2 blockers can also lead to central nervous system disturbances (mania, confusion), particularly in elderly patients, although it is not clear whether decreased GFR is a factor.11 Therefore the dosage of H2 blockers may merit reductions in cats with renal insufficiency, especially geriatric cats. Either reductions in the individual dose or extensions of the dosing interval are used in humans. Metoclopramide is also renally cleared. As a dopaminergic antagonist, metoclopramide can lead to tremors in some human patients.85 Standard constant-rate infusion (CRI) dosages (1 to 2 mg/kg per day) can cause tremor and ataxia in azotemic patients (observed in dogs), and lower doses (e.g., 0.25 to 0.5 mg/kg/day as a CRI) appear anecdotally to be better tolerated. Angiotensin-converting enzyme (ACE) inhibitors are recommended to reduce proteinuria in cats with renal insufficiency (International Renal Interest Society Guidelines; http://www.iris-kidney.com, accessed February 25, 2010). Benazepril does not depend solely on renal elimination and does not require dose adjustment in moderately azotemic cats.46 Benazepril therefore may be preferable to enalapril in cats with substantial azotemia. Although ACE inhibitors typically do not cause systemic hypotension at therapeutic dosages in cats, they can adversely affect GFR at high dosages, particularly in a dehydrated patient or with concurrent furosemide administration. It is therefore important to monitor blood urea nitrogen, creatinine, and electrolytes in cats treated with ACE inhibitors: for example, initially after 1 week, after 1 month, and then every 3 months, depending on clinical status. The use of NSAIDs can adversely affect GFR in patients with hypovolemia or underlying renal disease by blocking the elaboration of renal prostaglandins that otherwise autoregulate renal blood flow.44 Although meloxicam was generally well tolerated for chronic use in cats with osteoarthritis in one study (at 0.01 to 0.03 mg/kg daily), relatively few cats with chronic renal disease (3 of 46 treated cats) were enrolled.35 In addition, meloxicam has been implicated in episodes of acute renal failure in cats (Metacam label). Coxibs (cyclooxygenase-2 [COX-2]– selective NSAIDs) have the same potential for adverse renal events as do other NSAIDs.70 This is because COX-2 is expressed in the kidney and is important for regulating renal blood flow.39 For analgesia in renal insufficiency, buprenorphine

44


provides an alternative to NSAIDs, with comparable analgesic efficacy in cats.88 If an antiinflammatory effect is needed, NSAIDs should be dosed conservatively and cats should be monitored frequently for dehydration, inappetence, evidence of gastrointestinal ulceration, or increases in blood urea nitrogen and creatinine levels.

DRUG THERAPY CONSIDERATIONS IN HEPATIC INSUFFICIENCY In humans with inflammatory liver disease without failure, hepatic drug metabolism appears to be fairly well conserved. With hepatic dysfunction or cirrhosis, however, drugs that are normally extensively metabolized by the liver are not efficiently cleared. This leads to decreased first-pass clearance and increased oral bioavailability of certain drugs, such as propranolol and benzodiazepines. For these drugs 50% dosage reductions are recommended for human patients with impaired liver function.26 Other drugs that require dosage reductions (to 25% to 50% of regular dosages) in humans with cirrhosis are listed in Box 4-1. Although cirrhosis is uncommon in cats, significant hepatic dysfunction is common with fulminant hepatic lipidosis or portosystemic shunts. In these patients dosage reductions for the drugs listed in Box 4-1 may be indicated, although we do not have comparable studies in cats. Some therapies can worsen hepatic encephalopathy and are not recommended for cats at risk. Stored whole blood generates ammonia, which increases with time of storage (Figure 4-2).51 Although time-course studies of ammonia generation have not been performed for feline whole blood or packed red blood cell units, stored blood should be used with caution in cats with liver failure, such as those with lipidosis or acute hepatotoxicity. Screening blood units for high blood ammonia before transfusion, using an in-house analyzer, is one option, as

is using an in-house blood donor to obtain fresh whole blood. NSAIDs have the potential to exacerbate hepatic encephalopathy, either by causing gastrointestinal bleeding (which is a protein load in the gut) or renal decompensation (which increases blood urea nitrogen that subsequently recycles to ammonia).28 Furosemide can cause hypokalemia, dehydration, azotemia, and alkalosis, all of which can worsen hepatic encephalopathy.28 Finally, glucocorticoids, which lead to muscle catabolism,28 can enhance deamination of proteins and release of ammonia (NH3). Glucocorticoids also enhance peripheral lipolysis, which could exacerbate hepatic lipidosis, although this has never been directly evaluated in cats. The safest course is to stabilize clinical signs, control hepatic encephalopathy, and provide nutritional support before considering glucocorticoids in cats with any type of liver disease.

THERAPEUTIC CONSIDERATIONS IN NEONATES AND KITTENS The neonatal period in dogs and cats has been defined as the first 4 weeks of life, with the pediatric period defined as up to 12 weeks of age.34 Although drug therapy of neonates is common in human medicine, very few pharmacokinetic studies have been performed in newborns and infants. Given that neonatal pharmacology is even less well studied in cats, specific and valid recommendations are difficult to make. However, there

BOX 4-1 Drugs that Require Dosage Reductions in Humans with Severe Impairment in Hepatic Function37 Buspirone Butorphanol Cisapride Cyclophosphamide Diazepam Doxorubicin Fluconazole Fluoxetine Itraconazole Lidocaine

Loratidine Metronidazole Midazolam Mirtazapine Omeprazole Prednisone Propranolol Theophylline Vincristine

FIGURE 4-2 Whole blood and packed red blood cells can generate ammonia during storage. Transfusion of older units could exacerbate hepatic encephalopathy in cats with hepatic lipidosis or acute hepatotoxicities.


are certain physiologic differences between neonates and adults (based on studies in humans, dogs, rodents, and occasionally in cats) that can help guide rational drug therapy in these tiny and rapidly changing patients. Oral absorption may be different in newborn kittens compared with adult cats. Immaturity of gastric parietal cells leads to a relatively high gastric pH in neonates; for example, gastric pH is greater than 3.0 through 5 weeks of age in puppies.54 High gastric pH may decrease the bioavailability of drugs that require an acid environment for absorption, such as ketoconazole, itraconazole, and iron supplements.54 Fluconazole may be better absorbed in these neonates because its absorption is not affected by gastric pH, at least in humans.106 Oral absorption of some drugs may be affected by nursing because of the binding of drugs by milk components such as calcium. For example, the bioavailability of enrofloxacin, which is chelated by calcium, is low in nursing kittens, with overall bioavailability less than 35%.84 The subcutaneous route provides more reliable absorption in nursing kittens, with bioavailability closer to 85% for enrofloxacin.84 Hepatic cytochrome P450 activities are low in newborns but approach and even exceed adult levels by 7 weeks of age, as shown in puppies90; this is likely an evolutionary response to a wider variety of dietary chemicals encountered at weaning. Immature cytochrome P450 content is associated with delayed hepatic clearance of some drugs in neonates. For example, lidocaine and theophylline have prolonged elimination halflives in very young puppies (less than 1 to 2 weeks old).2,40 However, by the time most feline patients are brought to the veterinarian for their first vaccination, hepatic function has greatly matured. Newborn kittens have decreased GFR rates before 9 weeks of age, when GFR reaches rates found in adult cats.43 Before this age, kittens may be at greater risk for fluid overload because of impaired solute and water excretion and for toxicity resulting from renally eliminated drugs such as aminoglycosides. Classic early warning signs of nephrotoxicity, such as granular casts, are not consistently observed in neonatal pups given gentamicin, despite the development of renal tubular lesions and impairment of GFR.22 Aminoglycosides therefore should be avoided whenever possible in very young patients. In contrast, enrofloxacin, despite its renal excretion, is cleared efficiently in kittens as young as 2 weeks of age84 and does not appear to require dosage reductions in this age group.

45

confusion and errors in self-dosing; however, pharmacokinetic and pharmacodynamic factors are also involved. Geriatric veterinary patients have been defined as those that have reached 75% of their expected life span (Figure 4-3).12 In both geriatric cats and humans, changes in renal function, hepatic blood flow, body composition, and compensatory physiologic responses alter drug response. Age-related renal insufficiency is the most important factor affecting drug dosing in geriatric human patients.94 Even patients without overt azotemia are likely to have decreased GFR associated with aging. The prevalence of renal insufficiency in older cats has not been established but appears to be relatively high, at least according to anecdotal reports. This may lead to decreased elimination and increased toxicity of renally cleared drugs (see Table 4-2) in older cats. Enrofloxacin has been associated with retinal toxicity in elderly cats at the label dose of 5 mg/kg per day.32 Because this ocular toxicity is dosedependent,101 cases seen in older cats are likely due to decreased renal clearance of the drug. Although orbifloxacin and marbofloxacin are also cleared by the kidneys, they are less retinotoxic at higher dosages in young healthy cats101 and may be safer for geriatric cats. Older patients also tend to have decreased total body and interstitial water,94 which may contribute to increased susceptibility to dehydration when elderly patients are given diuretics such as furosemide. Aging is associated with decreased liver mass, with variable reductions in cytochrome P450 function in elderly human patients.27 Decreased liver blood flow also occurs with aging and can lead to decreased clearance of certain drugs.83 For example, propofol is a “blood flow–limited” drug, and its clearance is diminished in

THERAPEUTIC CONSIDERATIONS IN SENIOR AND GERIATRIC CATS Adverse drug reactions are reported to be two to three times higher in elderly human patients than in younger adults.94 Some of this risk can be attributed to patient

FIGURE 4-3 Geriatric cats have been defined as those that have reached 75% of their expected life span. This 17-year-old cat almost certainly has some degree of renal insufficiency, which may require dosing adjustments for some drugs.

46


older humans95 and geriatric dogs, with higher plasma drug concentrations and apnea seen in some older dogs given standard dosages.75 Other drugs that show impaired clearance in elderly human patients, owing to renal or liver impairment or other factors, are listed in Box 4-2. Although comparable feline studies are not available, these drugs probably should be dosed conservatively in older cats, and the owner should be taught to carefully monitor their pet for adverse effects. Middle-aged to older cats may be overweight, which can affect drug distribution. For relatively polar drugs with poor fat distribution, such as digoxin, dosing should be based on lean body weight (ideal body weight).16 For cats ideal body weight can be estimated from the patient’s body conformation or from previous medical records when the patient had a normal body condition score. For the polar drug gentamicin, dose reductions of 15% to 20% are indicated in obese cats, based on differences in pharmacokinetics between obese and lean cats.103 For lipidsoluble drugs, such as propofol and benzodiazepines, single or loading dosages are based on total body weight (lean body weight plus fat) in humans.13

DRUG COMPOUNDING FOR CATS Custom veterinary pharmacies abound in the United States and provide reformulation options such as flavored liquid suspensions, capsules, chew tabs, and compressed minitablets. Pharmacists in the United States are legally allowed to compound veterinary or human drugs for individual veterinary patients if no appropriate approved veterinary formulation exists.67 Pharmacists are not legally allowed to mass-produce compounded drugs, and as for all prescriptions, there must be a valid doctor–client–patient relationship. Practitioners often assume that because a custom formulation is available, it must be safe and effective; this

BOX 4-2 Drugs that Show Decreased Clearance (by 20% or More) in Elderly Human Patients95 Amikacin Amlodipine Atenolol Ciprofloxacin Diazepam Digoxin Diphenhydramine Famotidine Furosemide Gentamicin

Lidocaine Methylprednisolone Metoclopramide Midazolam Omeprazole Ondansetron Piroxicam Propofol Terbutaline Theophylline

is not always true. Unfortunately, the stability and bioavailability of veterinary custom-compounded drugs are usually not tested. In addition, owners may perform their own reformulations at home to ease adminis tration, such as crushing pills in food or water or combining medications in a capsule. Veterinarians usually have inadequate information to advise owners about these manipulations. However, some basic principles can help determine the advisability of a given reformulation. Crushing medications is not always benign. Sustainedrelease tablets, such as theophylline (Theo-Dur), diltiazem (Cardizem CD), enteric-coated fluoxetine (Prozac Weekly), and tramadol (Ultram ER), should never be crushed. Crushing of extended-release formulations can lead to rapid, high peak plasma concentrations and potential side effects. In addition, tablets that are enteric coated should not be crushed because this may lead to a bitter taste and degradation in the stomach. Examples include budesonide (Entocort), erythromycin, ome prazole capsules, and potassium citrate tablets. Antineoplastic drugs, such as cyclophosphamide and chlorambucil, should never be crushed by clients or by clinic staff because this results in aerosols and dust that can lead to systemic exposure.31 These drugs should be reformulated only by a licensed pharmacist, with an appropriate ventilated cabinet. Mixing drugs with water can also cause problems. Drugs in a blister pack, which are often moisture sensitive, should not be mixed with water,67 nor should lipophilic drugs, such as itraconazole and diazepam. The veterinarian should check the product insert to see whether a drug is highly lipophilic. Irritating drugs, such as doxycycline or clindamycin, should not be given as capsules to cats because capsules tend to lodge in the midcervical esophagus in cats.33 This can lead to esophagitis and even esophageal stricture from doxycycline or clindamycin in cats (Figure 4-4).4,6 Capsules can be chased with an ounce of food or a 6-mL bolus of water after each dose to ensure passage into the stomach.33,99 However, this may be impractical in inappetent or fractious cats. In these cases oral suspensions of doxycycline or clindamycin may be safer. Drugs that contain aluminum or other cationic minerals should not be crushed and combined with other drugs. For example, the aluminum in sucralfate or aluminum hydroxide forms complexes with many other drugs in the gastrointestinal tract and can markedly impair the absorption of fluoroquinolones, doxycycline, theophylline, digoxin, and amitriptyline.56 In addition, aluminum can decrease peak plasma concentrations of azithromycin in humans.30 Other cationic minerals, such as calcium, iron, zinc, and magnesium, found in multivitamins, may also chelate fluoroquinolones and impair their absorption.52 Similarly, the


A

47

B

FIGURE 4-4 This male neutered Persian (A) developed an esophageal stricture (B) after administration of clindamycin capsules. (From Trepanier L: Acute vomiting in cats, rational treatment selection, J Feline Med Surg 12(3):225-230, 2010.)

calcium in dairy products can decrease the absorption of doxycycline.59 Drugs that can be readily reformulated into capsules include cyclosporine emulsion, potassium chloride beads, omeprazole enteric-coated beads, and itraconazole beads; the number of beads in one original capsule can be counted and divided as needed for the desired dose. For cats with hypertension, amlodipine and benazepril can be reformulated in a single capsule without affecting bioavailability.9 Fluoroquinolones are reportedly quite stable in most vehicles and flavorings, such as molasses, fish sauce, or corn syrup.67 It is important, however, to make sure that the vehicle does not contain cationic minerals (e.g., iron, calcium) that will impair fluoroquinolone absorption. Other reformulated suspensions with demonstrated stability are summarized in Table 4-3.

ALTERNATIVE FORMULATIONS/ ROUTES FOR MEDICATING CATS Transdermal drug formulations are a common compounding product in the United States. Transdermal administration, in which the goal is therapeutic drug concentrations in the systemic circulation, is distinct from topical administration, in which the goal is local therapeutic drug concentrations in surface organs (skin, eye, ear canal). Effective transdermal drug delivery is much harder to achieve. Transdermal drugs are attractive because of their many potential advantages, which include better acceptance compared with pilling or injections, decreased gastrointestinal irritation, avoidance of first-pass intestinal and hepatic degradation, possible longer duration of action without peak side effects, and the ability to custom formulate the drug concentration to the patient’s size.

TABLE 4-3 Pediatric Suspensions with Demonstrated Stability64 Drug

Formulation

Stability

Aminophylline

5 mg/mL in bacteriostatic water

1 week refrigerated

Chlorambucil

2 mg/mL in methylcellulose and syrup

1 week refrigerated; protect from light

Cyclophosphamide

2 mg/mL in aromatic elixir (from injectable)

2 weeks refrigerated

Hydralazine

2 mg/mL in bacteriostatic water

24 hours at room temperature

Metronidazole

20 mg/mL in purified water USP and syrup

10 days refrigerated

Phenobarbital

10 mg/mL in bacteriostatic water (from injection)

3 months refrigerated

Sucralfate

200 mg/mL in purified water USP

2 weeks refrigerated Shake well

However, there are significant disadvantages and limitations to transdermal drug formulations as available through custom compounders. The transdermal route is inappropriate for drugs acting locally in the gastrointestinal tract and may be ineffective for prodrugs dependent on hepatic biotransformation for efficacy. There is a lack of immediate effect for most drugs needed in an emergency setting (nitroglycerin is an exception), and some cats resent the sensation of a transdermal gel. Compounding of transdermal drugs can add significantly to the prescription cost. Most important, many drugs are poorly absorbed transdermally and never reach therapeutic plasma concentrations.

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Transdermal drugs that are effectively absorbed in humans tend to have relatively high lipid solubility (so that they can traverse the waxy stratum corneum) and a low melting point (i.e., they are readily converted from a solid to a liquid at body temperatures). Very polar compounds, such as aminoglycosides and many peptides, are poorly absorbed without additional interventions, such as an electric field, microneedles, or ultrasonic disruption of the stratum corneum.73 Approved transdermal drugs for humans are typically small compounds (i.e., molecular weight less than 500 g/mol or 500 Da [daltons]).7,8 Small drugs advertised for transdermal formulations in cats include methimazole (114 g/mol), nitroglycerin (227 g/mol), fentanyl (336 g/mol), and amitriptyline (277 g/mol). Larger drugs that are less likely to be absorbed but are still offered by veterinary compounding pharmacies include itraconazole (705 g/ mol), ketoconazole (531 g/mol), and amikacin (585 g/ mol). Amikacin has the additional disadvantage of being poorly lipid soluble. Transdermal drugs that are approved for human patients tend to be those that are effective at very low dosages. For example, for fentanyl, lidocaine, nicotine, nitroglycerin, scopolamine, oxybutynin, and contraceptive hormones, total daily dosages range from 0.1 to 32 mg per day.73 Transdermal dosing is constrained by the physical limitations of permeation enhancers, as well as by practical limitations in the amount of skin coverage that patients will accept. Transdermal formulations of veterinary drugs that require higher total daily dosages (i.e., more than 50 mg per patient per day) are unlikely to be adequately absorbed, especially through the relatively small surface area of a cat’s pinna. Veterinary transdermal drugs are typically formulated in a permeation enhancer such as pluronic lecithin organogel (PLO), which increases the fluidity of the stratum corneum and enhances the formation of drug micelles. PLO also leads to exfoliation of the stratum corneum and low-grade inflammation with chronic use, which likely contributes to drug penetration. PLO separates at cold temperatures and should be discarded if this occurs. Another available permeation enhancer is Lipoderm, a commercial product with proprietary ingredients. Lipoderm is comparable to PLO but is less greasy and does not separate at cold temperatures. A second proprietary permeation enhancer, VanPen, is used for more lipophilic drugs. There are essentially no data to compare the efficacy of PLO, Lipoderm, and VanPen in the delivery of veterinary drugs. Dimethyl sulfoxide (DMSO), although an excellent permeation enhancer, is not recommended because it can be quite irritating. Several drugs have shown low bioavailability (less than 10% compared with oral) when given transdermally to cats as single doses: fluoxetine, diltiazem, dexamethasone, buspirone, and amitriptyline.18,25,57,102

Glipizide in PLO has about 20% bioavailability (relative to oral administration) after a single dose in cats. Despite relatively low absorption, transdermal glipizide was associated with a delayed decrease in blood glucose in some cats,5 and multiple-dose studies in diabetic cats are warranted. Multiple doses of transdermal methimazole in PLO were effective at lowering serum T4 in hyperthyroid cats and had fewer gastrointestinal side effects than oral methimazole.80 However, the risk of idiosyncratic drug toxicity (facial pruritus, hepatotoxicity, blood dyscrasias) appeared to be the same for both routes. Similar responses have been observed for transdermal carbimazole (a prodrug of methimazole) in Europe.10 Modest efficacy has been reported for transdermal atenolol (6.25 mg once daily, in propylene glycol–glycerin–Tween) in reducing heart rate in cats53 and for transdermal amlodipine (0.625 mg daily in Lipoderm) in reducing blood pressure in hypertensive cats (although the transdermal route was inferior to oral amlodipine).42 The transdermal route is not appropriate for empiric dosing of antimicrobials because of the considerable risk of poor absorption, subtherapeutic plasma concentrations, and potential selection for resistant bacterial strains. In contrast to transdermal administration, transmucosal drug delivery is typically associated with rapid absorption and relatively high bioavailability. This is because the mucous membranes are highly vascular and lack the stratum corneum. Drugs can be administered transmucosally by several routes (Table 4-4). Like transdermal administration, transmucosal administration bypasses first-pass intestinal and hepatic metabolism and may prevent gastrointestinal upset resulting from direct gastric irritation. However, this route cannot be used for irritating medications. Buprenorphine is often given by the transmucosal (buccal) route in cats. It is well accepted at 0.01 mg/kg of injectable solution in the buccal pouch and is absorbed as well as that administered by the intravenous route, with equivalent analgesia.76 It is hypothesized that the higher bioavailability in cats (compared to humans) is due to the relatively high pH in the feline mouth (pH 8 to 9), in which buprenorphine is mostly uncharged, which favors absorption across the mucosa.77 Fluticasone, a trifluorinated glucocorticoid with potent antiinflammatory activity, can also be administered by the transmucosal (pulmonary aerosol) route in cats, using a metered-dose inhaler with a spacer. The goal is high topical potency in the lungs with few systemic side effects. Inhaled fluticasone has been associated with decreased lower airway inflammation in cats with bronchitis,47 and dosages up to 220 µg every 12 hours have not been associated with adrenal suppression in cats.19 Although local irritation can lead to acute bronchospasm, inhaled fluticasone is anecdotally well tolerated by many cats with reactive airway disease.


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TABLE 4-4 Drugs that Are Effective When Given by the Transmucosal Route Drug

Route of Administration

Indication

Apomorphine

Conjunctival sac

Emesis (dogs only; emetic dosages in cats cause unacceptable central nervous system side effects)93

Buprenorphine

Buccal cavity77

Analgesia76

Desmopressin (DDAVP)

Nasal mucosa Conjunctival sac

Diabetes insipidus (rare in cats)

Diazepam

Intrarectal68 Nasal mucosa

Cluster seizures (efficacy demonstrated in dogs)72

Epinephrine

Pulmonary Through endotracheal tube

Cardiopulmonary resuscitation

Fluticasone

Pulmonary Via metered-dose inhaler

Reactive airway disease/feline asthma47

Finally, human recombinant regular insulin was recently marketed for transmucosal (pulmonary aerosol) administration in human diabetic patients (Exubera, Pfizer). This formulation was shown to lower blood glucose in healthy cats at high dosages (25 U/kg), with hypoglycemia even seen in some cats.24 Although this drug had a short duration of action and was recently discontinued because of poor market performance, it demonstrates proof of the principle that peptide drugs can be administered without injection to cats, which is an exciting development.

CONCLUSION The differences between cats and humans require the feline practitioner to be quite savvy when it comes to feline therapeutics. Dosage extrapolations to cats should always be made with attention to whether the drug is cleared by glucuronidation in humans and dogs. Drugs with narrow safety margins should be dosed with attention to the primary route of clearance in adult cats (or in other species if data in cats are lacking), young kittens, geriatric cats, or cats with renal or hepatic insufficiency. Drug compounding, although very appealing, should be undertaken with a critical eye toward factors such as original formulation (enteric coated or extended release), water solubility of the drug, and drug–drug and drug– mineral interactions. Transdermal drug administration should be reserved for drugs with good evidence of absorption or efficacy (or both) in cats.

References 1. Adelman RD, Spangler WL, Beasom F et al: Furosemide enhancement of experimental gentamicin nephrotoxicity: comparison of functional and morphological changes with activities of urinary enzymes, J Infect Dis 140:342, 1979.

2. Alberola J, Perez Y, Puigdemont A et al: Effect of age on theophylline pharmacokinetics in dogs, Am J Vet Res 54:1112, 1993. 3. Beale KM, Altman D, Clemmons RR et al: Systemic toxicosis associated with azathioprine administration in domestic cats, Am J Vet Res 53:1236, 1992. 4. Beatty JA, Swift N, Foster DJ et al: Suspected clindamycinassociated oesophageal injury in cats: five cases, J Feline Med Surg 8:412, 2006. 5. Bennett N, Papich MG, Hoenig M et al: Evaluation of transdermal application of glipizide in a pluronic lecithin gel to healthy cats, Am J Vet Res 66:581, 2005. 6. Bissett SA, Davis J, Subler K et al: Risk factors and outcome of bougienage for treatment of benign esophageal strictures in dogs and cats: 28 cases (1995-2004), J Am Vet Med Assoc 235:844, 2009. 7. Bos JD, Meinardi MM: The 500 Dalton rule for the skin penetration of chemical compounds and drugs, Exp Dermatol 9:165, 2000. 8. Brown MB, Martin GP, Jones SA et al: Dermal and transdermal drug delivery systems: current and future prospects, Drug Deliv 13:175, 2006. 9. Budde J, Head Pharmacist UoW-M, Veterinary Medical Teaching Hospital: Personal Communication, 2009. 10. Buijtels JJ, Kurvers IA, Galac S et al: [Transdermal carbimazole for the treatment of feline hyperthyroidism], Tijdschr Diergeneeskd 131:478, 2006. 11. Cantu TG, Korek JS: Central nervous system reactions to histamine-2 receptor blockers, Ann Intern Med 114:1027, 1991. 12. Carpenter RE, Pettifer GR, Tranquilli WJ: Anesthesia for geriatric patients, Vet Clin North Am Small Anim Pract 35:571, 2005. 13. Casati A, Putzu M: Anesthesia in the obese patient: pharmacokinetic considerations, J Clin Anesth 17:134, 2005. 14. Catalano-Pons C, Bargy S, Schlecht D et al: Sulfadiazine-induced nephrolithiasis in children, Pediatr Nephrol 19:928, 2004. 15. Chen M, Leduc B, Kerr SG et al: Identification of human UGT2B7 as the major isoform involved in the O-glucuronidation of chloramphenicol, Drug Metab Dispos 38:368, 2010. 16. Cheymol G: Drug pharmacokinetics in the obese, Fundam Clin Pharmacol 2:239, 1988. 17. Christensen EF, Reiffenstein JC, Madissoo H: Comparative ototoxicity of amikacin and gentamicin in cats, Antimicrob Agents Chemother 12:178, 1977. 18. Ciribassi J, Luescher A, Pasloske KS et al: Comparative bioavailability of fluoxetine after transdermal and oral administration to healthy cats, Am J Vet Res 64:994, 2003.

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19. Cohn LA, Declue AE, Cohen RL et al: Effects of fluticasone propionate dosage in an experimental model of feline asthma, J Feline Med Surg 12:91, 2010. 20. Court MH, Greenblatt DJ: Molecular basis for deficient acetaminophen glucuronidation in cats. An interspecies comparison of enzyme kinetics in liver microsomes, Biochem Pharmacol 53:1041, 1997. 21. Court MH, Greenblatt DJ: Molecular genetic basis for deficient acetaminophen glucuronidation by cats: UGT1A6 is a pseudogene, and evidence for reduced diversity of expressed hepatic UGT1A isoforms, Pharmacogenetics 10:355, 2000. 22. Cowan RH, Jukkola AF, Arant BS Jr: Pathophysiologic evidence of gentamicin nephrotoxicity in neonatal puppies, Pediatr Res 14:1204, 1980. 23. Czock D, Rasche FM: Dose adjustment of ciprofloxacin in renal failure: reduce the dose or prolong the administration interval? Eur J Med Res 10:145, 2005. 24. DeClue AE, Leverenz EF, Wiedmeyer CE et al: Glucose lowering effects of inhaled insulin in healthy cats, J Feline Med Surg 10:519, 2008. 25. DeFrancesco T: Transdermal cardiac therapy in cats: the NCSU experience. Annual Forum of the American College of Veterinary Internal Medicine, 2003. 26. Delco F, Tchambaz L, Schlienger R et al: Dose adjustment in patients with liver disease, Drug Saf 28:529, 2005. 27. El Desoky ES: Pharmacokinetic-pharmacodynamic crisis in the elderly, Am J Ther 14:488, 2007. 28. Faint V: The pathophysiology of hepatic encephalopathy, Nurs Crit Care 11:69, 2006. 29. Foster AP, Shaw SE, Duley JA et al: Demonstration of thiopurine methyltransferase activity in the erythrocytes of cats, J Vet Intern Med 14:552, 2000. 30. Foulds G, Hilligoss DM, Henry EB et al: The effects of an antacid or cimetidine on the serum concentrations of azithromycin, J Clin Pharmacol 31:164, 1991. 31. Gambrell J, Moore S: Assessing workplace compliance with handling of antineoplastic agents, Clin J Oncol Nurs 10:473, 2006. 32. Gelatt KN, van der Woerdt A, Ketring KL et al: Enrofloxacinassociated retinal degeneration in cats, Vet Ophthalmol 4:99, 2001. 33. Graham JP, Lipman AH, Newell SM et al: Esophageal transit of capsules in clinically normal cats, Am J Vet Res 61:655, 2000. 34. Grundy SA: Clinically relevant physiology of the neonate, Vet Clin North Am Small Anim Pract 36:443, 2006. 35. Gunew MN, Menrath VH, Marshall RD: Long-term safety, efficacy and palatability of oral meloxicam at 0.01-0.03 mg/kg for treatment of osteoarthritic pain in cats, J Feline Med Surg 10:235, 2008. 36. Hagen I, Oymar K: Pharmacological differences between once daily and twice daily gentamicin dosage in newborns with suspected sepsis, Pharm World Sci 31:18, 2009. 37. Hardman J, Limbard L: Goodman and Gilman’s the pharmacologic basis of therapeutics, ed 10, New York, 2001, McGraw-Hill. 38. Hardy ML, Hsu RC, Short CR: The nephrotoxic potential of gentamicin in the cat: enzymuria and alterations in urine concentrating capability, J Vet Pharmacol Ther 8:382, 1985. 39. Harris RC: COX-2 and the kidney, J Cardiovasc Pharmacol 47(Suppl 1):S37, 2006. 40. Hastings CL, Brown TC, Eyres RL et al: The influence of age on lignocaine pharmacokinetics in young puppies, Anaesth Intensive Care 14:135, 1986. 41. Hays MT, Broome MR, Turrel JM: A multicompartmental model for iodide, thyroxine, and triiodothyronine metabolism in normal and spontaneously hyperthyroid cats, Endocrinology 122:2444, 1988.

42. Helms SR: Treatment of feline hypertension with transdermal amlodipine: a pilot study, J Am Anim Hosp Assoc 43:149, 2007. 43. Hoskins JD, Turnwald GH, Kearney MT et al: Quantitative urinalysis in kittens from four to thirty weeks after birth, Am J Vet Res 52:1295, 1991. 44. House AA, Silva Oliveira S, Ronco C: Anti-inflammatory drugs and the kidney, Int J Artif Organs 30:1042, 2007. 45. Kidd LB, Salavaggione OE, Szumlanski CL et al: Thiopurine methyltransferase activity in red blood cells of dogs, J Vet Intern Med 18:214, 2004. 46. King JN, Strehlau G, Wernsing J et al: Effect of renal insufficiency on the pharmacokinetics and pharmacodynamics of benazepril in cats, J Vet Pharmacol Ther 25:371, 2002. 47. Kirschvink N, Leemans J, Delvaux F et al: Inhaled fluticasone reduces bronchial responsiveness and airway inflammation in cats with mild chronic bronchitis, J Feline Med Surg 8:45, 2006. 48. Krishnaswamy S, Hao Q, Von Moltke LL et al: Evaluation of 5-hydroxytryptophol and other endogenous serotonin (5-hydroxytryptamine) analogs as substrates for UDPglucuronosyltransferase 1A6, Drug Metab Dispos 32:862, 2004. 49. Kuehl GE, Bigler J, Potter JD et al: Glucuronidation of the aspirin metabolite salicylic acid by expressed UDP-glucuronosyltransferases and human liver microsomes, Drug Metab Dispos 34:199, 2006. 50. KuKanich B, Lascelles BD, Papich MG: Pharmacokinetics of morphine and plasma concentrations of morphine-6-glucuronide following morphine administration to dogs, J Vet Pharmacol Ther 28:371, 2005. 51. Latham JT, Jr, Bove JR, Weirich FL: Chemical and hematologic changes in stored CPDA-1 blood, Transfusion 22:158, 1982. 52. Lomaestro BM, Bailie GR: Absorption interactions with fluoroquinolones. 1995 update, Drug Saf 12:314, 1995. 53. Macgregor JM, Rush JE, Rozanski EA et al: Comparison of pharmacodynamic variables following oral versus transdermal administration of atenolol to healthy cats, Am J Vet Res 69:39, 2008. 54. Malloy MH, Morriss FH, Denson SE et al: Neonatal gastric motility in dogs: maturation and response to pentagastrin, Am J Physiol 236:E562, 1979. 55. Matal J, Jancova P, Siller M et al: Interspecies comparison of the glucuronidation processes in the man, monkey, pig, dog and rat, Neuro Endocrinol Lett 29:738, 2008. 56. McCarthy DM: Sucralfate, N Engl J Med 325:1017, 1991. 57. Mealey KL, Peck KE, Bennett BS et al: Systemic absorption of amitriptyline and buspirone after oral and transdermal administration to healthy cats, J Vet Intern Med 18:43, 2004. 58. Mensching D, Volmer P: Toxicology brief: managing acute carprofen toxicosis in dogs and cats, Vet Med 104(7):325, 2009. 59. Meyer FP, Specht H, Quednow B et al: Influence of milk on the bioavailability of doxycycline—new aspects, Infection 17:245, 1989. 60. Miyamoto K: Use of plasma clearance of iohexol for estimating glomerular filtration rate in cats, Am J Vet Res 62:572, 2001. 61. Morton DJ, Knottenbelt DC: Pharmacokinetics of aspirin and its application in canine veterinary medicine, J S Afr Vet Assoc 60:191, 1989. 62. Munar MY, Singh H: Drug dosing adjustments in patients with chronic kidney disease, Am Fam Physician 75:1487, 2007. 63. Myant NB: Excretion of the glucuronide of thyroxine in cat bile, Biochem J 99:341, 1966. 64. Nahata M, Hipple T: Pediatric drug formulations. ed 2, Cincinnati, 1992, Harvey Whitney Books. 65. Oliveira JF, Silva CA, Barbieri CD et al: Prevalence and risk factors for aminoglycoside nephrotoxicity in intensive care units, Antimicrob Agents Chemother 53:2887, 2009.

CHAPTER 4 Guidelines and Precautions for Drug Therapy in Cats 66. Olyaei AJ, Bennett WM: Drug dosing in the elderly patients with chronic kidney disease, Clin Geriatr Med 25:459, 2009. 67. Papich MG: Drug compounding for veterinary patients, AAPS J 7:E281, 2005. 68. Papich MG, Alcorn J: Absorption of diazepam after its rectal administration in dogs, Am J Vet Res 56:1629, 1995. 69. Parton K, Balmer TV, Boyle J et al: The pharmacokinetics and effects of intravenously administered carprofen and salicylate on gastrointestinal mucosa and selected biochemical measurements in healthy cats, J Vet Pharmacol Ther 23:73, 2000. 70. Pham K, Hirschberg R: Global safety of coxibs and NSAIDs, Curr Top Med Chem 5:456, 2005. 71. Plumb D: Plumb’s veterinary drug handbook, ed 6, Ames, 2008, Blackwell. 72. Podell M: The use of diazepam per rectum at home for the acute management of cluster seizures in dogs, J Vet Intern Med 9:68, 1995. 73. Prausnitz MR, Mitragotri S, Langer R: Current status and future potential of transdermal drug delivery, Nat Rev Drug Discov 3:115, 2004. 74. Rea RS, Capitano B: Optimizing use of aminoglycosides in the critically ill, Semin Respir Crit Care Med 28:596, 2007. 75. Reid J, Nolan AM: Pharmacokinetics of propofol as an induction agent in geriatric dogs, Res Vet Sci 61:169, 1996. 76. Robertson SA, Lascelles BD, Taylor PM et al: PK-PD modeling of buprenorphine in cats: intravenous and oral transmucosal administration, J Vet Pharmacol Ther 28:453, 2005. 77. Robertson SA, Taylor PM, Sear JW: Systemic uptake of buprenorphine by cats after oral mucosal administration, Vet Rec 152:675, 2003. 78. Rubio F, Seawall S, Pocelinko R et al: Metabolism of carprofen, a nonsteroid anti-inflammatory agent, in rats, dogs, and humans, J Pharm Sci 69:1245, 1980. 79. Salavaggione OE, Yang C, Kidd LB et al: Cat red blood cell thiopurine S-methyltransferase: companion animal pharmacogenetics, J Pharmacol Exp Ther 308:617, 2004. 80. Sartor LL, Trepanier LA, Kroll MM et al: Efficacy and safety of transdermal methimazole in the treatment of cats with hyperthyroidism, J Vet Intern Med 18:651, 2004. 81. Savides MC, Oehme FW, Nash SL et al: The toxicity and biotransformation of single doses of acetaminophen in dogs and cats, Toxicol Appl Pharmacol 74:26, 1984. 82. Schentag JJ, Gengo FM, Plaut ME et al: Urinary casts as an indicator of renal tubular damage in patients receiving aminoglycosides, Antimicrob Agents Chemother 16:468, 1979. 83. Schmucker DL: Age-related changes in liver structure and function: implications for disease? Exp Gerontol 40:650, 2005. 84. Seguin MA, Papich MG, Sigle KJ et al: Pharmacokinetics of enrofloxacin in neonatal kittens, Am J Vet Res 65:350, 2004. 85. Sirota RA, Kimmel PL, Trichtinger MD et al: Metoclopramideinduced parkinsonism in hemodialysis patients. Report of two cases, Arch Intern Med 146:2070, 1986. 86. Somogyi A: Renal transport of drugs: specificity and molecular mechanisms, Clin Exp Pharmacol Physiol 23:986, 1996. 87. Spivak W, Carey MC: Reverse-phase h.p.l.c. separation, quantification and preparation of bilirubin and its conjugates from native bile. Quantitative analysis of the intact tetrapyrroles based

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on h.p.l.c. of their ethyl anthranilate azo derivatives, Biochem J 225:787, 1985. Steagall PV, Taylor PM, Rodrigues LC et al: Analgesia for cats after ovariohysterectomy with either buprenorphine or carprofen alone or in combination, Vet Rec 164:359, 2009. Sweileh WM: A prospective comparative study of gentamicinand amikacin-induced nephrotoxicity in patients with normal baseline renal function, Fundam Clin Pharmacol 23:515, 2009. Tanaka E, Narisawa C, Nakamura H et al: Changes in the enzymatic activities of beagle liver during maturation as assessed both in vitro and in vivo, Xenobiotica 28:795, 1998. Taylor PM, Robertson SA, Dixon MJ et al: Morphine, pethidine and buprenorphine disposition in the cat, J Vet Pharmacol Ther 24:391, 2001. Touw DJ, Westerman EM, Sprij AJ: Therapeutic drug monitoring of aminoglycosides in neonates, Clin Pharmacokinet 48:71, 2009. Trulson ME, Crisp T: Behavioral and neurochemical effects of apomorphine in the cat, Eur J Pharmacol 80:295, 1982. Turnheim K: Drug therapy in the elderly, Exp Gerontol 39:1731, 2004. Turnheim K: Pharmacokinetic dosage guidelines for elderly subjects, Expert Opin Drug Metab Toxicol 1:33, 2005. Van Scoy RE, Wilson WR: Antimicrobial agents in adult patients with renal insufficiency: initial dosage and general recommendations, Mayo Clin Proc 62:1142, 1987. Verbeeck RK, Musuamba FT: Pharmacokinetics and dosage adjustment in patients with renal dysfunction, Eur J Clin Pharmacol 65:757, 2009. Weinberg MS: Renal effects of angiotensin converting enzyme inhibitors in heart failure: a clinician’s guide to minimizing azotemia and diuretic-induced electrolyte imbalances, Clin Ther 15:3, 1993. Westfall DS, Twedt DC, Steyn PF et al: Evaluation of esophageal transit of tablets and capsules in 30 cats, J Vet Intern Med 15:467, 2001. White SD, Rosychuk RA, Outerbridge CA et al: Thiopurine methyltransferase in red blood cells of dogs, cats, and horses, J Vet Intern Med 14:499, 2000. Wiebe V, Hamilton P: Fluoroquinolone-induced retinal degeneration in cats, J Am Vet Med Assoc 221:1568, 2002. Willis-Goulet HS, Schmidt BA, Nicklin CF et al: Comparison of serum dexamethasone concentrations in cats after oral or transdermal administration using pluronic lecithin organogel (PLO): a pilot study, Vet Dermatol 14:83, 2003. Wright LC, Horton CR, Jr, Jernigan AD et al: Pharmacokinetics of gentamicin after intravenous and subcutaneous injection in obese cats, J Vet Pharmacol Ther 14:96, 1991. Yoder Graber AL, Ramirez J, Innocenti F et al: UGT1A1*28 genotype affects the in-vitro glucuronidation of thyroxine in human livers, Pharmacogenet Genomics 17:619, 2007. Zhanel GG: Cephalosporin-induced nephrotoxicity: does it exist? DICP 24:262, 1990. Zimmermann T, Yeates RA, Riedel KD et al: The influence of gastric pH on the pharmacokinetics of fluconazole: the effect of omeprazole, Int J Clin Pharmacol Ther 32:491, 1994.

C H A P T E R

5

Fluid Therapy Katharine F. Lunn, Anthony S. Johnson, and Katherine M. James O U T L I N E Body Fluid Balance, 52 Steady State and the Concept of Maintenance, 52 Body Fluid Compartments, 53 Perfusion, 55 Salt Balance: Disorders of ECF Volume, 55 Water Balance: Disorders of Sodium Concentration, 56 Understanding Fluid Losses, 57

Body Response to Hypovolemia, 59 General Considerations for Fluid Therapy, 59 Fluid Types, 59 Routes of Administration, 69 Fluid Therapy Plans and Monitoring, 73 Intravenous Fluids During Anesthesia and Surgery, 82 Specific Disease Conditions, 82

Fluid therapy should be approached with the same attention to detail as drug therapy, and the foundation for this approach is an understanding of body fluid balance and perfusion. Without understanding these concepts, the clinician risks taking a “cookbook” or onesize-fits-all approach to fluid therapy. Potential adverse effects of oversimplified approaches to fluid therapy include persistent dehydration, fluid overload, hypoperfusion, acid–base imbalance, and electrolyte disorders, all of which have profound effects on morbidity in patients.

result from abnormalities in water balance. Salt and water balance will be discussed in more depth in later sections.

STEADY STATE AND THE CONCEPT OF MAINTENANCE With the exception of small, steady changes during growth, the amount of water coming into the body each day must equal the amount of water eliminated from the body over the same period. If not, the cat will have either a net water gain or a net water loss. Cats take in water by drinking, eating (food contains some water), and metabolizing nutrients to CO2 and water. Physiologic water losses result from the following:

BODY FLUID BALANCE Body fluid balance depends on both salt and water balance and the relationship between them. When referring to salt balance, we primarily consider the sodium ion (Na+) because it is the principal extracellular cation. Water balance refers to the amount of Na+ present relative to water. The concepts of salt and water balance are challenging, but they are essential for understanding the types, amounts, and rates of fluids to administer. It is perhaps counterintuitive that disordered salt balance does not cause abnormalities of serum sodium concentration but rather results in abnormalities of extracellular fluid (ECF) volume. Disorders of sodium concentration


• • • •

Obligate urinary loss Fecal loss Salivary loss Evaporation from the respiratory tract and the skin surface (insensible losses)

Pathologic loss of water can result from the following: • Vomiting or regurgitation • Diarrhea 52


CHAPTER 5 Fluid Therapy

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Total body water 60% body weight 3.6 L

6 kg

Intracellular

Extracellular

66% body water 2.4 L

Interstitial

33% body water 1.2 L 20% body weight

Transcellular

Bone/connective tissue Intravascular

20-24% Small volume body water 15% body water 8-10% 15% body weight (not included) (not included) body water 0.9 L 5% body weight 0.3 L

FIGURE 5-1 Body fluid compartments of the cat. The body’s two main fluid compartments are the intracellular fluid (ICF) and the extracellular fluid (ECF). Approximately 66% of functional total body water is located within the ICF compartment, and 33% is in the ECF compartment.

• • • • •

Bleeding Loss from wounds, burns, or drains Excessive urinary loss Excessive respiratory loss Excessive salivary loss

Electrolytes must also be consumed and eliminated in equal quantities on an approximately daily basis to maintain homeostasis. These continual losses that must be replaced promptly and nearly continually underlie the concept of “maintenance fluids.” Maintenance needs, normally met by eating food and drinking water, are largely dependent on the cat’s lean body mass. Sick animals that are no longer eating or drinking will continue to have daily obligatory fluid and electrolyte losses that can be addressed by fluid therapy to prevent negative fluid and electrolyte balance.

BODY FLUID COMPARTMENTS Water is a major contributor to a cat’s body weight. In healthy animals approximately 60% of body weight is water. This value can change slightly depending on age, lean body mass, degree of leanness or obesity, and gender. For example, neonatal and young kittens have a

relatively higher percentage of water in their bodies than do adults. Figure 5-1 depicts the cat’s body fluid compartments. The body’s two main fluid compartments are the intracellular fluid (ICF) and the ECF. Approximately 66% of functional total body water is located within the ICF compartment, and 33% is in the ECF compartment. The ICF is, of course, not a single compartment but rather a conceptualization of the result of combining the very small volumes of a body’s trillions of cells as one. This is useful for understanding physiology because of commonalities of ICF composition and behavior. The fluid inside cells is high in potassium (K+) and magnesium (Mg++) and low in Na+ and chloride (Cl−) ions. Additionally, fluid inside all cells will respond similarly to tonicity changes in the ECF. The ECF space is composed of four main subcompartments: interstitial, intravascular, transcellular, and bone and dense connective tissue. The intravascular fluid is that which is contained within blood vessels; it contributes only 8% to 10% of total body water (5% of body weight) and has been estimated to be approximately 45 mL/kg in cats.10 The interstitial compartment refers to that portion of the ECF located outside of the vascular space. Like the ICF, this is not a single space but rather a conceptualization,

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or “virtual space,” that would be created if all the interstitial fluid spaces were to be combined. It contributes approximately 22% to 24% to total body water (15% of total body weight). The fluid of bone and dense connective tissue provides about 15% of the total body water. However, this fluid is mobilized very slowly, decreasing its importance when considering the effects of acute fluid interventions. Transcellular fluid is a normally small compartment that represents all those body fluids that are formed from the transport activities of cells. It is contained within epithelium-lined spaces. It includes cerebrospinal fluid (CSF), gastrointestinal fluids, urine in the bladder, aqueous humor, and joint fluid. The electrolyte compositions of the various transcellular fluids are dissimilar, but they are small in aggregate volume. However, fluid fluxes involving gastrointestinal fluid can be significant in disease. The water in bone and dense connective tissue and the transcellular fluids, because of their slow mobilization, are subtracted from the total ECF volume to yield the functional ECF. It is important to note that when excess fluid builds up in transcellular or interstitial compartments in which fluid volume are normally small, the process is termed third spacing. Excess fluid in the peritoneal space, pleural space, or gastrointestinal tract can add considerably to body weight, while diminishing the effective ECF volume.

Fluid Movement in the Extracellular Fluid Compartment The water in the body’s ECF compartments is in a constant state of flux. Fluid moves across the capillary membrane, which is composed of endothelial cells that contain gap junctions through which fluid and solutes can flow. Solutes dissolved in fluid move from an area of higher to lower concentration along concentration gradients by the process of passive diffusion. The factors that regulate this transport of fluid and the electrolytes and other molecules it contains are called Starling forces (Box 5-1). The key factors are the hydrostatic and colloid oncotic pressure gradients between the intravascular and extravascular spaces. The hydrostatic pressure is greater in the capillary than in the interstitium, and the gradient favors fluid movement (filtration) out of the capillary. The colloid oncotic pressure, determined by protein concentration, is also greater in the capillary, and this tends to draw fluid into the capillary. Simplistically, at the beginning of the capillary the high hydrostatic pressure results in fluid egress into interstitium. As the fluid leaves along the length of the capillary, the hydrostatic pressure falls and the colloid oncotic pressure increases, resulting in fluid reentry into the capillary lumen toward the end of the capillary.

BOX 5-1 Starling Forces The Starling forces are defined by the equation Jv = Kf([Pc − Pi] − σ[πc − πi]) relating to the following six variables: capillary hydrostatic pressure (Pc), interstitial hydrostatic pressure (Pi), capillary oncotic pressure (πc), interstitial oncotic pressure (πi), filtration coefficient (Kf), reflection coefficient (σ). In the equation, ([Pc − Pi] − σ[πc − πi]) is the net driving force, Kf is the proportionality constant, and Jv is the net fluid movement between compartments. By convention, outward force is defined as positive, and inward force is defined as negative. The solution to the equation is known as the net filtration or net fluid movement ( Jv). If positive, fluid will tend to leave the capillary (filtration). If negative, fluid will tend to enter the capillary (absorption). This equation has a number of important physiologic implications, especially when pathologic processes grossly alter one or more of the variables.

Fluid also leaves the interstitial compartment by way of the lymphatics. Fluids in the ECF move continuously between the vascular space and the interstitial space across the capillary endothelium to achieve tissue perfusion. Edema results when the balance of the hydrostatic and colloid oncotic pressure gradients shifts such that fluid egress from the capillary is favored. All of the following promote edema formation: (1) decreased plasma oncotic pressure, (2) increased capillary hydrostatic pressure, (3) increased capillary permeability, and (4) lymphatic obstruction. The other key requirement for edema formation is Na+ retention: an increase in the ECF Na+ content.

Fluid Movement Between the Intracellular Fluid and Extracellular Fluid Compartments The ICF and ECF are separated by cellular membranes. The protein components of these membranes give them substantial and rapid permeability to water while carefully controlling their permeability to solutes such as ions. Cell membranes are also flexible. Thus, when water flows into or out of cells, those cells expand or shrink, respectively. Hydrostatic pressure, therefore, does not play a significant role in fluid movement between ECF and ICF compartments, because osmosis results in water flow rather than the development of pressure. Osmotic water flow occurs wherever there is a gradient of impermeable solute (such as Na+) across a water-permeable membrane (the body cell membranes). In the body the ECF and ICF compartments are always in osmotic equilibrium, even though the composition of the fluids within them is very different. Water flows


into or out of cells and changes their volume when an osmotic gradient exists between the ICF and ECF compartments.

PERFUSION Perfusion refers to the process in which blood carries oxygen and nutrients to body tissues and organs and transports waste products of cellular metabolism away. Perfusion is optimized when an animal is in a state of normal fluid balance. Oxygen delivery is a critical part of perfusion and is dependent on the animal’s cardiac output and the oxygen-carrying capacity of the blood. Cardiac output is a function of heart rate and stroke volume. Stroke volume depends on ventricular preload, ventricular afterload, and contractility. The amount of blood that enters the ventricle, causing the ventricular wall to stretch, thus affects the ventricular preload because the amount of wall stretch is directly proportional to the force of contraction. When there is adequate circulating volume, cardiac preload on the healthy ventricle results in a contraction of appropriate force. By contrast, in a cat with hypovolemia cardiac preload will be diminished, thus decreasing the force of ventricular contraction. Intravenous fluid therapy can affect cardiac preload by replenishing intravascular fluid volume in a hypovolemic animal.

SALT BALANCE: DISORDERS OF ECF VOLUME Sodium Content +

The Na content of the body determines the volume of the ECF and total body fluid volume. It does this because the osmolality of body fluids is regulated within a very narrow range. If Na+ ions (always with an accompanying anion) are added to the ECF space, more water molecules must be added to ECF space in the same proportion or the osmolality will increase beyond the relatively narrow range compatible with health and normal cellular function. Thus increasing the number of Na+ ions in the ECF (the Na+ content) increases the ECF volume. Similarly, if Na+ ions are removed from the ECF space, water molecules must leave in proportion, resulting in a decreased ECF volume, or the fluid’s osmolality would decrease beyond that which the body’s regulatory mechanisms will allow in health. In that sense, the Na+ content of the ECF fluid space determines its volume.

Regulation of Sodium Balance Regulatory mechanisms exist to control both Na+ content and Na+ concentration ([Na+]), and they are interrelated.

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Body Na+ content is regulated by mechanisms that control the renal excretion of Na+ and which operate in response to body fluid volume and not [Na+].9 Control of [Na+] is determined by the osmoregulatory control mechanisms. Evolutionarily, it appears that salt was a scarce commodity. Thus the kidney has evolved mechanisms to conserve salt. Na+ excretion in the urine can vary over 500-fold depending on Na+ intake and body need. The homeostatic mechanisms that control Na+ content are poorly understood. Regulation is generally a comparatively slow process. For example, many hours will pass before excesses in Na+ content (e.g., when isotonic saline is infused) are corrected by increased renal Na+ excretion. In contrast, excesses or deficiencies of water relative to Na+ (changes in [Na+]) activate the osmoregulatory mechanisms and are dealt with very rapidly. Many physiologists believe that a set point for Na+ regulation does not exist. Rather, Na+ is retained in low volume states until the volume deficit is corrected.12 Sodium excess results in augmented ECF volume, which increases urinary Na+ excretion. A useful analogy is a bucket with a hole in its side: When volume is at or below the hole, Na+ excretion is minimal while the bucket fills to the level of the hole. Once there, the inflow equals the outflow. When the volume of the bucket is above the hole (ECF expansion), the pressure of fluid in the bucket drives the fluid to flow out of the hole more quickly. For example, when dietary Na+ intake is increased, it takes several days to reach a new steady state of neutral Na+ balance. The following factors are known to affect renal Na+ excretion: 1. Arterial hypertension 2. Tubuloglomerular feedback 3. Circadian rhythm It is suspected that others also exist. The sensors (afferent signals) in the regulation of Na+ excretion are thought to include intrathoracic volume receptors, atrial pressure receptors, arterial baroreceptors, intrarenal baroreceptors, the macula densa, hepatic volume receptors, CSF volume receptors, and possibly tissue receptors. The mediators of Na+ conservation or excretion include the sympathetic nervous system, the renin– angiotensin–aldosterone system (RAAS), vasopressin, atrial natriuretic peptide (ANP), renal prostaglandins, the kallikrein–kinin system, nitric oxide, and renal pressure and flow phenomena (glomerular filtration rate [GFR], renal blood flow, and arterial pressure). Salt excess states include congestive heart failure, nephrotic syndrome, hepatic cirrhosis, hyperaldo steronism, Na+ channel defects, and pregnancy. In the pathogenesis of certain salt-retaining states, reference is made to the effective plasma volume. This is not a measurable quantity, and the concept lacks a precise definition.

56


It refers to the “fullness” of the vascular volume. It is the portion of the vascular volume that is being sensed by those mechanisms that regulate body fluid volume. An inadequate effective circulating volume is inferred when salt-retaining mechanisms are activated. Salt-deficient states are secondary to a number of disease conditions that result in losses of Na+ or inadequate intake. Extrarenal losses are localized to diseases of the gastrointestinal tract, skin, respiratory tract, and third space losses. Renal salt loss may occur with the following: 1. Diuresis (e.g., diuretic phase of acute tubular necrosis, postobstructive diuresis, or the use of diuretic medications) 2. Intrinsic renal disease (e.g., chronic renal failure, Fanconi syndrome, Bartter syndrome) 3. Defects in the RAAS system (e.g., hypoadrenocorticism, hyporeninemic hypoaldosteronism) 4. Disorders resulting in excesses of ANP The use of high-sodium, isotonic fluid types in fluid therapy is thus primarily for the administration of Na+. They augment the total ECF Na+ content and thus expand the functional ECF volume, both vascular and interstitial.

WATER BALANCE: DISORDERS OF SODIUM CONCENTRATION Permeant and Impermeant Solutes The next important concept to be understood is that of water balance. Cells must be in osmotic equilibrium with the fluid that surrounds them, insofar as their membranes are permeable to water. Although extracellular and intracellular fluids have very different compositions, they must have the same total solute concentrations because of the free movement of water. Looking at this concept “in reverse,” the water concentration of the ECF and the ICF must be the same. Inequalities of water concentrations in body fluid compartments can exist only transiently because water movement occurs rapidly to correct these inequalities. This basic concept underlies an understanding of fluid movement between intracellular and extracellular compartments during intravenous fluid therapy. The concentration of solutes in fluid defines the solution’s osmolality. Because cell membranes are water permeable and water movement will occur until solutions on either side of a membrane are iso-osmolar, the osmolality of plasma reflects the osmolality of the body fluid in total. It is important to distinguish between permeant and impermeant solutes. Permeant solutes (e.g., urea)

move freely across cellular membranes and thus do not induce net water movement across cell membranes when they are introduced into a solution; they are termed ineffective osmoles. Impermeant solutes (e.g., Na+) do not freely move across cell membranes and do induce water movement when introduced into a solution; thus they are effective osmoles.

Tonicity The term tonicity refers to the effect a solution has on cellular volume. Hypertonicity results when impermeant solutes are added to the ECF; this promotes cellular dehydration. Hypotonicity results from a decrease in the concentration of impermeant solutions; this results in water movement into cells and cellular swelling. Hypertonic solutions are always hyperosmolar. The reverse is not always the case: Hyperosmolar solutions are not necessarily hypertonic because ineffective osmoles contribute to osmolality but not tonicity. Plasma [Na+] is the key determinant of the osmolality of body fluids. Glucose and urea make minor contributions under normal circumstances. Plasma osmolality may be calculated using the following equation:

2 [ Na + ] (mEq l ) + [ glucose] (mg dL ) 18 + [ BUN ] (mg dL ) 2.8 The preceding equation is a simplification because it does not take into account the fact that plasma is only 93% water; that sodium salts are not completely dissociated in solution; or that calcium, magnesium, and potassium salts also contribute. However, these factors appear to cancel out because experimental evidence demonstrates that calculated osmolality and measured osmolality are in close agreement in normal patients. Plasma [Na+] reflects the plasma tonicity very well in normal patients. Urea is an ineffective osmole because it equilibrates freely across cell membranes and does not induce fluid shifts. Glucose normally can move across cell membranes in normal patients in the presence of insulin; therefore it is usually an ineffective osmole, similar to urea. In diabetic patients lacking insulin, it becomes an effective osmole. Thus plasma [Na+] predicts plasma tonicity when the glucose concentration is known. In hyperglycemia water leaves the cells because of the hypertonicity of the ECF. This serves to dilute the Na+, and hyponatremia is observed. It is important to remember that serum [Na+] does not reflect body salt balance. Salt balance determines ECF volume. Serum [Na+], instead, reflects the state of water balance. The term osmoregulation refers to the control of body fluid tonicity. By stabilizing body fluid tonicity, osmoregulation thus controls cell volume. Osmoreceptors are, in fact, hypothalamic cells that sense their own


cell volume. Changes in plasma osmolality sensed by these cells affect secretion of arginine vasopressin (antidiuretic hormone; ADH). ADH is the primary regulator of renal water excretion. Changes in plasma osmolality also strongly affect the thirst mechanism. This is why patients with central diabetes insipidus, who thus lack ADH, are able to maintain a relatively normal osmolality provided they have access to water and the ability to drink.

Regulation of Water Balance In contrast to salt balance, which is controlled by many factors and has a relatively slow response to changes in effective plasma volume, plasma osmolality is very tightly regulated. When plasma osmolality is altered, changes in thirst and ADH secretion, and the resulting renal response, are brisk. In addition to plasma osmolality, hypotension and hypovolemia also stimulate ADH release and thus this is a point where regulation of salt and water balance are interrelated. ADH release is not as sensitive to hemodynamic stimuli as it is to changes in osmolality; however, when the hemodynamic stimulus is sufficiently strong, the ADH response will be of higher magnitude. In the presence of a significant volume deficit, decreased water excretion by the kidney will in fact act to increase volume at the expense of a decrease in plasma osmolality. The primary function of ADH is to increase the water permeability of the luminal membrane of the collecting duct of the nephron. ADH, through a second-messenger system, causes water channels called aquaporins to be inserted into the cell membrane. Water reabsorption in the collecting duct occurs through these channels, thus allowing the kidney to conserve water.

UNDERSTANDING FLUID LOSSES Sensible and Insensible Fluid Losses Sensible fluid losses are those that can be measured and include fluid lost in the form of urine, feces, vomitus, body cavity effusions, and wound exudates. It is important in seriously ill patients actually to quantify these losses and incorporate them into the fluid prescription. For example, urine output can be determined by collecting voided urine or by weighing the bedding or litter when dry and again after urination. Similarly, vomitus or diarrhea can be weighed to allow the clinician to estimate fluid loss, given that 1 g is approximately equivalent to 1 mL water. For wounds with large volumes of exudate, an animal’s bandage material can be weighed before and after use to create a fluid loss estimate. For patients with drains or chest tubes in place, the amount of fluid produced from these devices can also be measured.

57

Insensible losses are those that cannot directly be measured. They include largely solute-free water in evaporative respiratory, sweat, and salivary losses. This classical definition of insensible losses is sometimes replaced with a clinical definition that includes fecal water loss. This is because the amount of normal daily fecal water loss is small and is rarely measured.16 As a gross approximation, sensible fluid losses account for half of a healthy animal’s daily fluid requirement and insensible losses account for the other half. However, this partitioning is variable and is species and environment dependent. For example, dogs as a species may have a higher percentage of insensible losses compared with cats because of the greater use of panting for thermoregulation. However, cats may have considerable salivary losses if they have increased grooming or lick their fur to promote evaporative cooling in hot weather.7 Insensible fluid losses are generally considered to be solute-free water because respiratory losses are the major contributor in small animal species, including cats. Insensible losses are estimated to be 12 to 30 mL/kg/ day, depending on the study and definition.16 In contrast to insensible losses, sensible fluid losses do contain solutes. Although a necessary oversimplification, this explains why maintenance fluid types are hypotonic. They replace the solute-free water of insensible losses and the solute-containing water of sensible losses. As a matter of practicality, given these estimates and variable definitions, it is reasonable to assume that half of daily maintenance fluids are to offset normal levels of obligate urine output required for daily solute excretion and are solute-containing fluid losses, and the other half, accounting for everything else, are solute-free water losses. This is important clinically when adjusting the fluid prescription for “ins and outs” because it provides a method to estimate how much of measured hourly urine production is abnormal losses in polyuric patients (who have excessive ongoing urinary fluid loss that must be met by the replacement portion of the fluid prescription) and how much is normal obligate urine (and thus met by maintenance portion of the fluid prescription).

Body Weight and Fluid Losses Total body water remains essentially the same day to day in a healthy animal. However in disease, excessive loss of fluid can occur associated with hemorrhage, vomiting, diarrhea, burns, fever, effusions, wound exudates, polyuria, and panting. Because rapid changes in body weight, over the span of hours to a few days, are largely due to changes in total body water, changes in an animal’s weight are an invaluable tool in the assessment of an animal’s hydration status. Because of the relative small size of cats, weighing animals on scales that can

58


accurately detect changes of a few ounces or several grams (human pediatric scales) are very important.

Relationship to Lean Body Mass Because lean body mass is so important in determining an animal’s daily fluid need, resting energy requirement (RER), or daily caloric requirement, is used to calculate an animal’s metabolic water requirements: To metabolize 1 kilocalorie of energy, 1 mL of water is consumed. As such, calculation of an animal’s RER can be extrapolated to determine the volume of fluid in mL required in a 24-hour period. Several equations may be used to calculate RER and hence water requirement.5 The following is one of the most commonly used: RER = 30 ( BWkg ) + 70 This formula is accurate for animals weighing more than 2 kg and less than 25 kg and thus is applicable to adult domestic cats. Kittens and cats weighing less than 2 kg require the use of a different formula: RER = 70 ( BWkg )

0.75

Terminology of Body Fluid Balance The terminology used to describe body fluid balance is at times unfortunately vague. Dehydration refers to a decrease in total body water: loss of fluid from the ICF and ECF compartments. However, the physical examination findings used to assess hydration, such as skin tenting and mucous membrane dryness, are specifically assessments of the ECF volume and subject to significant individual variation and inaccuracy. Thus when clinicians suggest that a patient “appears dehydrated,” they are referring specifically to clinical signs of ECF volume depletion. This is to be distinguished from hypovolemia, which refers to inadequate circulating intravascular fluid volume. The distinction is important because hypovolemia is a much more time-sensitive condition requiring rapid, aggressive treatment.

Assessment of Fluid loss Patients can be assumed to have a decrease in total body water in the presence of known excessive net losses, such as those produced by vomiting, diarrhea, anorexia, and marked polyuria, even without a demonstrable increase in skin tenting and mucous membrane dryness, which are detectable only when 4% to 5% of total body weight has been lost. Humans report headaches with dehydration, and presumably this may reflect some of the general lethargy seen in volume-depleted cats. At 7% total body weight loss, mild tachycardia could also be present. At 10% total body weight loss, the patient might

also have a palpably decreased pulse pressure. Signs of very severe total body water loss are sunken eyes, dry corneas, and altered mentation. Overt hypovolemia will occur with severe fluid loss (>12% body weight), even when chronic. It is important to note at this time that lethargy can be present with both underhydration and overhydration. This is particularly important in cats with oliguria because they are readily susceptible to overhydration. The aforementioned physical findings that are used to determine an animal’s total body fluid status are not used to assess hypovolemia. Peripheral perfusion should instead be assessed by capillary refill time (CRT), mucous membrane color, arterial blood pressure, pulse quality and rate, and temperature of extremities. The body responds to fluid loss by redistributing the functional ECF volume—that is, by pulling fluid into the intravascular space from the interstitial space to maintain circulating blood volume as the first priority. When the interstitial space can no longer replenish intravascular volume depletion, clinical signs of hypovolemia will result. In decompensated shock, severe hypovolemia results in a marked worsening of perfusion parameters. Hypotension, bradycardia, prolonged CRT, pale pink to gray or cyanotic mucous membranes, hypothermia, decreased central venous pressure, altered mentation, and decreased urine output will be present in decompensated shock. Table 5-1 gives examples of the types of fluid losses that would be expected with selected medical problems.

Assessment of Fluid Excess Overhydration, like dehydration, is detrimental to patients and should be avoided in patients on fluid therapy. Human and canine patients with ECF volume excess can have pulmonary edema, ascites, and generalized peripheral edema. Unique to the cat, possibly because of a difference in the anatomy of pulmonary venous drainage, pleural effusion may develop more readily than pulmonary edema or ascites. Cats with preexisting cardiac disease are more susceptible to pleural effusion or pulmonary edema with volume overload, depending on their underlying disease. Cats with oliguria or markedly decreased GFRs are also particularly at risk for overhydration, and measurement of urinary output is essential in such patients. Early signs of overhydration may include the more subtle findings of loss of appetite and mental dullness. An astute clinician will notice tachypnea or crackles on auscultation, insofar as pleural effusion or pulmonary edema develops before the onset of overt dyspnea. Careful and repeated weighing is important for prevention of volume overload, particularly in cats, because of their small size.


59

TABLE 5-1 Examples of the Types of Fluid Losses that Would Be Expected with Selected Medical Problems Condition

Dehydration

Hypovolemia X

Blood loss Vomiting

X

X (if severe)

Diarrhea

X

X (if severe)

Sepsis/vasodilation

X

Hypoadrenocorticism

X

Polyuria

X (depending on cause)

Hypodipsia or water deprivation

X

BODY RESPONSE TO HYPOVOLEMIA Intravascular volume status is sensed by baroreceptors in the carotid body and aortic arch. In euvolemic cats, stimulation of the stretch receptors triggers the vagus nerve to maintain an appropriate heart rate. In hypovolemia the baroreceptors sense a decrease in wall tension, and the sympathetic nervous system is activated. Norepinephrine and epinephrine release results in vasoconstriction, improved cardiac contractility, and an increase in heart rate. These effects are designed to compensate for decreased intravascular fluid volume by improving cardiac output and maintaining systemic blood pressure and, ultimately, perfusion. Hypovolemic shock results when intravascular volume is sufficiently reduced that these compensatory mechanisms are overwhelmed and decreased tissue perfusion results. Perfusion parameters that can be assessed include capillary refill time, blood pressure, heart rate, and temperature of extremities. Cats are unique in that the vasoconstrictor response to volume loss is blunted in the presence of hypothermia.13,14 For this reason, cats are more prone than other species to fluid overload when they have been volume resuscitated while hypothermic. Once body temperature returns to normal, the vasoconstrictor response returns and intravascular pressure rises. For this reason, hypothermia in cats is a potentiator of shock, as well as a result of shock. Cautious fluid resuscitation must coincide with aggressive rewarming efforts to prevent volume overload. Specific therapy and therapeutic endpoints for resuscitation are discussed in subsequent sections.

GENERAL CONSIDERATIONS FOR FLUID THERAPY Fluid therapy choices are often the product of educated guesswork. They certainly rely on the physiologic abilities of a normally functioning kidney for fine-tuning. Although there are many useful guidelines for selection of fluid types and rates, good fluid management demands careful monitoring of body weight, physical

X (depending on cause)

examination, and electrolyte concentrations. The veterinarian must be prepared to alter the fluid therapy prescription in response to changes in these parameters, and should understand that the initial fluid therapy plan merely provides a starting point. The clinician must also be more vigilant with fluid therapy monitoring in patients with cardiovascular or renal disease. It should be remembered that cats may have cardiac disease in the absence of a detectable murmur. As fluid bag sizes are not scaled down to the size of feline patients, it is helpful to use fluid pumps, burettes, and other devices to prevent fluid overload and pulmonary edema or pleural effusion (Figure 5-2).

FLUID TYPES The two main types of parenteral fluids, crystalloids and colloids, have fundamental differences that affect the way fluid distributes among body fluid compartments. Crystalloids are composed of smaller molecules that diffuse readily; therefore approximately 80% of the fluid infused will leave the intravascular space within 1 hour. Colloids, made of larger molecules, stay within the intravascular space longer, which is an important advantage when managing hypovolemia. The tonicity of fluids determines distribution rates to the intracellular and extracellular spaces. When the [Na+] of a fluid approximates that of plasma (145 mEq/L), it will equilibrate rapidly with the interstitial space. Remaining fluid that is not lost in urine or as other ongoing losses will distribute to the ICF in proportion to the normal size of those compartments: two thirds ICF and one third ECF. Hypotonic fluids, with a [Na+] lower than that of plasma, will dilute the plasma and drive water into cells to equilibrate the water concentration inside and outside cells. The decreasing plasma osmolality (pOsm) will also result in a decreased ADH production and, thus, increased water excretion by the kidney. Most of the Na+-free fluid thus either enters cells or is excreted. Hypertonic fluids with a [Na+] higher than plasma will draw water out of cells and into the ECF, thus increasing

60


B

A

C FIGURE 5-2 Because fluid bag sizes are not scaled down to the size of feline patients, it is helpful to use fluid pumps (A and B), burettes (C), and other devices to prevent fluid overdosing.

the intravascular and interstitial volumes but at the expense of taking water from the ICF compartment. Thus an understanding of which body compartments need to be replenished in any given patient is essential in fluid selection. This is true not only regarding fluid types selected but also in terms of route of administration. For example, fluids instilled into the subcutaneous space cannot be used readily to replenish the intravascular blood volume because they will be absorbed too slowly in a patient with hypovolemia.

Crystalloids A crystalloid is a solution that is able to pass through a semipermeable membrane, including the vascular endothelium. The ability of crystalloids to pass through the capillary endothelium allows them to replenish fluid losses both in the intravascular and interstitial compartments, making them ideal for rehydration therapy. All crystalloid fluids are true solutions, meaning that they are homogeneous and transparent, diffuse rapidly, and do not settle. Substances that are dissolved in crystalloids are termed solutes; these are predominantly electrolytes and dextrose.

Solutes contained in crystalloid fluids move freely from the intravascular space to the interstitial space. Movement of impermeant solutes such as ions and glucose into the intracellular compartment is comparatively slower, occurring by facilitated diffusion or active transport. As parenteral fluid solutions, most crystalloids are formulated with a solute concentration close to that of plasma to avoid osmotic cell damage, particularly red blood cell damage from tonicity-induced osmotic water movement. Some parenteral intravenous solutions, such as 0.45% NaCl and 5% dextrose in water (D5W) are hypotonic and can cause hemolysis if given too rapidly. The three categories of crystalloids are isotonic highsodium, hypotonic low-sodium, and hypertonic saline; they differ primarily in their sodium concentrations. Isotonic High-Sodium Crystalloids GENERAL CHARACTERISTICS AND INDICATIONS FOR ISOTONIC HIGH-SODIUM CRYSTALLOIDS

Isotonic high-sodium fluids are commonly referred to as replacement fluids because they are often used for rapid replacement of ECF volume deficits caused by vomiting


61

TABLE 5-2 Composition of Common Crystalloids*

+

Na (mEq/L) −

Cl (mEq/L) +

K (mEq/L) ++

Ca (mEq/L) ++

Mg (mEq/L) Osmolality (mOsm/L)

Plasma-Lyte 56 + 5% Dextrose

0.45% NaCl + 2.5% Dextrose

5% Dextrose

140

77

0

40

154

98

77

0

40

4

4

5

0

0

13

0

3

4

0

0

0

0

0

0

0

3

0

0

3

308

273

309

294

280

252

112

0/9% NaCl

Lactated Ringer’s Solution

Ringer’s Solution

Normosol-R

154

130

147

154

109

0

pH

5.6

6.6

Buffer (mEq/L)

0

Dextrose (g/L)

0

0

0

Calories (Kcal/L)

0

9

0

28 (Lactate)

5.4 0

6.6

4.3

4.3

0

0

0

25

50

50

15

85

170

175

27 (Acetate), 23 (Gluconate)

5.5 16 (Acetate)

*High-sodium “replacement” fluids are in red. Low-sodium “maintenance” fluids are in green.

and diarrhea. They have a [Na+] near that of ECF, ranging from approximately 130 mEq/L (e.g., lactated Ringer’s solution [LRS]) to a high of 154 mEq/L (e.g., 0.9% saline). Table 5-2 includes additional examples of replacement fluids, highlighted in red. Isotonic high-sodium fluids are used both for hypovolemia and for less severe ECF volume depletion, such as dehydration. When given rapidly, they can be used to restore the intravascular fluid volume in cats with hypovolemia. They are also used, when administered more slowly, to replace ECF volume in states of isotonic dehydration that are not immediately life threatening, such as occurs in patients with gastrointestinal or urinary fluid losses when oral intake is insufficient to balance losses. Isotonic high-sodium fluids are not suited for use as maintenance fluids. They lack sufficient solute-free water content to offset ongoing solute-free water loss, such as through respiratory evaporation. When used on a short-term basis, most patients with normal renal function will tolerate the excess Na+ that these fluids contain when they are being used primarily to compensate normal daily ongoing hypotonic fluid loss. This is particularly true when patients are able to drink some water in addition to their intravenous fluid therapy. Some patients can become hypernatremic after therapy with high-sodium fluid. There are also some patients for whom the use of high-sodium fluids is contraindicated, including those with congestive heart failure, oliguric renal disease, and some edema states. Isotonic high-sodium fluids are used to maintain patients with ongoing isotonic fluid losses, as, for

example, in vomiting or diarrhea. However, in these patients the fluids are in fact being used for replacement of these losses, rather than for true maintenance. It is critical to understand this distinction. Maintenance is a term used to reflect what is needed to replace only normal sensible and insensible losses, and such losses are not isotonic. Isotonic fluids may work to maintain fluid balance in animals with additional pathologic losses because such patients need the additional sodium and chloride. However, such patients need to drink to provide solute-free water; otherwise, hypernatremia will develop. In addition to the relative solute-free water deficit of high-sodium isotonic fluids, all of these fluids are also too low in potassium to be used as true maintenance fluids, unless K+ is added to the fluids. Patients with continuing ongoing losses for more than 1 to 2 days that stay on high-sodium fluids are likely to need nutritional support, which will also replace their hypotonic maintenance fluid needs. Some patients with readily corrected deficits and no ongoing losses will need to be transitioned to a maintenance-type solution, such as Normosol-M-D5 or Plasmalyte-56-D5, after their rehydration and electrolyte needs have been corrected and before the start of enteral or parenteral nutrition. The need to change to a true maintenance fluid will be indicated by a progressive increase in serum [Na+] in these patients. Changes should be made well in advance of the development of hypernatremia. Sick cats that have been anorexic for 2 to 3 days or longer should receive nutritional support. Generally, the provision of enteral or parenteral nutrition sufficient to

62


TABLE 5-3 Calculation Worksheet for Fluid Therapy*† Volume of Fluid Components of the Fluid Plan Deficits

Type of Fluid

mL/day

mL/h

Isotonic Hypertonic

Maintenance

Normal ongoing losses (Enteral contribution from feeding)

(

)

(

)

Net normal loss to be provided by fluids Abnormal ongoing losses

GI Urinary Other sensible Insensible

Totals

1.

1.

1.

2.

2.

2.

3.

3.

3.

*The enteral contribution includes what the cat is eating or drinking on its own plus any provision of food or water through tube feeding. It is indicated in parentheses ( ) to signify that this volume is subtracted from the calculated maintenance fluid needs to yield the net that must be provided to the cat as part of intravenous fluid therapy plan. † For a case example, see Table 5-8.

meet the patient’s caloric needs will also provide maintenance fluid needs. Thus the use of additional isotonic, high-sodium fluids in this setting will be to replace excessive isotonic losses, such as those associated with gastrointestinal loss or polyuria. Intravenous fluid rates can be greatly reduced in patients receiving either enteral or parenteral nutrition to a rate sufficient to meet additional ongoing losses only. In other words, the fluid therapy recipe should account for all sources of fluid intake (Table 5-3; also see Table 5-8). ACIDIFYING AND ALKALINIZING FLUIDS

Sick cats requiring fluid therapy may also have acid– base disorders, and fluid therapy can be used to mitigate these disturbances. Restoration of ECF volume will improve tissue perfusion and correct lactic acidosis. The replenishment of water and electrolytes in appropriate concentrations will also improve renal perfusion and normalize renal electrolyte handling, thus promoting an improved acid–base balance. The volume expansion and improved perfusion seen with appropriate fluid therapy will also promote the peripheral utilization of glucose and decrease production of lactate. The end result of this can be the normalization of acid–base balance without the need to resort to the use of sodium bicarbonate, which can have adverse effects, such as hypernatremia and central nervous system acidosis. High-sodium crystalloids will have a primary effect on the patient’s acid–base status, depending on their composition. As such, they can be classified as either acidifying or alkalinizing solutions. High-sodium fluids that contain more Cl− than is present in the patient’s ECF are acidifying. Although 0.9% saline has a high Na+ content and thus is frequently used to restore intravascular fluid in hypovolemic patients, it also has a high

Cl− content and will be acidifying. This fluid is most appropriate for treatment of patients with hypochloremic metabolic alkalosis because it provides the necessary Cl−. A common clinical scenario associated with hypochloremic metabolic acidosis is the vomiting of gastric contents. It is important to point out that although the measured pH of parenteral fluid solutions ranges from about 4 to 6.5, they are extremely weak acids. These low measured in vitro pH values will not reflect their effect on pH in the patient because of buffering. Alkalinizing fluids, by contrast, do not have a higher Cl− concentration than ECF fluid. Some of the chloride is replaced with another anion such as lactate, acetate, or gluconate. The anions are metabolized by the liver to bicarbonate. One example of a commonly used alkalinizing fluid is LRS. SUPPLEMENTS

In some situations fluids must be supplemented with additional electrolytes; this decision is based on an assessment of the history, physical examination findings, and measured electrolyte values. Commonly added electrolytes are listed in Table 5-4. Electrolyte additives may be appropriate for replacing deficits, providing replacement for normal maintenance losses in anorexic patients, compensation for transcellular movement of ions, or replacement of ongoing gastrointestinal or urinary losses. Potassium and magnesium are found in some low-sodium hypotonic fluids formulated as maintenance fluids. If not, they can be added to fluids to maintain homeostasis in animals that are not depleted. POTASSIUM All of the isotonic high-sodium fluids, apart from 0.9% NaCl, contain 4 or 5 mEq/L of potassium. Although this amount of potassium is within


63

TABLE 5-4 Concentration of Common Fluid Additives Product

Concentration per mL

KCl

2 mEq each

KPO4

4.4 mEq K+, 3 mM PO4

MgCl

1.97 mEq each

MgSO4

4.06 mEq each

Ca gluconate 10%

0.465 mEq Ca++

CaCl2

1.36 mEq Ca++

NaPO4

4 mEq Na+, 3 mM PO4

Dextrose 50%

500 mg

From Abbott Animal Health Fluid Therapy Module 2, courtesy Dr. Steve Haskins.

FIGURE 5-3 A constant-rate infusion is typically used to give K+

the normal range of plasma [K+], it is not in fact sufficient for maintenance of the patient. This is because therapy with intravenous isotonic high-sodium fluids typically causes a solute diuresis. The rate of flow of filtrate through the renal tubule is one of the factors regulating renal potassium excretion. As urine flow rate increases in response to intravenous fluid administration, K+ loss in the urine will also increase. The loss of K+ from the body will be further compounded by decreased intake in patients that are anorexic or hyporexic and by increased losses of K+ in gastrointestinal secretions in patients with vomiting or diarrhea. Thus when isotonic high-sodium fluids are used for maintenance of patients that are drinking or for support of patients with ongoing isotonic fluid losses, it is necessary to supplement the fluids with additional K+. A common level of supplementation for a cat that is normokalemic is the addition of 20 mEq/L of KCl to the isotonic high-sodium fluid. This amount is typically added to the K+ already present in the fluids; it is not necessary to subtract the small amount that is already present in the fluid. If K+ is not added to these fluids when they are used for more than a short time in normokalemic patients, hypokalemia will result. For patients that are hypokalemic, a sliding scale is used to calculate how much potassium to add to the fluid. One such scale is shown in Table 5-5. When using the potassium-containing replacement fluids for fluid resuscitation, it must be remembered that if the K+ concentration of the fluid exceeds 5 mEq/L, the fluid must not be infused rapidly for intravascular volume restoration because of the risk of hyperkalemia. Cats with anorexia, gastrointestinal losses, or polyuria are particularly at risk for K+ depletion. As an alternative to the sliding scale, a constant-rate infusion (CRI) is typically used to give K+ separately when the patient seems resistant to “normal” amounts of K+ supplementation, particularly in diabetic ketoacidosis (DKA) (Figure 5-3). This allows K+ to be adjusted separately

separately when the patient seems resistant to “normal” amounts of K+ supplementation, particularly in diabetic ketoacidosis.

TABLE 5-5 Sliding Scale for the Amount of KCl Added to Intravenous Fluids Depending on the Serum [K+]* Measured Serum K+ (mEq/L)

KCl Added (mEq/L)

>5.5

None

3.6-5.5

20

3.1-3.5

30

2.6-3

40

2-2.5

60

3 to 5 days) fluid or IV drug administration • Parenteral nutrition • Treatment with hypertonic or irritating fluids or drugs • Concomitant delivery of incompatible drugs or fluids • Frequent phlebotomy sampling • CVP monitoring • Transvenous pacing How to Place an Intravenous Catheter The jugular or saphenous veins are most commonly used to gain access to the central venous circulation. Preparation for placement of a catheter consists of several steps: gathering all necessary supplies, clipping the catheter insertion site with a well-lubricated 40 blade, applying a surgical prep to the catheter insertion site, and occluding the vein. When establishing intravenous access, caution should be used in very ill, dyspneic, or compromised patients, for whom the stress of physical restraint could cause an acute decompensation of their condition. Sites for indwelling catheters should be aseptically scrubbed with sterile gauze squares freshly soaked with antimicrobial solution, alternating with either alcohol or sterile water. A total of three scrubs should be performed, and contact time of the scrub solution with the skin surface should be 3 to 5 minutes. Care should be taken


71

TABLE 5-6 Features of Catheters that Are Used to Gain Vascular Access in Cats Type of Catheter

Indications

Advantages

Disadvantages

Comments

Peripheral

Short-term fluid and/or medication administration

Ease and speed of placement Low complication rate

Tip may fray, damaging vein Often becomes nonpatent May be resented or dislodged by patient

Available as over-the-needle or through-the-needle (former used more commonly)

Central venous

Hyperosmolar solutions (1-2 mL/kg per hour SVO2 >70% (mixed venous oxygen saturation): the SPO2 of blood being returned to the heart—a measure of how much oxygen the tissues are extracting. Low SVO2 indicates either excessive oxygen demand by the tissues or inadequate oxygen supply.

occluded. Lack of venous distention in vessels above the level of the heart may indicate hypovolemia. Obviously, this is a subjective assessment, but it can give some idea of relative volume status. Venous volume can also be indirectly assessed by measuring CVP. CVP is the hydrostatic pressure of the blood entering the heart, as measured by a catheter with its tip in the right atrium or vena cava. CVP is proportional to the volume of blood in the anterior vena cava and venous tone. This pressure is decreased by hypovolemia or venodilation and is increased by fluid therapy or venoconstriction. Several other factors can contribute to the accuracy of CVP measurement, such as cardiac or respiratory pathology, making it a somewhat unreliable (but useful) physiologic variable. CVP can be measured with a column manometer (the most common method) or a direct pressure transducer. The normal range is 0 to 10 cm H2O. However, because of variations in venous tone and other technical factors, single CVP values are often difficult to interpret without the aid of other monitoring. Normal and abnormal values can overlap; for example, CVP can range from −5 to +5 cm of H2O in hypovolemic animals and from 5 to 15 cm H2O in animals with volume overload. Therefore measurements should be considered meaningful to the fluid therapy prescription only if they are below 0 or above 10 cm of water and, more important, if the overall trend in CVP is considered. Taking into account all available parameters, if a patient’s CVP is consistently below 0 cm H2O, consideration should be given to either a bolus of fluids or an increased rate of fluid administration. If a patient’s CVP value is consistently above 10 cm H2O, fluid administration should be slowed or discontinued, and diuretic administration should be considered. CVP measurements are primarily indicated during volume restoration for shock and in patients for whom volume overload is a concern, such as patients in acute renal failure or those with concurrent cardiac disease.

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Observation of correct technique for CVP measurement is very important, insofar as there is considerable interoperator variability. For the most accurate and clinically useful results, the patient’s position should be recorded in the medical record and the same staff should perform the readings whenever possible. To measure CVP (see Figure 5-4), the patient is positioned in right lateral recumbency and the level of the right atrium (near the manubrium—the cranial tip of the sternum) is identified. The clinician should ensure that the stopcock is level with the right atrium (this line is known as the phlebostatic axis) using a bubble level. This serves as the reference point and is the “zero” mark on the manometer. With the stopcock closed towards the patient, the clinician opens the fluid bag line and fills the manometer to about 25 to 30 cm H2O. The clinician then opens the stopcock toward the patient (turning it off toward the fluid bag) and allows the fluid in the manometer to run into the patient. At some point the fluid will begin to oscillate with the patient’s heartbeat and will stop falling as it equilibrates with the pressure in the vena cava (usually about 25 to 30 seconds); this is the CVP measurement and should be noted in the patient’s record. Venous volume can also be very roughly estimated by evaluating the diameter of the caudal vena cava on a lateral thoracic radiograph. Normal diameter is roughly equivalent to one rib width. A small caudal vena cava diameter suggests hypovolemia, and further fluid administration may be indicated depending on the patient’s status. A large caudal vena cava diameter may suggest hypervolemia or heart failure, and the fluid therapy prescription should be re-evaluated. PARAMETERS RELATED TO LARGE ARTERIES

Physiologic parameters related to large arteries include pulse quality and arterial blood pressure. Pulse quality assessment through palpation is a reflection of stroke volume and the difference between systolic arterial pressure and diastolic arterial pressure, not a measure of blood pressure. For this reason, poor pulse quality does not always correlate with hypotension. Poor pulse quality can be associated with small stroke volumes, venoconstriction, or hypotension. Hypovolemia may be the most common cause of poor pulse quality, but it is also a feature of other conditions, such as poor cardiac contractility, tachycardia, restrictive heart disease, aortic stenosis, and positive pressure ventilation, none of which absolutely requires fluid therapy. If the cause of the poor pulse quality is determined to be hypovolemia by corroborating history, clinical signs, and other measurements, then fluid administration may be indicated. Mean arterial blood pressure is the average pressure of the pulse pressure waveform. Systolic arterial blood pressure is the highest pressure of the waveform and is primarily determined by stroke volume and arterial wall

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compliance. Diastolic arterial blood pressure is the lowest pressure before the next stroke volume and is primarily determined by systemic vascular resistance and heart rate. Arterial blood pressure can be measured indirectly (with a Doppler transducer, occlusion cuff, and sphygmomanometer) or directly (with an arterial catheter by way of a pressure transducer). Normal systolic pressure measurements range between 100 and 160 mm Hg, mean pressure measurements between 80 and 120 mm Hg, and diastolic pressure measurements between 60 and 100 mm Hg. The determinants of blood pressure (BP) are as follows: BP = CO × SVR , where CO is cardiac output in mL min and SVR is systemic vascular resistance in dynes sec cm 5. Determinants of CO are stroke volume (SV) and heart rate (HR). Taken as a whole, the equation is as follows: BP = ( HR × SV ) × SVR From this relationship, it can be seen that in order to maintain constant BP (an analog for perfusion) in the face of falling cardiac output (as with hypovolemia), either the heart rate has to increase or the systemic vascular resistance (as mediated by catecholamine release) must rise. Arterial blood pressure is not a very good measure of circulating blood volume because animals have a great ability to compensate for alterations in blood volume to preserve blood pressure. Eventually, however, severe hypovolemia will result in hypotension as heart rate may be maximized or the systemic vasculature may be maximally constricted. Hypotension may be caused by hypovolemia, poor cardiac output, or excessive vasodilation, as illustrated by the previous formula. If the cause of the hypotension is hypovolemia, further fluid therapy is indicated. Hypotension resulting from vasodilation, as seen with hypothermia in cats, should be treated with cautious fluid therapy concomitantly with external rewarming. When inappropriate vasodilation is due to vasoplegia, as with sepsis or distributive shock, treatment should consist of fluid therapy coupled with vasoactive substances (pressors or catecholamines) such as phenylephrine or dopamine. It is important to remember that catecholamines should not be administered until the veterinarian is fairly certain that adequate circulating volume has been restored, because their use while the patient is hypovolemic will only worsen ischemia, not improve it. When hypovolemia is due to heart failure, further fluid therapy is not indicated and disease-specific therapy is required. Another category of forward flow parameters is made up of variables that reflect precapillary arteriolar vasomotor tone. Increased vasomotor tone, or vasoconstriction, commonly occurs in conditions such as

hypovolemia, heart failure, hypothermia, and administration of vasoconstrictors. Decreased vasomotor tone, or vasodilation, commonly occurs in conditions such as septic shock, hypothermia or hyperthermia, and administration of vasodilators and some anesthetics. Arteriolar tone can be assessed by monitoring mucous membrane color and CRT. Normal mucous membrane color is pink. Vasoconstriction decreases capillary perfusion, causing the color of the mucous membrane to change from pink, to pale pink, and then to white as vasoconstriction progresses in severity. Vasodilation increases capillary perfusion, causing the color of the mucous membrane to change from pink to red as vasodilation progresses in severity. Ambient lighting, visual acuity, and patient pigmentation can make absolute assessment of mucous membrane color problematic, and it should be evaluated in concert with other variables and physiologic parameters. The most common sites to observe mucous membrane color are the unpigmented gingiva, tongue, and conjunctiva. Deoxygenated hemoglobin causes a bluish discoloration of the capillary beds as cyanosis progresses in severity. Cyanosis is usually caused by hypoxemia, which should prompt an evaluation of pulmonary function, but it occasionally can be caused by sluggish capillary blood flow or diminished cardiac output, which necessitates further evaluation of cardiovascular function. Anemia causes pale mucous membrane color and may warrant a hemoglobin infusion. Mucous membrane color is determined by the amount of oxygenated hemoglobin in the visible capillary beds. Arteriolar vasomotor tone determines the amount of blood in the observed capillary beds. CRT is primarily determined by arteriolar vasomotor tone. CRT is assessed by using digital pressure on mucous membranes until they turn white and then noting how long it takes for normal color to return. Normal CRT is 1 to 2 seconds. The most common site to evaluate CRT is on unpigmented gingiva. Vasoconstriction, which prolongs CRT, may be caused by hypovolemia, heart failure, hypothermia, and administration of vasoconstrictors. If the patient’s history and other cardiovascular parameters suggest hypovolemia, fluid therapy is indicated. Vasodilation shortens CRT. Vasodilation may be caused by septic shock, hyperthermia, and administration of vasodilators and some anesthetics. Vasodilation may cause hypotension, and blood pressure should be assessed in these patients. Another forward flow category, tissue perfusion, includes extremity temperature, urine output, lactic acidosis, and central venous partial pressure of oxygen. Urine output can be used in cats with functioning kidneys as an indirect measure of renal perfusion and vital organ perfusion. Hypovolemia and dehydration

reduce renal perfusion and GFR. In both situations there will be avid tubular reabsorption of Na+ and glomerular filtrate, thus reducing the urine volume. A decrease in urine volume is thus expected with hypovolemia or dehydration if renal function and urine concentrating ability are normal. Appendage temperature is a subjective assessment made by palpating the extremities. It can also be assessed by simultaneous measurement of core and toe web temperature. During vasoconstriction the extremities are not as well perfused as vital organs because of shunting of blood away from the periphery. Consequently, appendages cool toward ambient temperature. The normal core appendage temperature gradient is 2 to 4o C. Values in excess of this range suggest poor perfusion, most commonly caused by vasoconstriction or hypovolemia. Metabolic acidosis has several causes, one of which is poor perfusion. This occurs when lactic acid is generated in poorly oxygenated tissues because of inadequate perfusion and anaerobic metabolism. Acidosis is best assessed by means of a venous blood gas and may be identified by an elevated blood lactate concentration not caused by lactated fluid administration, a decrease in measured bicarbonate or total CO2 concentration, or a greater than normal base deficit. Normal blood lactate concentrations range between 0.5 and 2 mM/L. A pointof-care lactate monitor is available for veterinary patients (Accutrend, Roche Diagnostics), and lactate measurement should be considered for all hypotensive patients to help guide resuscitative measures. Rather than overinterpret any single value, normalization of elevated lactate after resuscitation can be used to indicate improved volume status and perfusion. Persistently elevated lactate values after initial fluid resuscitation should prompt a search for possible ischemic tissue (e.g., devitalized bowel) or a need for additional fluid therapy. Clinicians should not be overly surprised when finding elevated lactate in a compromised and hypotensive patient, but failure to normalize lactate should trigger a re-evaluation of the fluid prescription and possibly an evaluation for other causes of poor perfusion, such as cardiac disease or sepsis. Central venous partial pressure of oxygen (CvO2) is a measure of the relationship between oxygen delivery and oxygen consumption; alterations in either component will change CvO2. When oxygen delivery is diminished for any reason, including poor perfusion, tissues will continue to extract oxygen to meet metabolic demand. Continued extraction in the face of diminished oxygen delivery results in a greater percentage of oxygen extraction from the blood, resulting in a reduction of CvO2. Increased tissue demand for oxygen, as in a hypermetabolic state, will also decrease CvO2 if oxygen delivery does not increase. CvO2 can be assessed with point-of-care analyzers (such as the iSTAT, Abbott


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Laboratories; IRMA TruPoint, ITC Medical; or Stat Profile, Nova Biomedical) capable of performing blood gas analysis. Jugular venous blood should be used to assess CvO2 because peripheral venous values are highly variable and are considered unpredictable. Normal central venous CvO2 values range between 40 and 50 mm Hg. Values between 30 and 40 are common in critically ill patients and have no known adverse consequences. Values between 20 and 30 mm Hg are progressively more worrisome, and values below 20 mm Hg are considered to indicate life-threatening tissue hypoxia. If the cause of poor oxygen delivery is determined to be anemia, a hemoglobin infusion may be indicated. If the cause is determined to be hypoxemia, further evaluation of pulmonary function is indicated. If the cause is determined to be hypovolemia, further blood volume augmentation may be warranted. If the cause is determined to be heart failure or vasoconstriction, the underlying cause should be investigated and treated appropriately. Central venous PO2 values above normal may represent hyperperfusion of the tissues but are more often taken to represent poor oxygen uptake by the tissues secondary to impaired oxygen metabolism, such as occurs in sepsis. No adjustments in fluid therapy are likely to be necessary.

The Hemodynamically Stable Patient Development of a Fluid Therapy Plan The patient’s history, physical examination, laboratory results, and diagnosis are used to develop a fluid therapy plan by completing the following steps: 1. Determine the patient’s fluid therapy needs, considering the component of these needs that will be met through the provision of the patient’s nutritional requirements. This may occur if the patient is eating and drinking to meet some of its own needs or when parenteral or enteral nutritional support is provided. 2. Identify the ideal crystalloid(s) and/or colloid fluid to administer. 3. Determine the volume and rate of fluid administration for each fluid being administered. 4. Select the appropriate catheter type, size, and insertion site. 5. Develop a monitoring protocol, and make adjustments to the fluid therapy plan according to the patient’s response to treatment. HYDRATION STATUS VERSUS HYPOVOLEMIA

It is important to remember that hydration status is the total body water of the cat. It is reflected in the ECF volume (i.e., the crystalloid volume status of the ECF) and is determined by the ECF Na+ content because of the

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equality of ICF and ECF osmolality. The vascular fluid compartment is an integral component of the ECF compartment, but the association between the volume of the ECF (and thus total body water) and hypovolemia can vary. Blood volume status and hydration status must be evaluated independently because changes in intravascular volume status can occur independently of hydration. Patients can be hypovolemic without being dehydrated. Patients on therapy can be made hypervolemic without correcting a total body water deficit. Patients with edema may be hypervolemic as a result of fluid overload or hypovolemic as a result of vasculitis or hypoproteinemia. CREATING A FLUID PLAN

The fluid plan is generally divided into three categories, evaluated for each patient: deficits, maintenance, and ongoing losses. Within each category the clinician should determine the quantity and type of fluid to administer and also determine the fluid volume and rate for each type of fluid being administered. A worksheet such as that shown in Table 5-3 can be a useful tool for constructing a fluid plan. Although it is often preferable to use a single fluid because of cost considerations, it is not always appropriate to do this for complex cases or seriously ill cats. CORRECTION OF EXTRACELLULAR FLUID VOLUME DEPLETION

The first element of the fluid plan should address preexisting dehydration. To determine the degree of total body water depletion (dehydration), the veterinarian should assess skin turgor, mucous membrane moistness, recent changes in body weight, urine output, and blood solute concentrations. Most dehydrated patients have undergone isotonic fluid loss and thus have too low an ECF Na+ content. The magnitude of the deficit is first assessed by changes in skin turgor and moistness of the mucous membranes. The skin along the back or shoulders is lifted into a fold and released. In ECF volume–replete patients, the skin will snap back rapidly to its resting position. If it is detectably slow, the animal is estimated to be about 5% dehydrated. If the skin stands in a fold, the animal has life-threatening ECF volume depletion of about 12% of body weight. Intermediate skin turgor between these two levels of detection is interpolated between 5% and 12% dehydration. These are just rough estimates because of individual variation. Poor skin turgor in emaciated cats may overestimate dehydration, whereas obesity may cause it to be underestimated. Mucous membrane moistness can be assessed to add further support for the initial estimation. Body weight change, especially in the short term, is an excellent way to estimate the percentage of dehydration, provided recent and highly accurate body weights have been recorded. When patients have

a history consistent with the development of dehydration, such as vomiting, diarrhea, or polyuria coupled with poor intake, a 4% of body weight ECF volume depletion should be assumed even when skin turgor appears normal. The volume deficit is calculated by multiplying the percentage of dehydration by the patient’s body weight (in kg). For example, a 5-kg cat that is 5% dehydrated requires replacement of a fluid deficit of 250 mL, because 1 g equals 1 mL. This volume is then divided by the number of hours over which the deficit is to be restored to calculate the mL/hour fluid rate. Often, 24 hours is chosen for restoration of the deficit. However, the presence of azotemia believed to be prerenal or acute renal in origin requires a more rapid restoration of the deficit, such as within 4 to 6 hours. For a less critically ill patient or one with suspected or known heart disease, the clinician may elect to correct the deficit over as long as 36 hours or more. Again, it is important to recognize that these are merely guidelines, and the clinician should be prepared to periodically re-evaluate or change the rate of fluid administration in response to changes in the patient’s clinical status. When selecting the appropriate crystalloid, the clinician should always evaluate the history and clinical signs to understand how the deficit developed. This allows the clinician to make an educated guess as to the composition of the fluid that has been lost. When a serum chemistry panel with electrolytes becomes available, this can be used to confirm the best fluid composition for replacement. For example, fluids without calcium or potassium are indicated for patients with hypercalcemia or hyperkalemia. Fluids with a buffer will be indicated for patients with low serum bicarbonate. Table 5-7 illustrates the types of fluids recommended to replace specific types of losses. The ideal way to determine the amount of KCl to add to the fluids would be to measure the serum [K+] and then use the sliding scale in Table 5-5. However, if the patient’s current serum [K+] is not known, it is generally safe to use the empirical dosage of 20 mEq/L. When KCl is being added to parenteral fluids, it is important to mix the bag to distribute the KCl throughout the fluid. CORRECTION OF INTRACELLULAR FLUID VOLUME DEPLETION

Although uncommon, some patients may have hypertonic dehydration. This develops when solute-free water is lost in excess of isotonic fluid loss. It is more commonly observed in dogs because they suffer from heat stroke more commonly than do cats because of the very high respiratory evaporative heat loss required for thermoregulation. However, cats can suffer heat stroke as well, losing water through respiratory and salivary losses. Cats trapped in basements and closets may experience hypertonic dehydration because they have been


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TABLE 5-7 Assessment of Typical Fluid and Electrolyte Losses for Various Clinical Syndromes Electrolyte Balance

Acid–Base Status

Hypertonic Largely intracellular

Normal

Normal

Free water D5W

Very hypotonic

Hypertonic

K+ variable Na+ variable

M Acidosis

0.45% NaCl, followed by balanced electrolyte solution

Anorexia (still drinking)

Hypertonic

Hypotonic

Na+ lost K+ lost

M Acidosis

Balanced electrolyte solution w/KCl supplement

Anorexia (unable to drink)

Hypotonic

Hypertonic Largely intracellular

Na+ lost K+ lost

M Acidosis

0.45% NaCl w/KCl

Vomiting (gastric contents)

Hypotonic or isotonic

Isotonic or mildly hypertonic

Na+ lost K+ lost H+ lost Cl− lost

M Alkalosis

0.9% NaCl w/KCl

Vomiting (duodenal contents)

Hypertonic or isotonic

Isotonic or mildly hypertonic

Na+ lost Mg++ lost K+ lost HCO3− lost

M Acidosis

Balanced electrolyte solution w/KCl

Diarrhea

Hypotonic or isotonic

Isotonic or hypertonic

HCO3− lost K+ lost Mg++ lost Na+ lost

M Acidosis

Balanced electrolyte solution w/KCl

Diabetes mellitus

Hypotonic

Hypertonic extracellular & intracellular

Na+ lost PO4−− lost K+ lost Mg++ lost

M Acidosis HAG w/ DKA

Balanced electrolyte solutions w/KCl & Mg++ upon Rx, some need PO4−−

Hypoadrenocorticism

Hypertonic

Hypotonic

Na+ lost

M Acidosis

0.9% NaCl initially; if severe, balanced electrolyte solutions

Diabetes insipidus

Free water

Hypertonic largely intracellular

K+ lost Mg++ lost

M Acidosis

0.45% NaCl

Hypercalcemia

Hypotonic


Na+ lost

M Acidosis

0.9% NaCl w/KCl 0.45% NaCl if hypertonic

Chronic renal failure

Isotonic

Isotonic

Variable, depends on GFR H+ retained

M Acidosis

Balanced electrolyte solutions usually w/KCl

Acute renal failure

Variable, depends on urine output

Variable, depends on urine output

K+, H+, PO4− − retained Na+, Mg++ variable

M Acidosis

Variable

Urethral obstruction

Isotonic or hypotonic


K+, H+, PO4− − retained M Acidosis Na+, Cl− variable

0.9% NaCl initially Followed by balanced electrolyte solution w/KCl

Congestive heart failure (untreated)

Isotonic gains

Isotonic Overhydration

Na+ retention

R Alkalosis M Acidosis

D5W for KVO

Congestive heart failure (treated w/furosemide)

Dosage dependent

Variable

K+ lost Na+ variable

Variable, possible M alkalosis

Variable

Septic shock/SIRS

Isotonic

Isotonic

Na+ lost

M Acidosis

0.9% or hypertonic NaCl, balanced electrolyte solutions, colloids

Hemorrhagic shock

Isotonic

Isotonic

Na+ lost

M Acidosis

0.9% or hypertonic NaCl, balanced electrolyte solutions, colloids, blood

Abnormality

Type of Losses

Simple dehydration (water unavailable, stress, exercise fever)

Free water

Heatstroke

Type of Dehydration

Fluid Therapy

M, Metabolic; R, respiratory; HAG, high anion gap; DKA, diabetic ketoacidosis; Rx, prescription; GFR, glomerular filtration rate; SIRS, systemic inflammatory response syndrome. Modified from Muir WW, DiBartola SP: Fluid therapy. In Kirk RW, editor: Current veterinary therapy VIII, Philadelphia, 1983, Saunders, p 31.

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deprived of a source of oral water to replace losses. Hypertonic dehydration is detected by the presence of hypernatremia. The volume of a solute-free water deficit can be estimated from the plasma [Na+] concentration as follows: Free water deficit ( liters ) = 0.6 × body weight ( kg )

× [( plasma [Na + ] 148 ) − 1]

8

This type of volume deficit is given a separate line in the worksheet in Table 5-3 because the type of fluid required to replace the deficit is solute-free water. A water deficit can be replaced enterally or parenterally and is discussed in more detail in the section on fluid therapy for hypernatremia. MAINTENANCE

Normal ongoing sensible and insensible losses must be balanced with maintenance fluid intake, provided either through fluid therapy or nutritional support. The cat’s maintenance needs are calculated using the formula 30 × body weight (in kg) + 70. For example, for a 5-kg cat, this equals 220 mL. This is then divided by 24 hours to calculate a rate of 9 mL/hour. Maintenance fluid needs are replaced using a maintenance fluid type. Patients that are eating and drinking or are receiving enteral or parenteral nutrition support will have their maintenance fluid needs already fully or partially met. ONGOING LOSSES

The fluid prescription must also offset any abnormal ongoing losses. The goal is to pick the best crystalloid that will most likely replace the electrolytes lost in the pathologic condition being treated; this is often the same fluid type being used for replacement. Typical losses associated with various clinical conditions are detailed in Table 5-7. Gastrointestinal and urinary losses can be measured. However, to prevent underestimating the losses, estimates are often used, based on client information (e.g., the volume and frequency of vomiting) for the first few hours of fluid therapy before such measurements are made. Some patients also have abnormal insensible losses such as those due to increased respiratory loss or fever. These types of losses are insensible and replaced with solute-free water. Because they cannot be measured, they must be estimated. Allotting an additional one quarter to one third of maintenance rate, depending on severity, is a reasonable starting estimate. ACID–BASE

Acid–base status is important in fluid selection because many crystalloid fluids contain buffers. The three most prevalent buffers found in commercial crystalloid solutions are lactate, acetate, and gluconate; they are bicarbonate (HCO3−) precursors.

The cat’s acid–base status may be assessed from a serum total carbon dioxide concentration ([TCO2]), or a venous blood gas. [TCO2] provides an estimate of [HCO3−]. Metabolic acidosis occurs when the [TCO2] is lower than normal, and metabolic alkalosis occurs when the [TCO2] is higher than normal. It must be remembered that any metabolic acid–base derangement may be primary or compensatory. For example, a metabolic alkalosis may exist as a primary disorder owing to vomiting of gastric contents, or it may exist as a compensatory response to respiratory acidosis; thus [TCO2] must always be assessed in light of the cat’s history and clinical signs. For patients with severe or complex acid– base disorders, a blood gas is necessary for complete assessment. Buffers are used for prevention and treatment of metabolic acidosis because they replace HCO3− deficit. However, buffered solutions are considered contraindicated in patients with metabolic alkalosis. Cats rarely need to be treated for metabolic acidosis with HCO3− itself because the kidney is able to correct the acid–base imbalance after fluid replacement and treatment of the primary disease. However, when acidosis is severe (pH < 7.1), the mEq of sodium bicarbonate to administer is calculated by multiplying the body weight (in kg) by the base excess obtained from a blood gas sample and multiplying this by a value of 0.3, representing the ECF space to which the NaHCO3 will redistribute. Only metabolic acidosis, and not respiratory acidosis, should be treated with NaHCO3. Respiratory acidosis is treated by improving the cat’s ventilation. Typically, only one third to one half of the aforementioned calculated replacement dose of NaHCO3 is given intravenously, over 15 to 30 minutes, once the intravascular volume has been restored. After administration and time for equilibration, another blood gas may be sampled to re-evaluate the patient’s acid–base status. The goal is not to completely normalize the acidosis but to increase the pH to a value of 7.2. Although this is not ideal, when blood gas measurement is not available, the [TCO2] may be used to infer the severity of metabolic acidosis; [TCO2] below 8 mEq/L after rehydration suggests a need for NaHCO3 therapy. DEXTROSE

Dextrose is added to fluids as a method to provide solute-free water isotonically (dextrose moving intracellularly in the presence of insulin) and not as an energy source. 5% Dextrose contains 170 kcal/L of solution and will not provide meaningful calorie support. Each mL will contain only 0.17 kcal. Using the formula of 30 × body weight (kg) + 70, the resting energy requirement for a 5-kg cat is 220 kcal. The amount of 5% dextrose needed to meet the basal requirements of a 5-kg cat would be 1294 mL, about 6 times the daily maintenance fluid requirement.

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A CASE EXAMPLE

A case example, Table 5-8, illustrates how to develop a fluid plan for a 5-kg cat that is presented with a history of vomiting of 7 days’ duration. The vomiting is thought to be due to a flare-up of previously diagnosed inflammatory bowel disease and is not thought to be gastric in origin. The cat is estimated to be 7% dehydrated. Thus the fluid deficit volume would be estimated to be 0.35 kg, which is equivalent to 350 mL. This is likely to be an isotonic loss in which Na+, K+, Mg++, and HCO3− are lost. This is entered into the table as either 350 mL total or 14.5 mL/ hour. Because the dehydration developed slowly over the past week, the plan is to restore it over 24 hours. Until the measured electrolyte values are available from the laboratory, the clinician will assume a fluid concentration of 20 mEq/L K+ and use a fluid that also contains Mg++ at approximately 3 mEq/L. Thus a reasonable choice would be Normosol with 15 mEq/L additional KCl added. The next step is to determine the volume needed for normal ongoing losses for the cat and the most appropriate fluid to use for this purpose. This volume is meant to replace the normal ongoing sensible and insensible fluid losses, not including deficits or abnormal ongoing losses from persistent vomiting. Using the formula (30 × body weight in kg) + 70 to estimate the total volume of fluids in mL per 24 hours required by the patient, the clinician determines that a 5-kg cat requires 220 mL/day, or 9 mL/hour. For maintenance a low Na+ fluid such as Plasma-Lyte 56 + 5% dextrose is appropriate. It contains a buffer, Na+ and Mg++, and solute-free water for maintenance. The patient will be transitioned to partial parenteral nutrition to provide for its nutritional needs after approximately the first 24 hours of hospitalization, which will then provide its maintenance fluid needs.

Next, the clinician selects the type and rate type of fluid to administer to replace the abnormal ongoing loss. In talking with the client, the clinician estimates that the cat vomited about 40 mL in the previous 24 hours. The clinician will adjust the fluid plan if the measured volume differs from this estimate while the cat is observed over the next 12 hours. The cat does not have excess urinary or respiratory loss, diarrhea, fever, or known third spacing. Thus at present the only abnormal ongoing loss is vomiting. In anticipation of a similar amount of vomiting over the next 24 hours, an additional 40 mL (approximately 1.5 mL/hour) is added to the fluid plan. This will be provided as an isotonic fluid, such as the Normosol with supplemental potassium, as indicated previously for replacement therapy. With duodenal vomiting, metabolic acidosis can be expected. However, because the cat will likely be able to correct this itself when fully rehydrated, the clinician will usually wait for the serum chemistry result before considering any specific therapy for an acid–base disorder. Lastly, to calculate the drops per minute, the clinician takes the desired fluid rate (in mL/hour), multiplies it by the drops/mL designated for the particular fluid administration set, and then divides that number by 60 min/hour. The completed worksheet represents the fluid prescription for the cat. Next, the prescription should be translated into an administration plan. The fluid types can be administered concurrently using a T-port. Patient-Monitoring Recommendations Repeated measurements of body weight are the best way to assess improving hydration status. Because changes in lean body and fat mass do not occur rapidly, short-term changes in body weight reflect changes in body fluid. Body weight measurements should be

TABLE 5-8 Case Example Using the Calculation Worksheet for Fluid Therapy Volume of Fluid Components of the Fluid Plan 1. Deficits

mL/day

mL/h

Balanced crystalloid containing 20 mEq/L K and Mg++

350

14.5

Normal ongoing losses

Low-Na+ maintenance fluid

220

9

(Enteral contribution from feeding)

Will be added on day 2

(0)

(0)

220

9

Est 40

1.5

Urinary

0

0

Other sensible

0

0

Insensible

0

0

1. Normosol + KCL

1. 390

1. 16

2. Plasma-Lyte 56 + 5% Dextrose

2. 220

2. 9

3. n/a

3. n/a

3. n/a

Isotonic

Type of Fluid +

Hypertonic 2. Maintenance

Net normal loss to be provided by fluids 3. Abnormal ongoing losses Gastrointestinal

Totals

+

Balanced crystalloid containing 20 mEq/L K and Mg++

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performed every 4 to 12 hours depending on the severity of the cat’s condition and rate of fluid being given. It is important to use the same scale each time, and a human pediatric scale is likely to be the most accurate. Skin turgor can be used serially to assess improvement in hydration status. The skin tenting tendency can also be used to determine the presence of subcutaneous edema. When the skin of a normally hydrated patient is released, it returns rapidly to its resting position. With severe subcutaneous edema, digital pressure to the skin surface will actually cause a transient pit or dimple in the skin surface when the finger is removed. Edematous patients are already overloaded with crystalloids, and further crystalloid therapy is not warranted. Urine output can also be monitored to evaluate a patient’s hydration status. Normal urine output varies between 0.5 and 2 mL/kg/hr. Oliguria (urine output 40% on a dry matter basis) because protein increases lower esophageal tone. Feeding a high-fat (>25% on a dry matter basis) diet increases the caloric density of the diet; however, it delays gastric emptying. Therefore if gastric motility and emptying is a concern, a high-fat diet may not be indicated. Several options exist for nutritional management of cats with inflammatory gastroenteritis.106,280 In addition to pharmacologic therapy, cats may respond to elimination diets, whether it is a diet containing a novel protein source, a protein hydrolysate diet, or a homemade simple-ingredient diet. Inflammatory reactions are thought to occur through interaction of a protein with an antibody directed against it. Novel protein refers to a single dietary protein source that the cat has not been fed before; therefore an inflammatory response would not be evoked.106 A protein hydrolysate diet involves feeding a diet where the protein has been hydrolyzed to a size that is not recognized by antigen processing cells and antibodies, typically below 12,000 daltons.43 A homemade diet often comprises single unprocessed ingredients. In processing of foods, glycated protein end-products may be produced through the Mallard reaction and these glycated end-products may induce an inflammatory response. Feeding unprocessed foods decreases exposure to these glycation end products and subsequent inflammatory response.156 Cats with large intestinal disease may respond to an elimination diet or to a higher fiber (>5% on a dry matter basis) diet.63,202,247,280 Dietary fiber increases fecal bulk, which stimulates colonic contraction; however, it increases fecal volume, which could exacerbate constipation.247 Dietary recommendations for cats with inflammatory bowel disease are summarized in Box 18-2.61

Restricted- and Moderate-Fat Foods Dietary fat is more digestible and more energy dense than carbohydrate. Average fat digestibility is 74% to 91% in cats. Moderate-fat diets containing 15% to 22% (dry matter basis) are tolerable. Low-fat diets (35% on a dry matter basis. When using a limited protein (elimination) diet, restrict protein to one or two sources and use a protein source that the cat has not consumed previously (novel protein). 3. Fiber: 87% for protein and >90% for fat and digestible carbohydrate for highly digestible diet, or >80% for protein and fat and >90% for carbohydrate for high fiber diet.

1. An energy-dense diet containing >4.2 kcal/g 2. Protein: 30% to 45% on a dry matter basis unless hepatoencephalopathy is present: 25% to 30% on a dry matter basis 3. Arginine: 1.5% to 2% on a dry matter basis 4. Taurine: >0.3% on a dry matter basis 5. Potassium: 0.8% to 1.0% on a dry matter basis 6. L-carnitine: >0.02% on a dry matter basis 7. Vitamin E: >500 IU/kg 8. Vitamin C: 100 to 200 mg/kg

metabolism of drugs and toxins. The liver influences nutritional status through bile acid synthesis and excretion into the gastrointestinal tract and its central role in intermediary metabolism of proteins, carbohydrates, fat, and vitamins. The most common causes of feline liver disease include inflammatory conditions (cholangitis– cholangiohepatitis complex), lipidosis, neoplasia (particularly lymphoma), and portovascular anomalies.194 For more information on liver diseases, see Chapter 23. Nutritional management of hepatobiliary disease is usually directed at clinical manifestations of the disease rather than the specific cause. Goals of nutritional management of cats with liver disease include the following: • Maintaining normal metabolic processes and homeostasis • Avoiding and managing hepatoencephalopathy • Providing substrates to support hepatocellular repair and regeneration • Decreasing further oxidative damage to damaged hepatic tissue • Correcting electrolyte disturbances45

Animal Factors Animals with liver disease may demonstrate a variety of clinical signs, from none to hepatoencephalopathy (characterized by ptyalism, vomiting, depression, and possibly seizures). Weight loss and poor body condition may or may not be present depending on the severity and chronicity of the underlying disease. Cats may or may not have hyperbilirubinemia.

Dietary Factors Maintenance of body condition and weight is important; therefore adequate caloric intake is paramount. Hepatic

lipidosis is a result of negative energy balance with mobilization of peripheral adipose tissue and accumulation of intrahepatic lipid.46 In managing cats with hepatic lipidosis, reversing the negative energy balance is most important in reversing the disease process. Protein restriction is not necessary unless hepatoencephalopathy and hyperammonemia are present. Hypokalemia may occur with liver disease and has been reported in approximately one third of cats with hepatic lipidosis46; therefore diet should be potassium replete. Many hepatic diseases are associated with oxidative stress that may induce further hepatocellular damage. Feeding diets with additional antioxidants or supplementing with antioxidants may be beneficial. Hepatic dysfunction entails a dysregulation of lipid metabolism; this is particularly prominent with hepatic lipidosis. L-Carnitine is involved with lipid metabolism, and although L-carnitine deficiency does not occur with hepatic lipidosis,126 L-carnitine supplementation at 250 to 500 mg daily may be beneficial in cats with hepatic lipidosis.44 Dietary recommendations for cats with hepatobiliary disease are summarized in Box 18-3.194

Feeding Factors Feeding small meals or facilitating food intake using pharmacologic stimulation or feeding tubes may be required. Caution must be exercised with administration of medications that require hepatic metabolism, such as appetite stimulants, because side effects may occur.

ENDOCRINOLOGIC DISEASES: OBESITY Obesity is the most important nutritional disease of cats. With prevalence rate estimates of up to 40%,8,166,242 obesity must be considered a significant hazard to cats. Increased emphasis on pet health and preventive health programs

makes obesity prevention an important aspect of health maintenance programs in dogs and cats. Treatment for obesity varies from frustrating to rewarding, and evaluating and prescribing for successful, long-term weight loss and maintenance usually require management of multiple, interrelated patient and client factors. Diagnosis of disease secondary to obesity and the major task of client education and motivation are the province of the veterinarian. Obesity is a condition of positive energy balance and excess adipose tissue accumulation that adversely affects the quality and quantity of life. Obesity literally means increased body fatness, but measurement of fat fractions of body composition is difficult in practice. Therefore obesity can be defined as body weight in excess of 15% to 20% of ideal, owing to the accumulation of body fat.281 Negative health manifestations often begin at this level of weight excess and are a virtual certainty at a 30% excess over ideal weight. Associated health risks include musculoskeletal and cardiovascular disease, diabetes mellitus, hyperlipidemia, hepatic lipidosis, higher incidence of cancer, possible anesthetic and surgical complications, decreased heat tolerance and stamina, and reproductive problems. Obesity is a proinflammatory condition, and adipose tissue is an active endocrine organ that produces cytokines called adipokines.168,221 This may explain in part the association of obesity with inflammatory conditions such as osteoarthritis. The pathogenesis of obesity is multifactorial and is more than just “too much energy in and not enough energy out.”145 There are genetic, gender, and environmental influences. Apartment dwelling, inactivity, middle age, being male, neutered status, mixed parentage, and certain dietary factors are associated with being overweight.166,242 The pet owner’s contribution to the problem may be significant and must be understood and addressed. In one survey of more than 18,000 dog and cat owners in Australia and the United States, almost a third of owners reported their pets as overweight or obese, but fewer than 1% felt that obesity was a health problem.87 In another study of 120 German owners of indoor cats, questionnaire responses of owners of cats with normal body weight were compared with responses from owners of overweight cats.133 Owners of overweight cats were more likely to watch their cats eat and relented more frequently when their cats begged for food. Owners of overweight cats were less likely to spend time playing with their cats and appeared to have a different relationship with them, being more likely to anthropomorphize them and consider them a substitute for human companionship. Diagnosis of obesity is the first step in managing the disease. Determining whether a cat is overweight is not difficult; however, accurately determining the degree of overweight and the cat’s ideal weight is challenging. Many owners underestimate their cat’s body condition,

CHAPTER 18 Nutritional Management of Diseases

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and veterinarians may overlook obesity. Documenting body weight in the medical record is important; in fact, veterinarians may be part of the problem. In one study medical records dramatically underreported overweight and obesity in cats when body condition scoring (BCS) results were compared to reported diagnoses.166 For example, the prevalence of obesity defined by BCS in the population studied was 6.4% compared with 2.2% when defined by a recorded diagnostic code in the medical record. In addition to recording the body weight, it may be helpful to calculate the percentage change in weight since the last visit and compare it to a similar weight gain in a person. For example, an 8.8-lb (4-kg) cat that has gained 1 lb (0.5 kg) has increased its body weight by approximately 12%; this is equivalent to a 14-lb weight gain for a 120-lb person. Muscle condition scoring and BCS provide additional information regarding the appropriateness of the cat’s body weight to its overall condition.* Several BCS systems are available; the most widely used are the 5-point and 9-point scales (see Table 16-2).† In both scales the middle value (3/5 or 5/9) is considered optimal condition, and these cats have 15% to 25% body fat. Lower values on the scale are degrees of undercondition (cats having 2/5 or 3/9 have 5% to 15% body fat, and cats having 1/5 or 1/9 have 2%, can be extremely toxic to cats

GABA, Gamma-aminobutyric acid. Table reprinted with permission from Schwassman M, Logas D: How to treat common parasites safely. In August J, editor: Consultations in feline internal medicine, ed 6, St Louis, 2010, Saunders Elsevier, p 390.

CHAPTER 22 Dermatology

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FIGURE 22-12 Cat with classic flea allergy pattern. Note the hair loss over the lumbosacral area. Palpation of skin in this area reveals widespread crusted papules. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

FIGURE 22-14 Pyoderma. Note the excessive scaling typical of this condition. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

FIGURE 22-13 Pyoderma. Intact pustules, papules and small epidermal collarettes are present in this Rex cat. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

FIGURE 22-15 Eosinophilic plaque. This lesion was triggered by

(Figure 22-13). Epidermal collarettes are very subtle and small, often only 1 to 2 mm in size.41,104 The most common clinical presentation encountered is excessive scaling (Figure 22-14), especially over the lumbosacral areas. Close inspection of the hairs reveals scales pierced by hairs. Another common antibiotic-responsive skin lesion in cats is areas of self-trauma that have the clinical appearance of eosinophilic plaques105 (Figure 22-15). Before recognition of the antimicrobial responsiveness of these lesions, corticosteroid therapy was used. The diagnosis of feline bacterial pyoderma is similar to that in the dog: It is primarily a clinical diagnosis with confirmation most often based on response to antibiotic therapy. Glass slide skin impression smears are excellent for exudative or ulcerative skin lesions; however, acetate tape cytology preparations are much easier to use on other areas of the body. Exudative skin lesions will show neutrophils, eosinophils, bacteria, or Malassezia spp. However, samples from sites with predominant scaling may show only shed keratinocytes.

flea allergy and resolved not with glucocorticoid therapy but with combined bacterial and yeast therapy. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

Appropriate drugs for treatment are listed in Table 22-2. It is important to treat for at least 21 days and possibly longer. It is also important to remember that bacterial infections of the skin are often complicated by concurrent Malassezia overgrowth, and concurrent treatment of both is often needed. Feline pyoderma occurs because of an underlying trigger, and although it is important to treat these infections, there should always be a search for the underlying cause. The trigger may be a one-time event that has passed (e.g., flea infestation) or, more commonly, an underlying chronic skin disease or systemic disease. Malassezia Overgrowth As with bacterial pyoderma, overgrowth of Malassezia organisms is an underrecognized and underdiagnosed

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SECTION IV Feline Internal Medicine

TABLE 22-2 Select Antimicrobial Drugs for Treatment of Skin Disease in Cats ANTIBIOTICS Drug

Dose Range

Route

Amoxicillin–clavulanic acid

12.5-25 mg/kg q12h

PO, IM, SC

Cephalexin

15-30 mg/kg q12h

PO

Cefadroxil

20 mg/kg q12h

PO

*Cefpodoxime

5-10 mg/kg q24h

PO

Clindamycin

5.5 mg/kg q12h

PO

Doxycycline

5-10 mg/kg q12h

PO

Enrofloxacin

5 mg/kg q24h

PO, SC

Marbofloxacin

2-5 mg/kg q24h

PO

Lincomycin

20 mg/kg q12h

PO

Trimethoprim–sulfadiazine

15-30 mg/kg q12h

PO

Drug

Dose

Route

†Itraconazole

5-10 mg/kg q24h

PO

†Terbinafine

40 mg/kg q24h

PO

Fluconazole

10 mg/kg q24h

PO

ANTIFUNGALS

PO, Orally; IM, intramuscularly; SC, subcutaneously. *This is a third-generation cephalosporin, and use should be reserved for infections that cannot be treated with another drug. To minimize the development of methicillin-resistant infections, the drug should be used at the higher dosage range. †These drugs can be used daily or as a pulse therapy on a 1 week on/1 week off basis until the target infection is resolved.

cause of pruritic skin disease in cats. It is caused by overgrowth of Malassezia spp. yeast, which is part of the normal flora of the ear canals, mucosal surfaces (oral and anal), and anal sacs. There is a wide diversity in the species of Malassezia that vary in size and shape. The most commonly encountered clinical presentations include pruritic recurrent OE, recurrent chin acne, paronychia, and scaly and waxy seborrhea.1-2 Ears may contain a waxy black material or just excessive ceruminous debris. Waxy debris around the nail beds of cats is uncommon and is typical of Malassezia dermatitis. The one unifying clinical sign is pruritus that varies from mild to severe. Malassezia dermatitis is a common complication of allergic skin diseases, poor grooming, immunosuppression resulting from FIV or FELV, diabetes mellitus, and neoplasia.77 It is important to remember that the pathophysiology of Malassezia dermatitis includes a hypersensitivity reaction. Therefore the number of organisms seen may be disproportionate to the severity of the clinical signs. The author’s (KM) rule of thumb is that if the cat is symptomatic and clinical signs are compatible, any number of organisms seen is significant, and the cat should be

treated for yeast overgrowth. The sampling technique depends on the anatomic site affected: ear swabs for ears, spatula scrapings for nail beds and areas of follicular plugging and chin acne, and acetate tape preparation for skin sites. Samples should be examined carefully under oil immersion. It is important to remember that there are many species of yeast, and some species of yeast and recently divided organisms can resemble cocci. The major differentiating factor is the size of the organism. Cocci are approximately 0.2 to 2 µm in diameter, and yeast are much larger. When looking at a slide or describing the difference to clients, the veterinarian may find that a “moon versus earth” comparison works well. This is easiest to determine if there is a mixed population of organisms in the field for the purpose of comparison. Bathing is an important part of treatment in dogs and can be used in cats if the cat is cooperative. In most cases this is not a treatment option; however, grooming, whether by a professional or the owner, is very helpful in cats with yeast dermatitis. Removal of shed hairs, mats, and accumulated oils, combined with systemic therapy, is very helpful. If yeast overgrowth is localized to a focal area such as nail beds, chin, or ears, application of a topical combined antibacterial and antifungal shampoo or solution may be possible. In general, the use of products containing phytosphingosine (e.g., Douxo Calm Micro-emulsion Spray and Shampoo, Sogeval Laboratories, Coppell, Texas) is strongly recommended. This molecule is part of skin lipids responsible for maintaining normal skin cohesion, controlling local flora, and regulating moisture balance. These products may be used as shampoo substitutes. Most cats, however, require systemic treatment with an oral antifungal drug (see Table 22-2) such as itraconazole or terbinafine. Ketoconazole is not recommended because cats do not tolerate this drug well. Fluconazole has been used successfully by the author (KM) at 10 mg/kg orally, once daily for 30 days. Pharmacokinetic studies with itraconazole and terbinafine have shown that pulse therapy protocols can be used with these drugs. The most common protocol is 1 week on and 1 week off for two to three cycles.35,101 Yeast otitis is very pruritic, and an otic glucocorticoid is recommended. The author’s (KM) otic glucocorticoid of choice is a compounded solution of propylene glycol and dexamethasone injectable (2 mg/mL) in equal concentrations applied once daily to the ears. Cat breeds with abnormal hair coats (e.g., Rex, Sphynx) have increased oil production on the skin and are at increased risk for yeast overgrowth. This may involve the whole body, the nail folds, or both. Otherwise, it is important to remember that yeast overgrowth is always the result of an underlying skin disease or medical condition. Lack or response to therapy may be the result of an undiagnosed concurrent bacterial infection or persistent underlying skin disease.


Dermatophytosis This is the most common infectious and contagious skin disease of cats, and pruritus can vary. This skin disease is discussed in the section on scaling, crusting, and greasy skin.

Allergic Causes of Pruritus The most common allergic skin diseases of cats include flea allergy dermatitis, food allergy, feline atopic dermatitis, and feline insect bite hypersensitivity. The pathogenesis of these allergic diseases involves combinations of type 1 and type 4 hypersensitivity reactions to allergens. The diagnosis is based on history; compatible clinical signs; ruling out of other, more common causes of allergic disease; and response to treatment trials. In the case of feline atopic dermatitis, it is important to remember that allergy testing (in vitro or intradermal) reflects exposure and is not a definitive diagnostic test. In other words, it does not answer the question “Is this cat atopic or not?” Flea Allergy Dermatitis Flea allergy dermatitis is a very common feline skin disease caused by a hypersensitivity reaction to flea bites. Depending on the geographic region, the clinical signs can be seasonal or occur year round. Seasonal clinical signs are most common in regions where there are defined cold weather seasons; flea allergy tends to occur in the warm weather months, but not always. A viable population of fleas, sufficiently large to perpetuate flea bite dermatitis, can exist in homes over the winter months. Furthermore, small mammals living in or around homes can be a source of flea exposure year round. The clinical signs of flea allergy dermatitis are highly variable and can cause any of the well-recognized skin reaction patterns of cats (Box 22-2). The classic pattern is hair loss and miliary dermatitis over the lumbosacral region and hind legs; however, this may not be what is observed in clinical practice (see Figure 22-12). Clients

BOX 22-2 Feline Skin Reaction Patterns Head and neck pruritus Recurrent otitis Symmetric alopecia Self-induced alopecia with self-trauma Overgrooming without self-trauma Twitchy–itchy cat Eosinophilic patterns (often chronic and recurrent) Indolent ulcer Eosinophilic plaque Eosinophilic granuloma Miliary dermatitis

385

are increasingly aware of the importance of flea control in cats, and the use of spot-on products has made this practice much easier. Flea allergy dermatitis is a common cause of symmetric alopecia, recurrent papular pruritic lesions, recurrent bacterial and yeast overgrowth, eosinophilic diseases, and odd behaviors. Flea allergy is a major differential diagnosis in cats presented for frequent twitching of the skin; sudden, frantic attacks of the skin; and sudden episodes of hyperactive behavior wherein the cat appears to be chased or trying to escape. The author (KM) has noticed one consistent presentation of flea allergy in obese or geriatric cats that cannot groom themselves, particularly their abdomen or lumbosacral area. In response to pruritic areas of the skin that the cat cannot reach, the cat may overgroom or mutilate areas that it can reach (e.g., the tip of the tail, the paws). These behaviors can often be triggered in the examination room by scratching the lumbosacral area of the cat. Care must be taken because sometimes the pruritus is so intense that the cat will bite. Another presentation of possible flea allergy is unilateral, and often intermittent, small eosinophilic lip ulcers. The “rodent ulcer” reaction pattern of cats can be triggered by almost any trauma or inflammatory reaction, including a flea bite. Diagnosis of flea allergy dermatitis can be an easy or a difficult diagnosis. The presence of a compatible history, clinical signs, and fleas or flea excreta is compelling. Unfortunately, the latter are not commonly found on cats that are able to groom effectively. Intradermal testing with flea antigen and observation of a positive reaction are suggestive but not diagnostic. The best diagnostic tool is response to flea control. This can be met with resistance by clients because it involves treatment of all pets in the home and because “having fleas” still carries a stigma. In these cases it is often helpful to discuss the expense of a diagnostic workup for skin disease and to emphasize that even if the underlying cause is not fleas, year-round flea control is part of the management of cats with chronic skin diseases. Chronic skin diseases are expensive and time consuming to manage and tend to relapse, and it is important to know that the relapse is not caused by something as simple as fleas. One change in the response to treatment trials for flea allergy dermatitis in cats is that clinicians should be prepared to treat concurrently for secondary bacterial and yeast overgrowth; if left untreated, it may give the false impression that the flea control trial is unsuccessful. It is very common for the author (KM) to encounter cats referred for second opinions after having “failed” excellent flea control and food trials, only to find that the cat has an undiagnosed bacterial and yeast infection. Insect Bite Hypersensitivity Insect bite hypersensitivity is a skin disease caused by hypersensitivity reactions to bites from small biting

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FIGURE 22-16 Insect bite hypersensitivity. Note the multifocal

FIGURE 22-17 Insect bite hypersensitivity. In this cat the ears were

areas of hair loss on the nose and muzzle. This is a common presentation of this syndrome. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

attacked, and insect bites resulted in the rapid development of small eosinophilic granulomas. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

insects such as mosquitoes, Culicoides midges, and gnats.8 Insect bite hypersensitivity may occur in cats that freely roam outdoors or cats that have access to the outdoors on porches that are screened or have screens that allow entry of the insects. Clinical signs can occur year round depending on geography and the life cycle of the biting insect. Insect bites occur on the thinly haired areas of the cat, including the nose, inner and outer pinnae, periocular area, and foot pads near the junction of the haired and hairless areas.53 The insect bites result in papules that vary in severity from mild to severe. Clinical signs become more dramatic as the severity of the pruritus increases and can include widespread ulceration, hair loss, hyperpigmentation, or hypopigmentation (Figures 22-16 and 22-17). Foot pads may become hyperkeratotic, swollen, painful, or ulcerated. The author (KM) has observed regional to generalized lymphadenopathy and peripheral eosinophilia. Diagnosis is primarily based on history and clinical signs. Exposure to the outdoors, particularly in the morning or evening, should raise suspicion. Lesions will resolve within 1 week without treatment if the cat is confined indoors. Treatment is not necessary unless the pruritus is severe. Possible treatment options include antiinflammatory doses of prednisolone (0.5 mg/kg orally, once daily until lesions heal) or alternate-day doses of prednisolone if the cat cannot be housed indoors. Some evidence suggests that prednisolone is better absorbed in cats than prednisone.39 Alternately, repositol methylprednisolone acetate can be used every 6 to 8 weeks throughout the affected season (20 mg/cat subcutaneously or intramuscularly). Chronic prednisolone use is not appropriate for long-term therapy. Localized lesions

can be treated with topical glucocorticoids. Another useful drug is cyclosporine (5 mg/kg orally, once daily for 30 days and then every other day). It comes as two formulations: modified and unmodified. The modified formulation has improved absorption and is the only formulation recommended for use in cats (e.g., Atopica, Novartis). The disease can be prevented by keeping the cat indoors. If this is not possible, the cat should be kept indoors during the dawn and dusk periods. In homes where screened porches are areas of family congregation during the evening, this may be impossible or unreasonable. Improving the screening of porches is an option. The use of citronella candles is very helpful. The application of water-based pyrethrin products can also be used. Pyrethroid products must be used with care in cats, and products marketed for humans as repellants are commonly toxic to cats. The lesions of insect bite hypersensitivity can mimic feline atopy; food allergy; dermatophytosis; and, most important, feline plasma cell pododermatitis and PF. Cats that do not respond quickly to simple confinement or are refractory to low doses of prednisolone should be more aggressively investigated for other diseases. Food Allergy Food allergies in cats are caused by a hypersensitivity reaction to a food or food additive.100 Food allergies can develop at any age. At this time there are no studies documenting whether food allergies in cats are more common than atopy, as is anecdotally reported. The clinical signs of a food allergy are highly variable, and there is no classic presentation. Food allergies can present with or without gastrointestinal signs; however, in one study the presence of concurrent signs was the


most common presentation.44 Food allergies can be the cause of any of the commonly recognized skin reaction patterns of cats. What is unique about food allergies is that they are associated with nonseasonal pruritus, and response to glucocorticoid therapy is variable. Common questions about feline food allergies include the following: When is a diet trial indicated? Can it be diagnosed by allergy testing? What type of diet is best? In the author’s (KM) practice, a diet trial is pursued only after more common differential diagnoses have been ruled out. These include the following: • • • •

Response to treatment trial for demodicosis Response to flea control Negative fungal culture for dermatophytosis Lack of response to therapy for a combined bacterial and yeast infection

Using lime sulfur as a response to therapy for feline demodicosis will also rule out other parasite infestations, except for fleas. If the cat is still pruritic at this point, the most likely causes in an otherwise healthy cat are food allergy and feline atopic dermatitis. Food allergies in cats cannot be diagnosed by blood allergy tests or intradermal skin tests. One of the most difficult aspects of referral of the itchy cat is dealing with a client who is holding the results of a blood allergy test that has positive reactions to every test ingredient. These tests reflect exposure to the allergen, and positive reactions do not correlate with diagnosis. The only way to diagnose a food allergy is by implementing a strict diet trial followed by a provocative test.46 A dietary hypersensitivity is diagnosed when the target clinical sign (i.e., pruritus) resolves while the trial diet is being fed and recurs when the cat is fed its original diet. Diet trials must be conducted over extended periods of time (8 to 12 weeks) to be certain, and during this time there could be a change of season or another factor. Therefore positive proof by way of a challenge is required. There is no consensus among veterinary dermatologists regarding the best diet, nor studies to support one in particular. There are three major types of diets used for food trials: home-cooked diets, novel protein diets, and hydrolyzed diets. Whatever diet is used, it should be complete and balanced because this may be the cat’s diet for the remainder of its life. Client compliance increases with ease of feeding, which would suggest that commercial diets are superior; however, this is not necessarily the case. If a home-cooked diet is selected, the owner can devote 1 day a month to making the diet and freezing portions for the remainder of the month. The major drawback of home-cooked diets is that if a food allergy is confirmed, the owner either needs to continue to prepare the diet or search for a suitable alternative diet. Success of a diet trial is directly related to addressing a number of key issues. The test must be indicated and performed at the appropriate time in the workup. The

387

differential diagnoses must be narrowed to allergy (food or atopy). The client needs to be able and willing to do the diet trial, and questions regarding whether they can adhere to the feeding plan must be asked and positively answered. Food trials can be impossible in multiple-pet households if there is any chance that the cat will eat other food. Cats are less likely to be fed table scraps than dogs, but this is not always the case. For example, cats can and do climb on tables and chairs and can reach unwashed dinner plates and pans, and some cats steal food. The cat also must be kept indoors during the entire period of the food trial. The change from the original diet to the new diet can take several weeks in cats that are persnickety eaters. Palatability is an issue for many cats, and owners and veterinarians may have to use one diet type rather than another depending on what the cat will eat. Another major hurdle is the cat’s comfort during the trial. If the cat is severely pruritic, some type of antipruritic agent must be used during the trial. The author (KM) commonly uses cyclosporine modified (5 mg/kg, up to 25 mg/cat, PO, once daily) for the first 4 to 6 weeks of the trial. Once the cat is comfortable and eating the trial diet, the drug is gradually withdrawn between weeks 6 and 8. If the cat becomes pruritic after the cyclosporine is withdrawn, this particular diet is a failure. If not, the diet is continued for several weeks, and then provocative challenge is performed. It is important that clients understand that they may need to repeat a food trial with another type of diet if the original diet trial is a failure and all other causes of pruritus have been ruled out or if the cat is diagnosed with atopic dermatitis and there is inadequate response to immunotherapy. It is not uncommon for clients to stop food trials if the cat responds to cyclosporine. Clients want relief of pruritus for the cat, and if cyclosporine provides this relief, the client may not want to proceed with any further diagnostics. The author (KM) does not use glucocorticoid therapy during the first few weeks of the food trial for several reasons. First, if allergy testing is needed after the food trial, cyclosporine will not interfere with test results. Second, glucocorticoid therapy for long-term management of pruritus is fraught with well-known problems. Cyclosporine has been used successfully with few adverse effects and can be used for long periods. Third, if the client completes the food trial and a food allergy is diagnosed, the client has the option of feeding the cat the diet used in the trial, pursuing identification of the individual offending food allergen and then avoiding it, or using cyclosporine therapy for long-term management. Atopic Dermatitis The name of the skin disease caused by a type 1 hypersensitivity to environmental allergens in cats is a topic

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of much debate because the disease has not been as well characterized in cats as it has in dogs. In this discussion the term feline atopic dermatitis will be used; however, the reader may see other terms, such as feline atopic-like dermatitis, feline hypersensitivity dermatitis, and feline allergic dermatitis. There is no known sex or breed predilection for feline atopic dermatitis. In the author’s (KM) experience, owners usually report the development of clinical signs in their cats between the ages of 6 months and 3 years of age, although the cat may not be brought to the veterinarian for evaluation until it is much older. The author (KM) has documented a family of cats with atopy, and others have anecdotally reported a genetic component, but there is not as much evidence for a breed or genetic predisposition in cats as there is in dogs.59 It is rare to have information on the family of any particular cat. The hallmark of the disease is pruritus that is responsive to glucocorticoid therapy. If there are complicating factors such as a secondary bacterial and yeast overgrowth, response may not be complete. Clinical signs may be seasonal or year round and are variable. A working diagnosis of feline atopic dermatitis is made by ruling out other common causes of pruritus (i.e., parasites, infections, flea allergy, and food allergy) and having a compatible history and clinical signs. Owners may have difficulty confirming the presence of pruritus because they may not recognize it or notice behaviors associated with pruritus (e.g., licking). A history of vomiting hairballs or constipation may suggest overgrooming. Atopic dermatitis is a differential diagnosis for many feline reaction patterns. In addition to feline symmetric alopecia, some of the most common clinical signs include, but are not limited to, recurrent eosinophilic lesions (plaques, linear granuloma, miliary dermatitis, lip ulcers), “overall itchy cat complaint,” patchy alopecia, biting of the hair coat (Figure 22-18), hair loss on the medial and lateral aspects of the limbs (Figure 22-19), pedal pruritus (Figure 22-20), yeast overgrowth at the nail beds, recurrent yeast otitis, increased ceruminous discharge from the ears, symmetric alopecia, broken whiskers, hair loss on the chin and lips, and development of comedones. The hair coat may be dull, rough, or even damp. Nondermatologic signs may include rhinitis, sneezing, conjunctivitis, chronic coughing, and lymphadenopathy. The question always arises, “Where does allergy testing fit into the diagnosis of feline atopic skin disease?” It is important to remember that allergy tests reflect exposure and are not diagnostic for atopic dermatitis. Allergy testing is appropriate for cats in which immunotherapy is indicated as a treatment modality. It is also indicated in cats that fail food trials or for owners who will not do a food trial until the results of an allergy test are negative. Allergen identification can be done by way of intradermal skin testing or in vitro testing. As is the

FIGURE 22-18 Atopic cat. This cat had generalized pruritus, and the owner complained about the cat “madly biting itself.” (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

FIGURE 22-19 Atopic cat: Note the hair loss on the medial foreleg. Cytology by tape preparation revealed a combined bacterial and yeast infection, intensifying the pruritus. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

FIGURE 22-20 Atopic cat with pedal pruritus. This cat chewed its nails and had waxy debris at the nail base. Cytology revealed large numbers of yeast organisms. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)


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FIGURE 22-21 Heska 2nd Generation E-Screen Test. This test can

FIGURE 22-22 Positive intradermal test in a cat. Note the large

be used as a screening test to determine if a cat with clinical atopy is likely to have positive reactions on a full panel. If negative, an intradermal skin test should be considered. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

number of wheal and flare reactions. Unlike what is commonly reported in cats, this cat had a strong easily identified skin test reactions. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

case in dogs, there is much debate as to which test is best. Because intradermal skin testing requires drug withdrawals and a referral to a veterinary dermatologist, is more costly, and entails a more involved procedure, the author (KM) recommends in vitro allergy testing first. In the author’s (KM) practice, cats are screened with Heska 2nd Generation E-Screen (Heska Corp. Fort Collins, Colorado) (Figure 22-21), which is a miniscreen serum allergy test. In addition to positive and negative controls, there are three wells (for trees, weeds, and indoor allergens). If there is a positive reaction on this screening test, serum is submitted for a full screening. In a recent study in cats, there was strong agreement between a positive E-screen and in vitro allergy test (88%).30 If the test is negative, an intradermal skin test is performed. Preparation for intradermal skin testing in cats requires steroid and antihistamine drug withdrawals; however, cyclosporine need not be withdrawn before skin testing.37 Antihistamines must be stopped 7 days before testing. The time required for steroid withdrawal is varied, but generally it is no less than 4 weeks for a cat receiving an oral glucocorticoid and no less than 8 weeks after a single injection of a repositol glucocorticoid, and possibly longer. Intradermal skin test reactions in cats are typically, but not always, less dramatic than those seen in dogs (Figure 22-22). This makes interpretation more difficult. Feline atopic dermatitis can be managed but not cured. Management of the disease depends on whether the clinical signs are seasonal or year round; the severity of the pruritus during the cat’s allergy season; the distribution of affected sites; concurrent medical conditions; and, of course, what the owner is able or willing to do for the cat.

Avoidance of the offending allergen is rarely possible or feasible. However, if the cat regularly goes outdoors, keeping it indoors will decrease direct exposure to various seasonal allergens. Pollens can be decreased in the home by regular cleaning of household heating ducts and use of high-quality disposable furnace filters. For cats with allergies to house dust mites, old cat beds should be replaced by new beds that are washed at least once weekly. Carpets, mattresses, clothes, and furniture can be treated with benzyl benzoate (e.g., Acarosan Dust Mite Spray and Dust Mite Control Power, Bissell) once a month for 3 months and then every 3 months thereafter to kill and control house dust mite populations. Benzyl benzoate is not difficult to find and is the common ingredient in most over-the-counter products marketed to remove or kill house dust mites. It is important to use a high-quality vacuum cleaner to remove mites. Mites do not thrive well in dry environments, and decreasing relative humidity (1 month) or year-round allergies as the primary treatment for the pruritus or in conjunction with other treatments. If therapeutic response is good, the dose can be tapered to every other day. Glucocorticoid therapy can be used concurrently to provide a more immediate response. Immunotherapy is indicated in cats that do not respond to medical management. Currently, there are two protocols for administration of immunotherapy in

TABLE 22-3 Commonly Used Antipruritic Drugs for Atopic Cats Drug

Common Dose

Common Adverse Effects

Cetirizine HCl (e.g., Zyrtec, Reactine)

5 mg/cat, PO, q24h

None reported

Chlorpheniramine maleate (e.g., Chlor-Tripolon)

2-4 mg/kg, PO, q12h

Drowsiness, salivation from bitter tablets

Clemastine fumarate (e.g., Tavist)

0.68 mg/cat, PO, q12h

Diarrhea, lethargy

Diphenhydramine HCl (e.g., Benadryl)

0.5 mg/kg, PO, q12h

Hyperexcitability

Hydroxyzine HCl (e.g., Atarax)

5-10 mg/cat, PO, q12h

Depression, behavioral changes

Prednisolone

0.5-1.0 mg/kg, PO, q24h

Polyuria, polydipsia, polyphagia

Methylprednisolone acetate

5 mg/kg or 20 mg/cat, SC/IM

Cyclosporine modified* (e.g., Atopica)

5 mg/kg, PO, q24h; can be tapered to q48h

ANTIHISTAMINES

CORTICOSTEROIDS

PO, Orally; SC, subcutaneously; IM, intramuscularly. *Only the modified formulations of this drug should be used.

Vomiting, diarrhea


cats (traditional and rush therapy), and these are discussed in detail in other sources.95,96 Briefly, the difference is the administration of allergens in increasing amounts until a maintenance dose is reached over approximately 1 month (traditional) versus several days (rush). Afterwards, a maintenance dose of allergen is administered at regular intervals (e.g., every 7 to 10 days). In the author’s (KM) experience, a favorable response is seen in two out of three cats. For some cats it may be the sole therapy, whereas for others intermittent use of some type of adjunct antipruritic therapy may be necessary. On the basis of information from studies of dogs, maximum benefit may not be seen for up to 12 months. However in the author’s (KM) experience, some evidence of efficacy usually occurs in 3 to 6 months. Cyclosporine or glucocorticoid therapy can be used to manage the cat’s pruritus during this time and provide significant antipruritic relief.74,106 If the cat responds to cyclosporine therapy, the cost of immunotherapy versus cyclosporine therapy should be considered, insofar as cyclosporine therapy is inexpensive in small patients and may be less expensive for long-term management.85 Cats receiving long-term cyclosporine therapy should be screened for Toxoplasma spp. because this drug may predispose cats to fatal systemic toxoplasmosis.48 Owners should also take precautions to prevent new infections. The key precautions are to keep the cat indoors to limit exposure through predation of rodents and other potential intermediate hosts and consumption of water from the environment. Other important precautions are to clean the litter box daily, avoid feeding the cat raw meat or unpasteurized milk, control indoor rodent populations safely, and practice good hygiene when handling food for human consumption.

SCALING, CRUSTING, AND GREASY SKIN Scaling (“dandruff”) and crusts are common client complaints. Widespread crusting and exfoliation are uncommon and are usually associated with a medical problem or more serious dermatologic disease. Greasy hair coat can be focal or generalized. As with other dermatologic problems, the history can often provide key information that will narrow the possible differential diagnoses. Young cats and cats that roam freely are more likely to contract dermatophytosis and parasitic infestations. Older cats are more likely to have immune-mediated diseases and skin tumors. Evidence of transmission to other animals or people is compatible with a contagion. Prior treatments may help rule in or out drug eruptions. Response to glucocorticoid therapy may suggest allergic skin diseases. The cat’s breed may also provide useful information. The association of longhaired cats with dermatophytosis is the classic example.

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Excessive Scaling In general, the most common causes of scaling and crusting in cats are ectoparasites, bacterial and yeast infections of the skin, and dermatophytosis. Flea combing, skin scraping, and response to flea control are key core diagnostic tests and treatment trials (see previous discussion). As previously mentioned, excessive scaling with scales pierced by hairs is common in cats with bacterial infections of the skin. Response to antibiotic therapy is important to establish. Careful examination of skin impression smears and skin cytology are needed to determine if a concurrent yeast infection is present (see previous discussion). Finally, a dermatophyte culture is indicated at the first presentation to rule in or out the presence of a dermatophyte infection. It is not uncommon to encounter cats that start to shed hairs or scales excessively when stressed during an examination. Undoubtedly, this is biological in nature but is not a pathologic problem that requires treatment. Some clients report that their cat’s hair coat scales excessively when the relative humidity is low (e.g., in winter). This is most likely related to heat-seeking behavior and can be corrected by increasing humidity in the home and using humectants on the hair coat. Cats that cannot groom (e.g., because of obesity) may develop excessive scaling; this can sometimes be corrected by having the owner brush the hair coat on a regular basis. The largest collection of sebaceous glands is located on the cat’s dorsum, and routine grooming helps disperse these oils.

Dermatophytosis Dermatophytosis is the most common infectious and contagious skin disease of cats. The most commonly isolated pathogen is M. canis; however, cats can be infected with Trichophyton spp. and Microsporum gypseum. Because M. canis is the primary pathogen of cats, this discussion will focus on M. canis dermatophytosis, unless otherwise specified. Although cats are often referred to as the “reservoirs of infection” for M. canis, it is important to note that M. canis is not part of the normal fungal flora of cats.61,62 The clinical significance is that isolation of M. canis from the hair coat of cats is associated with one of the following situations: mechanical carriage of the spores, subclinical infection, or overt clinical disease. A decision about some type of action is required when a positive fungal culture result is obtained. The prevalence of the disease is not known because it is not reportable. In general practice, it accounts for approximately 2% of skin diseases presented to a primary care veterinarian.56 In a multiple-animal facility, prevalence depends on a number of factors, including, but not limited to, use of the facility (cattery, home, closed shelter, open shelter, rescue organization), number of cats present, geographic region (dermatophytosis is

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more common in warm, humid climates or seasons), age of the animals (dermatophytosis is more common in kittens than adults), health of the population (sick cats do not groom, which predisposes them to disease), and overall animal care practices and philosophies. Dermatophytosis is transmitted through contact with contaminated environments or other infected animals. For an infection to successfully establish itself, the arthrospores (infective material formed from segmentation and fragmentation of fungal hyphae) have to evade both mechanical, physiologic, and immunologic protective mechanisms. The cat’s most important protective mechanism is a healthy hair coat coupled with routine grooming. Infective spores are readily removed from the hair coat of cats. Fungal spores are small and can be carried on air currents. In addition, the author (KM) has isolated “culture-positive fleas,” and recently the common housefly was found to mechanically transmit spores.14 The dose of infective spores necessary to establish an infection is unknown; however, under experimental conditions at least 100 are required.25 Once the spores penetrate the hair coat and reach the skin surface, some type of trauma is needed to establish infection because spores cannot penetrate intact skin. Increased hydration and maceration of the skin favor penetration and germination of spores. In general, the normally dry skin and hair combined with fungistatic properties of serum and sebum are natural physiologic host defenses. Normal grooming behavior of cats distributes sebum from areas of high concentration and production (chin and dorsum) to other areas. It is easy to understand how flea infestations, pruritus from other causes, or even lack of grooming can predispose a cat to a dermatophyte infection. The incubation period is approximately 1 to 3 weeks from time of exposure to development of lesions. Recovery from infection depends on a strong cellular immune response; stress and immunosuppression compromise recovery. Dermatophytosis is a pleomorphic disease and cannot be diagnosed on the basis of clinical signs alone. The disease affects the hair follicle, and the most common clinical findings include hair loss, hair breakage, scaling, and crusting (Figure 22-23). Consequences of pruritus vary from none to self-mutilation. In cats, lesions may be focal, multifocal, or generalized in appearance. Because spores are easily spread over the entire body, the lesion distribution may be markedly more limited than the amount of infective material on the hair coat and skin. Hyperpigmentation is uncommon in feline skin diseases but is seen commonly in cats with dermatophytosis. Scaling may be focal or generalized and vary from fine scales to marked exfoliation. In severe cases the cat may look as if it has PF. The typical presenting complaint is hair loss, but because the disease is zoonotic, owners may complain of lesions that they or other family members have

FIGURE 22-23 Cat with dermatophytosis. This is a follicular disease, and the hallmark is hair loss. In this case lesions were present on the face and preauricular area. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

contracted. Cats with generalized dermatophytosis often ingest large amounts of hair while grooming and may have a history of vomiting, constipation, hairball problems, or any combination of these. Erythema and scaling of the inner or outer pinnae (or both) are also common presenting symptoms in adult cats. Patches of scale with minor alopecia or hair breakage is one of the most common presentations in longhaired cats. Feline skin reaction patterns for which dermatophytosis should be considered as a differential diagnosis include miliary dermatitis, symmetric alopecia, eosinophilic plaques, and indolent ulcers, especially unilateral ulcers in young cats. Dermatophyte lesions in kittens tend to consist of areas of hair loss and scaling; erythema is variable and is often difficult to detect in dark-haired cats. Lesions are often first seen as areas of hair loss on the muzzle, face, ears, and forelegs. Depending on the overall health of the kitten, lesions may be focal, multifocal, or generalized. Kittens with limited dermatophyte lesions that develop upper respiratory infections, gastrointestinal diseases, or both are at increased risk for the development of generalized lesions. M. canis can cause comedonelike lesions (i.e., chin acne) in young cats. Uncommon presentations of feline dermatophytosis include an appearance clinically identical to that of PF, with scaling and crusting over the bridge of the nose and the face, crusting exudative paronychia, or both. Unilateral or bilateral pinnal pruritus is another underrecognized presentation of M. canis. In the cats examined by one of the authors (KM), infected hairs were limited to the ear margin or long hairs within the “bell” of the ear (or both). M. canis is uncommonly a cause of recurrent OE.26 Granulomatous dermatitis, in the form of wellcircumscribed, ulcerated dermal nodules, is infrequently recognized in cats. The lesions occur on cats afflicted

with more generalized typical M. canis infections. These lesions have been called mycetomas, pseudomycetomas, and Majocchi’s granulomas. Diagnostic testing was described earlier in the chapter. All cats with skin lesions should be screened with a Wood’s lamp, and a fungal culture should be obtained. Again, a positive Wood’s lamp examination is suggestive, but not diagnostic, of an infection. The value of this test is that it allows the veterinarian to select hairs for direct examination or culture; toothbrush fungal cultures are the preferred culture technique. If spores are seen on direct examination, this is confirmation of infection, and treatment can start pending culture. Culture is always recommended to confirm the infection and species even if spores are seen on direct examination. It is also necessary to obtain a pretreatment culture so that the number of colony-forming units (CFUs) per plate can be monitored. This is an increasingly important method for monitoring response to therapy, particularly when there are multiple cats or screening programs in place. It is important to remember that this is a self-curing disease in otherwise healthy cats. The reason cats are treated is to speed resolution of the disease, limit spread to other animals and people, and minimize contamination of the environment. Without treatment cats and kittens will be cured in 60 to 100 days, whereas with treatment this time can be significantly shortened. Optimal treatment involves topical, systemic, and environmental modalities, each of which has a different role. Topical treatment reduces contamination on the hair coat, helps minimize re-infection of the host, and decreases spread of spores into the environment. Systemic treatment benefits the cat by reducing the number of weeks to complete cure by affecting the growth of the dermatophyte at the hair follicle stage. Environmental cleaning reduces the chances of re-infection and spread to other susceptible hosts. Clipping of the hair coat will mechanically remove fragile hairs that tend to fracture and spill spores onto the hair coat and into the environment. It also allows for more thorough application of a topical rinse and decreases the amount and duration of treatment. If the clipping is to be performed in a veterinary clinic, it is important to minimize spread of infective material. The only time that hair coat clipping would be done in a veterinary clinic would be if the entire cat needs to be clipped. The procedure should be done in an area where the cat is confined, such as a transport cage or an open animal carrier. After the cat is sedated (cats should not be clipped without sedation because of the risk of injury), it is placed on a large sheet of disposable surgical drape and clipped. The technician should wear protective clothing that can be removed and washed. Once the cat is clipped, it is immediately treated with a topical antifungal solution. All material in contact with the cat is


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then disposed of in a biohazard bag. The physical area used to confine the cat is mechanically cleaned. Instead of vacuuming, the veterinarian or staff member should use 3M Easy Trap Duster Sheets (3M, St. Paul, Minn.), which are similar to Swiffer Sweeper dry cloths but are sticky, thereby trapping hair and spores. Then the area should be washed with a detergent several times, finishing with a dilute bleach solution (1 : 10 to 1 : 100) and allowing 10 minutes of contact time. Clipping of the hair coat does put the cat at risk for thermal burns from the electric clippers. It may require sedation, which may not be possible or practical in some situations. It also may not be possible in multiple-cat situations. Finally, microtrauma can temporarily worsen the lesions. Clipping of localized lesions can be easily accomplished using disposable children’s scissors. For more generalized lesions, clipping of the hair coat with a No. 10 clipper blade is usually adequate. One of the authors (KM) has successfully treated shelter cats for mild to severe generalized dermatophytosis without clipping of the hair coat by using a combination of twice-weekly topical therapy and itraconazole.64,71,72 However, it is important to note that there was thorough application of the topical solution, concurrent use of a systemic drug, and confinement of the cats. Consistently effective topical antifungal rinses include lime sulfur, enilconazole, and miconazole. Lime sulfur (1 : 16 dilution) administered twice weekly is effective as an adjunct or sole therapy. There are many formulations of lime sulfur available, and no difference in the sporicidal efficacy against M. canis was found among them when the products were tested in vitro.31 Adverse effects include staining of the hair coat and drying of the foot pads and skin. Oral ulceration has not been observed in cats treated with lime sulfur by one of the authors (KM), even when cats were allowed to lick the diluted solution. Oral ulcerations anecdotally attributed to lime sulfur were more likely caused by viruses associated with upper respiratory infections. Enilconazole is not licensed for use in cats and is not available in the United States. The safety and efficacy of enilconazole have been evaluated in cats. In general, it is well tolerated, but some adverse reactions were noted, including hypersalivation, anorexia, weight loss, emesis, idiopathic muscle weakness, and slightly elevated serum alanine aminotransferase concentrations. Anecdotal reports of severe adverse reactions and death are uncommon but do exist, and cats should be prevented from grooming the wet solution from the hair coat. Miconazole is an effective antifungal agent, and synergism between miconazole and chlorhexidine has been demonstrated.78 This combination is available in shampoo and rinse formulations. Systemic antifungal drugs must be cost effective and well tolerated in cats. The two antifungal drugs of choice for systemic therapy in cats are itraconazole and

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terbinafine because both have been shown to have residual activity in the stratum corneum of cats. Both drugs are very effective and well tolerated by cats and can be used in pulse therapy, which is highly tolerable to both cats and owners. Itraconazole (5 to 10 mg/kg orally) can be administered daily or on a 1 week on/1 week off basis until the mycologic cure.101 Terbinafine (40 mg/kg orally) can be administered similarly.35 Adverse effects of either drug include vomiting, diarrhea, inappetence, elevations in serum liver enzymes, and facial pruritus (terbinafine). Fluconazole has been used by one of the authors (KM) at 10 mg/kg orally, but whether this drug can be used in pulse therapy is unknown. Lufenuron has been shown to be ineffective both as a treatment and preventive in feline dermatophytosis.27,60,63 Given the widespread availability of alternative drugs that are safer and better tolerated by cats, griseofulvin is not recommended for systemic antifungal therapy. Concurrent topical and systemic antifungal therapy should continue until mycologic cure, as defined by a minimum of two consecutive negative fungal cultures. Ideally, cultures should be performed at weekly intervals. Owners can be taught to perform toothbrush fungal cultures at home. It is important to stress application of the topical antifungal solution to the face, periocular area (Figure 22-24), and interior of the ears because these sites are often undertreated and persistent infections or apparent failure to cure is commonly traced to this problem. A common dilemma is what to do about other pets in the home. All animals should be examined for lesions and fungal cultured. Pending cultures, all animals should be treated topically with lime sulfur rinses twice weekly. If lesions and fungal cultures indicate that another animal is infected, that pet should receive concurrent systemic antifungal therapy. Otherwise, the veterinarian should continue to treat all animals topically until the infected cat is cured. The approach to management of dermatophytosis is not unlike that needed for contagious mites or fleas; all in-contact animals are to be treated. Ideally, cats should be examined every 2 to 4 weeks. Most cats with a healthy immune system will require 30 to 60 days to reach mycologic cure; longer treatment may be necessary in ill cats or those with severe infections. Fungal cultures should be observed daily, and instead of simply reporting the results as positive or negative, the veterinarian should record the number of CFUs. A successful treatment should show a decrease in the number of CFUs from one week to the next. Persistence of high numbers of CFUs indicates environmental contamination, persistence of lesions, or development of new lesions. As previously mentioned, seemingly resistant infections are almost always due to issues related to treatment. If there is any concern about an owner’s

FIGURE 22-24 Persistent dermatophytosis in a Persian cat. This cat was referred for “resistant infection,” but careful examination revealed glowing hairs in the periocular area. The client had not treated the face of the cat with the topical antifungal rinse. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

ability to thoroughly apply a topical antifungal rinse, daily antifungal therapy may be the best choice. The following strategies will minimize contamination of the home: • As soon as an infected animal is identified, isolate the cat to an easily cleaned room. • Remove clutter from the room, and keep closet doors closed. • Remove contaminated toys, and wash bedding. • Remove infected hairs by clipping, combing, or using a lint roller. • Use a topical antifungal rinse twice weekly. Lime sulfur is particularly safe and effective. • Routinely clean the home and use a triple-cleaning technique in the room where the cat is being confined. Specifically: • Mechanically remove gross debris by vacuuming. • Wash the area with a detergent that is safe to use around cats. • Repeat washing of an area is very effective in the mechanical removal of infected hairs and spores. • On nonporous areas use a 1 : 100 dilution of household bleach in water. • After the cat has been cured, the home should be thoroughly cleaned using the triple-cleaning technique. Surfaces that can be damaged by household bleach should be repeatedly cleaned with a cleanser indicated as safe for that surface. • If confirmation of decontamination is needed, the following sampling technique can be used. Wait 1 hour after an area or room has been cleaned, and then when surfaces are dry, wipe the area with a small section of sterile gauze sponge until soiled.


Seal the sample in a plastic bag, label it, and submit it for culture. This technique will readily detect spores and help identify areas that need additional cleaning. Special Considerations for Infected Multiple-Animal Facilities56 Space does not allow a detailed discussion of the management of dermatophytosis in animal shelters, and the reader is referred to recommended sources58,64 for more details; however, the major points are discussed in the subsequent paragraphs. Endemic dermatophytosis has a profound effect on the health, community reputation, and economic status of animal breeding colonies and animal shelters. Breeding programs must be interrupted because newborn animals are rapidly and easily infected, leading to debilitation and sometimes death. Adoption of shelter pets must be temporarily halted to prevent spread of the infection to new owners. Eradication of dermatophytosis from such a facility is completely possible but requires a commitment to a screening and treatment program and may not be practical or affordable in many facilities. It is important to do the job correctly the first time and institute preventive measures against future outbreaks. Using a standardized system of evaluation, culture, and treatment, eradication has been reported in as little as 2 months.16 It is important to recognize that animals with visible, obvious lesions represent only the tip of the iceberg in an endemic colony, particularly in a M. canis–infected facility. Many animals also have subclinical infections, and many more will be innocently carrying dermatophyte spores on their hair coats. Therefore the eradication process must begin by toothbrush culturing every animal in the facility, regardless of the animal’s clinical appearance. While the initial culture results are pending, the staff members should quarantine any animals with obvious or suspected infection. This precaution requires isolation in a separate contaminated room or building, with floor surfaces that can be disinfected easily. A Wood’s lamp is very helpful here, if the outbreak is caused by a fluorescing strain. A separate clean room or building must also be prepared, into which cured animals will be gradually moved. If new animals must be introduced into the colony during the eradication effort, a third intake room is recommended. Pending the results of the fungal cultures, all animals should be treated with topical lime sulfur 1 : 16 dilution twice weekly. This is very safe and easily and rapidly applied to animals using a garden sprayer. It is important to use warm water because this makes the application less objectionable, and the sprayer should be held as close to the skin as possible so that the skin and hair are thoroughly coated. Environmental decontamination procedures should begin immediately in all three rooms and

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continued indefinitely because the introduction of dermatophytosis into a shelter or multiple animal facility is always a risk. Once the initial culture results are known, the animals can be divided into two groups on the basis of culture results, assuming that the two groups of animals can be kept separate and cross-contamination is not likely. The first group consists of cats that are culture negative and are kept in the clean room. The second group consists of cats that are culture positive with or without lesions. All culture-positive cats should be treated with either itraconazole (10 mg/kg orally, once daily) for 21 days or terbinafine (40 mg/kg orally, once daily) for 21 days. In addition, twice-weekly application of lime sulfur should be continued until two negative consecutive fungal cultures are obtained. A 1 week on/1 week off dosing schedule for itraconazole is quite acceptable; however, if large numbers of cats are involved or multiple people are involved in the medication of the cats, the week on/ week off protocol becomes confusing and treatment lapses can occur. Animals in the clean room should be recultured once after being transferred to that room, as a precautionary measure. Animals in the contaminated room are cultured every week until each animal has a negative result on at least two successive times. Animals that initially had positive culture results but carried only a few spores (as opposed to being actively infected) will develop negative results rapidly, and when they achieve two cultures with negative results, they can be transferred to the clean room. This is easily recognized by a marked and rapid reduction in the number of CFUs on each fungal culture plate. It will soon become obvious which animals are truly infected because they will have multiple successive positive culture results even during treatment. Treatment is continued in the contaminated room until all animals are cured and moved to the clean room. At this point, the contaminated room should be thoroughly cleaned and decontaminated before further use. During the treatment period, it is important to watch for animals that have persistently positive fungal culture results with too many CFUs to count on the culture plate and little apparent resolution despite treatment. These animals, which will typically be only one or a few, may be chronically infected because of their failure to develop an appropriate cell-mediated immune response, and they represent a potent threat to the continued health of the entire colony. Testing these cats for FeLV and FIV is appropriate insofar as it may explain the lack of response, but test results will not change the treatment protocol unless the owners want to remove the infected cats from the population. If the hair coat has not been clipped, this is recommended. It is also recommended that daily antifungal treatment be started. In addition, these chronically infected animals should be either euthanized or removed to a separate facility for treatment.

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FIGURE 22-25 Disorder of keratinization. Increased greasy hair on the dorsal tail is a common form of disorder of keratinization in cats. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

If new animals are entering by way of the intake room, as each animal enters, it should be immediately toothbrush cultured and then given an antifungal bath and dip. Most animals will have negative culture results and can be transferred to the clean room as the culture results become known. Any animal that has a positive culture result is transferred to the contaminated room and treated as previously noted. After the eradication effort is concluded, this intake procedure should be maintained indefinitely.

Greasy Seborrhea Syndromes In general, it is uncommon for cats to have greasy hair coats because of their fastidious grooming habits; however, there are several well-recognized clinical presentations that clinicians should recognize. Cats do not simply stop grooming. Cats that develop greasy, unkempt hair coats do so because of illness or pain, and a careful physical examination and medical evaluation is needed. Greasy hair coats are common findings in cats with hyperthyroidism or diabetes mellitus, but they can occur in any cat that does not feel well. Another common presentation in healthy cats is a focal area of greasy hair on the proximal third of the tail (Figure 22-25). Sebaceous glands are present in large numbers on the dorsum of the cat and in particular in this area. This condition is called “stud tail” by lay people, which implies that it occurs more commonly in intact male cats; however, it can occur in intact or neutered male or female cats. This area can become secondarily infected. Depending on the severity of the greasy tail, management can vary from grooming the cat’s tail to bathing and grooming. Persian and Himalayan cats can develop an idiopathic facial dermatitis characterized by moderate to severe accumulations of adherent debris. This idiopathic facial fold dermatitis has been reported to be nonpruritic, but

FIGURE 22-26 Greasy-faced Persian cat: Persian cat with symmetric periocular and facial sebum-rich exudates. (From Rest J: Controversial and emerging diseases. In August J, editor: Consultations in feline internal medicine, ed 5, St Louis, 2006, Saunders Elsevier, p 270.)

pruritus is variable depending on whether secondary infections develop (Figure 22-26).9,11 These cats should be thoroughly evaluated because some may have underlying treatable diseases. They also need to be differentiated from cats with facial lesions caused by herpes virus.45 Management of these cats is difficult, but tacrolimus ointment has recently been reported to be useful, and there are anecdotal reports of cyclosporine therapy being helpful.18 However, it is important that clients understand that cleansing of the face may be a lifelong part of therapy. Greasy skin is a common finding in Rex and Sphynx cats.1,2,10 Malassezia overgrowth can be a chronic problem in some cats. Primary seborrhea can also be seen in some longhaired breeds as a primary disorder of keratinization. Bathing with Douxo Seborrhea Shampoo (Sogeval, Coppell, Texas), and use of the companion spray product (Douxo Seborrhea Micro-emulsion Spray, Sogeval, Coppell, Texas) is very successful in managing these cats. The spray can also be used as a shampoo substitute.

Sebaceous Adenitis Sebaceous adenitis is an immune-mediated disease in which the sebaceous glands are destroyed. It is more common in dogs than in cats, but this may be due to differences in presentation. The few cases described in the literature presented with either noninflammatory alopecia on the body, patchy areas of hair loss, or a periocular brown-black exudation around the eyelids and vulva.75 The disease is diagnosed using skin biopsy and can be managed with cyclosporine.

Pemphigus Foliaceus PF is an immune-mediated skin disease characterized by the loss of intercellular adhesion of cells in the epidermis. Autoantibodies attack the adhesion molecules causing the epidermal cells to detach (acanthocytes). Neutrophils invade the spaces in response to inflammatory mediators. The disease can occur spontaneously, or it can be the result of drug reactions. The disease is most common in middle-aged cats; however, the author (KM) has seen one case in a 6-monthold Siamese kitten. Clinically, the disease is characterized by waves of intact pustules that rupture and crust, resulting in crusting and scaling of affected areas.17,83 In cats lesions are most commonly seen on the face, nose, and inner pinnae (Figure 22-27). Lesions can also involve the paws, resulting in exudative paronychia and foot pad crusting (Figure 22-28). Lesions can become widespread and are more easily palpated than seen; small crusts covering areas of exudation are felt throughout the hair coat. Intact pustules are difficult to find and are most common on the inner pinnae and around the mammae. As mentioned before, lesions tend to develop in waves, and cats may become depressed and febrile just before the start of a wave of lesion development. Definitive diagnosis is made through histologic examination of skin biopsy specimens. A careful search for intact pustules must be made. In the absence of finding these lesions, numerous skin biopsies of crusted areas of the skin should be sampled. Micropustules are often found within characteristic lesions. Cytologic examination of exudate from an intact pustule can often provide a working diagnosis if large rafts of acanthocytes are seen (Figure 22-29). This is a disease that can be managed but not cured. Most cats do very well with therapy. Treatment options

FIGURE 22-27 Cat with pemphigus foliaceus. Note the lesions on the nose and ear tips. This disease presentation can mimic dermatophytosis. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)


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include glucocorticoid therapy; chlorambucil; adjunct topical steroids; and, most recently, cyclosporine. Corticosteroids are usually the first drug of choice insofar as remission can be rapidly induced. Oral prednisolone (2 to 4 mg/kg, once daily or divided) is administered until the lesions are in remission. The dose is then administered every other day and gradually reduced until the lowest possible dose is found that will maintain the cat in remission. It is important to note that in rare cases even short courses of prednisolone can cause diabetes mellitus in cats. Also, although rare, corticosteroid use has been associated with congestive heart failure in cats.81,91 Some cases of feline PF do not respond to prednisolone, and dexamethasone may be very effective in these cases. In cases where corticosteroids cannot be

FIGURE 22-28 Paw of cat with pemphigus foliaceus. Note the crusting on the paws. This is an excellent site to obtain cytology. Exudate can often be removed from beneath the crust to reveal acanthocytes. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

FIGURE 22-29 Cytology from paw in Figure 22-28. The large, deeply staining cells are rounded keratinocytes or acanthocytes and are strongly suggestive of pemphigus foliaceus. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

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used long term or do not provide adequate control, chlorambucil (0.1 mg/kg orally, once daily, or 0.2 mg/kg orally, every other day) can be given concurrently with a glucocorticoid. There is a lag time of 2 to 4 weeks before maximum benefit may be seen. Complete blood counts should be monitored every week for the first month and then every 2 to 4 weeks thereafter because this drug can cause bone marrow suppression. Azathioprine is contraindicated in cats because of serious bone marrow toxicity.5 Another option is the use of cyclosporine (5 mg/kg orally, once daily). Given that this drug has a lag period of 30 days before maximum benefit is seen, concurrent use of prednisolone therapy to induce remission is necessary.

Paraneoplastic Exfoliative Dermatitis The clinical signs of paraneoplastic exfoliative dermatitis may precede the development of the tumor in the thymus gland. Lesions start as a nonpruritic, erythematous dermatitis that rapidly becomes markedly exfoliative on the head, neck, pinnae, and body. Overgrowth of yeast is very common and present in alarmingly large numbers, and these organisms are readily found on skin biopsy. This skin presentation may be the only sign of the thymoma. Nondermatologic signs may include coughing, dyspnea, anorexia, lethargy, and weight loss. Thymectomy typically results in resolution of all clinical signs (including paraneoplastic signs) and results in prolonged survival.13,34,36,86,97

Epitheliotropic Lymphoma Epitheliotropic lymphoma is an uncommon cutaneous T-cell lymphoma characterized by pruritic exfoliative erythroderma with hair loss and scaling (Figure 22-30). Lesions can start with excessive scaling or just diffuse erytherma.90,94 Lesions can progress to areas of plaques and nodules. This neoplasia is diagnosed by skin biopsy.

Solar or Actinic Dermatitis Solar or actinic changes occur as a result of chronic exposure to sunlight and ultraviolet light; further, there is one report of a cat developing photosensitization during treatment with clofazimine for mycobacterial disease.6 This emphasizes the importance of a good history. The deleterious effects depend on the duration and frequency of exposure, intensity of the radiation, and the reactivity of the skin, which is based on genetically determined skin color, hair coat density, and genetic susceptibility.12 In cats, the early clinical signs appear on the ear margins of sparsely haired pinnae as erythema and fine scaling. As the lesions progress, erythema increases with crusting and scaling, pain, and ear twitching. Further progression of untreated lesions leads to ulceration and

FIGURE 22-30 Exfoliation. This cat has severe exfoliation and Malassezia overgrowth. The cat had a thymoma. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

hemorrhage. In addition to the lesions on the ear, solar or actinic lesions can occur on the eyelid and dorsal aspects of the nose. Major differential diagnoses include immune-mediated diseases; however, a history of chronic sun exposure and slow progression are compelling. Definitive diagnosis is made with biopsy. A key finding on biopsy is the presence of apoptotic epidermal keratinocytes.102 Clinical management ranges from limiting sun exposure to surgical excision of the affected area. Given the difficulty in limiting cats’ sun exposure, ultraviolet-blocking sun shades are more practical to use. Sunscreen can be used, but it is likely to be removed during grooming. If a sunscreen is applied, it should be one that is safe to use on infants, with the highest possible sun protection factor (SPF) available. Lip balm products are safe and easy to apply. For maximum benefit, the sunscreen needs to be applied 30 minutes before sun exposure. If actinic lesions are left untreated, transformation into malignant squamous cell carcinoma (SCC) is likely. Cats with SCC tend to be white or light colored, and lesions are most common on the nose, eyelids, and ears.

CHIN ACNE AND CHIN FURUNCULOSIS Chin acne has recently been extensively reviewed.47 Acne is considered a follicular disorder and varies in presentation from scattered comedones to severe chin furunculosis. This is a clinical diagnosis (Figures 22-31 and 22-32). It is important to remember that facial pruritus is a common clinical sign in cats with many diseases, and repeated rubbing of the face will result in hair loss and plugging of sebaceous glands or comedones. Useful diagnostic tests include cytology of the skin to


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ALOPECIA After pruritus, alopecia is the most common reason that cats are brought to the veterinarian for dermatologic examination. The most common cause of alopecia in cats is self-induced by licking. The diagnostic evaluation for most cases of alopecia should include a careful history, thorough examination, and a methodical diagnostic plan (Figure 22-33).

Feline Symmetric Alopecia FIGURE 22-31 Chin acne. This is a classical presentation with comedones and black debris. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

FIGURE 22-32 Chin pyoderma. This is a more purulent form of chin acne and is characterized by pustules and furuncles. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

look for bacterial and yeast overgrowth; often, the underlying trigger of the disease is gone, and the clinical signs will resolve with treatment. Skin scrapings and hair plucking should be performed to look for demodicosis. Rapid onset of chin acne in a household of cats can be caused by a bacterial infection, dermatophytosis, or D. gatoi. Oddly, the latter can develop in a stable population of pet cats in the home. Skin biopsy is not often necessary for diagnosis or as a part of the diagnostic evaluation but may be helpful in refractory cases. Facial washing with a mild antibacterial and antifungal shampoo can be helpful; in many cases, washing with plain warm water combined with systemic antimicrobial therapy is effective. Topical mupirocin ointment is very effective, but cats will lick this solution off the face, causing rupture of the hair follicles in the dermis and worsening the disease. Some cats have been reported to respond to cyclosporine. Manual expression of the lesions is never helpful.

Feline symmetric alopecia (FSA) is a clinical reaction pattern in which the cat presents with symmetric alopecia over the thorax, flanks, ventral abdomen, or pelvic regions. In most cases the underlying etiology is a pruritic disease that may be complicated by a secondary bacterial and yeast overgrowth. FSA can also develop after exposure to irritants or topical drugs; in one report two cats developed FSA within 2 weeks of exposure to diesel oil.28 Early in the diagnostic evaluation, it is important to determine if the overgrooming is associated with pain or a medical illness so that the cat does not suffer needlessly.103 Radiographs of the affected area may reveal fractures, particularly over the lumbosacral area (Figure 22-34). Excessive overgrooming of the ventral abdomen may indicate abdominal pain, particularly pain associated with the bladder. Increasingly, the author (KM) is seeing older cats with no history of prior skin disease being brought in for overgrooming of anatomic areas where radiographs reveal arthritic changes, particularly intervertebral arthritis. Resolution of the overgrooming and regrowth of the hair after alleviation of chronic pain provide compelling evidence that pain was the trigger. True behavioral causes of overgrooming are rare103 and, in this author’s (KM) experience, commonly associated with other behavioral problems (e.g., inappropriate urination or defecation). Treatment with behaviormodifying drugs should be a last resort because these drugs are not without risk. Treatment should alleviate the overgrooming, allowing the hair to regrow and return once the behavior-modifying drug is withdrawn. A very common scenario with obsessive–compulsive grooming in cats that have FSA is a history of a flea infestation that was successfully treated and followed by persistent grooming. The cats are referred for consultation when the behavior-modifying drugs are no longer effective; invariably, these cats respond to a treatment trial of combined antimicrobial therapy.

Telogen Effluvium Telogen effluvium is a nonpruritic and noninflammatory hair loss pattern characterized by easily epilated hairs.

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Dramatic clinical signs

Skin biopsy

Obvious history of pruritus

ALOPECIA

Pursue pruritus workup

Localized? Patchy/diffuse? Symmetric/generalized?

Initial Diagnostic Tests Skin scraping Hair trichography Flea combing Fungal culture Skin cytology

No diagnosis

Localized Hair Loss

Patchy/Diffuse Hair Loss

Symmetric or Generalized Alopecia

Trial of antibiotic/ antifungal therapy



No resolution

No response

Consider Cicatricial alopecia Traction alopecia Injection site vasculitis Steroid injection skin reaction Alopecia areata

Consider Keratinization defect Sebaceous adenitis Color dilution alopecia Follicular dysplasia Dermatomyositis

Good response

Resolved or improving

Bacterial/yeast overgrowth

Watch for relapse to find underlying trigger

Skin biopsy

No resolution

Consider Congenital alopecia/ hypotrichosis Telogen/anagen defluvium Color dilution alopecia Cutaneous neoplasia Pattern baldness Hair follicle dysplasia

Skin biopsy

No diagnosis

Consider Endocrine disease Metabolic disorder Behavioral cause

No definitive diagnosis Diagnosis

Treatment

Investigation

Result

Reconsider Is pet pruritic?

FIGURE 22-33 Diagnostic flow chart for alopecia in cats. (From Moriello K: Alopecia in cats, Clinicians Brief 7:19, 2009.)


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FIGURE 22-34 Symmetric alopecia. This is an unusual form of symmetric alopecia; however, this site and pattern are common in cats that have suffered pelvic fracture. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

FIGURE 22-36 Focal telogen effluvium. Approximately 2 weeks after recovery from a severe upper respiratory infection, this cat developed focal areas of easily epilated hairs. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

FIGURE 22-35 Telogen effluvium. This cat was from a shelter, and large amounts of hair were easily epilated. The hair coat regrew. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

Close inspection of the hair bulbs reveals that they are in telogen. Clinically, the hairs are easily removed with gentle traction, and often it appears as if the hair coat could almost be peeled off (Figure 22-35). This condition is common in cats or kittens from animal shelters that have a history of severe respiratory infection, especially accompanied by fever (Figure 22-36). The cause is unknown but may be related to a viral infection or overall debilitation. The nonpruritic hair loss resolves without treatment. In practice, the most common presentation of this would be a kitten with a sudden loss of hair that grows back quickly. Dermatophytosis is a major differential diagnosis, insofar as severe infection can result in massive hair loss caused by breakage of the hair shafts; however, usually the hair shafts are stubbly and the skin is inflamed in cats with dermatophytosis.

FIGURE 22-37 Congenital hair loss in a kitten. One kitten in a litter was born without hair follicles on the trunk. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

Congenital Hypotrichosis Congenital hypotrichosis is a rare disease in which one or more kittens in a litter are affected. Kittens are either born alopecic or lose their hair coats over the first month of life (Figure 22-37). Skin biopsy reveals absence of, or markedly atrophic, hair follicles. The problem is cosmetic, but care must be taken that the skin is not damaged owing to the lack of protection from the hair coat. Whether these cats are more susceptible to actinic changes in the skin or solar-associated skin neoplasia remains unknown.

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FIGURE 22-38 Paraneoplastic neoplasia. Note the alopecia, fine scales, and shiny skin. (Photo courtesy Dr. Susan Little.)

FIGURE 22-39 Pinnal alopecia. Bilaterally symmetric hair loss is present on the ears of a middle-aged cat. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

Paraneoplastic Alopecia Paraneoplastic alopecia is a rare skin disease in cats in which there is widespread alopecia. A unique feature of the skin is that it is shiny in appearance and remaining hairs easily epilate (Figure 22-38). It can be associated with overgrowth of bacteria and Malassezia organisms.79,93 It is seen most commonly in cats with systemic neoplasms and is reversible if the original neoplasm is removed. This is a clinical sign of systemic disease.97

Inflammatory Focal Alopecia The most common causes of inflammatory focal alopecia in cats are dermatophytosis, pyoderma with or without a secondary yeast infection, demodicosis, and selftrauma secondary to a parasite infestation. Close inspection of the skin reveals that these lesions are rarely solitary. Core diagnostics include fungal culture, skin cytology, trichogram, and skin scraping.

Preauricular and Pinnal Alopecia Preauricular hair loss is normal in cats but is most dramatic in dark-colored cats. Pinnal alopecia is uncommon and is characterized by episodic episodes of hair loss on the ear pinna (Figure 22-39). Siamese cats may be predisposed. This is a cosmetic problem, and no treatment is necessary.

Noninflammatory Focal Alopecia Associated with Treatments Focal areas of noninflammatory hair loss are typically well demarcated. A common presentation is a lesion in the interscapular area. These are increasingly common with the widespread use of spot-on flea control

products. Focal areas of hair loss can occur at the site of an injection of glucocorticoids. The author (KM) has not observed focal areas of noninflammatory alopecia at the site of vaccinations.

Alopecia Areata Alopecia areata is an immune-mediated skin disease that presents as single or multiple areas of noninflammatory alopecia. The areas are well demarcated and can occur anywhere on the body. Diagnosis is made by ruling out other causes of focal noninflammatory hair loss and by skin biopsy. Early lesions are rarely observed in the cat, but skin biopsy may reveal peribulbar and intrabulbar accumulations of inflammatory cells affecting anagen hairs. Older lesions reveal atrophic hairs or hairs in telogen or catagen. Chronic lesions may reveal an absence of hairs. There is no successful treatment; it is important to rule out infectious or contagious causes of hair loss.

ULCERS AND EROSIONS The most common causes of ulcers and erosions in cats are diseases that are pruritic or associated with scaling and crusting. These lesions can be very dramatic in appearance, and the immediate goal of the history and physical examination is to determine if the lesions are due to an infectious, contagious, immune-mediated, or otherwise life-threatening cause. In general, it is rare for cats with skin diseases to exhibit signs of systemic illness such as fever, anorexia, or weight loss. These signs warrant an aggressive medical workup in addition to dermatologic tests.


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FIGURE 22-41 Focal indolent ulcer. This lesion is at the site of FIGURE 22-40 Mucocutaneous ulceration. Mucocutaneous ulceration is uncommon in cats and is suggestive of severe infectious disease, gingival disease, or immune-mediated diseases. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

In most cases the most useful diagnostic tests in cats with ulcers or erosions are cytology of the lesion and exudate, fungal cultures, and skin biopsy. Dermatophytosis can mimic any skin disease, and one of the major differential diagnoses for ulcerative and erosive skin diseases is an immune-mediated disease or a disease that calls for glucocorticoid therapy. Diseases worsened by the use of corticosteroid therapy should be solidly eliminated from the differential diagnoses. For example, the lesions in the cat shown in Figure 22-40 reveal an erosive process suggestive of an immune-mediated disease, but this was a bacterial infection of the lip folds. Multiple skin cytology samples obtained with a glass microscope slide should be obtained. It is important not to heat fix these to prevent damage to cell integrity. Several slides should remain unfixed and unstained for submission to a reference laboratory if needed. Slides should be examined for the presence or absence of neutrophils, eosinophils, bacteria (intracellular and extracellular), neoplastic cells, and other infectious agents. In the absence of systemic signs of illness, septic neutrophilic or eosinophilic inflammation of the skin may be compatible with an antibiotic-responsive skin disease. Definitive diagnosis of many of the erosive and ulcerative skin lesions can be made only by histologic examination of skin biopsy specimens. It is important to include a list of differential diagnoses with the submission and to remember that knowing what a lesion is not may be as helpful as having a definitive diagnosis. In other words, lesions not compatible with neoplasia, immune-mediated diseases, infections agents, and drug eruptions are important as rule outs. A few conditions warrant special mention. Oral ulceration in cats is most commonly associated with viral diseases, and the immediate diagnosis is not usually

several M. canis–infected hairs. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

difficult. Although rare, pemphigus vulgaris and systemic lupus can occur in cats. The most likely presentation of either of these two diseases will be a middle-aged cat. In both diseases affected cats will show signs of systemic illness, and other mucocutaneous areas will be involved (e.g., eyelids, nasal area, genital and anal areas). Another rare disease is idiopathic ulcerative dermatitis. Affected cats have focal areas of intense pruritus, often in the scapular area. The diagnosis is one of exclusion after other causes of focal ulceration have been ruled out. The etiology is unknown, and the lesions are very difficult to manage. Some are so refractory to treatment that surgical excision is the only option. If neuropathic pain is involved, gabapentin may be a possible therapeutic option.

EOSINOPHILIC LESIONS Eosinophilic lesions are skin lesions characterized by eosinophils on cytologic examination of skin or histologic examination of skin biopsy findings. Peripheral eosinophilia is variable. In severe cases cats may have lymphadenopathy, and fine-needle aspiration may reveal reactive lymph nodes with a large number of eosinophils. Lesions tend to be pruritic and are most commonly associated with allergic skin disease.

Indolent Ulcer The term indolent ulcer108 describes a unilateral or bilateral erosive lesion on the upper lip of cats of any age (Figure 22-41). Recently, there is emerging evidence that some cats may have a genetic predisposition to develop lesions when exposed to allergic triggers, particularly fleas.8,82 Another interesting finding is that these lesions can also occur as a result of foreign bodies (e.g., cactus

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FIGURE 22-42 Miliary dermatitis. This papular crusted lesion is a common reaction pattern for many diseases of cats. Typical cutaneous cytology shows neutrophils and eosinophils. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

spines) or at the site of a focal insult, such as on the lip margins at the sites where dermatophyte-infected hairs, sticktight fleas, or ticks have previously been found.21 Indolent ulcers as a result of focal trauma are transient and often one-time occurrences and may explain why in some cats, particularly young kittens, lesions may develop and resolve without treatment and not recur. Lesions that persist or are recurrent are caused by a persistent trigger such as atopy or food allergies. Initial therapy with antibiotics is recommended. It may be necessary to treat lesions not responding completely to antibiotics with glucocorticoids until lesions resolve.

FIGURE 22-43 Facial ulceration. This is an area of self-trauma. The lesion is an eosinophilic plaque triggered by any disease that is pruritic. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

Miliary Dermatitis and Eosinophilic Plaques Miliary dermatitis refers to an erythematous crusted reaction pattern of the skin.108 Eosinophilic plaques are intensely pruritic, erosive, exudative raised lesions of varying size.108 Close inspection of many eosinophilic plaques often reveals that cats have concurrent miliary dermatitis–like lesions or that the plaques are a coalescence of these papulocrusted lesions (Figure 22-42). The most important new clinical finding is that these lesions are increasingly being recognized as the feline equivalent of canine pyotraumatic lesions (i.e., “hot spots”), and secondary overcolonization by bacteria or Malassezia spp. are common cytologic findings. Lesions are the direct result of self-trauma and are commonly seen on the face, abdomen, inguinal region, medial and caudal thigh areas, and neck (Figures 22-43 and 22-44). These lesions are most commonly triggered by an itch–scratch event, and recurrent lesions are often the hallmark of an underlying allergic disease, although this is not always the case. These lesions can also develop as a result of infections resulting from dermatophytosis, bacteria, and Malassezia spp.

FIGURE 22-44 Eosinophilic plaque. This is a raised, intensely pruritic lesion that is common in feline allergic diseases. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

Eosinophilic Granuloma Eosinophilic granulomas108 are the only true granuloma variant of feline eosinophilic diseases. There are two recognized clinical variations. The first is an ulcerated, proliferative lesion often present in the oral cavity (Figure 22-45). Depending on the location of the mass, dysphagia, drooling, abnormal mastication, and coughing may be present. The other form is characterized by a hard, noninflammatory swelling. Alopecia is variable, and the cat seems unperturbed by the lesion. Clinical presentations include linear pencil-thick lesions on the


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FIGURE 22-45 Oral eosinophilic granuloma. Oral proliferative lesions in the mouth may resemble oral neoplasia; biopsy is indicated. (Photo courtesy Dr. Susan Little.)

FIGURE 22-47 Chin granuloma. Fat lip syndrome is characterized by a hard swelling on the chin. The lesions are rarely bothersome to the cat. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

result of massive eosinophil infiltration and degranulation. Diagnosis of the underlying trigger is most important in these cases. These lesions are rarely problematic to the cat but are very corticosteroid responsive; lesions will recur if the underlying trigger is not identified.

Mosquito and Insect Bite Hypersensitivity FIGURE 22-46 Linear granuloma. Linear granulomas on the hind legs of cats are a classic presentation of the true granuloma complex. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

caudal thigh of young cats; linear lesions on limbs (Figure 22-46); “fat lips” or asymptomatic chin swelling (Figure 22-47); 1- to 5-mm firm, papular lesions on the ears of cats; and interdigital masses. The origin of these lesions has long been thought to be the result of collagen degeneration and degenerate eosinophils. Recently, a study was conducted in which the ultrastructure of these lesions was investigated, and the researchers found that collagen fibrils were not damaged but were separated from one another by edema and surrounded by eosinophils undergoing degranulation. In this study the authors demonstrated that the eosinophil recruitment and degranulation are the primary event triggers in this disease and the collagen fibers do not play an active role in the development of these lesions.4,33 This is a major challenge to the long-held belief that these lesions are caused by collagen degeneration; the lesions are the

Mosquito and insect bite hypersensitivity108 is characterized by a papular erosive eruption on the face, ear tips, nose, and foot pads of cats. Lesions tend to start in the thinly haired areas and may be more common in darkcoated cats. The lesions are intensely pruritic, and depigmentation, crusting, and exudates may occur. The lesions were first noted in cats exposed to mosquitoes but can result from the bites of other small flying insects, such as black flies and Culicoides species. Typically, affected cats have access to the outdoors, especially during the early morning or evening hours when these insects are feeding. It is important to remember that many of these biting insects are small enough to get through the holes used to screen most outdoor porches and windows. Although symmetric ulcerative facial lesions are the most commonly described clinical signs in individual case reports, a study of 26 cats from Japan found that the most commonly observed lesions were miliary dermatitis–like lesions on the ear pinnae.67 Crusty patches on the ear margins are common client complaints, and this report suggests that the prevalence of insect bite hypersensitivity may be underrecognized.

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FIGURE 22-48 Ehlers-–Danlos syndrome. This is a congenital collagen defect characterized by stretchy skin. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

Familial Eosinophilic Lesions Familial eosinophilic lesions108 have been described in specific pathogen-free laboratory cats by at least two investigators.19,82 These cats developed lesions between 4 and 18 months of age, and the lesions were observed to recur until the cats were at least 4 years of age. In one study 21 of 24 cats descended from these cats also developed lesions. The lesions tended to be most common during the spring and summer, suggesting a possible seasonal allergen, insect, hormonal, or reproductive trigger. A hereditary predisposition to eosinophilic lesions is not unexpected, particularly with regard to lesions that have allergic etiologies. Canine atopy has long been recognized to be heritable, and feline atopy was recently described in three littermates.59

FRAGILE SKIN Easily torn skin is uncommon in cats. The most common causes are Ehlers–Danlos syndrome (EDS), spontaneously occurring feline hyperadrenocorticism, excessive use of exogenous glucocorticoids, and drug reactions. EDS is most common in domestic shorthair and Himalayan cats (Figure 22-48). These cats are young and healthy, with hyperextensible skin usually noticed within the first year of life and gradually worsening as the cat gets older. The skin tears easily, with minimal pain associated with the injuries, and will heal. Diagnosis is clinical, with the skin being unnaturally stretchy. There is no treatment. Affected cats commonly die as a result of disease-related problems (e.g., ruptured aortic vessels) or are euthanized by their owners. Spontaneously occurring hyperadrenocorticism occurs in older cats. Affected cats exhibit signs of systemic illness, including, but not limited to, depression, lethargy, obesity or weight loss, anorexia, muscle weakness

FIGURE 22-49 Skin fragility syndrome. This cat has naturally occurring feline hyperadrenocorticism, and the skin was easily torn. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

or wasting, hepatomegaly, and easily torn skin (Figure 22-49). (See Chapter 24, the section on Adrenal Diseases.) In addition to the unkempt coat of cats with systemic illnesses, another early dermatologic clue may be easy bruising. Fragile skin as a result of excessive glucocorticoid use is not usually a difficult diagnosis.49 Invariably, there is a history of exogenous glucocorticoid use, and careful history taking almost always reveals that the glucocorticoids were being used to treat pruritus. The author (KM) has seen acute onset of skin fragility in a cat receiving sulfa antibiotics for gastrointestinal problems. In addition, the author (KM) has seen several cats with toxic epidermal necrolysis present with the complaint of “torn skin.” In these latter cats, the skin was tender and exudative. Skin biopsy may or may not identify an underlying cause for easily torn skin depending on the cause. Whether the condition is reversible depends on the underlying cause and treatment response. In the author’s (KM) experience, gentle handling of the cat and use of surgical stockinettes over the skin to provide protection from further tearing have been helpful. Until the underlying problem is resolved, the major problems that are encountered are infection and the need to protect the underlying granulation tissue.

HARD SKIN Focal areas of hard skin are most likely going to present as nodules and can be caused by bacterial or fungal infections, neoplasia, foreign bodies (e.g., bird shot), or sterile nodular panniculitis with pansteatitis. The most common cause of noninflammatory nodules in the skin is collagen degeneration; the most common trigger is insect bite hypersensitivity. Biopsy is indicated for diagnosis.


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orange cats. Flat, nonindurated macules ranging in size from 1 mm to 10 mm develop on the nose, lips, gingiva, ears, eyelids, or hard palate. These lesions may become more widespread as the cat ages. This is a cosmetic change, and no treatment is needed. The major differential diagnosis is melanoma; if there is a change in the size or nature of a lesion, a biopsy is indicated.

Depigmentation

FIGURE 22-50 Skin eschar that developed over an area of trauma. (Photo courtesy Dr. Susan Little.)

Linear or more diffuse areas are most likely to be caused by a true eosinophilic granuloma. Biopsy is diagnostic. A less common cause of hard skin is an eschar from a burn or traumatic injury. Careful examination of the lesion usually reveals a hardened plaque of dead tissue overlying a bed of granulation tissue. Eschars protect the underlying granulation tissue and will dislodge as the tissue beneath heals. Burns are underrecognized in cats because the hair coat hides the injury. Eschars can also develop as a result of trauma (Figure 22-50). Furthermore, the most common type of burn in cat is a radiant burn from close but not direct contact with a heat source such as a wood-burning stove. Many days to weeks may elapse before the injury is discovered. Although uncommon in cats, focal areas of calcification (calcinosis circumscripta) can occur at the site of injections or injury.76

PIGMENTARY CHANGES Postinflammatory Hyperpigmentation Postinflammatory hyperpigmentation is uncommon in cats. In the author’s (KM) experience, it is most common in cats with dermatophytosis. Focal areas of hyperpigmentation in inflamed skin should be closely examined because they are almost always due to follicular plugging. Skin scrapings, skin cytology, and fungal culture are indicated in feline patients with postinflammatory hyperpigmentation of an unknown cause. Skin cytology may reveal bacterial or yeast overgrowth. It can be difficult to sample areas near or around ears; acetate tape preparations or dry spatula collection techniques are helpful.

Lentigo The most commonly encountered focal area of noninflammatory hyperpigmentation is lentigo simplex of

Depigmentation is uncommon in cats, although idiopathic leukoderma of the pads of Siamese cats has been reported. In addition, Siamese cats may develop periocular leukotrichia (goggle syndrome) after pregnancy, dietary deficiency, or systemic illness.

Acromelanism Acromelanism is seen in Siamese, Himalayan, Balinese, and Burmese kittens that are born white and develop pigmented points as they mature owing to the influence of external temperatures. High temperatures produce light hairs, and low temperatures produce dark hairs. This is caused by a temperature-dependent enzyme involved in melanin synthesis. The temperaturedependent pigmentary change is most commonly encountered in practice when the hair coat is clipped and the hairs that regrow appear as a different color (usually darker). The normal coat color returns with the next hair cycle.

DISEASES OF PAW PADS, PARONYCHIA, AND ANAL SACS Paw Pads In cats, diseases of the paw pads are uncommon, but when they do occur, scaling and crusting, swelling, digital calluses and horns, and ulceration are the most common problems. The underlying causes are variable and include trauma, allergic diseases, infections, immune-mediated diseases, tumors, and viral diseases. The most common causes are discussed in this section. If scaling and crusting is present, the most common causes are dermatophytosis and PF. The author (KM) has noted that the paw pads of cats treated with lime sulfur may become dry and scaly. Although uncommon, scaling and crusting can be an early manifestation of hepatocutaneous syndrome in cats. Less commonly, pox virus infections can cause scaling. Ulcerations of one or more paws may be due to selftrauma, injuries, irritant reactions, plasma cell pododermatitis, infections, eosinophilic granulomas, tumors (Figure 22-51), and drug reactions. Diagnosis depends on history, thorough dermatologic and medical examination, and biopsy.

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FIGURE 22-51 Cutaneous lymphoma. This is a case of cutaneous

FIGURE 22-53 Digital pad callus. (Image courtesy Dr. Susan Little.)

lymphoma presenting as foot pad swelling and crusting. (Photo courtesy Dr. Susan Little.)

alternative drug for long-term use (doxycycline or cyclosporine) is used. Doxycycline (5 to 10 mg/kg orally, every 12 hours) or cyclosporine (5 mg/kg orally, every 24 hours) can be used to keep lesions in remission or induce remission in less severe cases. It can take 1 to 2 months to see maximum benefit. Digital pad calluses are common and may be bothersome to the cat (Figure 22-53). These can occur anywhere on the paws. Management varies from none to surgical excision of the lesion.

Paronychia

FIGURE 22-52 Plasma cell pododermatitis. This is a benign infiltrative skin disease that affects the paw pads. Note the swelling and “pillowlike” appearance. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

The most common cause of swelling of the foot pads is plasma cell pododermatitis (Figure 22-52). The swelling may or may not be painful. The color of the foot pads may appear red to purple, and clients may describe them as “pillowlike.” In the author’s (KM) experience, these lesions wax and wane and may ulcerate and crust. Definitive diagnosis is made by biopsy. Foot pads are painful to biopsy, and samples should be obtained from non–weight-bearing pads if at all possible. Alternatively, the veterinarian can use a 4-mm punch biopsy to obtain the specimen. If the pads are not tender or ulcerative, it is reasonable to make a clinical diagnosis, insofar as no treatment is needed. Tender or ulcerated pads require treatment. Prednisolone (4 mg/kg orally, once daily) induces the most rapid remission of lesions. Once lesions have resolved, the dose can be tapered while an

The two most common presentations of paronychia in cats are crusting and exudation and pedal pruritus with waxy exudate. The most common causes of crusting and exudation of the nail bed are bacterial infections, Notoedres infestation, dermatophytosis, and PF. Pruritic nail beds are almost always due to yeast overgrowth (Figure 22-54).20,68 Bacterial infections are characterized by swollen nail beds, which are painful for the cat. Exudation is common and malodorous. Multiple digits are typically involved, and causative agents include Staphylococcus spp., Streptococcus spp., Pseudomonas spp., and Proteus spp. In rare cases this can be a presentation of cryptococcosis. The diagnosis is based on clinical signs. Skin cytology and culture are used to guide therapy. Notoedres infestation is characterized by severe crusting with mild to severe pruritus. Similar clinical signs are usually present on the face and ears. Skin scrapings reveal mites. All in-contact cats should be treated with an appropriate miticide. Bathing and mechanical removal of crusts facilitates treatment. Ivermectin (0.2 to 0.4 mg/kg orally or subcutaneously) every 2 weeks for three treatments is effective; see previous discussion for other treatment options.

FIGURE 22-54 Nail bed. Accumulations of nail bed debris around the base of the nails is typical in cats with yeast pododermatitis. Yeast pododermatitis can result from a wide range of causes. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

PF in cats can begin with crusting of the nail beds and foot pads. Almost always, all the digits are involved. Careful examination of the cat may reveal other lesions compatible with PF, such as crusting on the face, ears, and body. Cytologic examination of exudate reveals neutrophils and rafts of acanthocytes. Intracellular or extracellular bacteria may also be present. Cats with a bacterial infection that does not respond to appropriate therapy and cats with negative cultures are highly suspect for PF. Definitive diagnosis is made by histologic examination of a skin biopsy. Severe dermatophytosis involving all of the digits can be indistinguishable from PF or bacterial infections. Discriminating criteria may be found in the history (e.g., age of the animal, other affected animals in the household). Wood’s lamp examination may reveal glowing hairs for direct examination or fungal culture. Close inspection of the whole cat almost always reveals other lesions suggestive of or diagnostic for dermatophytosis. The nail beds and proximal portions of the nails should be examined in cats that have severe pedal pruritus. Accumulations of waxy debris are not a normal finding on the nails of cats and are typical of Malassezia overgrowth (see Figure 22-54). This is a common problem in cat breeds with abnormal hair coats (e.g., Devon and Cornish Rex, Sphynx), cats with systemic illnesses (e.g., diabetes mellitus), and cats with allergic skin diseases. Large numbers of yeast organisms are readily apparent on cytologic examination of debris. Treatment with systemic antifungal agents will resolve the pruritus or significantly minimize it. If the condition is caused by an underlying disease, this must be treated or else the problem will recur. Management of breed-related Malassezia overgrowth is more difficult and requires a


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FIGURE 22-55 Perianal pruritus. This was an atopic cat with chronic anal sacculitis. The area became colonized with microbial overgrowth, magnifying the pruritus. The cat’s anal sacs were chemically cauterized, but this did not resolve the pruritus. The cat was diagnosed with atopy, and the perineal pruritus resolved with therapy for allergies. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

combination of systemic therapy and a lifelong regimen of bathing the paws and nail beds.

Tumors and other Swellings of Individual Toes Swelling of individual digits can be caused by neoplasia, foreign bodies, or infection. Biopsy is the most rapid way to diagnose the problem.

Anal Sac Diseases Anal sac diseases are uncommon in cats compared with dogs. The most common cause of anal sac problems in cats is perineal pruritus caused by allergies. The skin surrounding the perineal area becomes inflamed, the small superficial ducts become swollen, and excretions cannot be evacuated when the cat defecates. Cats with recurrent anal sac impactions or cats whose owners complain about excessive anal licking should be carefully examined for allergic skin diseases, including flea allergy, food allergy, and atopic dermatitis (Figure 22-55). The perineal skin is easily overcolonized by bacteria and yeast, which magnify the pruritus. Combined systemic antimicrobial therapy may be necessary to resolve this inflammation. Cats with uncomplicated perineal pruritus caused by allergies can be managed with topical glucocorticoid therapy, short courses of oral steroids if the problem is seasonal, or cyclosporine. Anal sac impaction is typically bilateral. The affected anal sac is distended and may elicit pain on palpation, and the contents, which are thick and dark in color, are not easily expressed. Discomfort may cause the cat to

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FIGURE 22-58 Anal sac abscess, after surgical débridement. This FIGURE 22-56 Anal sac abscess. This cat had chronic anal sac abscesses and exudates as a result of allergies. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

Anus

Vulva

FIGURE 22-57 Anal sac abscess. (Photo courtesy Dr. Susan Little.)

scoot the hind end on the floor. Tenesmus and licking at the perineum may also occur. The cause for anal sac impaction is not well understood. The contents normally empty during defecation. Retention of anal sac contents may lead to inflammation and infection. Anal sac abscesses and rupture can and do occur in cats. Typically, the problem is unilateral. Owners may complain of blood, vocalizing, and other indications of pain. Clinical signs are typical of an abscess (Figure 22-56), with swelling, pain, exudation, and possible rupture (Figures 22-57 and 22-58). Management varies from conservative (e.g., antibiotics, stool softeners, cleansings) to surgical

was a severe abscess that required placement of a surgical drain. (Photo courtesy Dr. Susan Little.)

débridement and irrigation with povidone–iodine solution. Laxatives that contain polyethylene glycol (e.g., Miralax, Schering-Plough HealthCare Products, Inc.) are effective stool softeners. These are tasteless powders that can be sprinkled on a small amount of food; approximately one-quarter of a teaspoon is administered daily for constipation and stool softening. Recurrent cases of anal sac abscess that are refractory to conservative management may be treated with anal sacculectomy, once inflammation and infection have resolved.

OTITIS There are three clinical presentations of otitis57 in cats depending on anatomic location: OE, OM, and otitis interna (OI).38,65 The underlying etiology and pathogenesis of feline otitis involves the interplay of predisposing factors, primary diseases, and secondary or perpetuating factors. Predisposing factors to consider in cats include, but are not limited to, living in a humid climate and increased maceration of the ear tissue caused by frequent grooming.38 Stenosis of the ear canal and deformed ear pinna secondary to aural hematomas may predispose cats to overgrowth of microbial organisms if the ear canal is occluded or if pain and secondary self-trauma are present. Cats can develop otitis secondary to overly aggressive or frequent ear cleanings. Predisposing factors unique to cats include OM secondary to acute or chronic upper respiratory infections or chronic sinusitis.29,88 Another factor is OE caused by a fixed

drug reaction or allergic contact reaction as a result of transdermal drug administration. Finally, in some cats with chronic otitis the only abnormal finding is retrovirus infection. Primary causes are diseases that directly cause ear disease.38 These include but are not limited to parasitic diseases, allergies, autoimmune diseases, neoplasia, keratinization disorders, facial dermatitis of Persian cats, congenital diseases (hairless cat breeds), foreign bodies, polyps, trauma (including thermal injuries and frostbite), and neoplasia. Perpetuating factors prevent the ear disease from healing.38 The most common perpetuating factors are bacteria and yeast. The most common causes of recurrent otitis in cats are undiagnosed OM, resistant infections, and obstructions of the ear canal. OE in cats includes, but is not limited to, any combination of the following clinical signs: erythema; hair loss; scaling; crusting; pruritus; pain; deformed ear pinna; thickening of the external pinna; odor; and exudate of variable color, amount, and consistency. The owner may report head shaking, ear twitching, fits of ear scratching after manipulation of the ear, changes in eating habits, changes in behavior (e.g., hiding or aggression) or changes in vocalization. Clinical signs may be unilateral or bilateral, persistent or intermittent, and acute or chronic. The initial presenting complaint may be unrelated to the ears; some cats are brought to the veterinarian because of facial lesions. OM is a common complication in cats with severe OE. OM is inflammation of the middle ear cavity, including the tympanic membrane and bulla. Many, but not all, cats with OM have concurrent OE. OM should always be suspected when cats exhibit severe purulent OE and chronic recurrent OE. Cats with OM without signs of OE may be brought to the veterinarian for head shaking, pawing at the ear, pain when the head is touched, changes in eating habits or appetite, pain when the mouth is opened, depression, and loss of hearing. Clinical signs may be unilateral or bilateral. Otoscopic examination of the ear canal typically reveals exudate and inflammatory changes in the canal when OE is also present. Manual manipulation of the ear is usually painful, and a “squishing” sound is common, indicating fluid in the canal. If the tympanic membrane can be visualized, bulging, discoloration, or rupture may be evident. OM can be present without signs of OE, but the tympanic membrane almost always appears abnormal. Cats with OM and a ruptured tympanic membrane often have copious malodorous liquid discharge on otoscopic examination. This may also be seen on the floor of the horizontal canal. Mucus may be seen with OM. It is important to note that mucus is not normally present anywhere along the external ear canal, but it does ooze from tympanic bulla through any tear in the tympanic membrane. If mucus is present on otoscopic


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examination of the external canal, there is a tear in the tympanic membrane. OM is underrecognized in cats. Chronic sinusitis can lead to bulla effusion and OM in cats.29 OI involves inflammation of the bony labyrinth, where the organs of hearing (cochlea) and vestibular apparatus (semicircular canals and vestibule) are located.7 Loss of hearing, head tilt, circling, falling, generalized incoordination, difficulty rising and ambulating, nystagmus, facial nerve paralysis, and Horner’s syndrome are common signs in cats with OI. In cases of concurrent OM, head tilt is toward the affected side, and the cat may circle and fall toward the affected side. Nystagmus may be spontaneous, horizontal, or rotary, with the fast phase away from the affected side and head tilt. OI caused by an infection can be the result of an ascending infection through the eustachian tube or secondary to OM with or without complicating OE. When vestibular signs are associated with concurrent signs of OE or OM, it is reasonable to assume that the cat’s OI is the result of this infection. Cats that exhibit signs of OI in the absence of signs of OE or OM present more of a challenge. These cats require an aggressive workup to determine if the vestibular signs are peripheral or central. In addition to a careful and thorough history and physical examination, there are a number of useful diagnostic tests to help diagnose the cause of the otitis. Mineral oil microscopy can be used for Otodectes spp. and demodicosis; it is an often overlooked diagnostic test in adult cats with pruritic ears. Dermatophyte cultures are recommended, especially when cats are young, free roaming, or recently acquired. Dermatophytosis is highly variable, and PF and dermatophytosis in longhaired cats can look very similar.84 Furthermore, early infections in cats often start on the face and ears; the hairs within the pinnae may be the first site of infection. Cytologic examination of ear exudate is mandatory regardless of the number of times that the cat is brought in for ear disease. It is not appropriate to assume that what was seen in the past is what is present at the current examination. Otic cytology helps guide further diagnostics and is a useful tool for monitoring therapy. Heat fixing slides before staining improves visualization of yeast. Bacterial overgrowth is generally uncommon in cats; when bacteria (rods or cocci) are seen, culture is indicated. The presence of leukocytes signals suppurative otitis (SO) and a need for aggressive medical therapy. Culture is indicated in SO. Yeast is a common finding in normal cats, and the determining factor as to their significance is whether the cat is symptomatic at the time of sampling.68,69 A recent study on the prevalence of Malassezia spp. in cats found that yeast was present in 23% of normal cats and 64% of cats with OE.69 Bacterial cultures should be performed by a reference laboratory. In addition, the laboratory should be able

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and willing to speciate pathogens and investigate sensitivities of multiple strains of a pathogen when indicated or requested. This becomes important in cases of chronic bacterial otitis. The presence of multistrain pathogens with variable sensitivities is common, especially when Pseudomonas spp. are isolated. Skin biopsy of the ear is an underused diagnostic test. It is strongly recommended when an immune-mediated skin disease, tumor, or proliferative disease is present. Depending on the location of the skin lesions, skin biopsy can be performed using a 4-mm skin biopsy punch, Tru-Cut biopsy needle, or otoscopic endoscope. Diagnostic imaging of the bullae can be helpful in diagnosing underlying OM, spaceoccupying lesions (i.e., tumors, polyps), or other obstruction in the ear canal. In cases of chronic OM, it may identify underlying sinonasal disease.

Otodectes Infestations Ear mite infestations are one of the most common causes of otitis in cats and one of the most successfully “treatable and curable” ear diseases of cats (see previous discussion). In one survey it was found to be the cause of otitis in 25% of cats presented for otitis.92 Complications are uncommon when proper treatment has been administered. Complications with the treatment of ear mite infestations include the following: • • • • • • •

Suppurative OE and OM Severe head and neck pruritus Otodectic whole body mange Classic infestation treatment failures Subclinical infestations Aural hematomas Deformed ear pinnae and chronic recurrent yeast infections (Figure 22-59)

• Concretions in the external ear canal, middle ear, or both The most common complication of ear mite infestations is an aural hematoma. Optimal management that will minimize recurrence and deformation of the ears includes surgical drainage of the blood and throughand-through suturing of the pinna to close the dead space. Obviously, the underlying cause must be addressed. Unlike the situation in dogs, atopic dermatitis does not appear to be a common trigger in cats.

Otic Demodicosis D. cati (long and slender) and D. gatoi (short and fat) both can be found on mineral oil microscopy from the ears of cats with pruritic OE. The two most common presentations encountered are young cats with pruritic ears and older cats with pruritic ears. It has also been reported to be the cause of ceruminous otitis in cats.42,98 In the latter case a concurrent systemic illness was either already diagnosed or diagnosed shortly thereafter. In young cats it is not uncommon to find concurrent Otodectes infestations and Demodex mites. There are no products licensed for the treatment of feline otic demodicosis. Successful treatments include milbemycin (0.5 mg/kg orally, once daily or on a week on/week off basis for 30 days), otic ivermectin, otic milbemycin, and otic preparations labeled for the treatment of ear mites in cats. Amitraz is not recommended for use in cats because it can be toxic. In young animals attention to general pediatric care will usually prevent recurrences. In older animals otic demodicosis can be difficult to resolve if the underlying disease process (e.g., neoplasia, hyperthyroidism, and diabetes mellitus) is not properly managed. Concurrent topical otic steroids may be helpful in relieving the pruritus.

Obstructive Otitis

FIGURE 22-59 Deformed pinna. Lack of appropriate treatment or chronic recurrent aural hematomas can lead to deformed pinnae. This will predispose the cat to chronic ear infections. (Photo courtesy Dr. Susan Little.)

The most common causes of obstructive otitis in cats are ear polyps (Figure 22-60), ear tumors, stenosis secondary to inflammation, ear deformity caused by untreated aural hematomas, and ear debris concretions. The most common clinical signs associated with space-occupying obstructive lesions are chronic recurrent OE or OM, head shaking, and malodorous suppurative discharge. These lesions tend to be unilateral but can be bilateral with ear polyps. Mast cell tumors in young cats, particularly Siamese cats, can present as obstructive lesions. In the case of space-occupying lesions, resolution of the problem requires imaging of the ear to locate the obstruction and surgical removal of the obstruction. Because these cases tend to be chronic, cats usually have a concurrent OM and need postoperative systemic and topical antimicrobial treatment based on culture and

FIGURE 22-60 Ear polyp. This is an obvious polyp; however, polyps are not always so obvious, and sometimes surgical exploration or imaging (or both) are required to visualize them. (Photo courtesy Dr. Carol Tice.)

susceptibility testing. Irrigation of the ear canal and bulla may also be needed. It is important to remember to perform otic cytology because this may help guide initial antibiotic selection and may be able to identify concurrent yeast otitis that may not be otherwise diagnosed. Concurrent treatment of both bacterial and yeast OM is common. Stenosis of the external ear canal of cats is most commonly, but not exclusively, seen as a result of aural hematomas that have healed without surgical intervention. If the obstruction is causing clinical discomfort and resulting in SO, intervention is needed. If the cat is not otherwise bothered by the problem, it is best left untreated.

Allergic Otitis Allergic otitis in cats is a common complication of atopy and food allergy. The ideal treatment is appropriate management of the underlying allergy (food or atopy). Seasonal atopy is common, and otic pruritus may be the only clinical sign. Owners may complain about an increase in ceruminous discharge. Otic cytology will often reveal a concurrent yeast otitis; treatment of the yeast otitis may diminish but does not fully eliminate the pruritus, and otic glucocorticoids will be needed.

Yeast Otitis Recurrent chronic yeast otitis in cats is most commonly seen in cats with allergic ear disease caused by atopy or food allergy, mild obstructive ear disease, and congenital hair coat abnormalities (e.g., Devon Rex and Sphynx). The most common treatment of choice is itraconazole (2 to 5 mg/kg orally, once daily) for 30 days or once daily


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on a 1 week off/1 week on protocol for 30 days. Fluconazole is increasingly being used as a treatment option because it is much less expensive than itraconazole. Ketoconazole is commonly used in dogs, but cats do not tolerate this drug; because of the increased potential for hepatotoxicity, its use is discouraged in cats. In mild cases or acute cases that are likely to be seen in primary care, combination antifungal and antiinflammatory topical products may be very suitable and appropriate. Chronic recurrent yeast otitis may be due to Malassezia OM. Definitive diagnosis may be made by way of diagnostic imaging or myringotomy with culture and cytology of exudate from the bulla. In the authors’ (KM) experience, these cases require aggressive ear irrigation and systemic therapy for resolution. A careful reassessment of the case history should be made to determine whether there is an underlying disease (e.g., allergies).

Otitis Media OM can be a sequela to an upper respiratory infection, it can occur as a complication of ear mite infestation or obstructive lesion such as a polyp, or it can be a primary disease when organisms from the retropharynx ascend through the eustachian tube into the tympanic bulla. The clinical signs of OM are described in the preceding sections, but it cannot be emphasized enough that OM should be suspected whenever there is recurrent unilateral or bilateral OE, especially if the cytology reveals septic inflammation. Core diagnostics include ear cytology and bacterial culture. Bacterial culture is particularly important if rods are seen; recurrent Pseudomonas spp. infections in the ear are difficult to treat. Opinions vary as to when diagnostic imaging is needed or cost effective. Conventional radiographs are widely available, and a major strength of this type of imaging is that it provides a global view of skull, nasal cavity, and bulla. The major problem, of course, is that there is superimposition of overlying structures. Computed tomography (CT) provides cross-sectional views, allowing for localization of lesions. If soft tissue opacity in seen in the tympanic bulla, it is either tissue or fluid, and differentiation on radiographs is not possible; CT imaging can make this differentiation because fluid will not contrast enhance. In general, diagnostic imaging is indicated when an obstruction is suspected (unilateral or bilateral); when otitis exists concurrent with signs of nasopharyngeal polyps, when there is a head tilt, or when septic otitis fails to respond to therapy. Medical Management for Otitis Media Not all cases of OM require the aggressive medical treatment described in this section. Middle ear irrigation is not without risk and cost. It is very reasonable to treat OM with systemic and topical antibiotics and antifungal drugs for 4 to 6 weeks. A gentle lavage of the ear may

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be necessary. In all cases antiinflammatory drugs and pain medication should be provided. The most common causes of otitis media in cats in one author’s (KM) experience are Malassezia and Pseudomonas. The following treatment plan is appropriate for OM: 1. Administer general anesthesia and analgesics in preparation for sample collection and flushing of the bulla. Perform an otoscopic examination of the ear canal to determine whether the tympanic membrane is ruptured. 2. If the tympanic membrane is intact, a myringotomy should be performed to collect cytology and culture specimens. This can be done with a video otoscope or with an operating head otoscope. Using an operating head otoscope, a sterile urethral catheter or 22-gauge, 6-inch spinal needle attached to a 3-mL syringe containing 1 mL of sterile saline is inserted through the tympanic membrane; the fluid is flushed into the bulla, loosening debris and exudates that can be aspirated for sampling (Figure 22-61). This fluid can be used for both cytology and culture. Another technique that is equally useful is to use a minitip culturette to perform both the stab incision and collect the sample. The minitip culture swab is passed through a sterile ear cone attached to the operating head otoscope. It is used to puncture the tympanic membrane and then pushed into the bulla. The tip is rotated to collect specimens. This is repeated to collect specimens for cytologic examination. The needle, catheter, or swab is inserted through the tympanic membrane at the 5 to 7 o’clock position. The caudal–ventral part of

FIGURE 22-61 Exudate from middle ear irrigation. Sterile saline was flushed into the tympanic membrane and loosened debris that can be used for culture or an aspirate. This technique can be used when video otoscopy is not available or possible. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

the tympanic membrane is the largest and safest area to pass tubes and instruments insofar as it avoids the important vasculature, nerves, and the hearing apparatus (which are located cranial– dorsal). 3. If the tympanic membrane cannot be visualized, it will be necessary to thoroughly clean and dry the ear canal using suction before collection of samples from the bulla. The cat’s face and eyes should be protected from ear cleaners and flushing fluid by gently wrapping the cat’s head in a towel. If the tympanic membrane is ruptured, samples can be collected from the bulla through the rent in the tympanic membrane for both cytology and culture. Care must be taken not to contaminate the tips of the instruments with debris from the external ear canal. This can be accomplished by using a double catheter technique in which a large lumen catheter is used to shroud a small catheter inside it. Once the large catheter is safely in the bulla, the tip of the smaller catheter is pushed into the bulla to collect a sample. If liquid cannot be aspirated, 1 mL of sterile saline is flushed into the bulla. The same “shrouding” technique can be done using a sterile ear cone attached to operating otoscope. A sterile urinary catheter is then passed through the cone and used to collect a specimen by aspirating fluid. Again, if no fluid is obtained, 1 mL of sterile saline can be flushed into the bulla and aspirated. 4. Once samples have been collected, the bulla is flushed with copious amounts of warm sterile lavage fluid. Dilute povidone–iodine solution is commonly used. Suction is used to remove the fluid. This process is continued until the fluid is clear. This process frequently dislodges large chunks of debris. A small amount of hemorrhage is also possible. 5. After flushing, instill an enrofloxacin otic drop and dimethyl sulfoxide–fluocinolone otic solution into the bulla to decrease inflammation and deliver a high concentration of antibiotics to the target area. 6. After the procedure patients are treated with oral prednisolone (1 to 2 mg/kg orally, daily for 2 weeks and then gradually tapered over the next 2 weeks). Steroids decrease inflammation, secretions, and exudation in the bulla. If oral medication is difficult, alternatives include the use of injectable methylprednisolone acetate or intravenous dexamethasone (0.2 mg/kg) at the time of treatment and then once weekly. 7. Many cases of OM in cats are due to Malassezia spp. or a combined bacterial infection. Pending culture and sensitivity results, the author (KM) often prescribes marbofloxacin (3 to 5 mg/kg orally, once daily) and itraconazole or fluconazole (3 to 5 mg/kg orally, once daily).

8. Severe OM necessitating middle ear irrigation and flushing of the bulla is best treated with concurrent topical antibiotics. Most commonly, one of the following is used: fluoroquinolones (e.g., ciprofloxacin, enrofloxacin, orbifloxacin), ticarcillin, or ceftazidime. It may be necessary to request that a compounding pharmacy make these otic solutions. 9. Most cats will require pain medication after ear flushing for at least 5 to 7 days. Tramadol (1 to 4 mg/kg orally, every 8 hours) is effective. 10. Long-term antibiotic therapy will be determined by the results of the cytology and culture results. It is not uncommon for the cytology to reveal large numbers of yeast organisms that are not evident on culture. Total treatment time varies, but owners should be expected to administer medication for at least 4 to 8 weeks. 11. Complications that can occur after flushing include head tilt, nystagmus, potential OI, and pain. Owners should be warned that small amounts of blood-tinged fluid may be seen after the procedure. This procedure is best done early in the day and the patient released as late as possible in the day. Overnight hospitalization is ideal because it allows the cat to recover fully and the clinician to monitor the cat for adverse effects. Neurologic side effects are often transient and gone within 24 hours of flushing. 12. Cats with OM should be reexamined every 2 to 4 weeks during the treatment period.

Vestibular Disease and Otitis Media and Otitis Interna57 Space does not allow a detailed discussion of vestibular disease in cats; however, there are several important points to remember. Cats with vestibular disease need a careful physical and neurologic examination to determine if the vestibular signs are peripheral or central in cause. If clinical signs of OE or OM are present, it is likely that the vestibular signs are associated with the OM. OM can occur without obvious signs of otitis, making this determination difficult. Neurologic examination and imaging are usually indicated in these situations. Diagnostic imaging is needed in cats with vestibular signs to ensure that there is no obstructive lesion (e.g., polyp) causing the signs and, it is to be hoped, to confirm the presence of OM. Animals with central vestibular disease (CVD) have a brainstem dysfunction. In peripheral vestibular disease (PVD), animals have a rotary or horizontal nystagmus that does not change with the animal’s head position. Although the nystagmus may not be a constant finding in chronic cases, sudden head movements usually can trigger the nystagmus, and its direction is constant. The


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head tilt is always toward the side with the otitis, but the fast phase of the nystagmus is away from the ear with the disease. Proprioception is normal in animals with PVD. In addition, PVD caused by OM or OI may be accompanied by ipsilateral facial nerve paresis and Horner’s syndrome. Animals with CVD can have any type of nystagmus, but vertical nystagmus is more common with CVD than with PVD. It has been reported that animals with CVD have a nystagmus that changes in character or direction with a change in head position. Most often the nystagmus does not change, but central disease is present if it does. Abnormalities of cranial nerves other than VII and VIII are suggestive of CVD, as is the presence of proprioceptive deficits. The most reliable signs to look for in CVD are proprioceptive deficits and changes in mentation. Proprioceptive deficits can be difficult to assess in cats, even more so if they are ataxic. The three major differential diagnoses for cats with PVD are OI, OM, nasopharyngeal polyps, and idiopathic feline vestibular disease. The latter is most common in the summer and fall and can affect cats of any age, but it seems to be more common in cats that go outside. There is a sudden onset of ataxia, nystagmus, and head tilt consistent with a peripheral vestibular lesion. Facial paralysis, Horner’s syndrome, and proprioceptive deficits are not features of this disease. It is important to rule out OM and OI. Neurologic signs typically improve spontaneously in approximately 2 weeks; this will not occur in cats with bacterial otitis. Some cats may have a mild persistent head tilt and ataxia. The cause is unknown, but it may be due to a virus or aberrant migration of Cuterebra larvae. Otitis causes vestibular disease by one of two mechanisms. Bacteria that infect the middle ear can produce toxins that inflame the labyrinth (OM), or bacteria may invade the labyrinth itself (OI). Bacterial OM or OI should be treated for at least 4 to 6 weeks with systemic antibiotics based on culture and sensitivity findings. Topical antibiotics are insufficient. Given that OM and OI can be difficult to diagnose by otoscopic examination and imaging, a treatment trial is recommended even if OM or OI cannot be identified conclusively. Owing to damage to the neuronal structures, some residual head tilt, facial paralysis, or Horner’s syndrome may be apparent.

Ototoxicity Concerns Aminoglycoside antibiotics (i.e., gentamicin, amikacin) have been shown to cause ototoxicity in particularly sensitive animals. The drug can reach very high concentrations in the ear, leading to toxic side effects. In general, the development of ototoxicity depends on the duration of treatment, cumulative dose, average daily dose, peak and trough serum concentrations, concurrent diuretic use, underlying disease status, and previous use of aminoglycoside antibiotics. The ototoxic effects are generally preceded by nephrotoxicity insofar as the drug is

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BOX 22-3 Differential Diagnosis of Nonhealing Wounds in Cats

FIGURE 22-62 Apocrine hidrocystoma. This is a common presentation of this benign disease in the ears. (Photo courtesy University of Wisconsin School of Veterinary Medicine.)

also readily accumulated in kidney tissue. In dogs hearing loss is the most common presentation. Cats, however, generally show vestibular symptoms when ototoxicity occurs. Symptoms may eventually resolve once the medication is withdrawn, although in some cases, the adverse effects are irreversible. Other drugs that have the potential to cause ototoxicity include chlorhexidine, polymyxin B, ethacrynic acid, furosemide, salicylates, and cisplatin. The use of chlorhexidine as an ear cleaner is not recommended for this reason.

Apocrine Hidrocystoma This is an uncommon, non-neoplastic condition in which cats have multiple or numerous nodules or vesicles in the external ear canal, inner pinnae, or eyelid (Figure 22-62). The vesicles are small, measuring less than 2 mm on average. These lesions are deeply colored (dark blue, brown, or black) and may be mistaken for pigmented neoplasms. Biopsy of the lesions will confirm the diagnosis. The condition has been seen in cats of all ages. Surgical removal or laser ablation may be beneficial in symptomatic animals. Other treatments include lancing the cysts with a needle or blade and using silver nitrate sticks as a chemical cautery. Within several weeks the cysts will dry and involute. After several weeks the remaining cysts can be treated. Chemical ablation with trichloroacetic acid has been used successfully to treat these cysts when they occur around the eyelids.15,73 Cysts are surgically débrided and then treated topically with 20% trichloroacetic acid.107

Proliferative Necrotizing Otitis Externa Young kittens between 2 and 6 months of age are primarily affected by proliferative necrotizing OE, a visually

Parasites Cuterebra Leishmaniasis Disseminated infections with Protista Leishmaniasis Fungal Microsporum canis subcutaneous granuloma Sporotrichosis Opportunistic fungal infections (e.g., mycetoma, phaehyphomycosis) Cutaneous involvement of systemic mycoses: cryptococcosis, coccidioidomycosis, blastomycosis, histoplasmosis Foreign bodies Neoplastic disease Bacterial infections Bacterial furunculosis Actinomyces/Nocardia infections Cutaneous bacterial granuloma Cutaneous mycobacterial infections Feline leprosy

distinctive condition. One case report, however, diagnosed the disorder in three young adult domestic shorthair cats between 3 and 5 years of age.54 It is a rare condition with unknown etiology. The disorder is characterized by well-demarcated, erythematous plaques with annular or serpiginous (wavy) borders. Thick keratinous debris is also present. Biopsy of the lesions will confirm the diagnosis. Lesions appear on the inner aspect of the pinnae, external ear canal, and sometimes the preauricular region on the face. Lesions develop rapidly and often progress to erosion and ulceration. The animal may be pruritic. Often, secondary bacterial and yeast infections may be present. Lesions generally regress spontaneously by the time the animal is 12 to 24 months of age. However, the disease may be more persistent in older cats. One study reported beneficial results when the animal was treated with once-daily tacrolimus ointment.54

NONHEALING WOUNDS The term nonhealing wound simply describes any lesion that does not resolve with what initially seems to be appropriate care. The causes of nonhealing wounds in cats are legion, and some of the more important differential diagnoses are listed in Box 22-3. Successful resolution of these lesions depends on using a cost-effective diagnostic approach. In general, the following are core diagnostic tests for nonhealing wounds: skin scrapings,

skin cytology, fine-needle aspirate of mass or tissue, culture of the tissue by excisional wedge, and skin biopsy. Depending on the geographic region of the veterinarian’s practice, some diseases may be more or less likely, and additional tests based on a high index of suspicion may be warranted. Because some of the agents are potential zoonoses, all cats with nonhealing wounds should be handled with gloves at all times. Special stains are often needed to identify infectious agents. It is critical to include a list of differential diagnoses so that these tests can be ordered promptly. Submission of several unfixed cytology specimens is helpful, as is submission of tissue imprints from the biopsy site. In order to maximize the usefulness of the latter, the excised tissue should be blotted on a paper towel until the blood is removed. Then the veterinarian makes several impressions of the tissue on a glass microscope slide and submits that with the biopsy specimen. The most diagnostic biopsy specimens are deep wedge sections; many pathogens are few in number in the skin and are found deep in the tissue.

Feline Leprosy Syndromes Feline leprosy refers to a mycobacterial disease in which multiple granulomas form in the skin or subcutaneous tissue.24 These organisms are difficult to culture and very slow growing, requiring special growth conditions. Three patterns of disease have been recognized.51 Mycobacterium lepraemurium occurs in young cats with nodular to ulcerative lesions on the legs. Lesions rapidly progress. There may be sparse to moderate numbers of acidfast bacteria (AFB) seen on cytology or histopathology. Confirmation of the diagnosis is based on polymerase chain reaction (PCR) testing. A second clinical presentation of feline leprosy is seen in old cats. Cats may have localized or disseminated disease, and disease progression is slow and protracted. In contrast to the case in young cats, large numbers of AFB are found on cytology or histopathology. Again, definitive diagnosis is made with PCR testing. Finally, a third presentation seen in western Canada and the United States called feline multisystemic granulomatous mycobacteriosis has been described.3 This is caused by the slow-growing Mycobacterium visibilis, which causes diffuse cutaneous disease and widespread dissemination to internal organisms. Treatment is challenging, and surgical excision, rifabutin, sulfa drugs, and clofazimine have been used.51

Rapidly Growing Mycobacterial Infections Atypical or rapidly growing mycobacterial infections52 are caused by the Mycobacterium fortuitum group, which grow within 7 days on appropriate culture medium. In cats the most common clinical presentation is a nonhealing wound in the inguinal area, often at the site of a cat


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bite abscess. The infection invades the surrounding skin and subcutaneous tissue. Affected areas are alopecic and have fistulous tracts and a watery discharge. Diagnosis can be made by cytologic examination of exudates and culture of exudates, but histologic confirmation may be needed. Treatment involving a combination of surgical excision and antimicrobial therapy with drugs such as clarithromycin may be required, although some species are susceptible to more routine antibiotics such as doxycycline or fluoroquinolones.

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19. Colombini S, Hodgin EC, Foil CS et al: Induction of feline flea allergy dermatitis and the incidence and histopathological characteristics of concurrent indolent lip ulcers, Vet Dermatol 12:155, 2001. 20. Colombo S, Nardoni S, Cornegliani L et al: Prevalence of Malassezia spp. yeasts in feline nail folds: a cytological and mycological study, Vet Dermatol 18:278, 2007. 21. Cornegliani L: Collagenolytic granuloma in three domestic shorthaired cats following foreign body penetration, Vet Dermatol 11:30, 2000. 22. Craig TM, Teel PD, Dubuisson LM et al: Lynxacarus radovskyi infestation in a cat, J Am Vet Med Assoc 202:613, 1993. 23. Curtis CF: Current trends in the treatment of Sarcoptes, Cheyletiella and Otodectes mite infestations in dogs and cats, Vet Dermatol 15:108, 2004. 24. Davies JL, Sibley JA, Myers S et al: Histological and genotypical characterization of feline cutaneous mycobacteriosis: a retrospective study of formalin-fixed paraffin-embedded tissues, Vet Dermatol 17:155, 2006. 25. DeBoer DJ, Moriello KA: Development of an experimental model of Microsporum canis infection in cats, Vet Microbiol 42:289, 1994. 26. DeBoer DJ, Moriello KA: Inability of two topical treatments to influence the course of experimentally induced dermatophytosis in cats, J Am Vet Med Assoc 207:52, 1995. 27. DeBoer DJ, Moriello KA, Blum JL et al: Effects of lufenuron treatment in cats on the establishment and course of Microsporum canis infection following exposure to infected cats, J Am Vet Med Assoc 222:1216, 2003. 28. Declercq J, De Bosschere H: Diesel oil-induced alopecia in two cats, Vet Dermatol 20:135, 2009. 29. Detweiler DA, Johnson LR, Kass PH et al: Computed tomographic evidence of bulla effusion in cats with sinonasal disease: 2001-2004, J Vet Intern Med 20:1080, 2006. 30. Diesel ADD: Allergen specific IgE in atopic and healthy cats— comparison of rapid screening immunoassay and complete panel analysis, Vet Dermatol 20:216, 2009. 31. Diesel A, Verbrugge M, Moriello KA: Efficacy of eight commercial formulations of lime sulphur on in vitro growth inhibition of M. canis, Vet Dermatol 19:107, 2008. 32. Ferrer-Canals G, Beale KM, Fadok V: Demodex gatoi infestation in cats presenting with noninflammatory alopecia, Vet Dermatol 20:224, 2009. 33. Fondati A, Fondevila D, Ferrer L: Histopathological study of feline eosinophilic dermatoses, Vet Dermatol 12:333, 2001. 34. Forster-Van Hijfte MA, Curtis CF, White RN: Resolution of exfoliative dermatitis and Malassezia pachydermatis overgrowth in a cat after surgical thymoma resection, J Small Anim Pract 38:451, 1997. 35. Foust AL, Marsella R, Akucewich LH et al: Evaluation of persistence of terbinafine in the hair of normal cats after 14 days of daily therapy, Vet Dermatol 18:246, 2007. 36. Godfrey DR: Dermatosis and associated systemic signs in a cat with thymoma and recently treated with an imidacloprid preparation, J Small Anim Pract 40:333, 1999. 37. Goldman C, Rosser Jr E, Petersen A et al: Investigation on the effects of ciclosporin (Atopica®) on intradermal skin test reactivity in dogs, Vet Dermatol 20:215, 2009. 38. Gotthelf LN: Diagnosis and treatment of otitis media in dogs and cats, Vet Clin North Am Small Anim Pract 34:469, 2004. 39. Graham CA, Rosser EJ: Bioavailabity and activity of prednisone and prednisolone in the feline patient, Vet Dermatol 15:7, 2004. 40. Gross TL, Ihrke PJ, Walder EJ et al: Skin diseases of the dog and cat: clinical and histopathologic diagnosis, ed 2, Ames, Iowa, 2005, Blackwell Science. 41. Guaguere E: Topical treatment of canine and feline pyoderma, Vet Dermatol 7:145, 1996. 42. Guaguere E MA, Degorce-Rubiales F: Feline demodicosis: retrospective study of 12 cases, Vet Dermatol 15:34, 2004.

43. Guaguere E, Pascal P: A practical guide to feline dermatology, Paris, 1999, Merial. 44. Guilford WG, Jones BR, Markwell PJ et al: Food sensitivity in cats with chronic idiopathic gastrointestinal problems, J Vet Intern Med 15:7, 2001. 45. Hargis AM, Ginn PE: Feline herpesvirus 1–associated facial and nasal dermatitis and stomatitis in domestic cats, Vet Clin North Am Small Anim Pract 29:1281, 1999. 46. Jackson HA: Diagnostic techniques in dermatology: the investigation and diagnosis of adverse food reactions in dogs and cats, Clin Tech Small Anim Pract 16:233, 2001. 47. Jazic E: Acne. In August J, editor: Consultations in feline internal medicine, vol 6, St Louis, 2010, Saunders Elsevier, p 375. 48. Last RD, Suzuki Y, Manning T et al: A case of fatal systemic toxoplasmosis in a cat being treated with cyclosporin A for feline atopy, Vet Dermatol 15:194, 2004. 49. Lien YH, Huang HP, Chang PH: Iatrogenic hyperadrenocorticism in 12 cats, J Am Anim Hosp Assoc 42:414, 2006. 50. Lopez RA: Of mites and man, J Am Vet Med Assoc 203:606, 1993. 51. Malik R, Hughes MS, Martin P, Wigney D: Feline leprosy syndrome. In Greene CE, editor: Infectious diseases of the dog and cat, ed 3, St Louis, 2005, Saunders Elsevier, p 477. 52. Malik R, Martin P, Wigney D, Foster S: Infections caused by rapidly growing mycobacteria. In Greene CE, editor: Infectious diseases of the dog and cat, ed 3, St Louis, 2005, Saunders Elsevier, p 482. 53. Mason KV, Evans AG: Mosquito bite–caused eosinophilic dermatitis in cats, J Am Vet Med Assoc 198:2086, 1991. 54. Mauldin EA, Ness TA, Goldschmidt MH: Proliferative and necrotizing otitis externa in four cats, Vet Dermatol 18:370, 2007. 55. Medleau L, Hnilica KA: Small animal dermatology: a color atlas and therapeutic guide, ed 2, St Louis, 2006, Saunders Elsevier. 56. Moriello K, DeBoer DJ: Dermatophytosis. In Greene CE, editor: Infectious diseases of the dog and cat, ed 4, 2012, Saunders Elsevier (in press). 57. Moriello K, Diesel A: Medical management of otitis. In August J, editor: Consultations in feline internal medicine, vol 6, St Louis, 2010, Saunders Elsevier, p 347. 58. Moriello K, Newbury S: Dermatophytosis. In Hurley KF, Miller L, editors: Management of infectious diseases in animal shelters, Ames, 2009, Wiley Blackwell, p 243. 59. Moriello KA: Feline atopy in three littermates, Vet Dermatol 12:177, 2001. 60. Moriello KA: Treatment of dermatophytosis in dogs and cats: review of published studies, Vet Dermatol 15:99, 2004. 61. Moriello KA, DeBoer DJ: Fungal flora of the coat of pet cats, Am J Vet Res 52:602, 1991. 62. Moriello KA, DeBoer DJ: Fungal flora of the haircoat of cats with and without dermatophytosis, J Med Vet Mycol 29:285, 1991. 63. Moriello KA, DeBoer DJ, Schenker R et al: Efficacy of pretreatment with lufenuron for the prevention of Microsporum canis infection in a feline direct topical challenge model, Vet Dermatol 15:357, 2004. 64. Moriello KA, Newbury S: Recommendations for the management and treatment of dermatophytosis in animal shelters, Vet Clin North Am Small Anim Pract 36:89, 2006. 65. Morris DO: Medical therapy of otitis externa and otitis media, Vet Clin North Am Small Anim Pract 34:541, 2004. 66. Muller GH, Kirk RW, Scott DW et al: Muller & Kirk’s small animal dermatology, ed 6, Philadelphia, 2001, Saunders. 67. Nagata M, Ishida T: Cutaneous reactivity to mosquito bites and its antigens in cats, Vet Dermatol 8:19, 1997. 68. Nardoni S, Corazza M, Mancianti F: Diagnostic and clinical features of animal malasseziosis, Parassitologia 50:81, 2008. 69. Nardoni S, Mancianti F, Rum A et al: Isolation of Malassezia species from healthy cats and cats with otitis, J Feline Med Surg 7:141, 2005.

CHAPTER 22 Dermatology 70. Neel JA, Tarigo J, Tater KC et al: Deep and superficial skin scrapings from a feline immunodeficiency virus–positive cat, Vet Clin Pathol 36:101, 2007. 71. Newbury S, Moriello K, Verbrugge M et al: Use of lime sulphur and itraconazole to treat shelter cats naturally infected with Microsporum canis in an annex facility: an open field trial, Vet Dermatol 18:324, 2007. 72. Newbury S, Moriello KA: Skin diseases of animals in shelters: triage strategy and treatment recommendations for common diseases, Vet Clin North Am Small Anim Pract 36:59, 2006. 73. Newkirk KM, Rohrbach BW: A retrospective study of eyelid tumors from 43 cats, Vet Pathol 46:916, 2009. 74. Noli C, Scarampella F: Prospective open pilot study on the use of ciclosporin for feline allergic skin disease, J Small Anim Pract 47:434, 2006. 75. Noli C, Toma S: Three cases of immune-mediated adnexal skin disease treated with cyclosporin, Vet Dermatol 17:85, 2006. 76. O’Brien CR, Wilkie JS: Calcinosis circumscripta following an injection of proligestone in a Burmese cat, Aust Vet J 79:187, 2001. 77. Ordeix L, Galeotti F, Scarampella F et al: Malassezia spp. overgrowth in allergic cats, Vet Dermatol 18:316, 2007. 78. Perrins N, Bond R: Synergistic inhibition of the growth in vitro of Microsporum canis by miconazole and chlorhexidine, Vet Dermatol 14:99, 2003. 79. Perrins N, Gaudiano F, Bond R: Carriage of Malassezia spp. yeasts in cats with diabetes mellitus, hyperthyroidism and neoplasia, Med Mycol 45:541, 2007. 80. Ployngam T, Tobias AH, Smith SA et al: Hemodynamic effects of methylprednisolone acetate administration in cats, Am J Vet Res 67:583, 2006. 81. Ployngam T, Tobias AH, Smith SA et al: Hemodynamic effects of methylprednisolone acetate administration in cats, Am J Vet Res 67:583, 2006. 82. Power HT, Ihrke PJ: Selected feline eosinophilic skin diseases, Vet Clin North Am Small Anim Pract 25:833, 1995. 83. Preziosi DE, Goldschmidt MH, Greek JS et al: Feline pemphigus foliaceus: a retrospective analysis of 57 cases, Vet Dermatol 14:313, 2003. 84. Preziosi DE, Goldschmidt MH, Greek JS et al: Feline pemphigus foliaceus: a retrospective analysis of 57 cases, Vet Dermatol 14:313, 2003. 85. Robson DC, Burton GG: Cyclosporin: applications in small animal dermatology, Vet Dermatol 14:1, 2003. 86. Rottenberg S, von Tscharner C, Roosje PJ: Thymoma-associated exfoliative dermatitis in cats, Vet Pathol 41:429, 2004. 87. Saari SA, Juuti KH, Palojarvi JH et al: Demodex gatoi–associated contagious pruritic dermatosis in cats—a report from six households in Finland, Acta Vet Scand 51:40, 2009. 88. Schlicksup MD, Van Winkle TJ, Holt DE: Prevalence of clinical abnormalities in cats found to have nonneoplastic middle ear disease at necropsy: 59 cases (1991-2007), J Am Vet Med Assoc 235:841, 2009. 89. Schwassman M, Logas D: How to treat common parasites safely. In August J, editor: Consultations in feline internal medicine, ed 6, St Louis, 2010, Saunders Elsevier, p 390. 90. Skorinsky I, Papadogiannakis E, Horowitz I et al: Epitheliotropic cutaneous lymphoma (mycosis fungoides) in a coati, J Small Anim Pract 49:204, 2008. 91. Smith S, Tobias A, Fine D et al: Corticosteroid-associated congestive heart failure in 12 cats, Intern J Appl Res Vet Med 2:159, 2004. 92. Sotiraki ST, Koutinas AF, Leontides LS et al: Factors affecting the frequency of ear canal and face infestation by Otodectes cynotis in the cat, Vet Parasitol 96:309, 2001. 93. Tasker S, Griffon DJ, Nuttall TJ et al: Resolution of paraneoplastic alopecia following surgical removal of a pancreatic carcinoma in a cat, J Small Anim Pract 40:16, 1999.

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94. Tobey JC, Houston DM, Breur GJ et al: Cutaneous T-cell lymphoma in a cat, J Am Vet Med Assoc 204:606, 1994. 95. Trimmer AM, Griffin CE, Rosenkrantz WS: Feline immunotherapy, Clin Tech Small Anim Pract 21:157, 2006. 96. Trimmer AM, Newton HM: Rush and conventional immunotherapy. In August J, editor: Consultations in feline internal medicine, ed 6, St Louis, 2010, Saunders Elsevier, p 357. 97. Turek MM: Cutaneous paraneoplastic syndromes in dogs and cats: a review of the literature, Vet Dermatol 14:279, 2003. 98. Van Poucke S: Ceruminous otitis externa due to Demodex cati in a cat, Vet Rec 149:651, 2001. 99. Verbrugge M, Kettings R, Moriello K: Effects of light and temperature variations on time to growth of dermatophytes using commercial fungal culture media, Vet Dermatol 19:110, 2008. 100. Verlinden A, Hesta M, Millet S et al: Food allergy in dogs and cats: a review, Crit Rev Food Sci Nutr 46:259, 2006. 101. Vlaminck KMJA, Engelen MACM: Overview of the pharmokinetic and pharmodynamic studies on the development of itraconazole for feline Microsporum canis dermatophytosis. In Hillier A, Foster AP, Kwochka K, editors: Advances in veterinary dermatology, ed 5, Oxford, 2005, Blackwell Publishing, p 130. 102. Vogel JW, Scott DW, Erb HN: Frequency of apoptotic keratinocytes in the feline epidermis: a retrospective light-microscopic study of skin-biopsy specimens from 327 cats with normal skin or inflammatory dermatoses, J Feline Med Surg 11:963, 2009. 103. Waisglass SE, Landsberg GM, Yager JA et al: Underlying medical conditions in cats with presumptive psychogenic alopecia, J Am Vet Med Assoc 228:1705, 2006. 104. Wildermuth BE, Griffin CE, Rosenkrantz WS: Feline pyoderma therapy, Clin Tech Small Anim Pract 21:150, 2006. 105. Wildermuth BE, Griffin CE, Rosenkrant, WS: Response of feline eosinophilic cutaneous plaques and eosinophilic lip ulcers to amoxicillin-clavulanate therapy, Vet Dermatol 20:223, 2009. 106. Wisselink MA, Willemse T: The efficacy of cyclosporine A in cats with presumed atopic dermatitis: a double blind, randomised prednisolone-controlled study, Vet J 180:55, 2009. 107. Yang SH, Liu CH, Hsu CD et al: Use of chemical ablation with trichloroacetic acid to treat eyelid apocrine hidrocystomas in a cat, J Am Vet Med Assoc 230:1170, 2007. 108. Young KM, Moriello, KA: Eosinophils and eosinophilic diseases. In August J, editor: Consultations in feline internal medicine, ed 5, St Louis, 2006, Elsevier Saunders, p 238.

HUMAN ALLERGIES TO CATS Daniel O. Morris

GENERAL INFORMATION The prevalence of human allergy to pet dander has risen rapidly over the past several decades as a consequence of lifestyle changes that have enhanced the exposure of people to pet-source allergens. During this time the popularity of cats as companion animals has increased substantially in industrialized nations, and changes in indoor climate control systems, furnishings, and hygiene practices have magnified the retention of allergens in public and private buildings. The net effect has been a rise in ambient exposure to cat dander in both the domestic and public environs.49,52,68 Human allergy to pet dander is a problem of global public health importance, insofar as the morbidity associated with allergic

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diseases disproportionately affects socioeconomically disadvantaged populations, particularly children.16,70 It is also an occupational hazard for some workers, such as animal health care professionals. Although the public often seeks advice from veterinary professionals regarding healthy pet ownership practices, including strategies for reducing pet dander exposure in the home, many misconceptions persist in the public domain regarding pet dander allergy. Perhaps the most prevalent is the belief that certain dog and cat breeds are “hypoallergenic” as a result of their hair coat type. The human diseases most commonly associated with sensitization to environmental allergens include allergic asthma, atopic dermatitis, urticaria, and allergic rhinitis– conjunctivitis (“hay fever”). Collectively referred to as atopic reactions, these diseases result from immediate or type 1 hypersensitivity responses and are characterized by production of elevated levels of allergen-specific immunoglobulin E (IgE) that can be detected by either serologic or skin-prick testing.79 Although atopic reactions likely evolved as protective mechanisms against parasites, they are purely pathogenic when directed against otherwise harmless allergens such as ubiquitous pollens and dander. A genetic predisposition is obvious from familial studies, although the atopic state is a complex trait that is likely influenced by multiple genes.42,54 Still, the rapid increase in the incidence of allergic diseases in human populations cannot be explained by genetic models alone; shifts in exposure or immunoreactivity must also be in play. Assuming exposure to be equal, failure to develop clinical allergy must result from either a lack of immune response to allergens (anergy) or a response that induces immunologic tolerance.61 Tolerance is the ability of an active immune response to prevent or redirect sensitization to an allergen and is thought to occur most commonly through natural or induced production of IgG4-blocking antibodies.61 Induction of blocking antibodies by immunization with allergen vaccines (also known as allergen-specific immunotherapy or “allergy shots”) may be an important medical treatment strategy for individuals with pet dander allergies.25 Similarly, natural exposure to high levels of environmental allergen (e.g., cat dander) may promote specific tolerance in some individuals (discussed later). The term dander refers to particles that are sloughed from animal skin. Although composed primarily of skin flakes, its physical properties cannot be standardized and defined accurately; hence the term is used in a generic sense. Dander serves as a vehicle for animal allergens, which are typically low-molecular-weight proteins or glycoproteins that arise from ubiquitous plant or animal sources. Allergens are designated by a systematic nomenclature maintained by a subcommittee of the World Health Organization/International Union of Immunological Societies. The designation is

derived from the first three letters of the source organism’s genus name, the first letter of the species name, and an Arabic numeral that indicates the chronology of the allergen’s discovery.14 For example, the first allergen purified from domestic cat (Felis domesticus) dander is Fel d 1. Allergens such as Fel d 1 can be carried on a diverse array of particles,24 many of which are of an aerodynamic size (less than 3 µm in diameter) such that attached allergens remain airborne for long periods after disturbance (i.e., continuously in occupied homes).11 Most organisms produce more than one type of allergen that can be recognized by an allergic person’s immune system, and when more than 50% of the allergic population is reactive to a particular allergen, it is referred to as a major allergen; minor allergens are recognized by less than 50% of the allergic population.66 Fel d 1 is a globulin secreted by the feline salivary,6,29 sebaceous,6,15,29 and perianal glands,22 with the skin and hair serving as reservoirs.15,22 Its physiologic function remains unknown. It is recognized by specific IgE produced by 85% to 95% of cat-sensitized people,49 and its production may be influenced by testosterone, as the sebaceous gland output of male cats is reduced after castration.81 In fact, a study of Fel d 1 levels in reservoir house dust showed reproductive status to be the only cat-dependent variable associated with allergen levels in homes. However, this was the opposite of what would be expected: The homes of sterilized cats harbored significantly more allergen than those housing sexually intact animals (effect size greater for males than females).56 Coat length, age, body mass, and time spent indoors showed no effect in a multivariable regression model.58 Allergen production did, however, vary with anatomic site, with the face producing dramatically higher levels than the chest.12 This makes sense considering the greater glandular distribution and secretory activity of the facial skin. Other minor (yet defined) cat allergens include Fel d 2, a serum albumin protein with extensive crossantigenicity to other mammalian serum albumins, and Fel d 3, a cysteine protease inhibitor produced in the skin (exact structure of origin unknown).37 These allergens are recognized by specific IgE of about 20% and 10% of cat-sensitized people, respectively.49 Finally, a lipocalin salivary protein designated Fel d 4, which was bound by specific IgE in 64% of sera from cat-allergic subjects, was characterized recently.69Although the majority of these sera samples harbored relatively low titres of anti–Fel d 4 IgE, 47% of them exceeded the corresponding titers of anti–Fel d 1 IgE. The clinical relevance of Fel d 4 allergen therefore merits additional investigation, insofar as it could be the most relevant allergen for some allergic individuals. The bulk of epidemiologic research on the topic of pet dander allergy has focused on Fel d 1, which is present

ubiquitously in the human environment, and because cats are the dominant source of animal-origin allergy of people. Whereas levels of Fel d 1 are much higher in households with current cat residence,27,33 it can be detected in homes without resident cats.7,33,34,55 In homes where there has never been a resident cat, there is a direct correlation of indoor allergen level with the prevalence of cat ownership in the community at large.33 The average level of allergen contamination in reservoir dust of U.S. homes, regardless of cat ownership,7 should be sufficient to both sensitize and elicit symptoms in genetically predisposed individuals based on current estimates of dose–response relationships.60,72 Fel d 1 is also detectible in many public places at levels capable of sensitizing susceptible individuals. This is especially relevant and problematic for children in schools and day care centers1,4,38,65,78 but also occurs in the workplace,51 automobiles,55 airplanes,51 cinemas,51 and even human hospitals.18 Secondary exposure (e.g., to a room where a cat has been previously) can be high enough not only to sensitize individuals but also to provoke acute allergic inflammation.80 The evidence for sensitization and exacerbation of cat dander allergy in school children is compelling. Epidemiologic studies have demonstrated that sensitization of children without regular cat contact may increase in a dose–response fashion according to the degree of contact experienced by their classmates.4,65 Elicitation of symptoms is also possible: non–cat-owning asthmatic children in classrooms with high cat ownership experienced a doubling of asthmatic symptoms and medication use in the 2 weeks after their return to school from holiday break. Those in classrooms with low cat ownership showed no such increases.4 Because of the risk to asthmatic children, reduced-allergen school environments have been studied.25,40,78 Measures such as banning pet ownership40,78 or providing school-issued clothing for students during the school day40 were successful in reducing ambient Fel d 1 concentrations, although the effects on allergic symptoms were not assessed. In schools and day care centers, mattresses have been shown to be a source of higher in-school allergen levels than settled dust.8,38 Mattresses are a known reservoir for dust mite and pet allergens, and the quantity of Fel d 1 increases with the advancing age of the mattress.26 Even newly purchased mattresses can contain detectible and relevant cat and dog allergen levels, although those wrapped in plastic when purchased are of less concern.21,23 A study in which customers in Swedish stores were allowed to try out floor model mattresses showed highly statistically significant increases in the deposition of dog, cat, and horse allergens. For cat and horse allergens, the concentrations detected strongly correlated with the duration of in-store display.23 In non–cat-owning homes, a combination of the presence of stuffed animals on the bed, lack of mattress and pillow encasements, and


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infrequent sheet washing were associated with significantly increased Fel d 1 levels in children’s bedrooms.58 The net experience suggests that use of allergenimpermeable encasements for mattresses and pillows may be useful components of allergen avoidance strategies, although the efficiency of Fel d 1 exclusion by such materials varies widely,57and controlled trials have not been reported. Also of interest is the finding that pillows stuffed with synthetic fibers trap significantly more pet allergens than feather pillows, an effect likely to be due to the tighter weave used in pillow covers to prevent extrusion of feathers.19 Sources of secondary exposure extend beyond the indoor environment. The clothing of classmates, playmates, and coworkers is commonly implicated.20,55 In fact, clothing is often the point source for indoor contamination, insofar as levels of Fel d 1 in the homes of people who do not own cats have correlated with the level of exposure experienced by their children in school, with the vehicle being clothing.3 Even human hair has been shown to serve as a vehicle for Fel d 1 dispersal.41,50 In societies where keeping of indoor pets is rare, the prevalence of sensitization to cat allergens is still similar to the rates observed in Western countries, which suggests that feral outdoor cats provide a sufficient degree of dander exposure to induce human allergy.13,32

MITIGATION STRATEGIES Avoidance Through Environmental Interventions Indoor lifestyle changes that may have contributed to the rise of human allergic diseases over the past several decades include the increasing prevalence of wall-towall fixed carpeting that cannot be removed for laundering24,46,60and improved efficiency of indoor climate control systems. The latter reduces air exchange with the outdoor environment (reducing dilution of indoor allergens), whereas upholstery and carpeting trap indoor allergens and complicate cleaning regimens.49 Because of the ubiquity of pet allergen dispersal, household and classroom intervention presents a difficult challenge. Randomized trials have shown that environmental reduction of pet dander allergens can be achieved, in some instances with modest clinical benefits.2,43,67 However, the measures necessary—such as extensive home-cleaning regimens, removal of carpeting and upholstered furniture, and encasement of mattresses and pillows with impermeable membranes—can be quite costly and burdensome to sustain. In addition, socioeconomic status is highly associated with environmental factors (e.g., housing characteristics, number of residents, pet ownership, and general home hygiene) that strongly influence allergic sensitization,10,16,70 and it

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is apparent that the populations bearing the greatest burden of disease are often those with least access to health care and other resources. Vacuuming can actually exacerbate dispersal of pet allergens from carpet reservoirs, and allergen leakage from the machine and the vacuum bag is of major concern.60 However, in the past decade improvements such as two- and three-layer microfiltration vacuum bags and high-efficiency particulate arresting (HEPA) filters in both vacuum machines and room air cleaners (which claim to capture 99.9% of particles 0.3 µm diameter or larger) have increased allergen uptake and reduced leakage.30,31,62,77 The use of such units has been correlated with decreased allergen in reservoir dust and improvements in asthmatic patients,62 although an evaluation of cat allergen levels after HEPA-filtrated vacuuming showed an actual increase in inhaled Fel d 1 when measured by nasal air sampling.30,31The authors attribute this to disturbance of allergen adhered to walls and other surfaces by all vacuum models caused by beater bar action, the back-and-forth motion of the cleaning head, and air exhaust flow from the machine. With regard to HEPA-filtered air cleaners, results have also been mixed, with some suggesting excellent utility in reducing airborne pet allergen levels,28,30,31,74 but not in reservoir dust, and not to a degree where they are likely to be effective alone.71,74-76 The effect of furniture dusting has also been evaluated in simulation studies; as might be expected, dry dusting of wood surfaces releases allergen, whereas application of a spray polish to the dusting cloth or wood surface significantly reduces aerosolization of Fel d 1.39,40,44 In addition to housekeeping regimens, laundering of clothing plays an important role in allergen reduction. Washing cotton fabrics in water is a simple and highly effective method for Fel d 1 removal,47 and use of detergents is a superior method for removing Fel d 1 compared with use of soap or water alone.73 It has also been demonstrated that removal of dog allergen from cotton sheets by mechanical washing machines can be highly effective at all temperatures. However, removal is significantly better at high temperature (60o C or 140o F) and when two rinse cycles are used.17 Dry cleaning of woolens significantly reduces Fel d 1 concentrations but does not abolish it entirely, and allergen-free items can actually become contaminated during the dry cleaning process.48

Pet-Directed Interventions It might seem that the most effective pet-directed intervention would be to remove the pet from the household. This recommendation has been part of several interventional studies, and not surprisingly, compliance has been low. Some physicians and public health professionals will also suggest banishing pets to the outdoors, a recommendation that, especially for cats, is unacceptable to

most veterinarians and pet owners. In addition, time spent indoors does not correlate with Fel d 1 levels in reservoir house dust.58 Also, it is known that some degree of cross-reactivity occurs between canine and feline dander allergens, and there is a high prevalence of human co-sensitization to dogs and cats.45,53,63,64 Finally, although removal of a pet is likely to reduce the overall allergen burden in a home, levels still may not fall below the sensitization or elicitation thresholds. In light of these facts, studies have been performed to assess the utility of pet bathing in reducing allergen burden. For both dogs and cats, bathing removes significant amounts of allergen from the pet, but it must be performed at least twice weekly to maintain a relevant reduction.9,36 For dogs this regimen achieves only a modest reduction of Can f 1 in room air.36 Commercial products Allerpet/C (for cats) and Allerpet/D (for dogs) (Allerpet, New York), available as shampoos and as moistened wipes for cats, claim to substantially reduce the quantity of pet-related allergens in the home. However, an evaluation study showed that Allerpet/C solution removed significantly less allergen than submersion in water and no more allergen than application of damp towels.59 Perhaps the most prevalent, but essentially irrelevant, question presented to veterinary health care professionals in relation to human allergies of pet origin is, which breed or hair coat type will be “hypoallergenic”? The widely held assumption that breeds that shed less produce less allergen has been disproved for dogs, and coat length of cats was not correlated with reservoir dust levels in homes.56 Recently, Allerca Lifestyle Pets (San Diego, California) has produced and marketed so-called hypoallergenic cats. These have been developed not through genetic engineering but rather by natural breeding of individuals deficient in Fel d 1 as a result of putative gene mutations. Although no refereed scientific reports have surfaced to date, the company offers many testimonials from satisfied clients and claims that blinded clinical trials conducted by a reputable allergist have proven efficacy (http://www.allerca.com; accessed December 31, 2009). Clearly, this is not a public health solution (especially at a price ranging from $6950 to $27,000 for a cat), but from a personal health perspective, it could be a welcome solution for individuals who are symptomatic only with direct pet exposure. However, as discussed previously, Fel d 1 is not the only dander allergen recognized by all cat-allergic people, so it is conceivable that these purpose-bred pets will not provide complete benefit for affected people. The human–animal bond is an undeniable facet of human health, both psychiatric and physical,35 and it is clear that pets are in our hearts and homes to stay. Despite significant advances in understanding of the epidemiology and immunology of pet dander allergies

over the past two decades, little progress has occurred in mitigating this problem on a population-wide basis. Fortunately, medical therapies for use on an individual basis have improved significantly over this same time frame,5 although access to health care remains a major roadblock in many human populations. Considering the sheer magnitude of morbidity that allergic diseases create—especially pediatric asthma—the primary focus for public health professionals, now and in the foreseeable future, should be the elimination of disparities in health care access. As a significant amount of misinformation persists among the general public and human health care providers, the primary role of veterinarians will, for the foreseeable future, continue to be education regarding healthy pet ownership practices.

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Digestive System, Liver, and Abdominal Cavity O U T L I N E Approach to the Vomiting Cat, 426 Step 1: Signalment and Clinical History, 428 Step 2: Physical Examination, 429 Step 3: Blood and Urine Testing, 429 Step 4: Imaging: Ultrasonography and Radiology, 430 Step 5: Intestinal (and Other Organ) Biopsies, 430 Therapeutics for Vomiting and Diarrhea, 431 Nonspecific Supportive Therapies for Vomiting, 431 Targeted Therapies with Specific Indications for Vomiting, 434 Nonspecific Supportive Therapies for Diarrhea, 435 Targeted Therapies with Specific Indications for Diarrhea, 436 Diseases of the Esophagus, 441 Clinical Presentation, 441 Diagnostic Approach, 442 Specific Diseases, 443 Diseases of the Stomach, 450 Clinical Presentation, 451 Specific Diseases, 452 Approach to the Cat with Diarrhea, 459 Overview, 459 Step 1: Signalment and Clinical History, 460 Step 2: Physical Examination, 462 Step 3: Fecal Assessment +/− Culture, 462 Step 4: Blood and Urine Testing, 463 Step 5: Imaging, 465 Step 6: Intestinal (and Other Organ) Biopsy, 465 Diseases of the Intestines, 466 Inflammatory Bowel Disease, 466 Intestinal Neoplasia, 469 Infectious Enteritis, 477 Intestinal Obstruction, 480


Constipation and Megacolon, 484 Anorectal Diseases, 490 Gastrointestinal Parasites, 496 Nematodes, 496 Cestodes, 500 Trematodes, 501 Protozoa, 501 Diseases of the Exocrine Pancreas, 513 Pancreatitis, 513 Pancreatic Cysts, Pseudocysts, and Bladders, 516 Pancreatic Nodular Hyperplasia, 517 Pancreatic Neoplasia, 517 Exocrine Pancreatic Insufficiency, 518 Diseases of the Liver, 522 Clinical Signs, 522 Routine Laboratory Tests, 522 Liver Function Tests, 524 Cholestasis and Icterus, 525 Portal Hypertension and Hepatic Encephalopathy, Ascites, and Acquired Portosystemic Shunting, 526 Miscellaneous Diseases: Hepatobiliary Neoplasia and Amyloidosis, 527 Hepatobiliary Imaging, 528 Liver Histopathology (Aspirates and Biopsies), 529 Therapy of Liver Disease, 530 Summary, 535 Approach to the Cat with Ascites and Diseases Affecting the Peritoneal Cavity, 538 Pathophysiology of Ascites, 538 Clinical Evaluation of Ascites, 538 Fluid Analysis and Classification, 541 Specific Causes of Ascites, 543

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APPROACH TO THE VOMITING CAT Randolph M. Baral Vomiting can be defined as the ejection of part or all of the contents of the stomach and/or upper intestine through the mouth, usually in a series of involuntary spasmodic movements. The disturbances in gastrointestinal (GI) motility are coordinated with respiratory and abdominal muscle contractions and mediated by the central nervous system (CNS). Vomiting begins with retching, a series of brief negative intrathoracic pressure pulses that coincide with positive abdominal contractions. These pressure changes occur as a result of repeated herniations of the abdominal esophagus and cardiac portion of the stomach into the esophagus. During retching, food freely moves back and forth in the esophagus, which is now dilated because of the ingesta. Ultimately, the diaphragm rapidly moves cranially, resulting in positive intrathoracic pressure that leads to expulsion of these contents.12 Vomiting is such an active process that it seems to involve the whole cat, and so it is little wonder that it concerns owners so much. Since vomiting is mediated by the CNS with input and influence from just about anywhere in the body, it is important to summarize this physiology so it can be appreciated when managing clinical cases. Vomiting results from stimulation of the “vomiting center,” which is located in the brainstem; there are four main pathways that stimulate the vomiting center,12 and these are summarized below and in Figure 23-1.

1. Peripheral sensory receptors a. Intraabdominal i. From stomach, intestines, pancreas, liver, peritoneum, kidneys, bladder ii. Via visceral afferent fibers in sympathetic and vagal nerves b. Heart and large vessels i. Via vagus nerve c. Pharynx i. Via glossopharyngeal nerve 2. Bloodborne substances can stimulate the chemoreceptor trigger zone (CTZ). The CTZ lacks a blood-brain barrier so that substances diffuse to it freely. a. Uremia b. Electrolyte imbalances c. Bacterial toxins d. Drugs (e.g., antibiotics, nonsteroidal antiinflammatories, chemotherapeutics) 3. Vestibular input a. Inflammatory processes b. Motion sickness i. Via acoustic nerve 4. Higher CNS centers a. Psychogenic i. Fear, stress, excitement by catecholamine release b. Inflammatory CNS lesions These complex pathways highlight the need to consider the whole cat and not just the cat’s gastrointestinal

FIGURE 23-1 Summary of the main pathways that stimulate the vomiting center.

CHAPTER 23 Digestive System, Liver, and Abdominal Cavity

tract when assessing a cat presenting for vomiting. The approach to managing a cat with vomiting must follow logical steps. When the underlying cause is gastrointestinal disease, a precise diagnosis can only be reached after obtaining biopsy samples. A summary of

diagnostic steps and possible underlying causes is shown in Figure 23-2. The diagnostic steps are 1. Signalment and clinical history 2. Physical examination FIGURE 23-2 Summary of diag-

Vomiting

Well

Check worming status, check teeth; if no specific abnormalities on examination, fast then plain foods

nostic steps and possible underlying causes of vomiting. Unwell

If persistent, follow up as per an unwell cat

Bacterial: Helicobacter, small intestinal bacterial overgrowth (SIBO), Salmonella

Full blood biochemistry, PCV, CBC, urinalysis to distinguish between primary and secondary GI processes

Rehydration and correct electrolyte imbalances

GI panel: Cobalamin, folate, fPLI, fTLI

Viral Primary Gastrointestinal Problem

Obstruction: Foreign body, neoplasia, intussusception, other Inflammation: Dietary, other antigen, idiopathic Parasites: Giardia, ascarids, Ollulanus

Metabolic/Systemic: Heart: heartworm, renal Endocrine: hyperthyroidism, diabetic ketoacidosis

Extra Gastrointestinal Problems

Toxins/Drugs: Chemotherapy, plants (e.g., lily), NSAIDs, antibiotics (e.g., clindamycin, amoxicillin/clavulanate) Other organs: Liver, pancreas, peritonitis (e.g., FIP or bladder rupture), neoplasia Neurological

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Imaging: Radiographs, ultrasound

Biopsy samples: Endoscopy or exploratory laparotomy

Therapeutic trials for inflammatory or infectious causes. Diet: try novel proteins. Treatment trials of antiparasitics/antibiotics: amoxicillin/clavulanate and metronidazole as four-quadrant therapy

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3. Blood and urine testing 4. Imaging (radiography, ultrasonography) 5. Biopsy samples 6. Treat and manage underlying problem The decision to proceed to steps 4 and 5 is based on the assumption that the prior steps have narrowed down the underlying cause as gastrointestinal, pancreatic, or hepatic in origin.

STEP 1: SIGNALMENT AND CLINICAL HISTORY The important aspects of the clinical history are given in Table 23-1. Signalment is important, because younger cats are more likely to have ingested foreign bodies

(though not all older cats have grown out of this habit). Some extragastrointestinal problems, such as hyperthyroidism and renal disease are more likely to occur in older cats. Most texts and references instruct clinicians to distinguish between vomiting and regurgitation, with the latter noted as being quite passive.3,11,12 In practice, it can be hard to make this distinction, because it is the author’s experience that cats with esophageal disease can have quite forceful, spasmodic movements when ejecting ingesta by regurgitation—although it is also possible for regurgitation to be a passive process. Given that the physiology of vomiting, as described above, results in ingesta being forced to and then evacuated from the esophagus, it is hardly surprising that it can resemble regurgitation. Fortunately, regurgitation and esophageal disease do vary from vomiting in other ways! Vomiting

TABLE 23-1 Clinical History for Vomiting Cats Question

Interpretation

Signalment

Younger cats more likely to ingest foreign bodies, hunt prey; older cats more likely to have systemic or chronic diseases

Diet

Regular diet, any dietary change; potential of food intolerance, food hypersensitivity, food sensitivity

Environment

Presence of various plants and foreign bodies, seen with prey, access to toxins; health status of other cats in the household

Duration and frequency

Regular vomiter? Acute versus chronic, and severity

Relationship to eating

Immediately after eating, some gluttonous cats will engorge themselves with a meal and vomit immediately thereafter If greater than 8 hours after eating, implies gastric outlet obstruction or a gastric motility disorder No relationship to eating implies a systemic or metabolic disease

Describe vomiting process

Vomiting (licking lips, salivation, multiple swallowing) versus regurgitation (can be passive but not always); nature of ingesta also helps distinguish

Appearance of vomitus

Blood–gastric mucosal damage, state of digestion, neoplasia, or ulcer Bile: reflux from small intestine, rules out complete pyloric obstruction Parasitism: adults in vomitus (Ollulanus tricuspis, Physaloptera spp.) Food: state of digestion Hair: hairballs, motility disorder Fecal odor: GI obstruction or bacterial overgrowth

Deworming history

Rules in/out GI parasites

Previous illnesses

Organ system affected, recurrence

Current medications

Drug reaction or toxicity

Behavioral changes

Ptyalism or repeated licking lips/swallowing implies nausea Anorexia implies increased severity Hyperactivity suggests hyperthyroidism Star-gazing, unresponsiveness suggests hepatic encephalopathy Polydipsia/polyuria suggests inability to concentrate urine

Co-existing systemic signs

Diarrhea and weight loss are consistent with GI disease (but can also suggest hyperthyroidism) Polydipsia, polyuria, or coughing suggest polysystemic disorders

Adapted from Hall JE: Clinical approach to chronic vomiting. In August JR, editor: Consultations in feline internal medicine, ed 3, Philadelphia, 1997, Saunders, p 63.


is usually preceded by the cat licking its lips, salivating, or making attempts to swallow. Regurgitated ingesta is often in a tubelike structure and if undigested can be covered with frothy saliva. Partially digested food suggests vomitus, and the presence of bile or digested blood confirms this. It is important to determine if the cat vomits regularly. Many owners have seen their cats vomit on a regular basis with no evidence of the cat being unwell, and this is noted frequently in the veterinary literature.3,12 Hairballs can cause gastric irritation, and it may be that eating quickly also stimulates the peripheral sensory receptors that contribute to vomiting. If a cat does vomit regularly, it is important to assess if the cat is presenting for a change in the vomiting pattern (e.g., frequency or timing in relation to eating) and if the cat is unwell in any way, such as anorexia or weight loss. The pattern of vomiting is important in all cases, because cats presenting with acute gastritis usually have a sudden onset of frequent vomiting compared with those with chronic disease processes that may vomit every few days. The timing in relation to eating can be helpful, because the stomach should empty by 6 to 8 hours after a meal; so, vomiting longer than 8 hours after a meal can suggest motility or retention disorders. The description of the vomitus can be helpful. If bile is present, the pylorus is not obstructed; the presence of blood (digested or fresh) indicates ulceration. Hair in the vomitus can indicate hairball gastritis, and the possibility of trichobezoar obstruction should be considered. Access to foreign bodies or toxins is an important aspect of the clinical history. Has the cat been seen playing with an insect, mouse, or other prey? Are there any medications unaccounted for (e.g., a dropped aspirin tablet)? Are lilies present in the house?

STEP 2: PHYSICAL EXAMINATION Vomiting is the major sign of gastric disease, but given the number of potential organ systems that can be involved, a thorough physical examination should be undertaken. Because linear foreign bodies are a common cause of vomiting, all cats presenting for anorexia or vomiting should have the underside of the tongue evaluated for the presence of string caught there. Applying gentle pressure with a thumb in the intermandibular space to elevate the tongue is an effective way to visualize lesions or foreign bodies in the sublingual area (see Figure 3-8). A thorough examination may reveal specific signs, such as a palpable thyroid nodule and tachycardia in the case of hyperthyroidism or palpably small kidneys with

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chronic kidney disease. The author has found that some cats with dental disease can gorge their food, resulting in vomiting; so, paying attention to the state of the teeth and gums is important. Of course, some cats have multiple problems, and correction of dental disease may not resolve vomiting if there is another process. In the examination, it is also important to note consequences of both the underlying process and the vomiting itself; these include the demeanor of the cat, hydration status, and abdominal pain. The physical examination findings, together with the clinical history, help determine the next appropriate steps. Well cats that are not continually vomiting and are appropriately hydrated, with no other specific signs, may be treated as outpatients by fasting them for 24 hours, then returning to food with a bland diet, such as plain cooked chicken or commercial, low-residue prescription diets designed for this purpose. Follow-up is important to ensure signs do not progress. Cats with nonspecific signs may require supportive care with subcutaneous or intravenous fluids and perhaps analgesia (with opioids). If clinical signs do not resolve, the pursuit of a specific diagnosis should be attempted. The practitioner must ask the following important questions: • Are ancillary tests appropriate? • Is supportive care necessary? • Are any medications required?

STEP 3: BLOOD AND URINE TESTING Routine Tests Routine serum/plasma biochemistries, hematology, urinalysis, and total thyroxine (T4) (for older cats) testing is not only important to distinguish primary from secondary gastrointestinal disease but to look for consequences of vomiting that may need to be addressed, such as hydration status and electrolyte abnormalities. Careful interpretations should be made. Severe azotemia, even with hyperphosphatemia, can occur as a result of primary gastrointestinal disease, and the distinction from renal disease usually requires an assessment of urine specific gravity.

Blood Tests for Gastrointestinal Disease Cobalamin, folate, feline trypsin-like immunoreactivity (fTLI), and feline pancreatic lipase immunoreactivity (fPLI) tests are useful markers of intestinal and pancreatic disease,7,8,9,10 but it is important to note that they mostly do not give a precise diagnosis. More detail about the utility of these tests is noted below in the section Approach to the Cat with Diarrhea.

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STEP 4: IMAGING: ULTRASONOGRAPHY AND RADIOLOGY Radiography is most useful for identifying foreign bodies or signs of intestinal obstruction from other causes. The major findings are noted below in the section Intestinal Obstruction. Contrast radiography can aid the diagnosis for both discrete and linear foreign bodies but should be used with caution, because intestinal perforation may be present. Nonionic iodinated agents that are typically used for myelography (such as iopamidol or iohexol) should be used, since barium irritates the peritoneum and oral iodine compounds are hypertonic. Hypertonic compounds may draw fluid into the stomach and intestines after oral administration, with the potential of creating further fluid and electrolyte imbalances in an already compromised patient.6 Ultrasonography is a useful diagnostic adjunct and helps to detect and characterize localized thickening of the stomach or intestinal wall, lymphadenopathy, radiolucent foreign bodies, and changes in the size and echogenicity of the pancreas, liver, kidneys, or spleen. Abdominal effusions can be assessed and sampled. Ultrasound-guided fine-needle aspiration can be used to sample masses, bile, or peritoneal fluid. It should be recognized that in most cases of gastrointestinal disease, imaging will not give a definitive diagnosis and biopsy will be required, usually using either endoscopy or laparotomy. Ultrasonography can be a considered as a means to “survey the field,” assessing • The nature of the underlying disease, such as • Thickened intestines with or without discrete layers • Lymph node involvement • Other organ involvement • The location of disease, for example, • Diffuse or focal • Proximal duodenum (reachable by endoscope) versus distal ileum These factors may be used to assess the appropriateness of endoscopy versus laparotomy to obtain diagnostic samples.

STEP 5: INTESTINAL (AND OTHER ORGAN) BIOPSIES Histologic evaluation of affected tissue is usually needed for diagnosis of most chronic gastrointestinal diseases. Intestinal biopsy samples can be obtained by the use of endoscopy, laparotomy, or laparoscopy, each of which has advantages and disadvantages. Laparotomy allows gross examination of and access to the entire intestinal tract as well as other abdominal organs. Laparotomy is the most invasive alternative, but with careful anesthesia

and analgesia, many cats recover uneventfully. One survey assessed that 83% of cats undergoing exploratory laparotomy survived the hospitalization, and although complications occurred in 26% of cats, these were more likely to be associated with the underlying disease process and not surgery or anesthesia.4 Laparoscopy is not readily available in all veterinary clinics. This alternative is less invasive and allows exploration of the abdomen but not as thoroughly as with laparotomy. Organs are usually exteriorized for biopsy. There is the possibility of anesthetic complications associated with insufflating the abdomen. Endoscopy is the least invasive procedure and is the only alternative that allows examination of the intestinal lumen. This option limits the parts of the gastrointestinal tract that can be biopsied; it does not allow examination or sampling of any other part of the gastrointestinal tract and does not enable full-thickness biopsy samples. One study found that, of cats investigated for gastrointestinal disease, 9 of 33 cats (27%) had no pathology recognized proximal to the jejunum (i.e., the effective length of diagnostic endoscopes would have precluded diagnosis), and other organs were affected in 9 of 10 cats with inflammatory bowel diseases and 7 of 8 cats with intestinal small cell lymphoma.1 Careful case selection for endoscopy from survey ultrasonography can reduce the number of missed diagnoses from endoscopy, but the possibility still remains. The quality of endoscopically obtained biopsy samples varies greatly with the skill of the endoscopist. It has been stated that “it is exceedingly easy to take inadequate tissue samples with a flexible endoscope.”5 In an assessment of endoscopically obtained biopsy samples, two laboratories were compared, one that received samples from any practitioner and the other that received samples ONLY from practitioners trained to take, mount, and submit endoscopy samples. All slides were reviewed by three pathologists who found that, of samples from the first laboratory, 15% of the slides were considered inadequate for diagnosis, 71% were considered questionable, and only 14% were adequate. By comparison, in the second laboratory (with samples from experienced practitioners) 0% of slides were inadequate, 21% were questionable, and 79% were considered adequate for diagnosis.13 In the case of distinguishing between lymphocytic intestinal infiltrates (commonly known as inflammatory bowel disease) and lymphocytic neoplasia (small cell lymphoma), endoscopically obtained samples can give an incorrect diagnosis.2 Many of these problems can be minimized with experienced operators and careful case selection from prior ultrasonography.

References 1. Baral RM: Laparotomy for gastro-intestinal biopsies, Science Week Conference Proceedings (Small Animal Medicine chapter), Gold


2.

3.

4. 5. 6. 7.

8.

9.

10. 11. 12.

13.

Coast, Queensland, Australia, 2006, Australian College of Veterinary Scientists, p 70. Evans SE, Bonczynski JJ, Broussard JD et al: Comparison of endoscopic and full-thickness biopsy specimens for diagnosis of inflammatory bowel disease and alimentary tract lymphoma in cats, J Am Vet Med Assoc 229:1447, 2006. Hall J: Clinical Approach to chronic vomiting. In August J, editor: Consultations in feline internal medicine, ed 3, Philadelphia, 1997, Saunders, p 61. Lester S, Welsh E, Pratschke K: Complications of exploratory coeliotomy in 70 cats, J Small Anim Pract 45:351, 2004. Mansell J, Willard MD: Biopsy of the gastrointestinal tract, Vet Clin North Am Small Anim Pract 33:1099, 2003. Shaiken L: Radiographic appearance of linear foreign bodies in cats, Vet Med 94:417, 1999. Simpson KW, Fyfe J, Cornetta A et al: Subnormal concentrations of serum cobalamin (vitamin B12) in cats with gastrointestinal disease, J Vet Intern Med 15:26, 2001. Steiner JM, Williams DA: Serum feline trypsin-like immunoreactivity in cats with exocrine pancreatic insufficiency, J Vet Intern Med 14:627, 2000. Steiner JM, Wilson BG, Williams DA: Development and analytical validation of a radioimmunoassay for the measurement of feline pancreatic lipase immunoreactivity in serum, Can J Vet Res 68:309, 2004. Suchodolski JS, Steiner JM: Laboratory assessment of gastrointestinal function, Clin Tech Small Anim Pract 18:203, 2003. Tams TR: A diagnostic approach to vomiting in dogs and cats, Vet Med 87:785, 1992. Twedt DC: Diseases of the stomach. In Sherding RG, editor: The cat: clinical diseases and management, ed 2, New York, 1994, Churchill Livingstone, p 1181. Willard MD, Lovering SL, Cohen ND et al: Quality of tissue specimens obtained endoscopically from the duodenum of dogs and cats, J Am Vet Med Assoc 219:474, 2001.

THERAPEUTICS FOR VOMITING AND DIARRHEA Katrina R. Viviano Therapeutic strategies used in the treatment of feline gastrointestinal diseases include nonspecific supportive therapies and targeted therapies based on the primary underlying disease process identified. The most effective therapies for treating feline vomiting and diarrhea are those directed at treating the primary underlying disease process. However, symptomatic supportive care is often necessary prior to arriving at a definitive diagnosis at the onset of targeted therapy or during periods of clinical relapse.

NONSPECIFIC SUPPORTIVE THERAPIES FOR VOMITING Antiemetics and Prokinetics Antiemetics and prokinetics are used to control or prevent vomiting through specific receptor interactions mediated either centrally or peripherally, making some more effective in cats than others. The five

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most commonly used antiemetics all control vomiting by different mechanisms and include mirtazapine, metoclopramide, dolasetron/ondansetron, maropitant, and the phenothiazines (Tables 23-2 and 23-3). Metoclopramide functions both as an antiemetic and prokinetic in cats, while cisapride functions solely as a prokinetic. Mirtazapine Mirtazapine, a piperazinoazepine, antagonizes the presynaptic alpha2-adrenergic receptor, increasing noradrenergic and serotonergic neurotransmission; the primary mechanism targeted for its use is as an antidepressant in humans. Mirtazapine is also a potent antagonist of the postsynaptic serotonergic receptors (5-HT2 and 5-HT3) and histamine H1 receptors. Because of its antiserotonergic and antihistaminic effects, mirtazapine is used as an entiemetic and appetite stimulant in cats. Anorexia is a common clinical problem in ill cats, and in some anorexic or partially anorexic cats the use of an appetite stimulant as adjunctive therapy to nutritional support (i.e. feeding tubes) may be of clinical benefit. Prior to the development of mirtazapine, cyproheptadine was used as an appetite stimulant in cats, with variable clinical results. Recently, the pharmacokinetics and pharmacodynamics of mirtazapine have been reported in cats. In a group of healthy cats, mirtazapine was found to be an effective appetite stimulant, with a shorter half-life than that reported in humans. The recommended oral dose is 1.88 mg/cat every 48 hours.55a In humans, age and kidney and liver dysfunction affect mirtazapine metabolism (hepatic CYP 450 enzymes) and clearance (excreted in urine and feces), suggesting that dose adjustment may be necessary.69a Side effects reported in cats treated with mirtazapine include behavior changes (vocalization and interaction), tremors, muscle twitching, and hyperactivity.9a,55a Metoclopramide Metoclopramide is both an antiemetic and prokinetic drug that acts peripherally on the gastrointestinal tract and centrally within the central nervous system (CNS). At low doses metoclopramide inhibits dopaminergic (D2) transmission, and at higher doses it inhibits serotonergic 5-HT3 receptors in the chemoreceptor trigger zone (CRTZ).15,23 Metoclopramide also acts peripherally as a prokinetic at the level of the gastrointestinal smooth muscle of the stomach and duodenum, triggering gastric emptying and duodenal contractions. Multiple mechanisms mediate metoclopramide’s prokinetic activity, including augmentation of acetylcholine release and increased smooth muscle sensitivity to cholinergic neurotransmission, which may in part be because of antagonism of dopamine, but more recently, serotonergic 5HT4 receptor activation has been suggested.23,56 Metoclopramide has been reported to increase the lower

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TABLE 23-2 Mechanism of Action and Adverse Effects of the Common Antiemetic and Prokinetic Drugs Used to Treat Vomiting in Cats Drug

Mechanism of Action

Adverse Effects

Metoclopramide (antiemetic and prokinetic)

D2 antagonism 5-HT3 antagonism 5-HT4 agonist

Extrapyramidal signs

Dolasetron (antiemetic) Ondansetron (antiemetic)

5-HT3 antagonism

Prolongation QT interval Arrhythmias

Maropitant (antiemetic)

NK-1 antagonist

Phenothiazines (antiemetic) Prochlorperazine Chlorpromazine

D2 antagonism H1, H2 antagonism Cholinergic antagonism alpha1, alpha2 antagonism

Extrapyramidal signs Sedation Decreases seizure threshold Hypotension

Cisapride (prokinetic)

5-HT4 agonist

Prolongation QT interval Arrhythmias

Mirtazapine (appetite stimulant and antiemetic)

5-HT2 , 5-HT3 antagonism H1 antagonism

Behavior changes Tremors, muscle twitching Hyperactivity

TABLE 23-3 Dosage Recommendations, Contraindications, Potential Drug Interactions, and Clinical Indications for Dosage Adjustments for the Common Antiemetic and Prokinetic Drugs Used to Treat Vomiting in Cats C: Contraindications DI: Drug Interactions DA: Dosage Adjustments

Drug

Dosage (Cats)

Metoclopramide

0.2-0.4 mg/kg SC, PO q8h 1-2 mg/kg/day CRI

C: GI obstruction DI: Phenothiazines: extrapyramidal signs DA: Azotemia

Dolasetron Ondansetron

0.5-1.0 mg/kg IV, SC, PO q12-24h 0.22-0.5 mg/kg IV, PO q8-12h

DI: Cisapride: prolonged QT interval and arrhythmias

Maropitant

1 mg/kg IV, SC, PO q24h (up to 5 days)

Phenothiazines prochlorperazine chlorpromazine

0.2-0.4 mg/kg SC q8h

C: Dehydration; hypotension; seizure hx DI: Metoclopramide: extrapyramidal signs

Cisapride

1.5 mg/kg PO q12h

C: GI obstruction DI: Dolasetron: prolonged QT interval and arrhythmias; azole antifungals: inhibition CYP3A isoenzyme

Mirtazapine

1.88 mg/cat PO q48h

DI: Concurrent administration with other MAO inhibitors (i.e., selegiline, amitraz, tramadol, amitriptyline, clomipramine) and/or SSRIs (i.e., fluoxetine) contraindicated DA: Kidney or liver dysfunction

CRI, Constant rate infusion; hx, history.

esophageal sphincter tone in humans,20 although in cats metoclopramide’s affect on the lower esophageal sphincter is reported to be weak.32 Adverse central nervous system, extrapyramidal signs occur secondary to dopamine (D2) antagonism, including excitement and behavior changes. Extrapyramidal signs are most often seen at the higher doses needed to block 5-HT3 receptors. Because of metoclopramide’s prokinetic properties, an intestinal obstruction should be ruled out prior to its use.

Dopamine is a less important neurotransmitter in the chemoreceptor trigger zone of cats than alpha2adrenergic and 5-HT3-serotonergic receptors, suggesting that D2-dopaminergic antagonist may be a less effective antiemetic in cats. Clinically metoclopramide com monly controls vomiting in cats, although this clinical response may be secondary to 5-HT3 antagonism and/ or its prokinetic effects.32,44 Extrapolated from the short elimination half-life of metoclopramide in dogs (90 minutes), frequent

intermittent dosing or delivery by a constant rate infusion (CRI) is necessary. Empirical dosing in cats is 0.2 to 0.4 mg/kg subcutaneously or orally every 8 hours or 1 to 2 mg/kg/day as a CRI. Approximately 25% of metoclopramide is excreted in the urine, thus dose reduction is recommended in cats with underlying renal azotemia.42 Dolasetron and Ondansetron Dolasetron and ondansetron are selective serotonin antagonists that inhibit central and peripheral 5-HT3 receptors. Their main antiemetic effect is through antagonism of the peripheral 5-HT3 receptors in the gastrointestinal tract. In cats 5-HT3 antagonism of the CRZT is also likely important in the antiemetic effect of dolasetron and ondansetron. Dolasetron and ondansetron were originally used for vomiting secondary to chemotherapy because of their superior clinical efficacy. The clinical use of dolasetron and ondansetron in cats has not been associated with reported side effects, and experimental studies report minimal toxicity in animals at doses 30 times the antiemetic dose.15 Side effects reported in humans include headaches, elevated liver enzymes, rare hypersensitivity reactions, prolongation of the QT interval, and arrhythmias.14,24 Dolasetron is commonly used for parenteral administration and ondansetron for oral administration, dictated primarily based on the tablet sizes available and cost. Recommended dosing of dolasetron is 0.5 to 1 mg/kg intravenously every 24 hours and ondansetron 0.5 mg/ kg orally every 12 hours. Maropitant Maropitant is a neurokinin-1 (NK-1) receptor antagonist, blocking the binding of substance P to the NK-1 receptors located in the emetic center, CRTZ, and the enteric plexus.55 In cats maropitant has been reported to be efficacious in treating xylazine-induced vomiting and motion sickness.31 Recommended dosing in cats is 1 mg/ kg intravenously, subcutaneously or orally every 24 hours for up to 5 days.31 Maropitant is reported to be well tolerated in cats. Phenothiazines Prochlorperazine and chlorpromazine are considered broad-spectrum antiemetics by antagonism of D2dopaminergic, histaminergic (H1 and H2), and cholinergic (muscarinic) receptors within the CRTZ and, at high doses, the alpha-adrenergic receptors (alpha1 and alpha2) within the vomiting center. In cats alpha2-receptors play a key role in emesis (recall xylazine is the emetic of choice in cats), suggesting cats may be more sensitive to the antiemetic effects of the phenothiazines. Prochlorperazine and chlorpromazine produce an antiemetic effect at relatively low doses, thus avoiding profound sedation; although, because of antagonism of the alpha-receptors, vasodilation and hypotension can


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be clinically significant side effects. Phenothiazines have the potential to lower the seizure threshold; their use is not recommended in patients with a known seizure history. Other CNS-associated side effects linked to D2 antagonism occur at higher doses and produce extrapyramidal signs, including rigidity, tremors, weakness, and restlessness. Antagonism of the histaminergic receptors carries the risk of sedation. Because of the need for frequent dosing (0.2 to 0.4 mg/ kg subcutaneously every 8 hours) and the risk of hypotension and sedation, the clinical use of phenothiazine antiemetics is limited to hospitalized patients with refractory vomiting and should be avoided in patients who are dehydrated or hypotensive. Cisapride Cisapride is a serotonergic 5-HT4 agonist that increases propulsive gastrointestinal motility from the lower esophageal sphincter to the colon. Cisapride binds serotonergic 5-HT4 receptors in the myenteric plexus, increasing the release of acetylcholine in gastrointestinal smooth muscle. In dogs cisapride has greater prokinetic activity in the stomach relative to metoclopramide.29 Cisapride has no direct antiemetic effect, although it is indicated in a vomiting cat with colonic dysmotility secondary to megacolon. Colonic distention can trigger the vomiting reflex in cats. Cisapride induces colonic smooth muscle contractions in cats with megacolon that is dependent on the influx of extracellular calcium and is only partially cholinergic dependent.30 Other potential indications include refractory generalized ileus or gastroesophageal reflux. Dosage recommendations based on the pharmacokinetics in healthy cats is 1.5 mg/kg orally every 12 hours.41 Prior to the use of cisapride, an intestinal obstruction should be ruled out because of its strong prokinetic effects. Side effects reported in humans are cramping and diarrhea. Potentially life-threatening side effects include QT prolongation and ventricular arrhythmias, the primary concern in humans that led to cisapride’s removal from the market in the United States.47 In cats QT prolongation associated with cisapride administration requires 20 times the therapeutic dose.37 Because of the risk of prolongation of the QT interval and ventricular arrhythmias, the concurrent use of cisapride and dolasetron is not recommended.14 Other potential drug interactions associated with cisapride include concurrent therapy with azole antifungals (ketoconazole and itraconazole), because of their inhibition of hepatic CYP3A isoenzyme system and the inhibition of cisapride metabolism.47

Dietary Modification Diet trials are commonly used in cats with idiopathic gastrointestinal signs or in cats with suspected or known

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food hypersensitivities. Dietary strategies used to control vomiting in cats focus on either a highly digestible diet or an elimination (novel protein/carbohydrate or hydrolyzed protein) diet.72 The empirical use of elimination diets in cats is reported to be relatively successful, with approximately 50% of cats with idiopathic gastrointestinal signs responsive to a novel protein/carbohydrate diets within 2 to 3 days.28 Interestingly, traditional diet trials are recommended for a minimum of 8 to 12 weeks, but in this group of diet-responsive cats with chronic gastrointestinal disease, clinical improvement was reported within days.28 Thus if a cat is going to be diet responsive, clinical improvement to a diet trial should be noted relatively early. Highly Digestible Diets Highly digestible diets enable more effective absorption and assimilation of nutrients in the face of a compromised digestive tract. These diets contain highly digestible proteins and carbohydrates, moderate to low fat, soluble fiber but low concentrations of insoluble fiber, and are supplemented with omega-3 fatty acids. Novel Protein/Carbohydrate or Elimination Diets These diets are recommended when food allergy or intolerance is suspected. These diets contain a single highly digestible novel carbohydrate source and novel protein source. Alternatively, diets formulated with hydrolyzed proteins can be used as an alternative to novel protein/carbohydrate diets.

TARGETED THERAPIES WITH SPECIFIC INDICATIONS FOR VOMITING Gastrointestinal Ulcers See Tables 23-4 and 23-5 for information on gastrointestinal ulcers. Famotidine Famotidine has no direct antiemetic effect but is a competitive inhibitor of the histamine (H2) receptors associated with the gastric parietal cells. The H2-receptor is the dominant receptor involved in gastric acid secretion. H2receptor antagonism is reported to result in a 70% to 90% reduction in acid production.13 Famotidine is more effective at suppressing gastric acid secretion relative to ranitidine. Famotidine is well tolerated, although, with chronic therapy, there is the potential for hypoacidity and gastric bacterial overgrowth. In humans dose reduction is recommended in association with renal dysfunction.21 Famotidine is not an inhibitor of the hepatic microsomal cytochrome P-450 enzyme system, therefore significant drug interactions are not anticipated.

TABLE 23-4 Mechanism of Action and the Adverse Effects of the Common Drugs Used to Treat Gastric Ulcers in Cats Drug

Mechanism of Action

Famotidine (increases gastric pH)

H2 antagonism

Ranitidine (increases gastric pH) (prokinetic)

H2 antagonism Anticholinesterase

Omeprazole (increased gastric pH)

H+/K+ ATPase inhibitor

Sucralfate (gastric ulcer healing)

Prevents H+ back diffusion, inactivates pepsin, absorbs bile acids, and increases gastric mucosal prostaglandin synthesis

Adverse Effects

Hypotension (IV)

TABLE 23-5 Dosage Recommendations, Contraindications, Potential Drug Interactions, and Clinical Indications for Dosage Adjustments for the Common Drugs Used to Treat Gastric Ulcers in Cats C: Contraindications DI: Drug Interactions DA: Dosage Adjustments

Drug

Dosage (Cats)

Famotidine

0.5 mg/kg IV, SC, PO q12-24h

DA: azotemia

Ranitidine

2.5 mg/kg IV q12h 3.5 mg/kg PO q12h

DA: azotemia

Omeprazole

0.5-1 mg/kg PO q24h

DI: inhibition CYP2C: diazepam Do not crush enteric coated tablets

Sucralfate

250 mg PO q12h

DI: decreases oral absorption of fluoroquinolones, tetracyclines, and digoxin

Hyperacidity alone is not considered a common cause for vomiting in cats, but famotidine is effective in treating vomiting in cats associated with gastric ulcers or gastritis. Recommended dosage in cats is 0.5 mg/kg every 12 to 24 hours. Ranitidine Ranitidine is also a competitive inhibitor of the H2 receptor associated with gastric parietal cells. In addition, ranitidine increases lower esophageal sphincter tone and functions as a prokinetic agent (increasing gastric emptying and stimulating intestinal motility, including colonic motility), because of its anticholinesterase

activity.40,54 Significant drug interactions associated with hepatic microsomal cytochrome P-450 enzyme system inhibition are not a clinical concern with ranitidine.46 An adverse effect to be aware of in cats treated with ranitidine is transient hypotension associated with ranitidine administered as an IV bolus.19 In humans dose reduction is recommended in patients with renal azotemia.39 Ranitidine is effective in decreasing gastric acid in cats.22 Ranitidine would be a logical choice in a cat with gastrointestinal ulceration and/or atony. The reported dosage recommendation for ranitidine in cats is 3.5 mg/ kg orally every 12 hours or 2.5 mg/kg intravenous every 12 hours.19 Omeprazole Omeprazole is a proton pump inhibitor that targets the H+/K+ ATPase pump on the luminal surface of partial cells. Omeprazole is effective at suppressing parietal cell acid secretion, and its effects persist for ≈24 hours after drug withdrawal because of drug accumulation in the parietal cell (by ion trapping). Indications for omeprazole therapy are for the treatment and prevention of nonsteroidal antiinflammatory drug (NSAID)–induced ulcers.9 Omeprazole is enteric coated to prevent its degradation by gastric acid; therefore oral formulations should not be crushed. Based on human studies, omeprazole is a hepatic microsomal cytochrome P-450 enzyme inhibitor with known drug interactions with diazepam.2 The extent of clinically significant drug interactions in cats has yet to be studied. Omeprazole is reported to be effective in reducing gastric acid secretion in cats.22 The recommended empirical dosage in cats is 0.5 to 1 mg/kg orally once daily. Long-term use in humans33 and dogs11 is associated with gastric polyps and parietal cell hyperplasia, respectively, but the effect of long-term use in cats is currently unknown. Sucralfate Sucralfate is a disaccharide complexed with aluminum that dissociates to sucrose octasulfate and aluminum hydroxide upon exposure to gastric acid. The sucrose octasulfate spontaneously polymerizes, producing a viscous material capable of binding ulcerative lesions in the gastric mucosa. Once bound to the exposed mucosa, it prevents back diffusion of H+, inactivates pepsin, absorbs bile acids, and increases mucosal prostaglandin synthesis, collectively supporting ulcer healing. Sucralfate is not systemically absorbed but does prevent the absorption of drugs capable of chelating with aluminum, including fluoroquinolones, tetracyclines, and digoxin. If sucralfate is indicated in a cat being treated concurrently with fluoroquinolones, tetracyclines, or digoxin, the recommendation is to administer the other drug 2 hours prior to the administration of sucralfate to optimize drug absorption.


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Clinical indications for the use of sucralfate in cats are for the treatment of gastric ulcers and esophagitis.36 Dosage recommendation in cats is 250 mg orally every 12 hours. Sucralfate can be crushed, suspended in water, and administered as slurry.

NONSPECIFIC SUPPORTIVE THERAPIES FOR DIARRHEA Dietary Modification Diet trials are used in some cats with diarrhea if the underlying cause is from known or suspected food hypersensitivities. Dietary management includes either a highly digestible diet, an elimination (novel protein/ carbohydrate or hydrolyzed protein) diet (see above for both), or a diet high in fiber.72 High-Fiber Diets High-fiber diets contain a mixture of both soluble and insoluble fiber that can be beneficial in patients with signs of large bowel diarrhea. Insoluble fiber, such as cellulose, functions to increase the bulk of the stool, bind fluid, and regulate intestinal motility. Soluble fiber, including fruit and vegetable pectins and beet pulp, functions as a source of butyric acid that can be used by the colonic mucosa and decreases proinflammatory cytokines.69,72

Vitamin Supplementation Cobalamin Cobalamin (vitamin B12) is an essential vitamin needed by a number of different enzymes, including key enzymes involved in methionine metabolism and the conversion of methylfolate to tetrahydrofolate needed for DNA synthesis. Cobalamin and folate are intimately linked, and hypocobalaminemia can lead to a functional deficiency of folate.57 Ingested cobalamin requires intrinsic factor binding for enterocyte absorption at the level of the ileum. Hypocobalaminemia is commonly associated with distal small intestine diseases in cats, including inflammatory bowel disease. In addition, low cobalamin has a negative impact on enterocyte function; therefore in many cats with intestinal disease and hypocobalaminemia, cobalamin supplementation is necessary for resolution of clinical signs.60,64 Quantification of serum cobalamin levels is recommended in cats with clinical signs of small bowel diarrhea, ones suspected to have an infiltrative disease of the small intestine (inflammatory bowel disease or gastrointestinal lymphoma), or ones with pancreatic dysfunction. When hypocobalaminemia is identified, supplementation is recommended

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(250 µg/cat every 7 days) while the underlying cause of cat’s malabsorption is being investigated and at initiation of targeted therapy.

Probiotics and Prebiotics Probiotics Probiotics are ingested live microorganisms intended to benefit the host, specifically to support the microflora environment of the gastrointestinal tract as well as to provide an overall benefit to the body’s immune function by immunomodulation.8,18,51 Probiotics chemically modify ingesta and intestinal mucus, as well as affect immune cells, enterocytes, and goblet cells within the intestinal mucosa through direct receptor interactions and indirectly through the action of cytokines. The microorganisms commonly used are nonpathogenic bacteria and yeast that have a vital role in gastrointestinal health, including Lactobacillus spp., Enterococcus faecium, Bifidobacterium spp., and Saccharomyces spp. For example, lactobacilli synthesize B vitamins, digestive enzymes, and folate coenzymes.63 Clinical indications for the use of probiotics are diverse, including primary gastrointestinal disease, chronic renal disease, and pancreatitis.71 The rational use of probiotics in the treatment of gastrointestinal diseases include their ability to modulate gastrointestinal flora, minimize colonization by pathogenic bacteria, and decrease the likelihood of bacterial translocation.17 In healthy cats, Lactobacillus acidophilus is reported to reduce fecal Clostridium counts.45 When Lactobacillus acidophilus was used adjunctively with antimicrobial therapy, fecal shedding of Campylobacter was reduced in cats with Campylobacter-induced diarrhea relative to cats treated with antimicrobials alone.3 Specifically, in cats with gastrointestinal disease, available research supports the probiotic Enterococcus faecium as clinically beneficial in resolving diarrhea in kittens.16 Relative to the control group, the kittens treated with probiotics had increased fecal Bifidobacteria and blood IgA concentrations and decreased fecal counts of Clostridium perfringens. Prebiotics Prebiotics are dietary supplements used to select for the more beneficial enteric flora, support gastrointestinal function, and prevent the overgrowth of pathogenic bacteria, including Salmonella, Escherichia coli, Clostridium, or Campylobacter. For a food additive to be considered a prebiotic, it must be nondigestible by the gastrointestinal tract (resistant to gastric acidity, gastrointestinal hydrolysis and absorption), yet fermentable by gastrointestinal microflora to short-chain fatty acids to stimulate the growth of “good” intestinal bacterial.72 Prebiotics include nondigestible oligosaccharides— commonly, oligofructose, fructo-oligosaccharides,

mannanoligosaccharides, inulin, chicory, and lactosucrose.72 Reports on the use of prebiotics in cats are limited to their use in healthy cats; healthy cats fed fructooligosaccharides were reported to have a trend toward an increase in fecal concentrations of Lactobacilli and a decrease in concentration of C. perfringens and E. coli relative to the controls.65 To date no reports are available on the use of prebiotics in cats with gastrointestinal disease. Probiotics and prebiotics potentially have a supportive role in the treatment of gastrointestinal disease in cats. The important clinical consideration in the use of probiotics as an adjunctive therapy is to ensure the use of live nonpathogenic microorganisms that have been documented to colonize the intestinal tract of cats. Gastrointestinal flora co-evolve with their host. Gastrointestinal microorganism colonization varies among species and within each individual animal. The distribution of fecal microflora for a given individual is considered unique but stable over time.68

TARGETED THERAPIES WITH SPECIFIC INDICATIONS FOR DIARRHEA Antimicrobials and Antiparasitics Antimicrobial and antiparasitic therapies for the treatment of feline diarrhea are indicated based on the specific diagnosis of infectious diarrhea, bacterial enteritis, or as adjunctive therapy for inflammatory bowel disease. Infectious pathogens more commonly associated with feline diarrhea include bacterial enteropathies (Clostridium, Campylobacter), protozoal enteropathies (Tritrichomonas foetus, Giardia spp.), and helminthic enteropathies associated with ascarids, hookworms, whipworms, and tapeworms. Only the more common anthelminthic, antimicrobial, and antiprotozoal therapies are discussed below (Tables 23-6 and 23-7). More information about antimicrobials and antiparasitics is found under specific infections in the discussions of Infectious Enteritis and Gastrointestinal Parasites. Fenbendazole Fenbendazole is an anthelmintic used to treat common helminth infections, including ascarids, hookworms, whipworms, and a single species of tapeworm, Taenia pisiformis. Giardia spp. are also considered susceptible to fenbendazole. Fenbendazole binds beta-tubulin subunits of microtubules, interfering with their polymerization. Side effects include vomiting and diarrhea, although both are considered rare. Fenbendazole is not approved for use in cats in North America but is commonly used clinically, and an empirical dosage of 50 mg/kg


437

TABLE 23-6 Mechanism of Action and Adverse Effects of the Common Antimicrobials and Antiparasitics Used to Treat Specific Causes of Diarrhea in Cats Drug

Mechanism of Action

Adverse Effects

Fenbendazole (anthelmintic)

Binds microtubule beta-tubulin subunits preventing polymerization

Vomiting Diarrhea

Pyrantel pamoate (anthelmintic)

Targets nicotinic acetylcholine receptors of parasites: depolarization and spastic paralysis

Metronidazole (antimicrobial)

Anaerobic environment: converted to unstable intermediates that disrupt bacterial DNA synthesis

Inappetence, anorexia Nausea, vomiting Hypersalivation Cerebellovestibular ataxia

Ronidazole (antimicrobial)

Anaerobic environment: converted to unstable intermediates that disrupt bacterial DNA synthesis

Hepatotoxicity Neurotoxicity

TABLE 23-7 Dosage Recommendations and Spectrum of Activity of the Common Antimicrobial and Antiparasitic Drugs Used to Treat Specific Causes of Diarrhea in Cats Drug

Dosage (Cats)

Spectrum

Fenbendazole

50 mg/kg PO every 24h × 5 days

Ascarids, hookworms, whipworms, Taenia pisiformis

Pyrantel pamoate

5 mg/kg PO once, repeat in 3 weeks

Ascarids, hookworms, Physaloptera

Metronidazole Metronidazole benzoate

10-15 mg/kg/day 20 mg/kg/day

Anaerobes, Giardia spp.

Ronidazole

30 mg/kg PO q24h

T. foetus

orally every 24 hours for 5 consecutive days is recommended. Pyrantel Pamoate Pyrantel pamoate is a nicotinic anthelmintic used primarily for the treatment of ascarids, but its spectrum of activity also includes hookworms and the stomach worm, Physaloptera spp. Pyrantel is toxic to susceptible parasites through its selective action on their nicotinic acetylcholine receptors, resulting in depolarization and spastic paralysis. Pyrantel is not approved for use in cats but is considered safe in cats and is commonly used clinically. The dosage recommendation in cats is 5 mg/ kg orally once, repeat in 3 weeks, and finally repeated in 3 months. Metronidazole Metronidazole is a nitroimidazole antibiotic with an anaerobic antibacterial spectrum with antiprotozoal activity against Giardia spp. In an anaerobic environment, metronidazole is converted to unstable intermediates (nitroso free radicals) that disrupt bacterial DNA synthesis. Immunomodulatory properties capable of inhibiting cell-mediated immunity have been described

for metronidazole, although its immunomodulatory properties are reported at dosages well beyond what is recommended for clinical use,62 raising questions about the clinical use of metronidazole as an adjunctive therapy for treating inflammatory bowel disease.34,43 Resistance to metronidazole is considered rare.43 The most common adverse reaction is gastrointestinal upset, including inappetence, anorexia, nausea, and vomiting. Profuse salivation can occur in cats after oral administration of metronidazole base (formulation used in standard tablets), which has lead to the use of metronidazole benzoate (a compounded formulation not approved by the Food and Drug Administration) in some cats because of its better oral palatability.61 At high doses (>200 mg/ kg/day) benzoic acid is reported to be neurotoxic in cats, but with appropriate clinical dosing of metronidazole benzoate benzoic acid toxicity is unlikely.6 Dose-related metronidazole toxicity in cats results in cerebellovestibular ataxia secondary to gamma-aminobutyric acid (GABA) inhibition at dosages greater than or equal to 58 mg/kg/day12,52; clinical signs include nystagmus, head tilt, ataxia, seizures, and obtundation. In cats with inflammatory bowel disease, the dosage recommendation for the metronidazole base is 10 to 15 mg/kg/day. Metronidazole benzoate contains app roximately 60% metronidazole base by weight, translating to an empirical dosage of 20 mg/kg/day of metronidazole benzoate (equivalent to 12.4 mg/kg/day of metronidazole base).61 Little is known about the safety of chronic metronidazole use in cats, but oral metronidazole has been reported to disrupt DNA within feline peripheral mononuclear cells following 7 days of therapy.61 This metronidazole-induced genotoxicity is reversible and is no longer detected 6 days after antibiotic therapy is discontinued. Ronidazole Ronidazole is a nitroimidazole antibiotic (similar to metronidazole) and available as a powder-on-feed antibiotic. Ronidazole is not approved for use in cats but has

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been used off-label to effectively treat tritrichomoniasis in naturally and experimentally infected cats (30 mg/kg orally every 12 hours for 14 days).25 T. foetus reduces nitroimidazoles to their nitroso free radicals. Ronidazole has been reported to have better in vitro and 10-fold higher in vivo activity against T. foetus relative to metronidazole.25,35,49 Ronidazole resistance is beginning to be reported in T. foetus isolates from cats with diarrhea.26 Side effects include hepatoxicity and neurotoxicity. Neurotoxicity is associated with high doses and has been reported in cats.59 The use of ronidazole is recommended only for confirmed cases of T. foetus, and dosing should not exceed 30 mg/kg once daily in cats, especially in cats at risk for neurotoxicity. Ronidazole is not registered for human or veterinary use in the United States; therefore its use in cats requires owner informed consent and client education of the potential human hazards.

Immunosuppressive Therapies Immunosuppressive therapies are considered the standard of care for cats with gastrointestinal biopsies consistent with inflammatory bowel disease (lymphoplasmacytic or eosinophilic inflammation). The common

immunosuppressive therapies used in cats with inflammatory bowel disease include glucocorticoids, cyclosporine, and chlorambucil (Tables 23-8 and 23-9). More information on the treatment of inflammatory bowel disease is found elsewhere in this chapter. Glucocorticoids Glucocorticoids are considered first-line therapy in the treatment of cats with inflammatory bowel disease. Glucocorticoids bind their intracellular glucocorticoid receptors, modifying the expression of genes with glucocorticoid response elements. Immunomodulation is achieved through inhibition of cytokine release and response, including decreasing leukocyte phagocytosis, chemotaxis, and antigen expression. The more common side effects in cats include gastrointestinal ulceration, opportunistic infections (e.g., urinary tract infections), pancreatitis, and diabetes mellitus. Cats are less susceptible to iatrogenic hyperadrenocorticism than dogs. Initial therapy is usually with oral prednisone or prednisolone. Prednisone is a prodrug that is metabolized to its active form prednisolone. Cats are reported to be less efficient in the conversion of prednisone to prednisolone27; therefore prednisolone may be preferred in cats, especially in cats refractory to prednisone therapy.

TABLE 23-8 Mechanism of Action and Adverse Effects of the Common Immunosuppressive Drugs Used to Treat Inflammatory Bowel Disease in Cats Drug

Mechanism of Action

Adverse Effects

Glucocorticoids

Immunomodulation: decreasing leukocyte phagocytosis, chemotaxis, and antigen expression

Gastrointestinal ulceration Secondary infections Pancreatitis Diabetes mellitus Hyperadrenocorticism

Cyclosporine

Attenuates T-lymphocyte activation and proliferation by inhibition of interleukin-2

Vomiting Secondary infections Hepatotoxicity

Chlorambucil

Alkylates and cross links DNA Lymphocyte cytotoxicity

Bone marrow suppression Neurotoxicity

TABLE 23-9 Dosage Recommendations and Drug Interactions for the Common Immunosuppressive Drugs Used to Treat Inflammatory Bowel Disease in Cats Drug

Types

Dosage (Cats)

Glucocorticoids

Prednisone/prednisolone Antiinflammatory Immunosuppressive Dexamethasone Budesonide

0.5-1 mg/kg/day 2-4 mg/kg/day Prednisone dose divided by 7 0.5-1 mg/cat/day

Cyclosporine

Cyclosporine modified (microemulsion)

4 mg/kg PO q12-24h

Ketoconazole: CYP3A inhibition

Chlorambucil

—

4-kg cat: 2 mg/cat q48h

—

NSAIDs, Nonsteroidal antiinflammatory drugs.

Drug Interactions NSAIDs: gastrointestinal ulceration

Alternative forms of glucocorticoids can be considered in specific patient populations. In patients with severe malabsorption, injectable dexamethasone may provide improved bioavailability and clinical response. Also dexamethasone maybe preferred in patients with a history of heart failure, fluid retention, or hypertension because of its lack of mineralocorticoid activity relative to prednisone/prednisolone. Dexamethasone’s potency is 4 to 10 times that of prednisolone; therefore a dose reduction is necessary when prescribing dexamethasone (the dexamethasone dose is one seventh that of prednisolone).4,10 Budesonide is an oral, locally active, highpotency glucocorticoid that is formulated to be released in the distal gastrointestinal tract (based on the pH differential between the proximal and distal small intestine), where it is absorbed and is locally immunomodulating at the level of the enterocyte. The amount of systemically absorbed budesonide is minimized, because 80% to 90% of the budesonide absorbed from the gastrointestinal tract undergoes first-pass metabolism in the liver. Some systemic absorption does occur, as evidenced by a blunted adrenocorticotropic hormone (ACTH) stimulation test in dogs treated with budesonide at 3 mg/m2 for 30 days.66,70 The use of budesonide in cats remains anecdotal, with a suggestive empirical dose of 0.5 to 1 mg/cat/day. Initial glucocorticoid therapy for cats with inflammatory bowel disease consists of antiinflammatory (0.5 to 1 mg/kg/day) to immunosuppressive (2 to 4 mg/kg/ day) dosages, with dosages based on the potency of prednisone/prednisolone. The goal of therapy is to achieve clinical remission and slowly taper the dose of glucocorticoids to the lowest dose that will control the cat’s clinical signs.67 Some cats may be completely weaned off therapy, while others require long-term lowdose therapy. The tapering of therapy should be slow, with a 25% to 50% dose reduction every 3 to 4 weeks. Cyclosporine Cyclosporine is considered a second-tier immunosuppressive drug used to treat inflammatory bowel disease in cats. Use of cyclosporine in the treatment of diarrhea associated with inflammatory bowel disease in cats is extrapolated from its use in dogs to treat glucocorticoid refractory inflammatory bowel diarrhea.1 Cyclosporine suppresses T-lymphocyte–mediated inflammation in the gastrointestinal tract secondary to suppression of inflammatory cytokines. Specifically, cyclosporine attenuates T-lymphocyte activation and proliferation through the inhibition of interleukin-2 (IL-2) production. Side effects of cyclosporine in cats include dose-dependent inappetence and vomiting, which may occur at the onset of therapy and are generally responsive to dose reduction. Other less common side effects reported in cats are opportunistic infections, including toxoplasmosis5 and hepatoxicity.


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The microemulsion formulation of cyclosporine has higher oral bioavailability and less variable pharmacokinetics.58 A suggested initial dosage of cyclosporine is 4 mg/kg every 12 or 24 hours. Serum cyclosporine levels can be used to monitor for excessive trough plasma concentration (>400 ng/mL) as determined using a highperformance liquid chromotography (HPLC) analytical method.53 Chlorambucil Chlorambucil is a slow-acting nitrogen mustard that alkylates and effectively cross links DNA, leading to altered protein production. The immunosuppressive effects of chlorambucil are the result of its cytotoxic effect on lymphocytes, similar to other nitrogen mustards. Bone marrow suppression is considered mild to moderate and is rapidly reversible. Neurotoxicity and myoclonus has been reported in a cat accidently overdosed with chlorambucil.7 Chlorambucil is used as a second-tier drug in cats to treat immune-mediated disorders, in part because of ease of administration and its low risk of myelosuppression. For the treatment of inflammatory bowel disease, the recommended dosing in cats is 2 mg/cat every 48 hours in cats greater than 4 kg and 2 mg/cat every 72 hours in cats less than 4 kg.50 Chlorambucil is commonly used in combination with glucocorticoids in the treatment of immune-mediated diseases, including inflammatory bowel disease,48,50 and as a chemotherapeutic agent in the treatment of gastrointestinal small cell lymphoma in cats.38

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9. Bersenas AM, Mathews KA, Allen DG, et al: Effects of ranitidine, famotidine, pantoprazole, and omeprazole on intragastric pH in dogs, Am J Vet Res 66:425, 2005. 9a. Cahil C: Mirtazapine as an antiemetic, Vet Forum 23:34, 2006. 10. Cantrill HL, Waltman SR, Palmberg PF, et al: In vitro determination of relative corticosteroid potency, J Clin Endocrinol Metab 40:1073, 1975. 11. Carlsson E: A review of the effects of long-term acid inhibition in animals, Scand J Gastroenterol Suppl 166:19, 1989. 12. Caylor KB, Cassimatis MK: Metronidazole neurotoxicosis in two cats, J Am Anim Hosp Assoc 37:258, 2001. 13. Coruzzi G, Bertaccini G, Noci MT, et al: Inhibitory effect of famotidine on cat gastric secretion, Agents Actions 19:188, 1986. 14. Cubeddu LX: Iatrogenic QT abnormalities and fatal arrhythmias: mechanisms and clinical significance, Curr Cardiol Rev 5:166, 2009. 15. Cunningham RS: 5-HT3-receptor antagonists: a review of pharmacology and clinical efficacy, Oncol Nurs Forum 24:33, 1997. 16. Czarnecki-Maulden G, Cavadini C, Lawler D, et al: Incidence of naturally occurring diarrhea in kittens fed Enterococcus faecium SF68. Supplement to Compend Contin Edu Vet 29:37, 2007. 17. Damaskos D, Kolios G: Probiotics and prebiotics in inflammatory bowel disease: microflora “on the scope”, Br J Clin Pharmacol 65:453, 2008. 18. Dotan I, Rachmilewitz D: Probiotics in inflammatory bowel disease: possible mechanisms of action, Curr Opin Gastroenterol 21:426, 2005. 19. Duran S, Jernigan A, Ravis W, et al: Pharmacokinetics of oral and intravenous ranitidine in cats [abstract], Proceedings of 9th Annual ACVIM Forum 1991, p 902. 20. Durazo FA, Valenzuela JE: Effect of single and repeated doses of metoclopramide on the mechanisms of gastroesophageal reflux, Am J Gastroenterol 88:1657, 1993. 21. Echizen H, Ishizaki T: Clinical pharmacokinetics of famotidine, Clin Pharmacokinet 21:178, 1991. 22. Fandriks L, Jonson C: Effects of acute administration of omeprazole or ranitidine on basal and vagally stimulated gastric acid secretion and alkalinization of the duodenum in anaesthetized cats, Acta Physiol Scand 138:181, 1990. 23. Freeman AJ, Cunningham KT, Tyers MB: Selectivity of 5-HT3 receptor antagonists and anti-emetic mechanisms of action, Anticancer Drugs 3:79, 1992. 24. Goodin S, Cunningham R: 5-HT(3)-receptor antagonists for the treatment of nausea and vomiting: a reappraisal of their side-effect profile, Oncologist 7:424, 2002. 25. Gookin, JL, Copple, CN, Papich, MG, et al: Efficacy of ronidazole for treatment of feline Tritrichomonas foetus infection, J Vet Intern Med 20:536, 2006. 26. Gookin JL, Stauffer SH, Dybas D, et al: Documentation of in vivo and in vitro aerobic resistance of feline Tritrichomonas foetus isolates to ronidazole, J Vet Intern Med 24:1003, 2010. 27. Graham-Mize CA, Rosser EJ Jr: Comparison of microbial isolates and susceptibility patterns from the external ear canal of dogs with otitis externa, J Am Anim Hosp Assoc 40:102, 2004. 28. Guilford WG, Jones BR, Markwell PJ, et al: Food sensitivity in cats with chronic idiopathic gastrointestinal problems, J Vet Intern Med 15:7, 2001. 29. Gullikson GW, Loeffler RF, Virina MA: Relationship of serotonin-3 receptor antagonist activity to gastric emptying and motorstimulating actions of prokinetic drugs in dogs, J Pharmacol Exp Ther 258:103, 1991. 30. Hasler AH, Washabau RJ: Cisapride stimulates contraction of idiopathic megacolonic smooth muscle in cats, J Vet Intern Med 11:313, 1997. 31. Hickman MA, Cox SR, Mahabir S, et al: Safety, pharmacokinetics and use of the novel NK-1 receptor antagonist maropitant (Cerenia) for the prevention of emesis and motion sickness in cats, J Vet Pharmacol Ther 31:220, 2008.

32. Hillemeier C, McCallum R, Oertel R, et al: Effect of bethanechol and metoclopramide on upper gastrointestinal motility in the kitten, J Pediatr Gastroenterol Nutr 5:134, 1986. 33. Jalving M, Koornstra JJ, Wesseling J, et al: Increased risk of fundic gland polyps during long-term proton pump inhibitor therapy, Aliment Pharmacol Ther 24:1341, 2006. 34. Jergens A: Feline idiopathic inflammatory bowel disease, Compend Contin Educ Prac Vet 14:509, 1992. 35. Kather EJ, Marks SL, Kass PH: Determination of the in vitro susceptibility of feline Tritrichomonas foetus to 5 antimicrobial agents, J Vet Intern Med 21:966, 2007. 36. Katz PO, Ginsberg GG, Hoyle PE, et al: Relationship between intragastric acid control and healing status in the treatment of moderate to severe erosive oesophagitis, Aliment Pharmacol Ther 25:617, 2007. 37. Kii Y, Nakatsuji K, Nose I, et al: Effects of 5-HT(4) receptor agonists, cisapride and mosapride citrate on electrocardiogram in anaesthetized rats and guinea-pigs and conscious cats, Pharmacol Toxicol 89:96, 2001. 38. Kiselow MA, Rassnick KM, McDonough SP, et al: Outcome of cats with low-grade lymphocytic lymphoma: 41 cases (1995-2005), J Am Vet Med Assoc 232:405, 2008. 39. Koch KM, Liu M, Davi, IM, et al: Pharmacokinetics and pharmacodynamics of ranitidine in renal impairment, Eur J Clin Pharmacol 52:229, 1997. 40. Kounenis G, Koutsoviti-Papadopoulou M, Elezoglou A, et al: Comparative study of the H2-receptor antagonists cimetidine, ranitidine, famotidine and nizatidine on the rabbit stomach fundus and sigmoid colon, J Pharmacobiodyn 15:561, 1992. 41. LeGrange SN, Boothe DM, Herndon S, et al: Pharmacokinetics and suggested oral dosing regimen of cisapride: a study in healthy cats, J Am Anim Hosp Assoc 33:517, 1997. 42. Lehmann CR, Heironimus JD, Collins CB, et al: Metoclopramide kinetics in patients with impaired renal function and clearance by hemodialysis, Clin Pharmacol Ther 37:284, 1985. 43. Lofmark S, Edlund C, Nord CE: Metronidazole is still the drug of choice for treatment of anaerobic infections, Clin Infect Dis 50(Suppl 1):S16, 2010. 44. Mangel AW, Stavorski JR, Pendleton RG: Effects of bethanechol, metoclopramide, and domperidone on antral contractions in cats and dogs, Digestion 28:205, 1983. 45. Marshall-Jones ZV, Baillon ML, Croft JM, et al: Effects of Lactobacillus acidophilus DSM13241 as a probiotic in healthy adult cats, Am J Vet Res 67:1005, 2006. 46. Martinez C, Albet C, Agundez JA, et al: Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists, Clin Pharmacol Ther 65:369, 1999. 47. Michalets EL, Williams CR: Drug interactions with cisapride: clinical implications, Clin Pharmacokinet 39:49, 2000. 48. Miller E: The use of cytotoxic agents in the treatment of immunemediated diseases of dogs and cats, Semin Vet Med Surg (Small Anim) 12:157, 1997. 49. Miwa GT, Wang R, Alvaro R, et al: The metabolic activation of ronidazole [(1-methyl-5-nitroimidazole-2-yl)-methyl carbamate] to reactive metabolites by mammalian, cecal bacterial and T. foetus enzymes, Biochem Pharmacol 35:33, 1986. 50. Moore L: Beyond corticosteroids for therapy of inflammatory bowel disease in dogs and cats [abstract], Proceedings 22nd Am Coll Vet Intern Med Forum 2004, p 611. 51. Nomoto K: Prevention of infections by probiotics, J Biosci Bioeng 100:583, 2005. 52. Olson EJ, Morales SC, McVey AS, et al: Putative metronidazole neurotoxicosis in a cat, Vet Pathol 42:665, 2005. 53. Papich MG: Immunnosuppressive drug therapy, Proceedings of 14th Annual Members Meeting of the American Academy of Veterinary Dermatology and American College of Veterinary Dermatology 1998, p 41.


54. Petroianu GA, Arafat K, Schmitt A, et al: Weak inhibitors protect cholinesterases from strong inhibitors (paraoxon): in vitro effect of ranitidine, J Appl Toxicol 25:60, 2005. 55. Prommer E: Aprepitant (EMEND): the role of substance P in nausea and vomiting, J Pain Palliat Care Pharmacother 19:31, 2005. 55a. Quimby JM, Gustafson DL, Samber BJ et al: Studies on the pharmacokinetics and pharmacodynamics of mirtazapine in healthy young cats, J Vet Pharmacol Ther (in press). 56. Rao AS, Camilleri M: Review article: metoclopramide and tardive dyskinesia, Aliment Pharmacol Ther 31:11, 2010. 57. Reed N, Gunn-Moore D, Simpson K: Cobalamin, folate and inorganic phosphate abnormalities in ill cats, J Feline Med Surg 9:278, 2007. 58. Robson D: Review of the pharmacokinetics, interactions and adverse reactions of cyclosporine in people, dogs and cats, Vet Rec 152:739, 2003. 59. Rosado TW, Specht A, Marks, SL: Neurotoxicosis in 4 cats receiving ronidazole, J Vet Intern Med 21:328, 2007. 60. Ruaux CG, Steiner JM, Williams DA: Early biochemical and clinical responses to cobalamin supplementation in cats with signs of gastrointestinal disease and severe hypocobalaminemia, J Vet Intern Med 19:155, 2005. 61. Sekis I, Ramstead K, Rishniw M, et al: Single-dose pharmacokinetics and genotoxicity of metronidazole in cats, J Feline Med Surg 11:60, 2009. 62. Sen P, Chakravarty AK, Kohli J: Effects of some imidazoles on cellular immune responses—an experimental study, Indian J Exp Biol 29:867, 1991. 63. Shahani KM, Ayebo AD: Role of dietary lactobacilli in gastrointestinal microecology, Am J Clin Nutr 33:2448, 1980. 64. Simpson KW, Fyfe J, Cornetta A, et al: Subnormal concentrations of serum cobalamin (vitamin B12) in cats with gastrointestinal disease, J Vet Intern Med 15:26, 2001. 65. Sparkes AH, Papasouliotis K, Sunvold G, et al: Effect of dietary supplementation with fructo-oligosaccharides on fecal flora of healthy cats, Am J Vet Res 59:436, 1998. 66. Stroup ST, Behrend EN, Kemppainen RJ, et al: Effects of oral administration of controlled-ileal-release budesonide and assessment of pituitary-adrenocortical axis suppression in clinically normal dogs, Am J Vet Res 67:1173, 2006. 67. Tams TR: Feline inflammatory bowel disease, Vet Clin North Am Small Anim Pract 23:569, 1993. 68. Tannock GW: New perceptions of the gut microbiota: implications for future research, Gastroenterol Clin North Am 34:361, vii, 2005. 69. Tedelind S, Westberg F, Kjerrulf M, et al: Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: a study with relevance to inflammatory bowel disease, World J Gastroenterol 13:2826, 2007. 69a. Timmer CJ, Sitsen JM, Delbressine LP: Clinical pharmacokinetics of mirtazapine, Clin Pharmacokinet 38:461, 2000. 70. Tumulty JW, Broussard JD, Steiner JM, et al: Clinical effects of short-term oral budesonide on the hypothalamic-pituitary-adrenal axis in dogs with inflammatory bowel disease, J Am Anim Hosp Assoc 40:120, 2004. 71. Wynn SG: Probiotics in veterinary practice, J Am Vet Med Assoc 234:606, 2009. 72. Zoran DL: Nutritional management of feline gastrointestinal diseases, Top Companion Anim Med 23:200, 2008.

DISEASES OF THE ESOPHAGUS Susan E. Little Esophageal disease is uncommon in the cat when compared with dogs, but it is also likely that problems such as esophagitis and esophageal strictures are often

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overlooked. Awareness about feline esophageal diseases is low, the clinical signs are often not specific, and imaging beyond survey radiographs may be required for diagnosis. The esophagus is composed of four layers (from inner to outer): mucosa, submucosa, muscularis, and adventitia (there is no serosal layer). In the dog, the muscle layer is entirely composed of skeletal muscle, but in cats, the distal third of the esophagus is composed of smooth muscle. The upper esophageal sphincter prevents reflux of esophageal contents into the pharynx and minimizes aerophagia. The lower esophageal sphincter prevents gastroesophageal reflux and relaxes during swallowing to allow food and fluid to enter the stomach.

CLINICAL PRESENTATION Clinical signs of esophageal disease include drooling, dysphagia, pain on swallowing (odynophagia), and, most classically, regurgitation. Weight loss may occur secondary to inadequate food intake when disease is severe or chronic. Other clinical signs, such as anorexia, cough, dyspnea, and fever, may occur if complications such as aspiration pneumonia or esophageal perforation occur. Regurgitation is passive expulsion of food or fluid from the esophagus. The food is undigested and often accompanied by mucus and saliva. Mucosal erosions may produce frank blood in the regurgitated material. Regurgitation must be differentiated from vomiting (Table 23-10). Vomiting is typically preceded by

TABLE 23-10 How to Differentiate Vomiting from Regurgitation Sign

Regurgitation

Vomiting

Prodromal nausea (salivation, licking lips, anxiety)

No

Usually

Retching (dry heaves)

No

Usually

Sometimes No Sometimes undigested

Sometimes Sometimes Sometimes (undigested or digested)

Volume produced

Variable

Variable

Timing relative to eating

Variable

Variable

Distention of cervical esophagus

Sometimes

No

Material produced: Food Bile Blood

Adapted from Willard MD: Clinical manifestations of gastrointestinal disorders. In Nelson RW, Couto CG, editors: Small animal internal medicine, St Louis, 2009, Mosby Elsevier, Table 28-1, p 354.

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salivation, retching, and abdominal contractions. The vomitus consists of partially digested food from the stomach and/or intestines and may be mixed with bilestained fluid. Some cats will have both vomiting and regurgitation. Expectoration may also be confused with vomiting or regurgitation. Expectoration is associated with coughing, but cats that cough excessively may also stimulate vomition so that a careful history is needed to characterize the clinical signs correctly. Coughing may also occur in cats that have aspirated as a result of regurgitation. Drooling, dysphagia, and odynophagia are most commonly seen with conditions of the oropharynx and/or proximal esophagus. Odynophagia is most commonly associated with esophagitis and foreign bodies. Dysphagia and regurgitation together most commonly indicate oral or pharyngeal dysfunction; if regurgitation is not accompanied by dysphagia, esophageal dysfunction is likely.55 Regurgitation in cats with esophageal disease is caused by obstruction or muscular dysfunction. Causes of obstruction include vascular ring anomaly, foreign object, stricture, and neoplasia. Causes of muscular dysfunction include congenital disease, esophagitis, myopathies, neuropathies, and dysautonomia. Regurgitation may occur immediately after eating if the lesion is in the proximal esophagus. However, a dilated esophagus provides a reservoir for food and fluid so that regurgitation may not be associated in time with eating.

Young cats with signs of esophageal disease should be suspected of congenital defects, such as vascular ring anomaly, or a foreign body. Adult cats with esophageal disease may have a recent history of general anesthesia, administration of certain oral medications, or ingestion of irritant chemicals. Acute onset of clinical signs may suggest a foreign body, while chronic, slowly worsening signs may indicate a stricture or tumor.

DIAGNOSTIC APPROACH All cats suspected of esophageal disease should have a minimum database as part of the diagnostic plan (complete blood cell count, serum chemistries, urinalysis, and other tests as indicated by age or concurrent diseases, such as serum total T4 and blood pressure measurement). An important part of diagnosis is observation of the cat while eating food, to localize the location of the dysfunction. If the cat is unwilling to eat while in the veterinary clinic, the owner can make a video of the cat eating at home for the clinician to view. The general diagnostic approach to regurgitation in cats is found in Figure 23-3. Plain and contrast radiography and endoscopy are important diagnostic tools for esophageal disease. Fluoroscopy is valuable for the diagnosis of motility disorders, but availability is limited to universities and referral centers because of the cost of equipment. Ultrasonography is limited to evaluation of

FIGURE 23-3 Diagnostic approach to regurgitation. (Adapted from Willard MD: Clinical manifestations of gastrointestinal disorders. In Nelson RW, Couto CG, editors: Small animal internal medicine, St Louis, 2009, Mosby Elsevier, Figure 28-1, p 354.)

Plain thoracic radiographs

Foreign body

Perforation

No foreign body or perforation

Esophagostomy, Surgery

Obvious megaesophagus

History, PE don’t agree

History, PE agree

Contrast esophagram

Obstruction

Acquired

Weakness

Congenital

Congenital

Acquired

Surgery

Supportive treatment

Determine cause

Uncertain

Repeat esophagram / Fluoroscopy / Esophagoscopy


the cervical esophagus and a small segment of abdominal esophagus between the cardia of the stomach and the diaphragm. The entire esophagus should be evaluated with cervical and thoracic radiographs. Thoracic radiographs may also show evidence of complications such as aspiration pneumonia or esophageal perforation. The normal esophagus is not visualized on plain radiographs, but may be seen if food or fluid are retained or a foreign body or mass is present. Radiographic contrast agents useful for esophagrams in cats include liquid or paste barium. A water-soluble iodinated contrast agent (e.g., iohexol, Gastrografin) is preferred if there is any risk the esophagus is perforated, because these agents are less irritating and more rapidly reabsorbed. Esophagrams are most useful for diagnosis of luminal obstructions, extraluminal compression, mucosal irregularities, and possibly alterations in motility. Dilute liquid barium can be administered with a syringe or it may be mixed with canned food, especially if a motility disorder or stricture is suspected. Multiple lateral radiographs are taken rapidly, starting within 10 seconds of swallowing the contrast agent. Contrast is rapidly cleared from the normal esophagus by peristalsis. If the contrast in the esophagus terminates abruptly, an obstruction is likely. If the contrast is retained throughout the esophagus, muscular dysfunction is suspected. Some conditions, such as esophagitis, are difficult to diagnose radiographically, because contrast agents may or may not adhere to ulcerated mucosa. Flexible endoscopy is a noninvasive diagnostic tool for esophageal disorders and is often used if plain and contrast radiographs have failed to establish a diagnosis. It is most sensitive for diagnosis of masses, ulcers, perforations, and obstructions. In addition, it is often possible to retrieve foreign bodies using endoscopy as well as to assist with dilatation of strictures or placement of gastrostomy feeding tubes if required. Biopsy of the esophageal mucosa is more difficult than biopsy of gastric or intestinal mucosa and is not commonly performed with the exception of mass lesions.

SPECIFIC DISEASES Esophagitis and Esophageal Strictures Esophagitis may result from various causes of inflammation, such as contact irritation from foreign bodies (including trichobezoars lodged in the esophagus), chemical irritants or caustic medications, gastroesophageal reflux, persistent vomiting, hiatal hernia, or general anesthesia. Inflammation disrupts the esophageal mucosa and exposes the submucosa. An important part of the treatment plan is identification and treatment of the underlying cause.

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Clinical signs include dysphagia, regurgitation, salivation, and repeated swallowing, although signs may be absent in cats with mild esophagitis. Cats with odynophagia may repeatedly extend the head and neck while swallowing. If the esophagitis or underlying disease is severe, weight loss and dehydration may occur secondary to anorexia. If the submucosa and muscularis are damaged, strictures may form as a result of the production of fibrous connective tissue and compromise the esophageal lumen.54 Neoplasia is an important cause of esophageal stricture in humans, but not in cats. Most cases have single strictures, but multiple strictures are possible. In two studies, the mean stricture diameter was reported as 5 mm.26,32 Most strictures are less than 1 cm in length. Clinical signs associated with strictures appear 5 to 14 days after the esophageal injury and may be present for weeks before definitive treatment is pursued. Regurgitation typically occurs immediately after eating, although if the stricture is long standing, a pouch may form cranial to the lesion where food accumulates. Survey radiographs may be normal in cats with esophagitis and strictures, but are useful to rule out other causes for the clinical signs, such as a foreign body, or to detect related problems, such as aspiration pneumonia. In some patients, dilation of the esophagus with fluid or air may be seen.45 A contrast esophagram may disclose irregularities of the mucosa in cats with severe esophagitis. Segmental dilation may occur with severe inflammation. Strictures may be diagnosed with an esophagram (Figure 23-4); however, in some cases, it may be difficult to differentiate a stricture from intramural thickening (e.g., because of neoplasia). Endoscopy is useful for diagnosis of esophagitis; findings include mucosal erythema, hemorrhage, and erosions or ulcerations. If gastroesophageal reflux is present, the lesions will be most severe in the distal esophagus, and the lower esophageal sphincter may be dilated. Endoscopy is often used for definitive diagnosis of esophageal stricture as well as to visualize the lesion during treatment by bougienage or balloon catheter dilation. Strictures appear as a ring of white fibrous tissue that narrows the esophageal lumen. If endoscopy is performed after a barium esophagram, 24 hours should be allowed to elapse between the procedures or the barium will obscure visualization with the endoscope.19 General anesthesia is an important cause of esophagitis (sometimes leading to stricture formation) in cats, probably because gastroesophageal reflux appears to occur commonly in anesthetized cats.* For example, in a series of seven cats with benign esophageal stricture, recent anesthesia for ovariohysterectomy was the suspected cause in five cases.1 Clinical signs appeared up to 21 days after anesthesia. *References 1, 8, 11, 15, 38, 43.

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FIGURE 23-4 Lateral barium contrast esophagram of a 4-monthold domestic shorthair (DSH) cat with an esophageal stricture associated with administration of doxycycline tablets. (Courtesy Dr. Emma Thom.)

Many preanesthetic drugs and induction agents reduce lower esophageal sphincter pressure.27,28 Other predisposing factors may be intraabdominal surgery and a head-down position on the surgery table. Reflux fluid with a pH less than 4 is likely to cause esophageal mucosal damage, as is prolonged contact time. Esophageal defense mechanisms include clearance of the reflux fluid by peristalsis and neutralization of the acidic pH by the bicarbonate present in saliva. In a study of 40 kittens less than 15 weeks of age, risk of gastroesophageal reflux during anesthesia was evaluated with use of a laryngeal airway mask versus endotracheal intubation.47 Gastroesophageal reflux was observed in 50% of kittens with use of the laryngeal airway mask but more importantly in 22% of kittens with endotracheal intubation. The reflux episodes occurred shortly after anesthesia induction. In a study of 50 cats anesthetized with thiopentone or propofol, gastroesophageal reflux occurred in 14%.16 Reflux also occurred shortly after anesthesia was induced and lasted for a mean of 23 minutes. It is unknown why esophageal strictures form only in a small number of cats that experience gastroesophageal reflux during anesthesia. Gastroesophageal reflux disease (GERD) is a commonly reported cause of esophagitis in humans, but it is rarely reported in cats when not associated with general anesthesia.24,33 The true incidence is unknown, and diagnosis may be hampered by scant knowledge about the clinical presentation and diagnosis. Clinical signs and diagnostic procedures are as for other causes of esophagitis. In one case series of three cats, diagnosis of GERD was based on clinical signs, contrast radiography, and endoscopic findings.24 Biopsy and histopathology of

abnormal esophageal tissue was performed in two cases. The authors noted that the esophageal mucosa may appear grossly normal, but submucosal inflammation may be found on histopathologic examination of biopsies. A consequence of chronic severe GERD in humans is the development of metaplastic columnar epithelium (Barrett esophagus) that replaces the normal squamous epithelium. One case series reported on Barrett-like esophagus in three cats.23 Two cases were associated with hiatal hernia and one with cardial incompetence. Drug-induced esophageal damage and stricture formation is well known in humans and cats (see Figure 4-4). In humans over 70 drugs have been implicated, and most are antibacterials or NSAIDs.30 Implicated drugs in the cat include tetracycline, doxycycline, and clindamycin in tablet or capsule form administered without a food or water bolus.4,17,32,36,37 Clinical signs (dysphagia, regurgitation, salivation, anorexia) appear 3 to 16 days after drug treatment is started. Strictures commonly form in the midcervical esophagus or over the heart base in the thoracic esophagus. Doxycycline hyclate is most commonly associated with esophageal strictures in cats, and the principle reason for its irritating properties is an acidic pH. The monohydrate salt of doxycycline is less irritating and is marketed as tablets and a palatable paste licensed for use in dogs and cats in some countries.48 In humans esophageal ulceration after doxycycline therapy is more common than stricture formation. Although the development of strictures in cats would appear to be uncommon, it seems possible the incidence of esophagitis is underestimated, because the clinical signs (e.g., odynophagia, chest pain) may go unrecognized. Esophageal transit studies of normal cats have shown that the passage time of dry-swallowed tablets and capsules is often prolonged (longer than 30 seconds).20,53 Complete entrapment (retention for more than 4 minutes) in the midcervical region occurs commonly. However, a small bolus of food or water is sufficient to ensure immediate passage of the medication into the stomach.20,53 The risk of esophageal retention can also be lessened by coating a tablet or capsule with butter or a gel dietary supplement (Nutri-Cal; Vétoquinol, Fort Worth, Tex.).21 One study determined that tablets or capsules administered using a one-step pill gun with flavored liquid (FlavoRx Pill Glide; FLAVORx, Columbia, Md.) or a pill delivery treat (Greenies Pill Pockets; Nutro Products, Franklin, Tenn.) ensured an average transit time of 60 seconds or less.6 Delayed esophageal transit of medications allows tablets and capsules to disintegrate within the esophagus, exposing the mucosa to irritating chemicals. Cats may be at risk of delayed esophageal transit, because they do not typically drink water with medication, and they do not have an upright posture. In addition, medications are often given to sick or dehydrated patients


that may be at greater risk of esophageal retention of medication. All oral medication given to cats in tablet or capsule form should be followed with food or a liquid. Mild esophagitis will resolve on its own, especially if an underlying cause can be removed or treated. Frequent meals of canned food should be provided. Cats with moderate to severe esophagitis will require medical therapy, and those with difficulty eating or weight loss may also require gastrostomy tube feeding. Esophagostomy or pharyngostomy feeding tubes should be avoided in these patients. Treatment is provided to control inflammation and promote healing while reducing gastric acid secretion and increasing lower esophageal sphincter tone. The length of medical treatment will vary from about one week to several weeks, depending on the underlying cause and severity of disease. Medications indicated for esophagitis include prokinetics, H2-receptor antagonists, proton pump inhibitors, and sucralfate (Table 23-11). Prokinetic drugs enhance gastric emptying and increase lower esophageal sphincter tone. Metoclopramide also has antiemetic effects, which may be beneficial in patients with chronic vomiting. It can be administered by the subcutaneous (SC) route, an advantage in a vomiting or regurgitating patient. Cisapride may be more effective at enhancing both gastric emptying and lower esophageal sphincter tone, but it must be

TABLE 23-11 Drugs Used in the Treatment of Esophagitis and Esophageal Strictures Drug

Dose

Mechanism

Cisapride

1.5 mg/kg, q12h, PO

Prokinetic; increases lower gastroesophageal sphincter pressure, promotes gastric emptying

Famotidine

0.5-1.0 mg/kg, q12-24h, PO or IV

H2-receptor antagonist; reduces gastric acid secretion

Metoclopramide

0.2-0.4 mg/kg, q6h, SC or PO

Prokinetic; increases lower gastroesophageal sphincter pressure, promotes gastric emptying

Omeprazole

0.5-1.0 mg/kg, q24h, PO

Proton pump inhibitor; reduces gastric acid secretion

Ranitidine

2.5 mg/kg, q12h, IV or 3.5 mg/kg, q12h, PO

H2-receptor antagonist; reduces gastric acid secretion

Sucralfate

0.25 g/cat, q6-8h, PO

Adheres to and protects damaged mucosa

Drug doses from Trepanier L: Acute vomiting in cats: rational treatment selection, J Feline Med Surg 12:225, 2010.

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obtained from a compounding pharmacy in most countries and can only be given orally. H2-receptor antagonists are competitive inhibitors that block parietal H2 receptors and decrease the amount of gastric acid produced. Proton pump inhibitors are noncompetitive inhibitors that act on the H+/K+ ATPase enzyme system at the secretory surface of gastric parietal cells. They are considered superior for decreasing gastric acid secretion and are therefore the first choice, despite their greater cost.45 A drawback of proton pump inhibitors is that they must be administered orally. Sucralfate may be beneficial for reflux esophagitis, because it binds to mucosal erosions in an acid environment and provides a protective barrier. It is given as oral slurry, ideally separate from meals or other medications. Antibiotics are not commonly recommended unless aspiration pneumonia is present or the eroded mucosa is at risk of bacterial infection in a patient with severe disease or a compromised immune system. Corticosteroids are often recommended for cats with esophagitis to reduce esophageal inflammation and impair the formation of fibrous connective tissue. However, the benefit of corticosteroids in cats with esophagitis has not been investigated and administration must be weighed against potential adverse effects, especially in patients with aspiration pneumonia. Treatment of esophageal stricture typically requires dilation with either bougienage or a balloon catheter; both are used with endoscopic visualization under general anesthesia. Appropriate analgesia should be provided, because dilating the stricture is painful. It does not appear that placement of a gastrostomy feeding tube is specifically required to recover from dilation procedures, although a tube may be placed in some anorexic cats to ensure nutritional intake and administer oral medications. A bougie is a long, narrow, oblong, mechanical dilator available in various sizes (typically 9- to 12-mm sizes are used in cats) that is gently passed through the stricture, usually over a guide wire. Established criteria for selection of bougie diameter and dilation end points are not available. In one study, the initial bougie chosen was approximately the same size as the estimated diameter of the stricture, or no more than 2 mm larger.8 Once the first bougie is passed, subsequent bougies of increasing diameter are employed. Two to four bougies of increasing size may be passed in a single session, with the goal of dilating the stricture without causing esophageal tear or perforation. Determining when dilation should be stopped is a matter of clinical judgment. The procedure may be repeated as needed to maintain improvement; the total number of procedures required is variable. In one retrospective case series of eight cats treated with bougienage, the median number of procedures was 4.5, and a good outcome was achieved in 75% of the cases.8 In some cases, the endoscope tip itself has been used for

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bougienage when bougies or balloon catheters were not available. Balloon catheter dilation has become a popular method in recent years.26,32,38 Although some clinicians feel this is a safer procedure than bougienage, there is no data in the literature to support this assumption. The catheter can be placed through the endoscope biopsy channel, alongside the endoscope, or with the aid of a preplaced guide wire. As for bougienage, established criteria for selection of balloon diameter and dilation end points are not available, and the clinician’s best judgment must be used. Various balloon sizes are available; in one study, the size was selected so that the inflated diameter was 4 mm larger than the stricture diameter.32 The balloon is passed into the stricture with endoscopic guidance. It is then inflated to a predetermined pressure for 1 to 2 minutes to stretch the stricture, usually with saline, but contrast agents may also be used if fluoroscopy is used. As for bougienage, some cases may require more than one dilation procedure (typically two to four). Cuffed endotracheal tubes are not appropriate substitutes for balloon catheters. Regardless of the method used, after the dilation procedure, the endoscope should be used to look for other strictures and should be passed into the stomach to look for potential causes, such as causes of chronic vomiting. After treatment, medical management to decrease ongoing gastroesophageal reflux, resolve inflammation, and prevent further stricture formation should be instituted (as described previously). Most cats are able to eat the day following the dilation procedure. Corticosteroid treatment after dilation is controversial, and no controlled studies in animals are available. Antibiotics are not routinely recommended. The prognosis for cats undergoing esophageal dilation is generally good based on the ability to eat canned food with minimal episodes of regurgitation. However, published studies show 10% to 30% of cats died or were euthanized despite multiple episodes of dilation, and up to 30% could only be fed liquid diets.1,8,32,38 Even among cats with good outcomes, a return to a dry kibble diet may not be possible. The dilation technique employed may be dictated by the clinician’s experience, the equipment available, and the cost. Potential complications of both methods include esophageal tear or perforation, hemorrhage, infection, and aspiration. Esophageal tears or perforations may lead to pneumothorax or pneumomediastinum. Repeated stricture formation is also possible, leaving only less desirable treatment options, such as long-term percutaneous gastrostomy tube feeding or surgery. Esophageal surgery is generally avoided whenever possible, because it is difficult and invasive (requiring a thoracotomy), with risk of serious complications, such as failure of anastomosis, necrosis, and stricture formation. Closure of incisions in the esophagus is

difficult, because there is no serosa, and the muscles are oriented longitudinally. Indications for esophageal surgery include repair of perforations, treatment of strictures that fail to respond to dilation, and tumor resection. Stent placement has recently been described in cats with esophageal strictures with variable results. A 1-year-old cat presented with a 4-week history of dysphagia and regurgitation caused by a single cervical esophageal stricture after treatment with oral clindamycin.18 Guided balloon dilation was performed 6 times over a period of 3 weeks, but stricture formation always recurred. A self-expanding metal stent was placed using endoscopy and fluoroscopy after another dilation procedure. The cat did well eating a canned diet from an elevated position for 10 months, but by 12 months, the cat was no longer able to eat even liquid food and was euthanized. On necropsy, the stent had migrated and was obstructed by swallowed hair. In another case, a biodegradable self-expanding stent was used to successfully treat an 11-year-old cat that presented with a stricture in the cervical esophagus after anesthesia for dentistry.3 Balloon dilation was performed twice, but regurgitation recurred 5 days after the last procedure. The stricture was dilated a third time with a balloon catheter, and a tubular selfexpanding polydioxanone stent was placed with fluoroscopic guidance. The life span of the stent was estimated to be 10 to 12 weeks, sufficient time to allow healing of the esophagus.

Foreign Bodies Foreign bodies are less commonly found in the esophagus of the cat than in other gastrointestinal locations. Reported foreign bodies include string, needles, fish hooks, and bones. Trichobezoars may cause obstruction when they become lodged in the esophagus during vomiting (Figure 23-5). Recurrent esophageal trichobezoars have been infrequently reported in the literature.12,51 It is not known if an esophageal motility disorder is the underlying cause for recurrent obstructions. In one case, an esophageal diverticulum developed in association with recurrent trichobezoars.12 Treatment for recurrent trichobezoars includes prokinetic drug therapy (e.g., cisapride), moderate to high-fiber diets, and shaving of long-haired cats. Common areas for foreign bodies to lodge include the thoracic inlet, the heart base, and the esophageal hiatus in the diaphragm.5 Obstruction of the esophageal lumen may be complete or partial. Clinical signs include acute onset of gagging, salivation, repeated swallowing, dysphagia, and regurgitation. However, chronic esophageal foreign bodies have been reported in cats with dysphagia, intermittent regurgitation, and weight loss over a period of weeks or months.2

FIGURE 23-5 Lateral esophagram of a cat with a trichobezoar esophageal foreign body. Trichobezoars may cause obstruction when they become lodged in the esophagus during vomiting. (Courtesy Dr. John Graham.)

Cough, mucopurulent nasal discharge, and fever may be found if aspiration has occurred. Trauma to the esophagus may cause esophagitis and even esophageal stricture. Perforation of the esophagus by the foreign body may lead to pneumothorax, pneumomediastinum, or pyothorax with signs of depression, anorexia, fever, and dyspnea. If the perforation occurs in the cervical esophagus, swelling, cellulitis, and drainage of serous or purulent material may be noted. Many foreign bodies are readily diagnosed with survey radiographs, especially if they are radiopaque. Other radiographic findings include an esophagus dilated with fluid or air. Radiolucent objects may be detected with an esophagram. Care must be taken when performing esophagrams on cats that may have an obstruction, because aspiration is a concern. If abnormalities that could be consistent with an esophageal perforation (e.g., periesophageal gas or fluid, pleural effusion) are detected on survey radiographs, an aqueous iodine contrast solution should be used. Removal of esophageal foreign bodies should be performed as soon as possible to minimize esophageal trauma and pressure necrosis. Endoscopy can be used to confirm the diagnosis and often to remove the object. Both rigid and flexible endoscopes may be used along with accessories such as various forceps and Foley catheters. Care should be taken to remove the object as atraumatically as possible, especially if the object is sharp or pointed. If the object is in the caudal esophagus and it cannot be grasped and removed, an attempt should be made to gently push it into the stomach, where it can be retrieved using laparotomy and gastrotomy. If esophageal perforation has occurred, esophagotomy is recommended and is described elsewhere.5,14 Removal of fish hooks may require a combination of surgery and endoscopy.5,39 A surgical approach to the esophagus is made, but the esophagus is not incised; rather, the portion of the hook protruding through the esophagus is cut and removed, and the endoscope is used to retrieve the remainder.


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Following uncomplicated foreign body removal, the esophagus should be carefully inspected for lesions and bleeding before the endoscope is withdrawn. Food and water should be withheld for 24 to 48 hours. Supportive care includes fluid therapy and analgesia; a gastrostomy feeding tube may be required in selected cases for nutritional support. Broad-spectrum antibiotics are administered to control bacterial infection and therapy for esophagitis should be instituted as described previously. Careful follow-up should include evaluation for stricture formation. If an esophageal perforation has occurred, conservative management may be sufficient if the defect is small. A broad-spectrum antibiotic should be administered along with other supportive care, such as fluid therapy and analgesia. Feeding through a gastrostomy tube for several days is recommended as well as close monitoring for complications such as pleuritis. Large perforations require thoracotomy for surgical repair.

Megaesophagus Megaesophagus is a diffuse hypomotility disorder that may be classified as congenital versus acquired or idiopathic versus secondary to other diseases. It is uncommon in cats compared with dogs. At least two dog breeds have been identified with heritable congenital megaesophagus. A heritable form of megaesophagus has been suggested for cats, particularly for Siamese cats, although no detailed studies have been performed.13,29 It is often frustrating to determine the underlying cause of acquired megaesophagus. Megaesophagus may be a manifestation of neuromuscular diseases, such as dysautonomia or myasthenia gravis (see Chapter 27). Megaesophagus may also develop secondary to esophagitis from chronic vomiting or GERD.24,43 Other uncommon causes of megaesophagus are found in the literature. One case report describes a young cat with megaesophagus secondary to a large nasopharyngeal polyp that extended into the cervical esophagus.10 Megaesophagus resolved once the polyp was removed. In another report, a young cat with diaphragmatic hernia was diagnosed with megaesophagus and gastric dilation.31 Megaesophagus resolved with medical treatment and surgical correction of the diaphragmatic defect. Clinical signs are typically those of esophageal dysfunction; regurgitation is the most consistently found sign. Regurgitation may not be closely related in time to eating if the esophagus is markedly distended and holds food. Cats with long-standing disease may suffer from weight loss or secondary rhinitis. The appetite is typically normal or increased. Additional signs may occur if systemic neuromuscular disease is present. Aspiration pneumonia may cause fever, dyspnea, and cough. Two case reports describe cats with idiopathic

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FIGURE 23-6 Lateral esophagram of a 5-month-old kitten with megaesophagus. (Courtesy Dr. Emilia Monachino.)

megaesophagus and chronic vomiting associated with intermittent gastroesophageal intussusception.35,50 Survey and contrast radiographs may identify a dilated esophagus (Figure 23-6), but contrast fluoroscopy is the diagnostic tool of choice when available, because it allows for assessment of peristalsis. Care must be taken with contrast studies because of the risk of aspiration. Treatment of megaesophagus is largely symptomatic and supportive unless an underlying disorder can be identified and treated. Frequent small meals are offered with the cat feeding in an upright position. The upright position should be maintained for at least 10 minutes after eating to allow for gravity-assisted passage of food into the stomach. This is best accomplished by having the owner hold the cat over their shoulder so that the esophagus is in a vertical position.44 Different types of diets should be offered to determine which is best for the individual patient; calorically dense diets may be beneficial for patients with weight loss. Prokinetic drugs, such as cisapride, stimulate smooth muscle, but since most of the esophagus is skeletal muscle, the efficacy of such drugs is questionable for treatment of megaesophagus. Prokinetic drugs also increase lower esophageal sphincter tone and may increase esophageal transit time, neither of which is desirable in patients with megaesophagus.

Vascular Ring Anomaly Vascular ring anomalies are congenital malformations of the great vessels that entrap the thoracic esophagus and cause obstruction. The most commonly reported anomaly is persistent right aortic arch. The esophagus is entrapped by the aorta on the right, the ligamentum arteriosum and the pulmonary trunk on the left, and the heart base ventrally. Other vascular anomalies are rarely described in cats, such as a double aortic arch described in a Siamese cat.56 Onset of clinical signs occurs around the time of weaning to solid food so that most affected cats are presented at less than 6 months of age. The most common

clinical sign is regurgitation, and most patients are underweight. A distended cervical esophagus may be palpated, and secondary aspiration pneumonia may occur. A history of regurgitation since weaning is very suggestive of a vascular ring anomaly, but other causes of regurgitation must be ruled out. Survey radiographs show a dilated esophagus cranial to the heart, while the caudal esophagus is usually normal. The bulge of the aortic arch normally seen on a ventrodorsal radiographic view is absent. An esophagram is used to confirm the location of the obstruction and the severity of disease. Definitive treatment is surgical repair of the vascular defect (i.e., ligation and transection of the ligamentosum arteriosum). Some patients will require nutritional support through gastrostomy tube feeding and treatment for aspiration pneumonia before surgery. Early diagnosis and surgical intervention brings the best prognosis for return of normal esophageal function. Some affected cats are left with residual esophageal hypomotility, which is managed as for idiopathic megaesophagus.

Neoplasia Esophageal neoplasia is rare in the cat as in the dog. Although parasitic granulomas caused by Spirocerca lupi are associated with esophageal neoplasia in dogs, this parasite does not infect cats. Both primary and metastatic esophageal tumors can occur in the cat. Squamous cell carcinoma is the most common primary esophageal tumor in cats and is often found in the caudal two thirds of the esophagus.7,22,25,46 Affected cats are middle aged or older. Clinical signs are typically those associated with esophageal obstruction, such as regurgitation, dysphagia, odynophagia, and salivation. Patients with advanced disease may suffer anorexia, depression, and weight loss. On physical examination, an esophageal mass may or may not be palpable. Survey and contrast radiographs reveal esophageal dilation, a soft tissue mass, or periesophageal lesions that displace the esophagus. Computed tomography is useful to identify periesophageal or intraluminal masses. Definitive diagnosis is made with endoscopy and biopsy. Mucosal biopsies are difficult to obtain, because the esophageal mucosa is tough; exfoliative cytology may also be helpful. Treatment is rarely undertaken, because disease is often advanced at the time of diagnosis, and many patients have complications such as aspiration pneumonia. Palliation may be attempted with chemotherapy or radiation, although data on efficacy is unavailable. In general, squamous cell carcinomas in other anatomic locations respond poorly to treatment. Surgical resection may be attempted if anastomosis can be accomplished without excessive tension.


A

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B

FIGURE 23-7 Lateral (A) and ventrodorsal (B) esophagrams of a cat with a hiatal hernia showing protrusion of the distal esophagus and stomach through the esophageal hiatus of the diaphragm into the thoracic cavity. (Courtesy Dr. John Graham.)

Hiatal Hernia Disorders of the hiatus are rare in cats. Hiatal hernia is protrusion of the distal esophagus and stomach through the esophageal hiatus of the diaphragm into the thoracic cavity; the protrusion may be intermittent (“sliding”) or persistent. Other organs are occasionally involved, such as the omentum.40 This is distinct from a gastroesophageal intussusception where the stomach is prolapsed into the lumen of the distal esophagus.35,49 Both congenital and traumatic hiatal hernias have been described in cats.9,23,41,42,52 Congenital hernias appear to be more common than acquired hernias, and affected cats typically present with clinical signs before 1 year of age. It is suspected that increased inspiratory effort associated with upper airway obstruction, such as a nasopharyngeal polyp, may also lead to development of hiatal hernia.23 Hiatal herniation reduces lower esophageal sphincter pressure. Clinical signs associated with hiatal hernia, such as intermittent vomiting and regurgitation, may be because of reflux esophagitis, hypomotility, or obstruction. Large hernias and secondary aspiration pneumonia may be associated with respiratory distress. Survey radiographs may reveal a gas-filled soft tissue density in the caudal dorsal mediastinum. An esophagram will show the gastroesophageal junction and gastric rugae cranial to the diaphragm (Figure 23-7). Both fluoroscopy and endoscopy may be useful for diagnosis but are not typically necessary. The prognosis for cats with hiatal hernia is considered to be good. A trial of medical management (as for reflux esophagitis) for 1 month has been recommended before

surgery.34 Surgery is the treatment of choice for large defects, especially in young cats with congenital disease or cats that have failed medical management. Various reconstructive surgical techniques have been described.14

References 1. Adamama-Moraitou KK, Rallis TS, Prassinos NN et al: Benign esophageal stricture in the dog and cat: a retrospective study of 20 cases, Can J Vet Res 66:55, 2002. 2. Augusto M, Kraijer M, Pratschke KM: Chronic oesophageal foreign body in a cat, J Feline Med Surg 7:237, 2005. 3. Battersby I, Doyle R: Use of a biodegradable self-expanding stent in the management of a benign oesophageal stricture in a cat, J Small Anim Pract 51:49, 2009. 4. Beatty JA, Swift N, Foster DJ et al: Suspected clindamycinassociated oesophageal injury in cats: five cases, J Feline Med Surg 8:412, 2006. 5. Bebchuk TN: Feline gastrointestinal foreign bodies, Vet Clin North Am Small Anim Pract 32:861, 2002. 6. Bennett AD, MacPhail CM, Gibbons DS et al: A comparative study evaluating the esophageal transit time of eight healthy cats when pilled with the FlavoRx pill glide versus pill delivery treats, J Feline Med Surg 12:286, 2010. 7. Berube D, Scott-Moncrieff JC, Rohleder J et al: Primary esophageal squamous cell carcinoma in a cat, J Am Anim Hosp Assoc 45:291, 2009. 8. Bissett SA, Davis J, Subler K et al: Risk factors and outcome of bougienage for treatment of benign esophageal strictures in dogs and cats: 28 cases (1995-2004), J Am Vet Med Assoc 235:844, 2009. 9. Brinkley CH: Hiatus hernia in a cat, Vet Rec 127:46, 1990. 10. Byron JK, Shadwick SR, Bennett AR: Megaesophagus in a 6-monthold cat secondary to a nasopharyngeal polyp, J Feline Med Surg 12:322, 2010. 11. Cottrell BD: Post anaesthetic oesophageal stricture in the cat, Vet Rec 118:645, 1986.

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12. Durocher L, Johnson SE, Green E: Esophageal diverticulum associated with a trichobezoar in a cat, J Am Anim Hosp Assoc 45:142, 2009. 13. Forbes DC, Leishman DE: Megaesophagus in a cat, Can Vet J 26:354, 1985. 14. Fossum T, Hedlund C: Surgery of the digestive system. In Fossum TW, editor: Small animal surgery, ed 3, St Louis, 2007, Mosby Elsevier, p 339. 15. Galatos AD, Rallis T, Raptopoulos D: Post anaesthetic oesophageal stricture formation in three cats, J Small Anim Pract 35:638, 1994. 16. Galatos AD, Savas I, Prassinos NN et al: Gastro-oesophageal reflux during thiopentone or propofol anaesthesia in the cat, J Vet Med A Physiol Pathol Clin Med 48:287, 2001. 17. German AJ, Cannon MJ, Dye C et al: Oesophageal strictures in cats associated with doxycycline therapy, J Feline Med Surg 7:33, 2005. 18. Glanemann B, Hildebrandt N, Schneider MA et al: Recurrent single oesophageal stricture treated with a self-expanding stent in a cat, J Feline Med Surg 10:505, 2008. 19. Glazer A, Walters P: Esophagitis and esophageal strictures, Comp Contin Edu Pract Vet 30:281, 2008. 20. Graham J, Lipman A, Newell S et al: Esophageal transit of capsules in clinically normal cats, Am J Vet Res 61:655, 2000. 21. Griffin B, Beard DM, Klopfenstein KA: Use of butter to facilitate the passage of tablets through the esophagus in cats [abstract], J Vet Intern Med 17:445, 2003. 22. Gualtieri M, Monzeglio MG, Di Giancamillo M: Oesophageal squamous cell carcinoma in two cats, J Small Anim Pract 40:79, 1999. 23. Gualtieri M, Olivero D: Reflux esophagitis in three cats associated with metaplastic columnar esophageal epithelium, J Am Anim Hosp Assoc 42:65, 2006. 24. Han E, Broussard J, Baer K: Feline esophagitis secondary to gastroesophageal reflux disease: clinical signs and radiographic, endoscopic, and histopathologic findings, J Am Anim Hosp Assoc 39:161, 2003. 25. Happe RP, van der Gaag I, Wolvekamp WT et al: Esophageal squamous cell carcinoma in two cats, Tijdschr Diergeneeskd 103: 1080, 1978. 26. Harai BH, Johnson SE, Sherding RG: Endoscopically guided balloon dilatation of benign esophageal strictures in 6 cats and 7 dogs, J Vet Intern Med 9:332, 1995. 27. Hashim MA, Waterman AE: Effects of thiopentone, propofol, alphaxalone-alphadolone, ketamine and xylazine-ketamine on lower oesophageal sphincter pressure and barrier pressure in cats, Vet Rec 129:137, 1991. 28. Hashim MA, Waterman AE: Effects of acepromazine, pethidine and atropine premedication on lower oesophageal sphincter pressure and barrier pressure in anaesthetised cats, Vet Rec 133:158, 1993. 29. Hoenig M, Mahaffey MB, Parnell PG et al: Megaesophagus in two cats, J Am Vet Med Assoc 196:763, 1990. 30. Jaspersen D: Drug-induced oesophageal disorders: pathogenesis, incidence, prevention and management, Drug Saf 22:237, 2000. 31. Joseph R, Kuzi S, Lavy E et al: Transient megaoesophagus and oesophagitis following diaphragmatic rupture repair in a cat, J Feline Med Surg 10:284, 2008. 32. Leib MS, Dinnel H, Ward DL et al: Endoscopic balloon dilation of benign esophageal strictures in dogs and cats, J Vet Intern Med 15:547, 2001. 33. Lobetti R, Leisewitz A: Gastroesophageal reflux in two cats, Feline Pract 24:5, 1996. 34. Lorinson D, Bright RM: Long-term outcome of medical and surgical treatment of hiatal hernias in dogs and cats: 27 cases (19781996), J Am Vet Med Assoc 213:381, 1998. 35. Martinez NI, Cook W, Troy GC et al: Intermittent gastroesophageal intussusception in a cat with idiopathic megaesophagus, J Am Anim Hosp Assoc 37:234, 2001.

36. McGrotty Y, Knottenbelt C: Oesophageal stricture in a cat due to oral administration of tetracycline, J Small Anim Pract 43:221, 2002. 37. Melendez L, Twedt D, Wright M: Suspected doxycycline-induced esophagitis with esophageal stricture formation in three cats, Feline Pract 28:10, 2000. 38. Melendez LD, Twedt DC, Weyrauch EA et al: Conservative therapy using balloon dilation for intramural, inflammatory esophageal strictures in dogs and cats: a retrospective study of 23 cases (1987-1997), Eur J Comp Gastroenterol 3:31, 1998. 39. Michels G, Jones B, Huss B et al: Endoscopic and surgical retrieval of fishhooks from the stomach and esophagus in dogs and cats: 75 cases (1977-1993), J Am Vet Med Assoc 207:1194, 1995. 40. Mitsuoka K, Tanaka R, Nagashima Y et al: Omental herniation through the esophageal hiatus in a cat, J Vet Med Sci 64:1157, 2002. 41. Owen MC, Morris PJ, Bateman RS: Concurrent gastro-oesophageal intussusception, trichobezoar and hiatal hernia in a cat, N Z Vet J 53:371, 2005. 42. Papazoglou L, Patsikas M, Rallis T et al: Hiatal hernia with esophageal stricture in a cat, Feline Pract 28:10, 2000. 43. Pearson H, Darke PG, Gibbs C et al: Reflux oesophagitis and stricture formation after anaesthesia: a review of seven cases in dogs and cats, J Small Anim Pract 19:507, 1978. 44. Ridgway MD, Graves TK: Megaesophagus, Clin Brief 8:43, 2010. 45. Sellon RK, Willard MD: Esophagitis and esophageal strictures, Vet Clin North Am Sm Anim Pract 33:945, 2003. 46. Shinozuka J, Nakayama H, Suzuki M et al: Esophageal adenosquamous carcinoma in a cat, J Vet Med Sci 63:91, 2001. 47. Sideri AI, Galatos AD, Kazakos GM et al: Gastro-oesophageal reflux during anaesthesia in the kitten: comparison between use of a laryngeal mask airway or an endotracheal tube, Vet Anaesth Analg 36:547, 2009. 48. Trumble C: Oesophageal stricture in cats associated with use of the hyclate (hydrochloride) salt of doxycycline [letter], J Feline Med Surg 7:241, 2005. 49. Van Camp S, Love N, Kumaresan S: Gastroesophageal intussusception in a cat, Vet Radiol Ultrasound 39:190, 1998. 50. Van Geffen C, Saunders JH, Vandevelde B et al: Idiopathic megaoesophagus and intermittent gastro-oesophageal intussusception in a cat, J Small Anim Pract 47:471, 2006. 51. Van Stee EW, Ward CL, Duffy ML: Recurrent esophageal hairballs in a cat (a case report), Vet Med 75:1873, 1980. 52. Waldron DR, Moon M, Leib MS et al: Oesophageal hiatal hernia in two cats, J Small Anim Pract 31:259, 1990. 53. Westfall D, Twedt D, Steyn P et al: Evaluation of esophageal transit of tablets and capsules in 30 cats, J Vet Intern Med 15:467, 2001. 54. Weyrauch E, Willard M: Esophagitis and benign esophageal strictures, Comp Contin Edu Pract Vet 20:203, 1998. 55. Willard M: Clinical manifestations of gastrointestinal disorders. In Nelson RW, Couto CG, editors: Small animal internal medicine, ed 4, St Louis, 2009, Mosby Elsevier, p 351. 56. Yarim M, Gultiken ME, Ozturk S et al: Double aortic arch in a Siamese cat, Vet Pathol 36:340, 1999.

DISEASES OF THE STOMACH Susan E. Little The stomach is a frequent site for gastrointestinal problems in cats, and the most common gastric problems are described in this chapter. Some conditions such as gastric dilatation-volvulus are often reported in dogs but rarely reported in cats. In one report of three feline cases, all were associated with diaphragmatic hernia.15 Gastric parasites, the diagnostic approach to the vomiting cat,


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FIGURE 23-10 Endoscopic appearance of normal gastric folds in the cat. Prominent rugal folds are visible in the greater curvature of the stomach. (Courtesy Prof. Danièlle Gunn-Moore.)

FIGURE 23-8 The five regions of the feline stomach. (From Twedt DC: Diseases of the stomach. In Sherding RG, editor: The cat: diseases and clinical management, ed 2, Philadelphia, 1994, Saunders, Figure 38-1, p 1182.)

FIGURE 23-11 Ultrasonographic appearance of the normal feline stomach showing the characteristic rosette or wagon wheel appearance. (Courtesy Dr. John Graham.)

FIGURE 23-9 Endoscopic view of the normal feline pylorus. The pylorus is readily visible during endoscopic examination, and may be open or closed. (Courtesy Prof. Danièlle Gunn-Moore.)

and therapeutics for vomiting are covered elsewhere in this chapter. The anatomy of the feline stomach is similar to that of other mammals having a simple glandular stomach. Most of the stomach is situated on the left side of the abdominal cavity. It has five regions, starting from the lower esophageal sphincter: cardia, fundus, body, antrum, and pylorus (Figure 23-8). The pylorus of the cat is unique compared with other species in that it is narrow and has high resistance in order to maintain a tight seal (Figure 23-9). The normal stomach has a characteristic appearance when viewed using endoscopy (Figure 23-10) or ultrasonography (Figure 23-11).

The gastric emptying time of normal cats is shorter than that of other mammals. In one study, the gastric emptying half-time for solid food in normal cats was 1.4 to 3.6 hours.53 This implies prolonged fasting (longer than 8 hours) in preparation for anesthesia and surgery is unnecessary.

CLINICAL PRESENTATION The main clinical sign of gastric disease is vomiting, but it is important to note that vomiting is also associated with many nongastric problems, including concurrent intestinal disease, such as enteritis or colitis. Vomiting patients therefore require a thorough physical examination and diagnostic plan to determine the cause. Vomiting must be distinguished from regurgitation, which is primarily associated with esophageal disease (see Table 23-10). Vomitus often contains food, hair, refluxed bile,

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or blood. Fresh blood may appear as large or small clots. Older blood clots have a brown “coffee ground” appearance. Gastric bleeding may also cause melena. Other clinical signs may be associated with gastric disease, such as anorexia, weight loss, pain, lethargy, bloating, and nausea.

SPECIFIC DISEASES Gastritis Gastritis may be acute or chronic in nature, and this distinction may be useful in assessing the potential cause. For example, cats with acute gastritis may be suspected of foreign body or plant ingestion, drug or toxin exposure (see Chapter 31), or dietary indiscretion. Cats with chronic gastritis may be suspected of parasitism, Helicobacter spp. infection, or dietary intolerance or hypersensitivity (see Chapter 17). Chronic lymphocytic plasmacytic gastritis of unknown etiology is also a common cause of chronic vomiting. Whenever possible, a specific underlying cause should be sought and treated. Acute Uncomplicated Gastritis Patients with sudden onset of vomiting may have an obvious cause in the history (e.g., dietary indiscretion), but in many cases, the cause is not apparent. Abdominal radiographs should be taken if foreign body ingestion is possible, especially in a young cat. If the patient is systemically well, further diagnostic testing may be postponed pending response to therapy. Treatment for uncomplicated acute gastritis is symptomatic and supportive. Clinical signs are expected to resolve in 24 to 48 hours; if signs persist, re-evaluation and further investigation is warranted. Subcutaneous fluid therapy using an isotonic balanced electrolyte solution may be used to correct mild fluid deficits (40%) in some locations.1,27,37,47,58 The importance of Helicobacter as a cause of gastric disease is cats is unclear; the bacteria may be found in the stomach of both clinically normal cats and cats with gastritis. The prevalence of Helicobacter infection is not higher in cats with gastritis compared with normal cats.61 Determination of the role of Helicobacter is also hampered by the paucity of controlled clinical trials that evaluate eradication of gastritis and clinical signs in infected cats. An immune response to infection characterized by gastric lymphoid hyperplasia is common, although the local immune response in cats is generally less severe than the response in humans infected with H. pylori. To date gastrointestinal ulcers have not been associated with Helicobacter infection in cats. Recent studies have suggested a possible association between Helicobacter infection and gastric lymphoma in cats, although more research is needed to confirm the association and understand the pathogenesis.7,32 Helicobacter spp. may be commensal in most cats, and perhaps loss of tolerance explains the development of gastritis in some individuals.49 Another possibility is that the inflammatory response is normally well managed and disease may

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result when there is an abnormality of the immunoregulatory system.21 The most commonly used methods for diagnosis of Helicobacter infection in cats are based on gastric specimens obtained during endoscopy (or laparotomy): exfoliative cytology, histopathologic examination of biopsy specimens, and rapid urease testing of biopsy specimens.28 However, it is important to note that even when Helicobacter organisms are identified, the infection may not be the cause of the patient’s clinical signs, and other causes of vomiting should always be evaluated. Exfoliative cytology is the least expensive and most easily performed diagnostic test. In one study, it was also the most sensitive diagnostic method when compared with urease testing and histologic examination.20 Brush cytology samples gathered during endoscopy are airdried on microscope slides and stained with Wright’s stain. The slide is examined at 100× magnification under oil immersion. Spiral bacteria are readily seen if present. At least 10 oil-immersion fields on two slides should be examined before determining a specimen is negative for Helicobacter-like organisms.28 Since Helicobacter produce abundant urease, a rapid urease test (e.g., CLOtest, Ballard Medical Products, Draper, Utah) may be used for diagnosis.38 The kit consists of an agar gel impregnated with urea and a pH indicator. A gastric biopsy sample is applied to the gel, and if urease is present, ammonia will form and change the pH (and thus the color) of the gel. The gel may change color rapidly (within 30 minutes), but 24 hours must elapse before the test can be considered negative.28 The more rapidly the color changes, the higher the bacterial load. Both false-positive and false-negative results are possible with rapid urease testing for various reasons, giving the test a sensitivity of 70% to 90%.28,37 Histopathologic examination of gastric biopsy samples using hemotoxylin and eosin (H&E) or silver stains is highly sensitive and specific in human studies for detection of Helicobacter-like organisms. The organisms are not equally distributed; so, examination of biopsy specimens from multiple sites will increase sensitivity. The bacteria may be seen in mucus on the surface epithelium as well as in the gastric pits, glandular lumen, and parietal cells. Organisms may also be seen submucosally within gastric lymphoid follicles.46 Histopathologic examination of biopsy samples also allows for assessment of other abnormalities. Mild to severe lymphocytic-plasmacytic or lymphocytic gastritis may be present. In humans combination therapy with antibiotics and antisecretory drugs is recommended to reduce the risk of gastric ulcers and cancer from H. pylori infection. Treatment is highly successful at eradicating both clinical signs and histologic changes in the gastric mucosa. Since Helicobacter infection is common in cats, yet no clear pathogenic role has been established, it is difficult

to know when treatment should be attempted. One expert recommends treating only patients with clinical signs of gastritis that have biopsy-confirmed Helicobacter infection with a treatment regimen of amoxicillin (20 mg/kg, every 12 hours, PO), clarithromycin (7.5 mg/ kg, every 12 hours, PO) and metronidazole (10 mg/kg, every 12 hours, PO) for 14 days.49 A common dilemma would be determining the treatment of choice for patients with lymphoplasmacytic inflammation of the stomach and small intestine and confirmed Helicobacter infection. Are such patients best treated for inflammatory bowel disease, Helicobacter infection, or both? Currently, guidelines for determining the best treatment approach are lacking. Also, few studies on the efficacy of combination therapy have been conducted in cats. Long-term eradication of infection may be difficult, and histopathologic resolution of gastritis may not be possible, which raises the question of whether Helicobacter is the true underlying cause.38,41 In one study, two cats with clinical gastritis and Helicobacter infection were treated with oral metronidazole, amoxicillin, and bismuth subsalicylate for 3 weeks and were also fed a commercial elimination diet.25 Posttreatment gastric biopsies were obtained a mean of 7 weeks after the cessation of treatment. Resolution of clinical signs occurred rapidly, and clearance of Helicobacter spp. was achieved at that time point, but gastric inflammation persisted in post-treatment biopsies. In another study, 13 cats with asymptomatic Helicobacter infection were treated with oral omeprazole, amoxicillin, metronidazole, and clarithromycin for 14 days.26 Treatment failed to eradicate infection in 4 of the cats based on molecular analysis of post-treatment gastric biopsies. It is unclear if treatment failure is because of recrudescence or reinfection. The reader is referred to excellent reviews of Helicobacter in cats for more information.27,38,48 Chronic Gastritis Chronic gastritis is common in cats with chronic intermittent vomiting. Ollulanus tricuspis is a worm that infects the stomach of cats, causing chronic gastritis, and it is difficult to diagnose (see below, Gastrointestinal Parasites). The worm is occasionally found on histologic examination of gastric biopsy samples.9 It is reasonable to treat empirically (fenbendazole 10 mg/kg, once daily, PO × 2 days) for this parasite when the cause of gastritis is not apparent.49 The frequency of vomiting in cats with chronic gastritis is highly variable, ranging from once or twice per week (and not necessarily every week) to more than once daily. Most patients are otherwise well, although other clinical signs (inappetence, anorexia, depression, or weight loss) are possible depending on disease severity. Results of routine laboratory testing are typically normal but may show neutrophilic leukocytosis,

FIGURE 23-14 Histopathologic image (40×) of a stomach biopsy from a 10-year-old cat with a history of chronic vomiting. Small lymphocytes are increased in number in the lamina propria; cellular debris is evident within some gastric glands. (Courtesy Dr. Sally Lester.)

eosinophilia, or hypoproteinemia. Survey and contrast radiographs are often normal. The most common finding on histopathologic examination of biopsy samples is lymphocytic plasmacytic (LP) gastritis (Figure 23-14). Some patients will also have concurrent evidence of LP inflammation in the small intestine, pancreas, and/or liver. Such patients will be treated for their concurrent problem; treatment of inflammatory bowel disease, pancreatitis, and cholangiohepatitis is covered elsewhere in this chapter. Some cats with chronic LP gastritis respond to treatment for dietary intolerance or hypersensitivity with a limited antigen diet (see Chapter 17). Patients with moderate to severe LP gastritis may be best treated with a limited antigen diet and immunosuppressive therapy (prednisolone 1 to 2 mg/kg/day, PO tapering to every other day at the lowest dose that controls clinical signs). Patients that fail this initial treatment approach may require additional immunosuppressive therapy, such as chlorambucil (see Table 23-9). Occasionally, cats with chronic gastritis are diagnosed with eosinophilic inflammation on histopathologic examination of biopsy specimens. Treatment is similar to that for LP gastritis, although such patients should be evaluated for evidence of hypereosinophilic syndrome and eosinophilic enteritis. Eosinophilic fibrosing gastritis was suspected to be caused by toxoplasmosis in one case report.33

Gastric Ulceration Gastric or gastroduodenal ulcerations are uncommon in the cat compared with the dog and may be caused by a variety of disorders, both gastric and nongastric.29 Classical clinical signs include vomiting, hematemesis, and melena. However, in one review of eight cats, hematemesis and melena were present in less than one third of


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cases.29 Depending on the underlying cause and severity of disease, abdominal pain, anorexia, lethargy, pale mucous membranes, and drooling may also be seen. Cats with neoplastic disease may have prolonged clinical signs and are more likely to present with anorexia and weight loss.29 Cats with perforated ulcers may or may not present with signs of shock. Diagnosis may be problematic because the clinical signs and physical examination findings are often not specific, even in cats with perforated ulcerations.8 The causes of gastric ulceration in cats are not well characterized. In dogs the most common cause is the administration of ulcerogenic drugs, particularly NSAIDs, either alone or in combination with corticosteroids. Several cases of NSAID-induced gastroduodenal ulceration or perforation have been reported in cats.8,34,45 Additional cases may be reported in the future, because long-term administration of these drugs is gaining in popularity for treatment of chronic diseases such as osteoarthritis. NSAIDs cause direct mucosal damage and interfere with prostaglandin synthesis. Although inhibition of the COX-1 enzyme is thought to be the cause of adverse effects, such as gastric ulceration, even COX-2–selective drugs have been associated with adverse effects, and safety in sick cats is not well evaluated. Recently, guidelines for the long-term use of NSAIDs in cats were published by the International Society of Feline Medicine and the American Association of Feline Practitioners.51 The recommendations include administering NSAIDs either with or shortly after food, withholding therapy if inappetence or anorexia develops, determining dose based on lean body weight, and titrating to the lowest effective dose. Neoplastic causes of gastric ulceration include systemic mastocytosis, mast cell tumor, lymphosarcoma, adenocarcinoma, and gastrinoma (Zollinger-Ellison syndrome). Cats with chronic renal disease may suffer mucosal damage from uremic toxins and increased gastric acid production secondary to hypergastrinemia (because of decreased renal metabolism of gastrin).18 Hepatic disease is a cause of gastric ulceration in dogs but is uncommonly reported in cats.23 Recent anesthesia and surgery have been implicated as a cause of gastric ulceration and perforation, perhaps through hypovolemia, hypoperfusion, or stress.8,29 Other non-neoplastic causes reported for gastric or gastroduodenal ulceration in cats include parasites (e.g., Ollulanus tricuspis, Toxocara cati, Aonchotheca putorii, Gnathostoma spp.), bacterial infections, toxins, inflammatory bowel disease, and foreign bodies. One case report describes a cat with severe gastric ulceration caused by intoxication with Dieffenbachia leaves.36 In some case reports, the cause for the gastric ulcerations could not be determined. A minimum database should be collected for cats suspected of gastric ulceration, to identify underlying diseases. Anemia, usually regenerative, may be present.

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Other findings will be dependent on the presence of underlying diseases; for example, azotemia and isosthenuria may indicate renal disease. Electrolyte and acid– base abnormalities may be because of chronic vomiting and anorexia. Survey and contrast radiographs and ultrasonography are primarily useful to rule out other causes for the clinical signs, such as foreign bodies. Cats with perforated ulcers may have evidence of pneumoperitoneum (sometimes severe) on plain radiographs or ultrasonographs, and this is an indication for surgical exploration.6,8,24,31,34 Evidence of peritonitis on imaging studies should be followed with peritoneal fluid analysis. A definitive diagnosis may be made using endoscopy, which allows direct visualization of lesions and collection of biopsy samples. However, some cats with gastric ulceration present in poor condition, which may preclude the use of endoscopy because of anesthetic risk and risk of ulcer perforation.29 The location of ulcers is typically pyloroantral or fundic in cats with nonneoplastic disease.8,29 Areas of erosion may appear pale or hemorrhagic; the mucosa is often friable and bleeds easily. Fresh or clotted blood may be seen in the stomach lumen. In some cases, mucosal ulceration must be distinguished from ulcerated tumors. NSAID-induced ulcers are typically found in the antrum and do not have marked mucosal thickening; ulcerated tumors frequently have thickened edges and surrounding mucosa.49 Biopsy samples should be taken at the periphery of the ulcer to avoid perforation. Treatment should be directed at any underlying disorder. Treatment for NSAID toxicity is described in Chapter 31. General supportive measures include fluid therapy and electrolyte replacement; blood transfusion may also be required (see Chapter 25). Gastric acid production can be decreased with the use of H2-receptor blockers or proton pump inhibitors, and sucralfate is used as a mucosal protectant (see Table 23-5). Sucralfate may inhibit absorption of other oral medications and should be given 2 hours apart from other drugs. If vomiting is severe or persistent, antiemetic therapy is warranted (see Table 23-3). Analgesia should be provided for painful patients; a good choice is the opioid buprenorphine (see Table 6-1). Broad-spectrum antibiotic therapy is indicated for patients with significant mucosal barrier dysfunction, perforation, leukopenia and/or neutrophilia, fever, and melena. Surgical intervention is warranted for patients with life-threatening hemorrhage, failure to respond to medical management, or evidence of perforation.29 The entire abdominal cavity and gastrointestinal tract should be thoroughly explored to locate extragastrointestinal lesions, non-perforated ulcers, and multiple ulcers. In one case series, nonperforated ulcers were detected at laparotomy by association with adhesions or a gastric mass.29 Surgical management includes débridement and

suturing of the ulcer site as well as collection of biopsy samples for histopathologic examination. The prognosis for recovery was excellent in two studies, particularly for cats with non-neoplastic causes of gastric or gastroduodenal ulceration.8,29 In one study of seven cats with perforated gastric or duodenal ulcers, the survival rate was low (14%).23

Gastric Motility Disorders and Delayed Gastric Emptying Disorders of gastric motility are better characterized in dogs than in cats. The most common clinical sign is vomiting of undigested food 8 hours or more after a meal. If outflow obstruction is present, vomiting may be projectile. There may also be a history of recurrent trichobezoars. Various disorders are associated with impaired gastric motility, such as chronic gastritis, drug therapy (e.g., anticholinergic and narcotic drugs), dysautonomia, gastric neoplasia, metabolic disorders (e.g., hypokalemia), and temporary postsurgical gastroparesis. In some cases of chronic motility dysfunction, no cause can be identified. Outflow obstruction may be caused by neoplasia, foreign bodies, and extragastric masses. Pyloric stenosis is infrequently documented in young cats, often Siamese cats.4,40,55 Since the range of underlying disorders is diverse, the diagnostic approach should allow for detection of both gastric and nongastric disorders. A minimum database (CBC, serum chemistries, urinalysis, feline leukemia virus [FeLV] and feline immunodeficiency virus [FIV] serology) is used to establish overall health status. Radiographs are used to confirm presence of food in the stomach for longer than 8 hours. Ultrasonography may detect gastric lesions, such as masses. Endoscopy is used to identify outflow obstruction as well as other lesions, such as ulcers, and evidence of gastritis. Assessment of gastric emptying using nuclear scintigraphy is the most accurate method but is limited to referral centers. Gastric emptying times for liquids, canned food, and dry diets have been established using nuclear scintigraphy.11,16,17 However, emptying times are variable, depending on the amount and type of diet fed as well as the amount of water ingested. Even the shape of kibble affects emptying time.2 Radiographic contrast series are widely used, but gastric emptying times are variable for barium in either liquid form or mixed with canned food. Contrast radiography using liquid barium (8 to 10 mL/kg) is performed in a fasted patient. Radiographs are taken immediately after administration of the barium and again at 15 and 30 minutes, in some cases, also at 1 and 3 hours. Liquid barium is expected to enter the duodenum no more than 30 minutes after administration, and the stomach should be completely empty of barium within 3 hours. The clinician should be aware that some cats with gastric motility disorders will have

a normal gastric emptying time with liquid barium. Barium can also be mixed with canned food and fed as a meal; retention of barium-containing food in the stomach for more than 8 to 12 hours is abnormal. Gastric emptying time may also be established with the use of barium impregnated polyspheres (BIPS; Med I.D. Systems, Grand Rapids, Mich.) and radiography. Gastric emptying times for BIPS have been established in healthy fasted and fed cats as well as in sedated cats,10,52 but the values do not correlate well with scintigraphic studies.17 A mixture of small (1.5 mm) and large (5 mm) spheres are administered with food, and two to four radiographs are taken over the next 24 hours. The small spheres are intended to mimic liquid transit time and the large spheres solid transit time. However, studies assessing the clinical relevance of this method are lacking. One review concluded that BIPS are probably sufficiently sensitive to detect grossly delayed gastric emptying.60 Treatment of gastric emptying disorders is directed at identifiable causes. Treatment for gastric ulcers, chronic gastritis, and foreign bodies is described elsewhere in this chapter. Pyloric stenosis is managed surgically. If no outflow obstruction exists, treatment with prokinetic agents, such as metoclopramide or cisapride, may be beneficial (see Table 23-3).

Gastric Neoplasia Gastric tumors account for less than 1% of malignancies in dogs and cats.30 Benign gastric tumors are even less common than gastric malignancies. Gastric smooth muscle hamartoma has been reported in one 11-year-old cat.50 Although adenocarcinoma is the most common gastric cancer of the dog, lymphoma is the most common gastric cancer in the cat. Feline gastrointestinal lymphoma occurs as two major types: small cell (lymphocytic) and the more aggressive large cell (lymphoblastic) form. Small cell lymphomas are more frequently enteric.57 In one study of 12 cats with gastric lymphoma, diffuse large B-lymphocyte tumors of immunoblastic nuclear type predominated.42 Gastric lymphoma is not associated with FeLV, and the role of Helicobacter in the development of gastric lymphoma in cats requires investigation.7 Adenocarcinoma,12,13,54 plasmacytoma,62 and gastric carcinoid44 have also been described. The Siamese cat may be predisposed to adenocarcinoma.12,54 As would be expected, most cats with gastric neoplasia are older cats. As for most gastric diseases, vomiting is the most common clinical sign of neoplasia. The vomitus may contain blood and melena may be present. Other clinical signs include anorexia, weight loss, bloating, and depression. Perforation of the tumor may occur, leading to pneumoperitoneum or septic peritonitis. Clinical signs present gradually and are often present for weeks to


457

A

B FIGURE 23-15 Radiographic (A) and ultrasonographic (B) images of a cat with a gastric mass that was determined to be lymphoma on biopsy. (Courtesy Dr. John Graham.)

months. Physical examination findings are nonspecific, although occasionally a gastric mass or gastric thickening may be palpated if the stomach is markedly enlarged. Results of routine diagnostic testing are generally nonspecific; anemia may be associated with ulceration. Survey or contrast radiography may reveal a mass (Figure 23-15, A); other findings include delayed gastric emptying, impaired motility, and mucosal ulceration. Ultrasonography is also useful for diagnosis and can be used to guide needle aspirates of masses (Figure 23-15, B). Endoscopy allows for visualization of lesions as well as the ability to obtain partial thickness biopsy samples. Problems with interpretation of endoscopic biopsy samples include detection of necrosis, inflammation, and ulceration rather than the primary lesion. In dogs some neoplastic lesions are submucosal, making it very difficult to obtain diagnostic samples by endoscopy. Therefore several biopsies should be taken and masses should be biopsied multiple times in the same place to sample deeper tissues. The center of ulcerated lesions should not be biopsied. Surgical biopsies are more reliable for diagnosis.

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FIGURE 23-16 Surgical appearance of a gastric mass caused by small cell lymphoma. (Courtesy Dr. Randolph Baral.)

Surgical resection is the most common treatment for gastric neoplasia other than lymphoma (Figure 23-16). The prognosis for most patients is poor, typically because of debilitation, concurrent diseases, and recurrent or metastatic disease.30 The success of chemotherapy for lymphoma depends on cell type, with small cell tumors carrying a better prognosis than large cell tumors.

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13. Dennis MM, Bennett N, Ehrhart EJ: Gastric adenocarcinoma and chronic gastritis in two related Persian cats, Vet Pathol 43:358, 2006. 14. Durocher L, Johnson SE, Green E: Esophageal diverticulum associated with a trichobezoar in a cat, J Am Anim Hosp Assoc 45:142, 2009. 15. Formaggini L, Schmidt K, De Lorenzi D: Gastric dilatationvolvulus associated with diaphragmatic hernia in three cats: clinical presentation, surgical treatment and presumptive aetiology, J Feline Med Surg 10:198, 2008. 16. Goggin JM, Hoskinson JJ, Butine MD et al: Scintigraphic assessment of gastric emptying of canned and dry diets in healthy cats, Am J Vet Res 59:388, 1998. 17. Goggin JM, Hoskinson JJ, Kirk CA et al: Comparison of gastric emptying times in healthy cats simultaneously evaluated with radiopaque markers and nuclear scintigraphy, Vet Radiol Ultrasound 40:89, 1999. 18. Goldstein R, Marks S, Kass P et al: Gastrin concentrations in plasma of cats with chronic renal failure, J Am Vet Med Assoc 213:826, 1998. 19. Haesebrouck F, Pasmans F, Flahou B et al: Gastric helicobacters in domestic animals and nonhuman primates and their significance for human health, Clin Microbiol Rev 22:202, 2009. 20. Happonen I, Saari S, Castren L et al: Comparison of diagnostic methods for detecting gastric Helicobacter-like organisms in dogs and cats, J Comp Pathol 115:117, 1996. 21. Harbour S, Sutton P: Immunogenicity and pathogenicity of Helicobacter infections of veterinary animals, Vet Immunol Immunopathol 122:191, 2008. 22. Hayes G: Gastrointestinal foreign bodies in dogs and cats: a retrospective study of 208 cases, J Small Anim Pract 50:576, 2009. 23. Hinton L, McLoughlin M, Johnson S et al: Spontaneous gastroduodenal perforation in 16 dogs and seven cats (1982-1999), J Am Anim Hosp Assoc 38:176, 2002. 24. Itoh T, Nibe K, Naganobu K: Tension pneumoperitoneum because of gastric perforation in a cat, J Vet Med Sci 67:617, 2005. 25. Jergens AE, Pressel M, Crandell J et al: Fluorescence in situ hybridization confirms clearance of visible Helicobacter spp. associated with gastritis in dogs and cats, J Vet Intern Med 23:16, 2009. 26. Khoshnegah J, Jamshidi S, Mohammadi M, Sasani F: The efficacy and safety of long-term Helicobacter species quadruple therapy in asymptomatic cats with naturally acquired infection, J Feline Med Surg 13:88, 2011. 27. Lecoindre P, Chevallier M, Peyrol S et al: Gastric heliocbacters in cats, J Feline Med Surg 2:19, 2000. 28. Leib M, Duncan R: Diagnosing gastric Helicobacter infections in dogs and cats, Comp Contin Edu Pract Vet 27:221, 2005. 29. Liptak J, Hunt G, Barrs V et al: Gastroduodenal ulceration in cats: eight cases and a review of the literature, J Feline Med Surg 4:27, 2002. 30. Liptak JM, Withrow SJ: Cancer of the gastrointestinal tract. In Withrow SJ, Vail DM, editors: Withrow & MacEwen’s small animal clinical oncology, ed 4, St Louis, 2007, Saunders Elsevier, p 455. 31. Lykken JD, Brisson BA, Etue SM: Pneumoperitoneum secondary to a perforated gastric ulcer in a cat, J Am Vet Med Assoc 222:1713, 2003. 32. Marini RP, Fox JG, White H et al: Helicobacter spp. influences the development of primary gastric lymphoma in cats: a viable hypothesis, Gut 49:A52, 2001. 33. McConnell JF, Sparkes AH, Blunden AS et al: Eosinophilic fibrosing gastritis and toxoplasmosis in a cat, J Feline Med Surg 9:82, 2007. 34. Mellanby RJ, Baines EA, Herrtage ME: Spontaneous pneumoperitoneum in two cats, J Small Anim Pract 43:543, 2002. 35. Michels G, Jones B, Huss B et al: Endoscopic and surgical retrieval of fishhooks from the stomach and esophagus in dogs and cats: 75 cases (1977-1993), J Am Vet Med Assoc 207:1194, 1995.

36. Muller N, Glaus T, Gardelle O: [Extensive stomach ulcers because of Dieffenbachia intoxication in a cat], Tierarztl Prax Ausg K Klientiere Heimtiere 26:404, 1998. 37. Neiger R, Dieterich C, Burnens A et al: Detection and prevalence of Helicobacter infection in pet cats, J Clin Microbiol 36:634, 1998. 38. Neiger R, Simpson K: Helicobacter infection in dogs and cats: facts and fiction, J Vet Intern Med 14:125, 2000. 39. Papich MG, Davis CA, Davis LE: Absorption of salicylate from an antidiarrheal preparation in dogs and cats, J Am Anim Hosp Assoc 23:221, 1987. 40. Pearson H, Gaskell CJ, Gibbs C et al: Pyloric and oesophageal dysfunction in the cat, J Small Anim Pract 15:487, 1974. 41. Perkins SE, Yan LL, Shen Z et al: Use of PCR and culture to detect Helicobacter pylori in naturally infected cats following triple antimicrobial therapy, Antimicrob Agents Chemother 40:1486, 1996. 42. Pohlman LM, Higginbotham ML, Welles EG et al: Immunophenotypic and histologic classification of 50 cases of feline gastrointestinal lymphoma, Vet Pathol 46:259, 2009. 43. Poortinga E: Copper penny ingestion in a cat, Can Vet J 36:634, 1995. 44. Rossmeisl JH Jr, Forrester SD, Robertson JL et al: Chronic vomiting associated with a gastric carcinoid in a cat, J Am Anim Hosp Assoc 38:61, 2002. 45. Runk A, Kyles A, Downs M: Duodenal perforation in a cat following the administration of nonsteroidal anti-inflammatory medication, J Am Anim Hosp Assoc 35:52, 1998. 46. Serna JH, Genta RM, Lichtenberger LM et al: Invasive Helicobacterlike organisms in feline gastric mucosa, Helicobacter 2:40, 1997. 47. Shojaee Tabrizi A, Jamshidi S, Oghalaei A et al: Identification of Helicobacter spp. in oral secretions vs. gastric mucosa of stray cats, Vet Microbiol 140:142, 2010. 48. Simpson K, Neiger R, DeNovo R et al: The relationship of Helicobacter spp. infection to gastric disease in dogs and cats, J Vet Intern Med 14:228, 2000. 49. Simpson KW: Diseases of the stomach. In Ettinger SJ, Feldman EC, editors: Textbook of veterinary internal medicine, ed 6, St Louis, 2005, Saunders Elsevier, p 1310. 50. Smith TJ, Baltzer WI, Ruaux CG et al: Gastric smooth muscle hamartoma in a cat, J Feline Med Surg 12:334, 2010. 51. Sparkes AH, Heiene R, Lascelles BDX et al: ISFM and AAFP consensus guidelines: Long-term use of NSAIDs in cats, J Feline Med Surg 12:521, 2010. 52. Sparkes AH, Papasouliotis K, Barr FJ et al: Reference ranges for gastrointestinal transit of barium-impregnated polyethylene spheres in healthy cats, J Small Anim Pract 38:340, 1997. 53. Steyn PF, Twedt D, Toombs W: The scintigraphic evaluation of solid phase gastric emptying in normal cats, Vet Radiol Ultrasound 36:327, 1995. 54. Turk MA, Gallina AM, Russell TS: Nonhematopoietic gastrointestinal neoplasia in cats: a retrospective study of 44 cases, Vet Pathol 18:614, 1981. 55. Twaddle AA: Congenital pyloric stenosis in two kittens corrected by pyloroplasty, N Z Vet J 19:26, 1971. 56. Tyrrell D, Beck C: Survey of the use of radiography vs. ultrasonography in the investigation of gastrointestinal foreign bodies in small animals, Vet Radiol Ultrasound 47:404, 2006. 57. Valli VE, Jacobs RM, Norris A et al: The histologic classification of 602 cases of feline lymphoproliferative disease using the National Cancer Institute working formulation, J Vet Diagn Invest 12:295, 2000. 58. Van den Bulck K, Decostere A, Baele M et al: Identification of non-Helicobacter pylori spiral organisms in gastric samples from humans, dogs, and cats, J Clin Microbiol 43:2256, 2005. 59. Van Stee EW, Ward CL, Duffy ML: Recurrent esophageal hairballs in a cat (a case report), Vet Med 75:1873, 1980.


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APPROACH TO THE CAT WITH DIARRHEA Randolph M. Baral

OVERVIEW Diarrhea can be defined as increased volume and/or increased frequency of defecation of stools with increased water content. Approaches to diarrhea, as for any clinical sign, need to take into account the individual animal. For example, neoplasia is much less likely to occur in a kitten than in a geriatric cat. In many cases, the precise diagnosis of gastrointestinal disease cannot be reached without biopsy samples. The decision to obtain biopsy samples should follow a logical pathway that is appropriate to the cat’s condition. These are summarized in Figure 23-17. For example, many cases of acute diarrhea in a well cat can resolve with limited or no intervention, and so do not require a precise diagnosis. The diagnostic steps are 1. Signalment and clinical history 2. Physical examination 3. Fecal assessment 4. Blood and urine testing 5. Imaging (radiography, ultrasonography) 6. Biopsy samples These steps do not include treatment/diet trials or other empiric therapies that are appropriate in many cases. Steps 3 and 4 are often undertaken at the same time, and there is no definite order for these steps. They are divided here for reasons of clarity. In a younger cat, where infectious causes are more likely, thorough fecal testing is more important; in an older cat, extragastrointestinal diseases, such as hyperthyroidism, are more likely; so, blood and urine testing is more important, but fecal assessment should not be neglected. The decision to proceed to Step 4 (and each subsequent step) should take into account several considerations. The main considerations in assessing and managing a cat with diarrhea are • Is there an acute onset or a chronic time course? • Are there any dietary changes or indiscretion?

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Diarrhea

Chronic

Large intestine: Mucus. Straining. Increased frequency/urgency, small amounts. Red if blood. No weight loss. If vomiting as well, not associated with eating.

Acute

Small intestine: Watery, profuse, black if blood. If vomiting, usually related to eating. No mucus, not painful or urgent. There may or may not be weight loss.

Well: Deworm. Fast 24-36 hours then feed bland food (e.g., cooked white chicken meat).

Unwell: Deworm. Assess hydration status and consider fluid therapy.

If continues, further investigation as per chronic

Deworm

Well

Unwell

Fast for 24 hours. Then try a low-residue diet such as plain cooked chicken or commercial diet for GI.

Full blood biochemistry, hematology, and urinalysis: To rule out secondary disease and assess secondary effects such as azotemia, hypoalbuminemia. / T4 Fecal examination: Check for oocysts, maldigestion (Salmonella/Campylobacter?)

Consider treatment trials: Antibiotics (e.g., amoxicillin/ clavulanate metronidazole). Food trials with novel proteins (e.g., rabbit, kangaroo, venison).

Imaging: Radiography, ultrasound

Invasive diagnostics: Endoscopy vs Laparotomy (fresh and formalinized)

FIGURE 23-17 Diagnostic approach to the cat with diarrhea.

• Is the cat well or unwell? • Is there primary or secondary gastrointestinal disease? • Is there small or large bowel diarrhea?

STEP 1: SIGNALMENT AND CLINICAL HISTORY The components of the clinical history for cats with diarrhea are detailed in Table 23-12. After establishing the cat’s age, breed, vaccination, and deworming history, it is important to establish the duration and nature of the

diarrhea. Chronic diarrhea is usually defined as greater than 3 weeks in duration and mostly warrants at least some degree of a diagnostic workup, whereas acute diarrhea is often self-limiting in a well cat. A description of the feces helps determine whether the diarrhea is small or large bowel in origin (Table 23-13); this will affect how any investigations might proceed. Important questions to ask concern frequency of defecation (and how this compares with the normal state), tenesmus (straining usually indicates large bowel diarrhea, since an irritated colon leads to urgency), volume of feces (smaller volumes are typical of large bowel diarrhea; larger volumes are more typical of small


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TABLE 23-12 Clinical History for Cats with Diarrhea Signalment

Age? Young cats are prone to dietary, infectious, and parasitic causes of diarrhea; older cats are more likely to have inflammatory, metabolic, and neoplastic causes of diarrhea.

Vaccination status

Appropriate panleukopenia, FeLV vaccination?

Diet

Detailed dietary history as well as recent dietary changes. Adverse reactions to food are common causes of diarrhea. Diarrhea that ceases when an animal is not fed suggests osmotic diarrhea.

Environment

Presence of various plants, chemicals, and foreign objects? Health status of cats in the household? Outdoor cats are more likely to develop parasitic, toxic, and infectious disorders.

Travel history

Infectious potential or enzootic area (fungal or parasitic diarrhea)?

Current medications

Drug reaction or toxicity? Drug therapies that can cause diarrhea should be noted (e.g., antibiotics, anti-inflammatory agents, cardiac glycosides).

Past medical and surgical problems

Organ system affected? Recurrence? Response to previous treatment?

Onset and duration of diarrhea

Acute versus chronic? Acute diarrheas are abrupt in onset and of short duration, and generally they are self-limiting. Chronic diarrheas persist usually longer than 3 weeks and fail to respond to symptomatic therapy.

Appearance of diarrhea

Quantity and quality of the stool (color, consistency, character, presence of blood or mucus)? Loose to watery feces that contain fat droplets, undigested food, melena, and variable colors suggests small intestinal disease. The volume is always increased with small intestinal disease. Loose to semisolid feces containing excess mucus and fresh blood (hematochezia) indicates large intestinal disease. The volume may be normal to slightly decreased with large intestinal disease.

Description of defecation process Tenesmus (straining) and dyschezia (painful defecation)? These are hallmarks of large intestinal disease (e.g., inflammatory or obstructive lesions of the colon, rectum, or anus). Frequency of defecation

Frequency is normal to slightly increased with small bowel disease, but greatly increased with large bowel disease.

Associated physical signs

Vomiting, anorexia, weight loss, and dyschezia may help localize the disorder to a specific part of the gastrointestinal tract. Clinical signs relating to problems in other organs or body systems should be noted and may suggest a more generalized disease. Vomiting may occur as a consequence of small intestinal inflammation in some cats with diarrhea. Weight loss may result from decreased caloric intake (anorexia), decreased nutrient assimilation (maldigestion/malabsorption), or excessive caloric loss (protein-losing enteropathy or nephropathy). Weight loss is observed uncommonly with large bowel disease.

FeLV, Feline leukemia virus. From Hall JE: Clinical approach to chronic diarrhea In August JR, editor: Consultations in feline internal medicine, ed 4, Philadelphia, 2001, Saunders, p 130.

TABLE 23-13 Distinctions Between Small and Large Bowel Diarrhea Observation

Small Bowel Diarrhea

Large Bowel Diarrhea

Frequency of defecation

Normal to slightly increased

Very increased

Fecal output

Large volumes

Small volumes frequently

Urgency or tenesmus

Absent

Present

Dyschezia

Absent

Present with rectal disease

Mucus in feces

Absent

Present

Exudate in feces

Absent

Present sometimes

Hematochezia (red blood)

Absent

Present sometimes

Melena (digested blood)

Present sometimes

Absent

Steatorrhea

Present sometimes

Absent

Flatulence and borborygmus

Present sometimes

Absent

Weight loss

Present sometimes

Rare

Vomiting

Present sometimes

Rare

From Sherding RG: Diseases of the intestines. In Sherding RG, editor: The cat: diseases and clinical management, ed 2, New York, 1994, Churchill Livingstone, p 1215.

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bowel), how formed the stool is (from soft stool to cow-pat consistency to liquid tea; usually more watery stool relates to small intestinal disease), color (darker indicates digested blood), and presence of any mucus or blood (presence relates to large bowel). Most household toxins, such as plants, cause signs additional to diarrhea such vomiting or neurological signs,11 but it is important to ascertain if the cat has had access to anything unusual. Likewise, it is important to find out if the cat has had any possible exposure to dietary indiscretions; this can include if the cat has been seen with or is known to hunt prey including insects. Cockroaches carry pathogenic bacteria12,18 and other prey such as birds and rats can carry Salmonella; salmonellosis in cats has been dubbed songbird fever.6 Simple causes of self-limiting diarrhea include dietary change (either a new flavor or a new style of food, such as dry food for the first time); so, the owner must also be quizzed if anything new has been offered, either new cat food or treats (such as greasy fish or chicken). Although the physical examination will usually determine how unwell a cat is, the owner’s impressions are also important, because cats can hide signs from strangers, particularly in a practice setting. Lethargy and inappetence are important signs, as ill cats typically do not eat well.

STEP 2: PHYSICAL EXAMINATION The cat’s general demeanor can be an indicator of how unwell a cat is and therefore dictate the extent of diagnostic testing required. This can be noted by assessing how interested the cat is in its surroundings or any behavior changes from previous visits, such as if a normally difficult-to-handle cat is placid. Body weight should be assessed and, if possible, compared with that of previous visits (even those noted on a clinical record from another veterinarian). The body condition score (BCS) should also be assessed and can be very important when there is no prior weight information. Dehydration is usually a sign that a cat needs more involved management. Abdominal palpation should be performed to assess pain (where?), any masses (foreign bodies, lymph nodes, or even focally thickened intestines, such as with neoplasia), or turgid intestines. Fever often indicates infection but can also reflect neoplasia or other inflammatory changes. A thorough examination of all body systems should always be performed, no matter what a cat presents for. In the case of diarrhea, extragastrointestinal signs can be of vital importance, such as a palpable thyroid and tachycardia suggesting hyperthyroidism. After the clinical history has been taken and the physical examination performed, the veterinarian must make the important decisions of whether any interventions are required and whether the patient should be

managed as an inpatient or outpatient. The veterinarian should be asking • Are ancillary tests appropriate? • Is supportive care necessary? • Are any medications required? In many cases, the answers to these questions are obvious. For example, a cat may seem well but has had access to lilies (the author has seen diarrhea as a primary presenting sign for this!) or has a palpable abdominal mass. Substantial weight loss is an indicator that further investigations are warranted sooner rather than later. If the decision is made for empiric management and outpatient care, it is vital to follow up either by scheduling a recheck visit or calling the client, because simple acute problems can turn into complicated chronic problems.

The Well Cat with Acute Onset Diarrhea If the diarrhea has been present for less than a week and the cat has no weight loss, dehydration, fever, or palpable abdominal abnormalities, it is appropriate to manage the cat as an outpatient. Even in the absence of fecal testing, it is appropriate to deworm the cat (see the section Gastrointestinal Parasites). The cat should be fasted for 24 hours (12 hours, if less than 4 months old) and then fed a bland diet (such as plain, cooked, skinless chicken, or low-residue prescription diets designed for cats with gastrointestinal problems). It is appropriate to maintain the cat on the low-residue diet for at least 7 to 10 days and then slowly reintroduce the regular diet.

STEP 3: FECAL ASSESSMENT +/− CULTURE Fecal assessment is mostly used to assess infectious agents, such as parasite-associated diarrhea, but the importance of assessing feces, even when parasitic or bacterial infections are not suspected, should not be underestimated. Gross examination of feces can determine if melena or fresh blood or mucus are present to help distinguish large from small bowel disease when the owner’s observations may be misleading. Occult fecal blood can be an indicator of gastrointestinal inflammation in cases of subtle disease, and undigested starches and fats can indicate maldigestion or malabsorption.8 For assessment of feces for parasites, the fecal sample should ideally be fresh (3 weeks) of gastrointestinal signs, including vomiting, diarrhea, and weight loss 2. Nonresponse to symptomatic therapy alone (such as parasiticides, antibiotics, and dietary trials) 3. No specific cause after thorough investigation 4. Histologic confirmation of non-neoplastic intestinal inflammatory changes These distinctions are not always straightforward to make for either the clinician or the pathologist reading the histology! The most common inflammatory infiltrates30,66,74,80,171 are 1. Lymphocytic/plasmacytic (70% to 100% of cases) 2. Eosinophilic 3. Neutrophilic 4. Mixed inflammatory 5. Granulomatous

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Clinicians often consider the assessment of histologic samples to be out of their hands; however, it is important to work with the pathologist by providing good quality samples and a good clinical history, as well as having an open dialogue if the findings are not within expectations. For example, with lymphocytic/plasmacytic infiltrations, the pathologist has the difficult task of distinguishing diseased from normal tissue in a site that is laden with lymphocytes in the healthy state. Once deciding the tissue has pathology, the pathologist’s next task is distinguishing inflammatory infiltrate from neoplastic infiltrate with normal, mature lymphocytes (as seen in small cell lymphoma). Inflammatory change also results in changes to normal tissue architecture, with thickened villi, edema, or erosion of the epithelium being typical changes. Clinicians should expect morphologic descriptions as well as assessments of degree and type of inflammation. These difficulties are further compounded with the recognition that histologic grading of mild, moderate, or severe does not necessarily correlate with severity of clinical signs. This means that a cat with severe clinical signs of weight loss and vomiting or diarrhea may have only mild histologic changes (and vice versa).

Other Organs Concurrently Affected Concurrent inflammation of the pancreas and liver with intestinal inflammation was first described in the mid-1990s,171 and despite constant reference to this phenomenon at conferences and veterinary websites, there has been little description since then, though one study found 70% of IBD cases had liver inflammation and 30% had pancreatic inflammation.6 The term “triaditis” has frequently been used, but the author prefers to spell this “tri-iditis” to distinguish it from inflammation of the hepatic portal triads. There has been no assessment of prognosis when the pancreas and/or liver are involved, but the author has found no difference in prognosis.

Dietary Therapy Many cases diagnosed with intestinal inflammatory infiltrates have these changes because of dietary sensitivity. In one study, 29% of cats with histologic gastrointestinal changes improved with dietary elimination therapy alone. Interestingly, improvement was noted within 4 days compared with the longer duration of 8 weeks often recommended for improvement of dermatologic manifestations of food sensitivities. This careful study made note of the cat’s prior diets and likely dietary causes of sensitivities.55 Another study found dietary therapy to be unsuccessful in 52 of 60 cats but no specifics of diets tried are noted.58 As with any

therapeutic trial, follow-up visits are vitally important. Many cats with small intestinal disease may show initial improvement simply because of the diet having lower residue, since there is decreased substrate for intestinal bacteria to digest and lower osmotic potential. The corollary of this is that failure of one novel protein diet does not mean that all novel protein diets will fail. When food sensitivities are responsible for gastrointestinal clinical signs in cats, the responsible food ingredient is usually a dietary staple. Commonly incriminated ingredients are beef, fish, wheat, and corn gluten.55 A careful dietary history is therefore important. Large bowel inflammation typically improves with higherfiber diets,38,58 and attempting a trial with such a diet is certainly appropriate.

Drug Therapy Immune suppressive therapy is the mainstay of IBD treatment, and glucocorticoids, such as prednisolone, are most commonly used. Sulfasalazine use for large bowel signs has not been critically evaluated but seems safe and effective. In cats with substantial weight loss or severe clinical signs, such as chronic diarrhea, the author prefers to start with corticosteroid therapy, even if dietary causes have not yet been ruled out. The diet should also be changed to one containing a novel protein, and, if and when clinical signs resolve, an attempt is made to wean the cat from corticosteroid therapy, hopefully to the point of being discontinued. A diet challenge can then be used to confirm the diagnosis of food sensitivity. There are no universal guidelines for doses of corticosteroids. The author prefers the use of orally administered prednisolone to reduce the chance of side effects and will choose the starting dose based on the severity of disease. The starting dose is usually 2 mg/kg, once daily, PO (10 mg/cat/day for most cats) starting 10 days after biopsies have been obtained to allow time for the mucosa to heal. If there is an improvement noted after a recheck at 2 weeks, the higher dose is maintained for a further 2 to 4 weeks, at which point, many cats are back to their normal weight and are not exhibiting clinical signs. If this is the case, the corticosteroid dose can be weaned down to 1 mg/kg, PO (often 5 mg/cat/day) for several months, with continued rechecks scheduled to assess weight, clinical signs, and diet. The goal is to wean down to the lowest effective dose. If hypocobalaminemia is present, cobalamin supplementation may be required.144 Cobalamin is administered parenterally at 250 µg/cat subcutaneously weekly for 6 weeks, then every second week for 6 weeks, then monthly. Owners can be shown how to inject their cats (as practitioners routinely do with diabetics).


Some cats seem resistant to conventional therapy. If this is the case, the diagnostic findings should be re-assessed to ensure no steps were missed or findings disregarded; the cat should be reexamined to look for emergence of other signs; and the pathologist who reads the histology should be contacted to recheck the findings. Some cases of apparently resistant IBD are actually food sensitive, but it can be difficult to find the incriminating diet source, and commercial diets are not always effective. If underlying infectious causes have been entirely ruled out and the practitioner is certain of the diagnosis of idiopathic disease, immune suppressive therapy can be increased by either increasing the dose of prednisolone or using other agents, such as chlorambucil, typically at 2 mg/cat, PO, every second day. It has been suggested that cats with eosinophilic inflammation may be more likely to be refractory to standard therapy. Side effects of immunosuppressive therapy are rare but include inducing diabetes mellitus, immune suppression, delayed healing, and gastrointestinal ulceration. Reported doses of sulfasalazine to manage large bowel IBD are 10 to 20 mg/kg, PO, once daily for 7 to 10 days.174 Because this drug is usually only available as 500 mg tablets, one eighth of a tablet, providing a dose of 62.5 mg, is usually appropriate for most cats. In some countries, it is possible to have a compounding pharmacist formulate the drug into more convenient tablet sizes or as an oral suspension. Cats are generally regarded as susceptible to salicylates, and possible side effects include vomiting or diarrhea, or anemia. The exact pharmacodynamics of this drug are not known; so, caution for extended use should be exercised and the drug withdrawn if any possible adverse signs are noted, but there are anecdotal reports of extended use of this drug without adverse consequences.

INTESTINAL NEOPLASIA A survey of the online Veterinary Cancer Registry (http://www.vetcancerregistry.com) identified 6% of all submitted feline tumors to be intestinal tumors. Approximately 74% of reported feline small intestinal tumors were lymphomas. Adenocarcinomas accounted for 17%, and other tumor types reported included mast cell tumors and leiomyosarcomas.135 “Lymphoma in veterinary medicine: no longer a oneword diagnosis” was the title of an editorial in a recent issue of the Veterinary Clinical Pathology journal,95 and this is nowhere truer than in the feline gastrointestinal tract! A recent study classified 50 cases of feline gastrointestinal lymphoma both histologically and immunophenotypically, and it found eight different categories according to the Revised European and American Lymphoma/World Health Organization (REAL/WHO) classification system and six categories according to the

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National Cancer Institute Working Formulation (NCI WF) system.116 For most veterinarians in practice, the most important distinction is the histologic grade, because low-grade (lymphocytic or small cell) lymphoma has a much better prognosis (and requires different treatment) compared with high-grade (often lymphoblastic) or intermediategrade lymphoma. For the purposes of simplicity and practicality, only small cell lymphoma and high-grade lymphoma will be addressed here. The prognosis and treatment for intermediate-grade intestinal lymphoma should be considered as for high-grade lymphoma.

Intestinal Small Cell (Low-Grade) Lymphoma Small cell lymphoma was first described in human pathology in 1966.122 Earlier, small lymphocytes were considered end-stage cells without the ability to divide. In cats small cell lymphoma is most commonly associated with the gastrointestinal tract or skin.163 Small cell neoplasia can be a confusing concept, since our traditional ideas of malignant neoplasia focus on rapidly dividing cells. The confusion is compounded by various terms used in the literature, such as lymphocytic lymphoma, low-grade lymphoma, well-differentiated lymphoma, or diffuse lymphoma; another term, epitheliotropic malignant lymphoma predominantly applies to small cell lymphoma, and other papers fail to distinguish these lymphomas from lymphoblastic lymphosarcoma (the traditional, aggressive form). “Small cell lymphoma” seems to be most widely used term, though the author prefers “lymphocytic lymphosarcoma,” since it is more descriptive. Intestinal small cell lymphoma can be considered as a severe lymphocytic intestinal infiltrate, the most common form of which is commonly called IBD. Not only is lymphocytic IBD hard to distinguish histologically from lymphocytic lymphosarcoma, but the approaches and treatments are similar. Several reports have suggested a relationship between the two conditions in that inflammatory infiltrates may become neoplastic over time.27,43,90 Prevalence The true prevalence of intestinal small cell lymphoma is unknown, but several recent studies have indicated similar rates to inflammatory bowel diseases, with Kleinschmidt et al noting 10 small cell lymphoma cats compared with 14 with intestinal lymphocytic infiltrates,74 Evans et al reporting 10 cases compared with 12 with IBDs40, and Baral et al diagnosing 8 cases compared with 10 with IBDs.6 Traditionally, 90% of feline lymphosarcoma is regarded as intermediate or high grade,163 but this may not be the case within the gastrointestinal tract. Fondacaro et al found 75% of gastrointestinal lymphoma to be lymphocytic43; a more recent paper found

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approximately equal numbers of high-grade and lowgrade gastrointestinal lymphoma.84 Patient Signalment and Risk Factors Older cats are more at risk of small cell lymphoma, with mean or median ages reported from 9 to 13 years. Younger cats with the disease have, however, been recognized.40,43,73,84 No breed or gender predispositions have been definitively recognized. Two larger studies have suggested a skew to males with 28 males compared with 22 females in one report,43 and 24 males compared with 17 females in the other73; most other studies looking at gender and breed did not clearly distinguish between lymphoblastic and lymphocytic neoplasia. Clinical Signs Clinically, it is impossible to distinguish cats with IBDs from cats with small cell lymphoma. This is hardly surprising when even histologic distinction can be difficult! Therefore cats will present with weight loss or vomiting or diarrhea at a similar frequency to those with IBD. Weight loss has been recognized as a presenting sign in 82% to 100% of cases, diarrhea in 25% to 60% of cases, and vomiting in 25% to 73% of cases, with various combinations of these signs also possible. Other variable signs are lethargy and inappetence or, conversely, polyphagia.40,43,73,84 These findings can be summarized by stating that cats with gastrointestinal small cell lymphoma can present with any combination of signs relating to the gastrointestinal tract. Location and Other Organ Involvement Intestinal small cell lymphoma is typically a diffuse disease, and therefore multiple areas of the alimentary tract are usually affected. In studies where different locations of the small intestine were assessed, the jejunum was most commonly affected (100%), with the ileum frequently affected (93% to 100%), and duodenal pathology slightly less prevalent (83% to 90%).40,84 Although the numbers of cats assessed in these studies are small, the important fact that the duodenum is not always affected needs to be recognized, which has important implications for how biopsy samples are obtained, because lesions beyond the duodenum are likely to be beyond the reach of an endoscope. Further difficulties in precise diagnosis may arise, since non-neoplastic lymphocytic infiltrates (e.g., IBD) are often found in other locations along the intestinal tract.27,40,84 The stomach is also affected in 14% to 40% of small cell lymphoma cases.40,43,84 Although not fully assessed, involvement of the colon appears rare.84 Local lymph node involvement is common, being noted in up to 59% of cases.84 This percentage may be even higher, because many studies assessed lymph node cytology from ultrasound-guided fine-needle aspirates, which may miss spread to the lymph node, because the

population of neoplastic lymphocytic cells is indistinguishable from the normal population of lymph node cells. Histology is required to assess changes in lymph node architecture. Liver involvement is not uncommon but not thoroughly assessed. One study noted liver lymphocytic neoplasia in 8 of 38 cats with small intestinal lymphocytic neoplasia,73 another found 5 of 15 affected cats in which the liver was biopsied,84 another noted 2 of 4 cats had liver involvement,27 and a further study detected neoplasia “in the lymph nodes, liver, or both” in all 10 cats with intestinal small cell lymphoma.40 The pancreas may also be involved.73,84 This may be akin to the noted association of lymphocytic inflammation of intestine, pancreas, and liver171 that has been dubbed tri-iditis. Ultrasound findings may not suggest extragastrointestinal involvement. In the case of liver pathology, ultrasonography may show no changes in as many as 75% to 80% of cases.40,84 Focal nodular changes and hepatomegaly have been recognized as ultrasonographic signs of hepatic small cell lymphoma.7 Pathophysiology Both lymphocytic IBD and lymphocytic neoplasia are often recognized simultaneously in the same cat,40,84 and numerous authors have suggested that lymphocytic IBD may be a precursor to intestinal lymphoid neoplasia.90,125 If this is the case, then antigenic factors, such as bacterial population changes or food sensitivities, could be considered primary initiating factors for small cell lymphoma since they are potential underlying etiologies of IBDs.79 However, neoplasia also requires genetic mutations to occur (often affecting regulation of cell death and cell survival), and these may be initiated by the inciting antigenic factors or the ongoing inflammatory changes.154 As opposed to other feline lymphoid neoplasia, no association has been made with FeLV infection.27,43,73,125 Intestinal lymphocytic lymphosarcoma begins in the superficial mucosa and progresses to involve the entire mucosa and submucosa; then advancing in a perivascular pattern into the tunica muscularis, eventually infiltrating all four intestinal tunics.43 Lymph node and other organ (such as liver or pancreas) involvement likely represent metastasis through lymphatics and perhaps hematogenously. More distant metastasis is not reported. Diagnosis Serum or plasma biochemistry and hematologic findings are typically nonspecific. However, this testing is important as part of the diagnostic workup to rule out extra-GI disease, such as hyperthyroidism or diabetes mellitus. Common biochemistry findings are mild to moderate increase of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or

alkaline phosphatase (ALP).27,40,43,84 As with IBDs, these liver enzyme changes may or may not represent overt hepatic disease.67 Albumin may be reduced43 but is normal in most cases27,43,84; azotemia may be present and may be of prerenal origin or represent concurrent renal disease. In one study, 25 of 32 cats were hypocobalaminemic; 1 of 27 cats had low folate, but 10 of 27 had elevated folate; and 12 of 16 cats had increased fTLI.73 Hematologically, a mature neutrophilia with or without monocytosis is sometimes present, representing the inflammatory response; lymphopenia may be present as a stress response. Anemia may be present and may occur as a result of chronic slow GI blood loss, and in some cases, ulceration, or it may be because of chronic disease; hemoconcentration is also possible, reflecting dehydration.27,40,43,84 Palpable or ultrasonographically visible thickened intestines (30% to 41% of cases)27,40,43,84 or mesenteric lymph nodes (20% to 50% of cases)27,40,43,84 are no more or less likely to be present in comparison with IBDs. There are no defined ultrasound guidelines for cats with intestinal small cell lymphoma, because most prior papers do not distinguish between small cell and lymphoblastic neoplasia.54,113 A more recent paper found 9 of 15 cats undergoing ultrasound examination had diffuse small intestinal wall thickening, with a mean of 4.3 mm (range, 3.4 to 5.0 mm; median, 4.5 mm), and focal mural thickening of 20 mm was noted in one cat.84 In many cases, against expectations, intestinal wall layering was preserved. These findings also mean that 5 of 15 cats had ultrasonographically normal intestinal wall thickness (≤2.8 mm for the duodenum and ≤3.2 mm for the ileum).50 If affected, jejunal lymph nodes may appear as hypoechoic and enlarged; in the same study, 12 of 15 cats had lymph node changes with a mean diameter of 15.9 mm (range, 6.5 to 30 mm; median, 10 mm)84 compared with the normal diameter of less than or equal to 5.0 mm.132 None of these findings can definitively distinguish small cell lymphoma from IBDs; although one recent paper has suggested that ultrasonographic thickening of the muscularis layer is more likely in cats with intestinal small cell lymphoma (Figure 23-20) than those with IBD, this change was also seen in 12% of cats with a normal small intestine. However, thickening of the muscularis layer together with lymphadenopathy was recognized in 26% of those cats with small cell lymphoma compared with 4% of those with IBD and 2% of cats with no small intestinal pathology.177 Biopsy samples and histopathology are required for definitive diagnosis. An example of jejunal and mesenteric lymph node appearance at laparotomy is shown in Figure 23-21. As noted for IBDs, it is important to work with the pathologist by providing good quality samples and a thorough clinical history, as well as having an open dialogue if the findings are not within expectations.


SI

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2 1

FIGURE 23-20 Ultrasonographic findings of small cell lymphoma; duodenal wall measurements at the two locations numbered D1 and D2 are 2.9 mm and 3.4 mm, respectively. Note that the prominence of the muscularis propria layer in the second measurement compared with the ultrasonographic appearance of inflammatory bowel disease (IBD) in Figure 23-19, in concordance with findings of Zwingenberger et al.177

FIGURE 23-21 The appearance of intestinal small cell lymphoma at laparotomy. Note the erythematous and generally thickened intestines and prominent mesenteric lymph nodes.

It is difficult to distinguish between lymphocytic inflammation and small cell lymphocytic neoplasia in any location; some histopathologic features that might help in differentiating the ends of the spectrum may include 1. Demonstration of small lymphocyte domination (sometimes referred to as monotonous or monomorphous population) in small cell lymphoma, compared with morphologically mixed cell populations in IBD27,40 2. Infiltration into deeper layers (submucosa and muscle wall) in lymphocytic neoplasia27,40,43

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3. No mucosal congestion, edema, or fibrosis in lymphocytic neoplasia,43 compared with IBD 4. Epitheliotropism, or homing of neoplastic T lymphocytes to the mucosal epithelium in lymphocytic neoplasia27 These features can be seen in Figure 23-22. Each of these criteria may be useful but are unlikely to be definitive. Further studies that may not be routinely available but which may be helpful are 1. Immunophenotyping; most reports have found purely T lymphocytes in most cases of intestinal small cell lymphoma27,73,84,116 (Figure 23-23). 2. Clonality; the detection of a clonal population of cells, as recently described for intestinal lymphocytic lymphosarcoma,101 would be closest to providing the basis for definitive diagnosis. Drug Therapy Effective treatment of feline intestinal small cell lymphoma was brought to light by Fondacaro et al43 and has

therefore become known as the Fondacaro protocol. This consists of a combination of prednisolone and chlorambucil given orally by the client at home (Table 23-15). The rationale is that a slow alkylating agent, such as chlorambucil, is more appropriate to use for the slowly dividing, well-differentiated lymphocytes that cause disease. This can be contrasted to the aggressive chemotherapeutic agents required for the rapidly proliferating cells in lymphoblastic neoplasia that is typically associated with lymphosarcoma. Reported response rates to this protocol are excellent, with 59% to 76% of cats achieving complete clinical remission, reported median survival times ranging from 20 to 30 months for those cats responding to therapy, and reports of individual cats surviving as long as 76 months.43,73,84 The original reported protocol comprised prednisolone (10 mg/cat, PO or 2 mg/kg, PO) given daily with chlorambucil pulsed by administration of 15 mg/m2 for 4 days every 3 weeks. A more recent study73 dosed prednisolone similarly, but chlorambucil was given as continuous therapy of 2 mg/cat, PO every second or third day.

200 m

200 m

FIGURE 23-23 Photomicrograph of small intestinal mucosa in a

FIGURE 23-22 Photomicrograph of small intestinal mucosa in a cat with intestinal small cell lymphoma. There is marked cellular infiltrate of the lamina propria, extending through the lamina muscularis into the submucosa. Villous morphology is distorted by the infiltrate.

cat with intestinal small cell lymphoma. Immunohistochemical labeling with a pan–T-lymphocyte marker reveals positive labeling of the infiltrating cells, consistent with a T-lymphocyte origin. CD3-positive cells can be seen in the mucosal epithelium but no Pautrier abscesses are evident.

TABLE 23-15 Comparison of Small Cell Lymphoma Protocols, All Drugs Dosed Orally Protocol

Chlorambucil 2

Prednisolone

Median Survival (Months)

Pulsed

15 mg/m /24h for 4 days every 3 weeks43

10 mg/cat/24h or 3 mg/kg/24h84

17 (range 0.33-50)43 15 (range 0.5-77)84

Continuous

2 mg/cat/48h73 or 1 mg/cat/24h

10 mg/cat/24h73 or 5 mg/cat/12-24h73

25 (range 1.5-67)73

Reference citations are from the section Diseases of the Intestines.

43

Similar protocols are used in humans with both lowgrade (i.e., lymphocytic) lymphosarcoma and chronic lymphocytic leukemia.117,151 Some studies with humans have indicated that continuous therapy with chlorambucil results in prolonged survival,64 although metaanalyses have not been able to determine optimum dosing and scheduling of administration of chlorambucil or other alkylating agents in these conditions in humans.20,72 Although we do not have enough data to critically compare pulsed therapy to continuous dosing, the study assessing continuous dosing appeared to have a lower number of cats completely responding, although those cats that did respond had a longer median survival73 than those in the studies assessing pulsed chlorambucil dosing.43,84 The differences may also relate to the definitions used for complete response. The chlorambucil dose of 2 mg/cat, PO every second day (or third day) is often chosen because of the ready availability of 2 mg coated tablets, the breaking of which can expose the owner to these cytotoxic medications. Chlorambucil can be compounded into smaller doses, thus allowing daily dosing of 1 mg capsules. The author has used this dose to apparent good effect, but there has been no critical assessment. It is unknown whether involvement of lymph nodes or other organs, such as the liver, affects prognosis. The only study of substantial size to include extra-GI locations found anatomic location was not prognostic for response or survival time.73 In another study, of the five cats with liver involvement, two cats did not survive more than 5 months, yet the other three lived longer than 2 1 2 years, with two surviving longer than 4 1 2 years.84 A study of hepatic small cell lymphoma suggests the density of neoplastic lymphocytes may influence survival, and density may relate to the stage of the disease when diagnosis occurs.7 Adverse effects of chlorambucil are rare, but gastrointestinal signs, myelosuppression, and myoclonus have all been reported. Gastrointestinal signs, such as vomiting, diarrhea, or inappetence, can be difficult to distinguish from continuation of the gastrointestinal disease diagnosed. These signs are usually self limiting. Myelosuppression is also possible with thrombocytopenia reported.57,84 Monoclonus has been reported on one occasion.17 It is ideal to check hematologic parameters every 2 months for cats receiving chlorambucil. Continuous therapy using lower doses of chlorambucil may be less likely to lead to these adverse effects. High doses of corticosteroids can induce diabetes mellitus, and thus blood glucose should be checked regularly. If diabetes occurs, the author has found that budesonide (1 mg budesonide is generally considered to be equivalent of 5 mg prednisolone) can be substituted for prednisolone, since it has reputed lower systemic effects (though no assessments of this drug’s effectiveness in cats have been made). An alternative is for the


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cat to be weaned off corticosteroids, with chlorambucil continued as monotherapy (as is often the case with humans). Iatrogenic diabetes mellitus usually needs to be managed with insulin therapy, at least initially (see Chapter 24).

Intestinal High-Grade (Lymphoblastic) Lymphoma High-grade lymphoma or lymphosarcoma is the traditional style of aggressive, rapidly dividing lymphoid neoplasia that carries a much poorer prognosis than small cell lymphoma. Prevalence Most early studies do not distinguish grade of neoplasia; so, the prevalence of low-grade and high-grade alimentary lymphoma are difficult to assess. Several recent studies found a similar prevalence of each,84,116 but the seminal paper describing small cell lymphoma found only 17 cases of lymphoblastic lymphoma compared with 50 cases of small cell lymphoma.43 This ratio of approximately one high-grade GI lymphoma case for every three low-grade cases more closely approximates the rate found in the author’s practice. Patient Signalment and Risk Factors The reported median ages of affected cats range from 10 to 12 years, but cats as young as 1 year old have been diagnosed. Most papers note that males are overrepresented, and Siamese cats may also be overrepresented although most affected cats are domestic shorthairs.43,49,90,116,176 Precise signalment is difficult to determine from the literature, because many papers assess all anatomic locations of lymphoma without necessarily breaking down epidemiologic data for each anatomic site. Also, there are few comparisons to a reference population. Pathophysiology The association of lymphoma with FeLV infection is well established and documented139 and is covered in Chapter 28; FIV has also been shown to be lymphomagenic.12,139 Since the control of FeLV through vaccination began in the 1980s, nonretroviral-associated lymphoid neoplasia has become more common, and the rates of intestinal lymphoma have, in fact, increased since FeLV infection rates have decreased.86 The underlying causes for this increase are not known. The association with inflammation from IBDs was noted for small cell lymphomas, and perhaps there is a spectrum from lymphocytic IBD to small cell lymphoma to high-grade lymphoma. That some cats are more likely to have inflammatory changes become neoplastic is suggested by a paper noting higher lymphoma rates in cats with vaccine-associated sarcomas (a neoplastic condition where the role of chronic inflammation is well noted).89

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Whether the underlying cause is retroviral or chronic inflammation or anything else, the pathogenesis of highgrade intestinal lymphoma, as with small cell lymphoma and other neoplasia, depends on chromosomal changes that affect regulation of cell growth and death, resulting in malignant transformation and clonal expansion of immature lymphocytes.152 Metastasis can occur in one third to two thirds of cases,90,92 with involvement of mesenteric lymph nodes most commonly noted, but spread to liver, spleen, kidneys, and thorax is also possible.90 A recent survey of gastrointestinal lymphoma found that most cases (37 of 50) involved the small intestine (including 3 that also involved the stomach and 4 that also involved the large intestine), and 4 of 50 cases involved the large intestine only.116 Clinical Signs Cats with high-grade alimentary lymphoma often present similarly to those with other gastrointestinal diseases. Typical clinical signs are weight loss, anorexia, lethargy, vomiting, diarrhea, or a combination of these signs. Repeated studies have found cats with no vomiting or diarrhea; in one study, 13 of 28 cats had only anorexia or weight loss on presentation.90 Cats with large bowel pathology usually present, as with other causes of colitis, with increased urgency, and small, frequent amounts of diarrhea, often with blood or mucus. Cats with large bowel neoplasia of any form can present for constipation caused by intestinal obstruction. Palpation of an abdominal mass has been recognized in 59% to 85% of cases,43,90 but the corollary of this is that 15% to 41% of cases did not have a palpable mass. It is also important to note that up to 50% of cats with intestinal small cell lymphoma, and a number with IBDs, have palpable mesenteric lymph nodes; so, a palpable abdominal mass is not a specific indication of high-grade neoplasia. Many cats have palpably thickened bowel loops.124 Diagnosis Hematology and plasma or serum biochemistry findings are also nonspecific. Increased liver enzymes may or may not indicate liver involvement. Anemia may be recognized and can be non-regenerative, reflecting chronic disease or slow blood loss, or regenerative if there is more substantial blood loss associated with mucosal ulceration. Hypoalbuminemia can be because of blood loss or intestinal protein loss. Hypercalcemia of malignancy is a possibility but not commonly reported. Despite nonspecific signs, laboratory testing is important to rule out extra-GI diseases and help manage consequences of enteric disease, as with small cell lymphoma and IBDs. Ultrasonography commonly shows a focal intestinal thickening (of 5 to 25 mm) with partial or complete loss

1 SI

FIGURE 23-24 Ultrasonographic image of intestinal lymphoblastic lymphoma; the intestinal wall measurement is 8.6 mm. Note the total loss of layering.

1

2 LN

FIGURE 23-25 Ultrasonographic image of lymph node of a cat with intestinal lymphoblastic lymphoma, measurements are 10.4 mm and 9.3 mm (normal lymph nodes are 85%) but low sensitivity ( dogs Most common primary tumor in dogs

Diagnosis by biopsy (FNA cannot differentiate normal from adenoma) Surgical removal is curative

Adenoma most common bile duct tumor in cats and frequent cause of cholestasis (rare in dogs) Carcinoma more common in dogs

Carcinomas (both species) are highly metastatic (lymph nodes and lung) and 80% have metastasized at the time of diagnosis in cats

Unusual in cats but carcinoid tumors reported occasionally

Can be intrahepatic or extrahepatic; if solitary can be excised, but no therapy if diffuse (more common in dogs)

All are rare, but reported occasionally in cats (40% metabolizable energy [ME]) and have lower amounts of carbohydrates (30

25-60

35-75

Specific gravity

1.025

Not applicable

Not applicable

Nucleated cells (×109/L)

5

0.25-20

1-20, depending on peripheral count

Predominant cell types

Macrophages Mesothelial cells

Macrophages Mesothelial cells Lymphocytes Erythrocytes Neutrophils (nondegenerate) +/−Neoplastic cells

Neutrophils (non-degenerate, or degenerate, if bacterial) Macrophages Erythrocytes +/− Neoplastic cells

Small lymphocytes Neutrophils Macrophages

Erythrocytes Neutrophils Macrophages Mesothelial cells Neoplastic cells

Adapted from Tasker S, Gunn-Moore D: Differential diagnosis of ascites in cats, In Practice 22:472, 2000.

Transudates Transudates are a consequence of altered fluid dynamics. Protein-poor transudates (commonly referred to as pure transudates) form predominantly as a result of severe hypoalbuminemia, which causes a lowered colloid osmotic pressure. Since there is no change in endothelial or mesothelial permeability, as fluid accumulates, there is no concurrent cell leakage; so, there is a decrease in the cell count through a dilutional effect. Consequently, transudative effusions are typically clear and colorless.10,23,32 Other pathologic causes of proteinpoor transudates include cirrhosis, lymphatic obstruction, and noncirrhotic portal hypertension (presinusoidal and sinusoidal). Since hypoalbuminemia is the most common cause of transudates, serum albumin concentrations must be measured to guide further diagnostics. If the serum albumin concentration is normal (or only minimally decreased), then radiographs, abdominal ultrasonography, and/or echocardiography are indicated to assess cardiac function and for urinary bladder rupture.10 One review of feline ascitic cases found 24% of effusions were protein-poor transudates, of which 82% were the result of hepatic failure or primary renal disease.34

fluid to leach out of the liver into the abdominal cavity. Since cell membrane permeability does not change, cells do not accumulate in the effusion.10 Modified transudates can also result from increased vascular permeability in the early stages of an inflammatory process, in which case cellularity will be increased. Modified transudates were described as the most common type of ascitic effusion identified in cats in one study, with most being resulting from neoplasia and congestive cardiac failure; however, this study partially included cases prior to 1987, when right-sided heart failure associated with dilated cardiomyopathy (DCM) was prevalent.34 The recognition of the role of taurine deficiency in this condition and the subsequent addition of this amino acid to feline diets now means that right-sided heart failure is only rarely encountered as a cause of ascites in cats.

Exudates

Modified Transudates

Exudates are a consequence of altered mesothelial and/ or endothelial permeability. This permeability results from a cytokine-mediated inflammatory response of any underlying cause (e.g., infectious, neoplastic, immune mediated). Exudates have high protein and moderate to high cell concentrations and are classified as nonseptic or septic.

Modified transudates can result from increased hydrostatic pressure within the postsinusoidal vessels of the liver secondary to right-sided congestive heart failure (e.g., tricuspid insufficiency) or potentially from mass lesions (such as neoplastic masses) obstructing blood flow from the hepatic vein or caudal vena cava into the right side of the heart. The increase in hydrostatic pressure within the vessels of the liver causes a protein-rich

Exudates are often primarily composed of neutrophils. Nondegenerate neutrophils (and the absence of organisms) points to a nonseptic exudate (mostly FIP but also neoplasia). FIP is the most common cause of exudative effusion in cats and was the most common cause of feline ascites diagnosed over a 10-year period at the Feline Centre at the University of Bristol.32 The presence of neoplastic cells rules in neoplasia, but the absence of

such cells does not rule out this diagnosis since many cases of neoplastic ascites are not associated with exfoliated neoplastic cells. Other causes of nonseptic exudates include pancreatitis, lymphocytic cholangitis, and viscus rupture, such as the gall bladder or urinary bladder. Degenerate neutrophils typify septic exudates (i.e., septic peritonitis), and their presence should instigate investigation for causes of infection (mostly leakage of gastrointestinal contents).34

Chylous Effusions Chylous effusions appear as milky or pink opaque fluid, and small mature lymphocytes initially predominate in cell counts. After drainage, more macrophages and nondegenerate neutrophils may be found. Chyle is typically classified as an exudate, but its physical characteristics can be consistent with a modified transudate (protein content between 25 and 40 g/L); biochemical analysis of triglyceride and cholesterol levels in the fluid are required to confirm the diagnosis. Pseudochylous effusions resemble true chyle both in appearance and cytology but do not contain fat. Similar conditions result in both chylous and pseudochylous effusions. Chylous abdominal effusions are rarely reported in the cat and only accounted for 7% of cases of ascites in one study.34 The described causes of chylous ascites in cats are predominantly neoplastic. In a series of nine cats, chylous ascites was associated with nonresectable abdominal neoplasia in four cases (i.e., hemangiosarcoma and paraganglioma), with intestinal and mesenteric lymphoma in two cases and lymphangiosarcoma of the abdominal wall in another.13 One described case in a 10-year-old cat was thought to be because of FIP.28 Figure 23-71 shows an ultrasonographic image of a cat with chylous abdominal effusion associated with pancreatitis. Other potential causes include right-sided congestive cardiac failure, steatitis (inflammation of fat), biliary cirrhosis, and lymphangiectasia.

Hemorrhagic Effusions Hemoperitoneum in companion animals is categorized as traumatic or spontaneous. Traumatic hemoperitoneum is further divided into blunt causes of trauma (i.e., motor vehicle accidents and high-rise falls) and penetrating trauma (i.e., gunshot wounds and bite wounds).8,21 Inadvertent splenic aspiration, venipuncture, or acute severe hemorrhage should be suspected if the cytology is consistent with peripheral blood including platelets but without erythrophagocytosis or if the blood clots readily. When there is no history of trauma, coagulopathy or spontaneous rupture of a vascular neoplasm should be considered. In one study of 16 feline cases of spontaneous hemoperitoneum, 12 cases (75%) were associated


543

with hepatic pathology such as neoplasia, necrosis, and amyloidosis.21 In another study of 65 cases of spontaneous hemoperitoneum, 46% (30 of 65) of cats had abdominal neoplasia, and 54% (35 of 65) had non-neoplastic conditions. Cats with neoplasia were significantly older and had significantly lower packed cell volumes (PCVs) than cats with non-neoplastic disease. Hemangiosarcoma was the most often diagnosed neoplasm (18 of 30, 60%), and the spleen was the most common location for neoplasia (11 of 30, 37%). Coagulopathies (8 of 35, 23%) and hepatic necrosis (8 of 35, 23%) were the most common causes of non-neoplastic hemoperitoneum.8 Other nonneoplastic causes of hemoperitoneum include ruptured bladder, hepatic rupture secondary to hepatic amyloidosis, gastric/duodenal ulcer, hepatic hematoma, hepatitis, perinephric pseudocyst, feline infectious peritonitis– induced liver rupture, and feline infectious peritonitis– induced nephritis.8,21 The prognosis of cats with spontaneous hemoperitoneum is poor. In two studies, only approximately 12% of cases survived to be discharged from hospital.8,21 Median survival time for cats that were discharged in one of those studies was 54 days (range, 5 to 1825 days).8

SPECIFIC CAUSES OF ASCITES Feline Infectious Peritonitis Feline infectious peritonitis (FIP) comprised 50% of cats with recognized ascites over a 10-year period at the Feline Centre at the University of Bristol,32 and, as a rule of thumb, when ascites is recognized in a younger cat, FIP should be considered the major rule-out. The abdominal effusion found with FIP is typically straw to golden yellow (although the color can be very variable, for example, chyle may be present), may contain fibrin clots, and has a high protein concentration. The total protein content is greater than 35 g/L and often greater than 45 g/L, with globulins comprising 50% or more.31 One study described an effusion with total protein greater than 80 g/L as 90% specific, 55% sensitive, and having a 0.78 positive predictive value to diagnose FIP.31 The Rivalta test evaluates the fluid’s globulin content, and was found to be very sensitive but only 80% specific; this test is performed by adding one drop of acetic acid (98%) to 5 mL of distilled water. This fluid is mixed thoroughly, and then one drop of effusion is gently placed on the surface of the mixture. If the drop stays at the top of the fluid or slowly floats to the bottom, the test is considered to be positive. This test can give inaccurate results if inappropriate technique is used or if there is a significant temperature difference between the fluid sample and the acetic acid solution. A positive Rivalta test can result from lymphosarcoma, septic, or FIP effusions; these can be distinguished by cytology and culture.

544


Immunofluorescence staining of coronavirus antigen in macrophages had a positive predictive value of 1.00 but a negative predictive value of 0.57.15 The potential clinical presentations, diagnosis, and management of FIP are covered in detail in Chapter 33.

Neoplasia One study found neoplasia to be the most common cause of ascites in cats,34 and neoplasia should be considered the major rule-out in older cats with ascites. The effusion from cats with ascites resulting from neoplasia may be a modified transudate, resulting from compression of hepatic veins or the caudal vena cava, or metastases to the peritoneum; hemorrhage from neoplasia can cause hemoperitoneum; chylous effusions may result from reduced lymphatic drainage or rupture of lymphatic vessels; and raised vascular permeability caused by neoplastic infiltration can result in an exudative effusion. Carcinomas, mesotheliomas, and discrete (round) cell neoplasms (e.g., lymphoma, mast cell tumors, malignant histiocytosis) exfoliate cells into effusions more readily than sarcomas, and of these, lymphosarcoma is the most common malignancy of cats. Cytology of ascitic fluid reveals neoplastic cells in less than a quarter of cases; so the absence of such cells does not rule out a diagnosis of neoplasia. In these circumstances, the diagnosis may be achieved by ultrasound-guided fine-needle aspiration of affected organs, or even biopsy samples obtained at laparotomy. The specific approaches will depend on the specific neoplasia diagnosed.

Septic Peritonitis Exudates caused by septic inflammation usually result from bacterial contamination of the peritoneal cavity secondary to gastrointestinal tract leakage or penetrating wounds associated with trauma. Gastrointestinal tract leakage may occur as a result of ulceration associated with neoplasia or inflammatory disease or as a result of penetration of a sharp object ingested (such as a toothpick), it can also occur subsequent to prior abdominal surgery.7,9,17,24 Primary septic peritonitis in which no apparent cause can be identified has also been described in cats.26 Septic exudates are usually yellow to tan in color, with yellow particulate matter and are foul-smelling. Microscopically, the fluid is characterized by the presence of degenerate neutrophils and bacteria. Bacteria are often seen intracellularly within neutrophils. The condition is associated with high morbidity and mortality rates, with survival rates reported between 32% and 80%.7,9,17,24,26 The history and clinical signs are often vague and nonspecific but can include abdominal pain, vomiting, lethargy/depression, and anorexia. Abdominal pain is an inconsistent finding, being recognized in

only 62% of cats in one study7 and 43% in another.24 Some cats may have an inappropriately low heart rate.7,26 Hematologic and serum biochemistry findings are also inconsistent; neutrophilia with a left shift may be present, as may neutropenia or a normal neutrophil count. Similarly, cats may be hypoglycemic, hyperglycemic, or normoglycemic, and they may be hypoalbuminemic.7,24,26 One study recognized ionized hypocalcemia in 89% of cats with septic peritonitis at the time of diagnosis,17 and another suggested hyperlactatemia, when present, may be associated with a poorer prognosis.24 Radiographic findings are usually typical of ascites of any cause, but presence of pneumoperitoneum in a cat that has not undergone recent surgery may suggest the presence of gas-forming bacteria or rupture of an abdominal viscus and warrants immediate surgical intervention. Ultrasonography does not directly aid the diagnosis of septic peritonitis.7 Exploratory laparotomy to determine and correct an underlying problem, such as full-thickness gastrointestinal perforation (often requiring partial resection) is required, as is copious abdominal lavage with sterile, warmed fluids (Figure 23-73). There are no statistically significant survival differences between postsurgical primary closure, open peritoneal drainage, or closed suction drainage postsurgical lavage; however, a trend toward a higher survival rate has been seen in cats treated with primary closure.24,26 Treatment also involves antibiotics, initially parenterally, based on culture and sensitivity findings. Consistent with intestinal contents, most bacteria recognized are gram-negative aerobes, such as E. coli or Enterobacter spp., but mixed infections are usually found.7,24 Anaerobes seem more common in cats with primary septic peritonitis,26 which perhaps suggests these cases may result from healed over-bite wounds into the abdomen. Amoxicillin/ clavulanate would be an appropriate empirical choice of

FIGURE 23-73 Fulminant peritonitis associated with gastrointestinal perforation. In this case, the effusion volume was low but the high degree of serosal inflammation is evident.

antibiotics while awaiting sensitivity results. There are no definitive guidelines for duration of antibiotic treatment; the author uses extended treatment courses of 4 to 6 weeks. Supportive care with intravenous fluids to maintain fluid and electrolyte balances is also required perioperatively.

Bile Peritonitis Bile peritonitis is infrequently reported in cats but has been recognized in association with gunshot20 or motor vehicle2 trauma, with biliary obstruction from gall stones2,22 and subsequent to percutaneous ultrasoundguided cholecystocentesis in a cat with infectious cholangitis.4 Concurrent bacterial infection was recognized in each case; this increases severity of inflammation and worsens the prognosis, although full recovery was achieved in most reported cases.2,4,20 Bile peritonitis has the potential to result in small-volume effusions; so, if abdominocentesis does not yield a sample of effusion but bile peritonitis is high on the differential list, then diagnostic peritoneal lavage is appropriate. Since repair of or removal of the gall bladder and abdominal lavage are required, exploratory laparotomy is an appropriate means to diagnose this condition. Management should be considered as for septic peritonitis of other causes.

Uroabdomen Trauma, including blunt abdominal trauma, urethral catheterization, and bladder expression, is the most common cause of uroperitoneum in cats.1 It is also recognized as a complication of ureteral surgery.18 The bladder is the most frequent site of urine leakage after blunt abdominal trauma, whereas the urethra is most commonly injured following catheterization. Cats with ruptured bladders may still have a palpable bladder and the ability to urinate. Common historical complaints are anuria (53.8%) and vomiting (50%). Azotemia is a common finding, and hyperkalemia is seen in around 50% of cases. Drainage of urine from the peritoneal cavity seems to improve patient stabilization. Morbidity and mortality depended largely on the severity of associated injuries.1 Regardless of the site of injury or the cause of uroabdomen, the first goal of treatment is patient stabilization. Isotonic replacement fluids are used for initial resuscitation. Treatment of hypovolemic shock, if present, is the first order of fluid therapy. After fluid resuscitation, drainage of urine from the abdomen should be established. Continuous passive drainage of the urine is necessary for stabilization and allows effective diuresis to occur. Indwelling catheterization of the urinary bladder is recommended to keep the bladder decompressed and reduce urine flow into the abdominal cavity in patients with bladder and proximal urethral injury. If the urethra is traumatized and a catheter cannot


545

be placed, prepubic tube cystostomy may be necessary to achieve temporary urinary diversion. The decision to treat the uroabdomen patient surgically or conservatively should be based on the location and severity of the underlying injury, the condition of the patient at presentation, and the patient’s response to initial stabilization.1,12

Right-Sided Congestive Heart Failure Congestive heart failure has become an uncommon cause of ascites in cats since the late 1980s/early 1990s, from which time dilated cardiomyopathy has been largely eradicated.32,34 Ascites does still result from rightsided congestive heart failure in conditions such as tricuspid insufficiency,6 arrhythmogenic right ventricular cardiomyopathy,16 myocardial fibrofatty infiltration,14 or restrictive cardiomyopathy.29,34 Concurrent pleural effusion or pulmonary edema is often, but not necessarily, present with cardiac induced ascites. A heart murmur is not necessarily noted. Noting a jugular pulse or thrill is helpful diagnostically, if present. The ascitic fluid is typically a modified transudate, but a chylous effusion is also possible. Cardiac diseases are covered in Chapter 20.

Hepatopathies In some cases, hepatic lipidosis has been reported to cause ascites, particularly in association with pancreatitis. These cats are often hypoalbuminemic, with the possibility of intravenous fluid therapy contributing to the ascites by raising hydrostatic pressure.11 Other liver diseases which can result in ascites include lymphocytic cholangitis,19,25 neutrophilic cholangitis, cirrhosis,13 necrosis, neoplasia, and suppurative cholangiohepatitis.34 Portosystemic shunts in cats rarely result in ascites, compared with dogs.3 Hypoalbuminemia and hepatic failure result in transudates; portal hypertension and cirrhosis cause higher protein ascites because of raised capillary hydrostatic pressure causing leakage of high protein lymph. Hepatopathies are covered in detail elsewhere in this chapter.

References 1. Aumann M, Worth L, Drobatz K: Uroperitoneum in cats: 26 cases (1986-1995), J Am Anim Hosp Assoc 34:315, 1998. 2. Bacon NJ, White RAS: Extrahepatic biliary tract surgery in the cat: a case series and review, J Small Anim Pract 44:231, 2003. 3. Blaxter AC, Holt PE, Pearson GR et al: Congenital portosystemic shunts in the cat: a report of nine cases, J Small Anim Pract 29:631, 1988. 4. Brain PH, Barrs VR, Martin P et al: Feline cholecystitis and acute neutrophilic cholangitis: clinical findings, bacterial isolates and response to treatment in six cases, J Feline Med Surg 8:91, 2006. 5. Bray J: Diagnosis and management of peritonitis in small animals, In Practice 18:403, 1996.

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6. Closa J, Font A: Traumatic tricuspid insufficiency in a kitten, J Am Anim Hosp Assoc 35:21, 1999. 7. Costello MF, Drobatz KJ, Aronson LR et al: Underlying cause, pathophysiologic abnormalities, and response to treatment in cats with septic peritonitis: 51 cases (1990-2001), J Am Vet Med Assoc 225:897, 2004. 8. Culp WTN, Weisse C, Kellogg ME et al: Spontaneous hemoperitoneum in cats: 65 cases (1994-2006), J Am Vet Med Assoc 236:978, 2010. 9. Culp WTN, Zeldis TE, Reese MS et al: Primary bacterial peritonitis in dogs and cats: 24 cases (1990-2006), J Am Vet Med Assoc 234:906, 2009. 10. Dempsey SM, Ewing PJ: A review of the pathophysiology, classification, and analysis of canine and feline cavitary effusions, J Am Anim Hosp Assoc 47:1, 2011. 11. Dimski DS: Feline hepatic lipidosis, Clin Tech Small Anim Pract 12:28, 1997. 12. Gannon KM, Moses L: Uroabdomen in dogs and cats, Compend Contin Educ Vet 24:604, 2002. 13. Gores BR, Berg J, Carpenter JL et al: Chylous ascites in cats: nine cases (1978-1993), J Am Vet Med Assoc 205:1161, 1994. 14. Harjuhahto TAI, Leinonen MR, Simola OTM et al: Congestive heart failure and atrial fibrillation in a cat with myocardial fibrofatty infiltration, J Feline Med Surg 13:109, 2011. 15. Hartmann K, Binder C, Hirschberger J et al: Comparison of different tests to diagnose feline infectious peritonitis, J Vet Int Med 17:781, 2003. 16. Harvey AM, Battersby IA, Faena M et al: Arrhythmogenic right ventricular cardiomyopathy in two cats, J Small Anim Pract 46:151, 2005. 17. Kellett-Gregory LM, Mittleman Boller E, Brown DC et al: Retrospective study: ionized calcium concentrations in cats with septic peritonitis: 55 cases (1990-2008), J Vet Emerg Crit Care 20:398, 2010. 18. Kyles AE, Hardie EM, Wooden BG et al: Management and outcome of cats with ureteral calculi: 153 cases (1984-2002), J Am Vet Med Assoc 226:937, 2005. 19. Lucke VM, Davies JD: Progressive lymphocytic cholangitis in the cat, J Small Anim Pract 25:249, 1984.

20. Ludwig LL, McLoughlin MA, Graves TK et al: Surgical treatment of bile peritonitis in 24 dogs and 2 cats: a retrospective study (19871994), Vet Surg 26:90, 1997. 21. Mandell DC, Drobatz K: Feline hemoperitoneum 16 cases (19861993), J Vet Emerg Crit Care 5:93, 1995. 22. Moores AL, Gregory SP: Duplex gall bladder associated with choledocholithiasis, cholecystitis, gall bladder rupture and septic peritonitis in a cat, J Small Anim Pract 48:404, 2007. 23. O’Brien PJ, Lumsden JH: The cytologic examination of body cavity fluids, Semin Vet Med Surg (Small Anim) 3:140, 1988. 24. Parsons KJ, Owen LJ, Lee K et al: A retrospective study of surgically treated cases of septic peritonitis in the cat (2000-2007), J Small Anim Pract 50:518, 2009. 25. Prasse KW, Mahaffey EA, DeNovo R et al: Chronic lymphocytic cholangitis in three cats, Vet Path 19:99, 1982. 26. Ruthrauff CM, Smith J, Glerum L: Primary bacterial septic peritonitis in cats: 13 cases, J Am Anim Hosp Assoc 45:268, 2009. 27. Saunders WB, Tobias KM: Pneumoperitoneum in dogs and cats: 39 cases (1983-2002), J Am Vet Med Assoc 223:462, 2003. 28. Savary KC, Sellon RK, Law JM: Chylous abdominal effusion in a cat with feline infectious peritonitis, J Am Anim Hosp Assoc 37:35, 2001. 29. Saxon B, Hendrick M, Waddle JR: Restrictive cardiomyopathy in a cat with hypereosinophilic syndrome, Can Vet J 32:367, 1991. 30. Seim HB: Management of peritonitis. In Bonagura JD, Kirk RW, editors: Kirk’s current veterinary therapy XII: small animal practice, Philadelphia, 1995, Saunders, p 764. 31. Sparkes A, Gruffydd-Jones T, Harbour D: Feline infectious peritonitis: a review of clinicopathological changes in 65 cases, and a critical assessment of their diagnostic value, Vet Rec 129:209, 1991. 32. Tasker S, Gunn-Moore D: Differential diagnosis of ascites in cats, In Practice 22:472, 2000. 33. Walters JM: Abdominal paracentesis and diagnostic peritoneal lavage, Clin Tech Small Anim Pract 18:32, 2003. 34. Wright KN, Gompf RE, DeNovo RC Jr: Peritoneal effusion in cats: 65 cases (1981-1997), J Am Vet Med Assoc 214:375, 1999.

C H A P T E R

24

Endocrinology O U T L I N E Endocrine Pancreatic Disorders, 547 Overview, 547 Diabetes Mellitus, 547 Gastrinoma, 567 Insulinoma, 567 Thyroid Gland Disorders, 571 Hyperthyroidism, 571 Hypothyroidism, 584 Adrenal Gland Disorders, 592 Hyperadrenocorticism, 592 Catecholamine-Secreting Adrenal Tumors, 602 Sex Hormone–Secreting Adrenal Tumors, 602 Hyperaldosteronism, 602 Hypoadrenocorticism, 606

Pituitary Disorders, 610 Anatomy and Physiology, 611 Diseases of the Pituitary Gland, 611 Disorders of Calcium Metabolism, 625 Calcium Homeostasis, 625 Approach to the Cat with Hypercalcemia, 626 Increased Parathyroid Hormone with Hypercalcemia, 629 Decreased Parathyroid Hormone with Hypercalcemia, 630 Normal Parathyroid Hormone with Hypercalcemia, 632 Other Causes of Hypercalcemia, 633 Treatment of Hypercalcemia, 634 Hypocalcemia, 636

ENDOCRINE PANCREATIC DISORDERS

DIABETES MELLITUS

Randolph M. Baral and Susan E. Little

Epidemiology

OVERVIEW The endocrine pancreas comprises multitudes of islands of cells within the exocrine pancreas known as the islets of Langerhans. The islets represent only 2% of the pancreas and comprise several types of cell. Each cell type secretes a different hormone. The major cell types and the hormones they produce are found in Table 24-1. The close interrelationship among these different cell types allows for direct control of secretion of some hormones by other hormones. For example, insulin inhibits glucagon secretion and somatostatin inhibits the secretion of both insulin and glucagon. Activity of beta cells and production of insulin are of main importance for diabetes mellitus (DM).24


The prevalence of feline DM is in the order of 1 in 100 to 1 in 200 cases, with higher numbers of cases seen in referral practice than in first opinion practice.5,62,93,95 The number of diabetes cases in cats appears to be increasing (Figure 24-1), and this may relate to higher obesity rates and more cats being fed high-carbohydrate diets.93 Male cats appear to be at greater risk, representing approximately 60% to 70% of all diabetics.5,62,89,93,95 Increasing age also correlates with increasing risk of DM, with approximately 20% to 30% of diabetics diagnosed at 7 to 10 years of age and 55% to 65% of diabetics diagnosed when older than 10 years of age.5,89,93,95 Numerous studies have indicated that Burmese are at higher risk of diabetes than other cats in Australia and New Zealand,5,62,95,114,121 and a United Kingdom survey has indicated likewise.77 This does not appear to be the case in North America,

547


548


where the Burmese breed appears to be genetically distinct. One North American study indicated an overrepresentation of Siamese cats,89 but a subsequent study did not confirm this.93

Clinical Signs and Diagnosis According to one authority, “Currently, there are no internationally accepted criteria for the diagnosis of diabetes in cats.”94 Despite this statement, DM is usually recognized as persistent hyperglycemia above the renal threshold for normal cats, which is blood glucose (BG) greater than 16 mmol/L (288 mg/dL), with consistent clinical signs (polyuria, polydipsia, and weight loss). Elevations of BG above the renal threshold result in glycosuria. Caution must be taken to rule out stress hyperglycemia (reportedly as high as 60.4 mmol/L [1087mg/ dL]).59 In many cases serum fructosamine concentration will be normal with stress hyperglycemia. Ruling out stress hyperglycemia can also be achieved by treating underlying conditions and then rechecking blood and urine glucose on a subsequent day. This is particularly

TABLE 24-1 The Major Cell Types of the Endocrine Pancreas and the Hormones They Produce Cell Type

Hormone

Alpha cells (20%-25% of each islet)

Glucagon

Beta cells (60%-80% of each islet)

Insulin

Delta cells (10% of each islet)

Somatostatin

Gamma cells have two subtypes: PP (or F) cells

Pancreatic polypeptide

D cells

Vasoactive intestinal peptide

EE (or enterochromaffin) cells

Serotonin, motilin, substance P

important if the BG is less than 20 mmol/L (360 mg/ dL), intercurrent disease is present that could cause stress hyperglycemia, or typical clinical signs of DM are absent. A second test is not usually required if BG is greater than 20 mmol/L (360 mg/dL). Evidence of gluconeogenesis (ketosis or ketonuria) supports a diagnosis of DM.94 All diabetic cats in a recent study had at least some elevation of the plasma ketone, beta-hydroxybutyrate. Using a plasma value of 0.22 mmol/L beta-hydroxybutyrate as the cutoff value for diagnosis of DM gave a false positive rate of 9%, whereas 0.58 mmol/L reduced the false positive rate to 1.2%. No cat with moderate or severe stress-related hyperglycemia had beta-hydroxybutyrate concentrations above 0.22 mmol/L.132 Fructosamine is the term used to describe glycated plasma proteins, and serum concentration of fructosamine is related to BG concentration. Serum fructosamine concentration may be used to aid the diagnosis of DM, but care must be taken because in cats a single serum fructosamine concentration measurement most likely reflects the mean BG concentration for approximately the past week (compared with longer durations in other species). Further, serum fructosamine may not exceed the reference range in cats with moderate hyperglycemia of less than 17 mmol/L (306 mg/dL),64 making serial BG testing a more reliable indicator of diabetes. Most cats with newly diagnosed DM will have serum fructosamine levels higher than 400 µmol/L.16 Other serum or plasma biochemistry changes in DM are variable but commonly include elevations in the hepatic enzymes, alanine aminotransferase (ALT), and alkaline phosphatase (ALP). These values return to normal on successful treatment of diabetes. Hematology is typically normal but a stress leukogram of mild neutrophilia and lymphopenia may be recognized. Concurrent infection resulting in a more pronounced neutrophilia, perhaps with a left shift, can

Diabetes mellitus per 10,000 cats

140 120 100 80 60 40 20 0 1970 1972 1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 Year

FIGURE 24-1 Hospital prevalence of feline diabetes mellitus. Veterinary Medical Data Base, 1970-1999. (From Prahl A, Guptill L, Glickman NW et al: Time trends and risk factors for diabetes mellitus in cats presented to veterinary teaching hospitals, J Feline Med Surg 9:351, 2007.)

CHAPTER 24 Endocrinology

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be present, and successful management of diabetes requires treatment of underlying infection. Glycosuria should be considered as part of the diagnostic criteria because this arises as a result of BG above the renal threshold. Urine may be dilute and associated with polydipsia but not necessarily so as some affected cats have concentrated urine. One study showed that 13% of cats with DM had urinary tract infection (UTI),4 and as with other infections, UTI must be treated to aid diabetic control.

Pathophysiology Successful management of DM requires an understanding of its pathophysiology. Hyperglycemia resulting in DM comprises three processes: 1. Lack of insulin production 2. Lack of insulin receptivity (insulin resistance) 3. Hepatic gluconeogenesis In the healthy individual, for most organs, insulin must bind to insulin receptors at the periphery of cells to allow entry of glucose from the bloodstream into the cell. When insulin binds to the receptor, intracellular mechanisms are activated that result in glucose transporters (contained within intracellular vesicles) moving to the cell membrane. At least 12 glucose transporter proteins (GLUTs) have been described. GLUT4 is responsible for insulin-mediated glucose uptake. GLUT4 vesicles dock on the cell membrane, and then GLUT4 fuses to the cell membrane to allow intracellular diffusion of glucose. This is a complex process mediated by at least three genes in all mammals. Glucose in the bloodstream is mostly from metabolized food.63 These processes have been simplified, as depicted in Figure 24-2. There are two major organs with important differences in glucose metabolism: 1. The liver has enhanced uptake of glucose that is mediated as described previously but also stores glucose in the form of glycogen. In most species hepatic glycogen is split back into glucose (gluconeogenesis) in times of fasting, such as between meals. In cats gluconeogenesis is reported to be active even in the fed state.38 Cats have low levels of glucokinase, an enzyme that facilitates conversion of glucose to glucose 6-phosphate, but high levels of glucose 6-phosphate. Glucose 6-phosphate plays a vital role in glycogen production and glycolysis (energy production).43 The full implications of these feline-specific differences are not yet understood but may prove vital in our evolving understanding of the pathogenesis of feline diabetes. 2. Brain cells are permeable to glucose and can use glucose without the intermediation of insulin. The brain normally uses only glucose for energy and can

FIGURE 24-2 Normal physiology of glucose metabolism; beta islet cells of pancreas produce and secrete insulin, insulin binds to insulin receptors at cells of organs around body (e.g., heart, lungs, kidney), which increases the number of plasma membrane glucose transporters (GLUTs). GLUTs enable glucose uptake by cells.

use other substrates (e.g., fat) for energy only with difficulty (as opposed to other organs). For these reasons it is essential that BG concentration does not fall too low because hypoglycemic shock can result.38 With insulin deficiency or lack of insulin receptivity, cells become deprived of glucose; glucose remains in the bloodstream; and, once the renal threshold is reached, glucose spills into the urine. Because cells are deprived of glucose, negative feedback from the cells drives appetite, resulting in polyphagia, but insofar as there is reduced cellular metabolism, concurrent weight loss also results. Weight loss is also contributed to by muscle and protein catabolism to provide substrates for gluconeogenesis. Glycosuria results in osmotic loss of water from the kidneys, so polyuria occurs. To maintain hydration the animal has a compensatory polydipsia. Because there is less cellular recognition of glucose, another negative feedback mechanism stimulates gluconeogenesis in the liver. Ketones are a by-product of gluconeogenesis, and there is a resultant increase in ketone concentrations in the blood and urine. However, ketones can create nausea and, paradoxically, make the animal inappetent. Type 1 DM is due to lack of insulin (Figure 24-3). It is rarely described in cats. It is most often associated with

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FIGURE 24-3 Type 1 diabetes mellitus, rarely described in cats; lack of production of insulin results in reduced number of plasma membrane glucose transporters (GLUTs). Fewer GLUTs means that glucose is less able to enter cells.

immune-mediated destruction of beta islet cells but has also been described with exocrine pancreatic insufficiency.107,118,131 Type 2 DM is far more common in cats.94 The initiating factor is insulin resistance (Figure 24-4). This may be associated with decreased number of insulin receptors,110 reduced receptor activity,115 direct effect on GLUT4,9 or a combination of factors. Initially, the body responds by producing more insulin. This chronic hyperfunction of the beta islet cells contributes to their eventual failure and the inability to secrete sufficient insulin. Insufficient insulin production may affect potassium metabolism, insofar as insulin allows potassium to enter cells. In DM the lack of insulin or the lack of receptors means that less potassium is able to get into the cells. Hence there is an increase of potassium in the blood, which is cleared by the kidneys, especially with polyuria. Therefore serum/plasma potassium is even less reflective of the total body potassium than usual. In addition, insufficient insulin production may affect lipoprotein lipase (LPL) activity. LPL works in conjunction with insulin in fatty acid metabolism. The reduced LPL activity may be significant enough to result in lipemia. The lipemia may be due to triglycerides (TGs) or cholesterol, but TGs are more governed by chylomicrons (CMs) and very low-density lipoprotein (VLDL), which have more dependence on LPL activity.127

FIGURE 24-4 Type 2 diabetes mellitus is instigated by insulin resistance. The insulin receptor processes do not function appropriately, so fewer plasma membrane glucose transporters (GLUTs) are formed. Fewer GLUTs means that glucose is less able to enter cells. The body initially responds by producing more insulin. Chronic hyperfunction of the beta islet cells contributes to their eventual failure and the inability to secrete sufficient insulin.

Underlying Causes Pancreatic Factors Even without any overt exocrine pancreatic dysfunction, diabetic cats produce amylin (an amyloid precursor) that is deposited in islet cells, leading to decreased insulin production. In humans genetic assessments have indicated that many of the genes associated with type 2 diabetes are associated with insulin secretion from beta islet cells.102 Additionally, exocrine pancreatic disease occurs as a comorbidity with diabetes, and elevated serum feline pancreatic lipase immunoreactivity (fPLI) has been recognized in diabetic cats.31 Pancreatic diseases such as pancreatitis, pancreatic adenocarcinoma,94 and genetic associations may play a role.61 Peripheral Factors DM arises as a consequence of complex interactions of both pancreatic and multiple peripheral factors in any individual. The most common peripheral causes cited are age, gender, and breed predispositions as well as obesity, dietary carbohydrates, corticosteroid administration, and concurrent conditions such as infection. Epidemiologic studies in cats consistently show DM to be a disease of older cats, with the incidence increasing markedly in cats over the age of 8 years.5,89,93,95 Age

associations with insulin resistance are controversial in people with discordant results, most likely because of general health, physical training, and changes in liver size.10,28 Multiple studies have indicated increased insulin resistance in male cats (in particular after neutering) that is consistent with the overrepresentation of males among diabetic cats.3,44,46 There are now several studies indicating that Burmese are more at risk of DM than other cats in Australia, New Zealand, and the United Kingdom.* Breed predispositions are likely to be analogous to the situation for humans, wherein DM is more prevalent in various indigenous groups such as Australian Aborigines, African Americans, and Pima Indians.17,55,67 Genetic studies in humans have identified 20 common genetic variants associated with type 2 diabetes. Most of these genes are associated with regulation of insulin secretion from beta islet cells in response to insulin resistance, but there are also genes related to glucose transport and insulin sensitivity. Many associated genes have unknown roles. In most instances multiple genes are affected in individuals.102 The increasing availability of genomewide assessments will make searches for specific genes easier in cats, but the complex interactions of multiple genes in humans may make interpretation more difficult in cats, wherein the number of cases assessed will be far less than in studies of people. Obesity has been directly related to insulin resistance in cats as well as humans3,9 and specifically reduces GLUT4 expression.9 Other consequences of obesity in people, such as decreased insulin signaling and glucose disposal rates,63 are also likely to be relevant in cats. For obesity (and insulin resistance generally) to be associated with type 2 diabetes, the beta islet cells must be unable to compensate fully for the decreased insulin sensitivity.63 Weight loss is therefore an important component of diabetes management. In comparison to most mammals, cats have very low hepatic activity of the enzyme glucokinase, which plays the important role of acting as a “glucose sensor.” Cats are able to compensate by having elevated levels of glucose 6-phosphate. This altered glucose-sensing pathway in the feline liver may represent an evolutionary adaptation to a low-carbohydrate diet.43 These changes create challenges for all cats to handle the high glucose loads provided by high-carbohydrate diets and, if coupled with insulin resistance (from any cause), can result in diabetes. Recent studies have demonstrated improved remission rates when cats are fed lowcarbohydrate/high-protein diets compared with highfiber diets.7,32,76 Specific infections in people (e.g., hepatitis C) have been correlated with insulin resistance,47 although the reasons for the associations are not elucidated. *References 5, 62, 77, 95, 114, 121.


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Additionally, tumor necrosis factor-alpha (TNF-alpha), a cytokine involved in systemic inflammation and the regulation of immune cells, has been demonstrated to play a role in the pathophysiology of insulin resistance.8 Managing underlying infections is an important component of reducing insulin resistance. Azotemia associated with renal disease18 and hyperthyroidism,50 both common diseases in older cats, have also been demonstrated to contribute to insulin resistance. Management of concurrent conditions can therefore aid diabetic control. Glucocorticoids impair insulin-dependent glucose uptake by peripheral cells and enhance hepatic gluconeogenesis as well as inhibiting insulin secretion from beta islet cells.2A recent study found that high doses of corticosteroids increased serum glucose in all 14 study cats assessed, but clinical signs were seen in only one cat.68 Catecholamines and a number of other hormones released during stress states contribute to the development of hyperglycemia by directly stimulating glucose production and interfering with tissue disposal of glucose. In a normal individual hyperglycemia stimulates the secretion of insulin and inhibits the secretion of glucagon, effects that will diminish the degree of hyperglycemia resulting from direct actions of stress hormones on glucose production and disposal. Cats with impaired islet responses to glucose will be particularly prone to the development of marked hyperglycemia during stress states because they may be unable to respond to the influence of hyperglycemia.39 Hyperglycemia itself suppresses the insulin response in three distinct ways that relate to chronicity of hyperglycemia: 1. Glucose desensitization: a normal physiologic response that is a rapid and reversible refractoriness of beta cells after short exposure to hyperglycemia 2. Beta cell exhaustion: a reversible depletion of the readily releasable pool of intracellular insulin caused by more prolonged hyperglycemia 3. Glucotoxicity: the slow and progressively irreversible direct toxicity of the beta cells induced by chronic hyperglycemia through functional change and cell death A continuum exists between beta cell exhaustion and glucotoxicity in that the changes are reversible until a particular point in time.92

Treatment Principles It was not so long ago that the principle aims of therapy for diabetic cats were simply to control hyperglycemia safely (reduce the chance of ketosis) and resolve clinical signs of disease (e.g., polyuria, polydipsia, weight loss). Now the aim is to induce diabetic remission for as long as possible. Clinicians have better

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tools than ever (e.g., improved insulin and dietary therapy, home monitoring techniques) to achieve this more stringent goal. However, it must not be forgotten that successful treatment of DM includes an assessment of impact on quality of life for both cat and owner. Owners that perceive the treatment will have a negative impact on quality of life may be more likely to choose euthanasia over treatment. Recently, a series of 29 specific DM-associated questions centered on both owner and animal were designed as a quality-of-life tool for diabetic cats. The tool was tested with 221 owners of diabetic cats predominantly in the United States and the United Kingdom, about half of whom performed home BG measurements. Nine of the top 10 items judged by owners to have negative impact were related to their own quality of life rather than that of the cat. These were issues such as difficulty boarding the cat, difficulty leaving the cat with family or friends, worry about the disease, worry about hypoglycemia, and changes to work and social life.86 In a review of the pathophysiologic factors of type 2 DM detailed in the previous section, those factors that are unable to be influenced can be struck off, leaving those that should be addressed: • Pancreatic factors • Reduced insulin • Peripheral factors: • Age predispositions • Sex predispositions • Breed predispositions • Obesity • High-carbohydrate diet • Underlying infection • Corticosteroid usage • Concurrent conditions (e.g., azotemia, hyperthyroidism) Therefore management of the diabetic cat should be a multipronged approach incorporating insulin, dietary therapy (to reduce carbohydrate load and induce weight loss if the cat is overweight), weaning off corticosteroids when possible, and management of any infection or concurrent condition. If peripheral insulin resistance factors can be overcome, the cat may be weaned from insulin as long as the beta islet cells have not suffered irreversible damage from chronic glucotoxicity. With early intervention and good glycemic control, diabetic remission was achieved in 84% to 100% of cats in two recent studies.73,104 Loss of control of peripheral factors such as a return to a high-carbohydrate diet, recurrence of obesity, or azotemia may result in a return to an insulindependent state. Two recent studies have looked at factors associated with an increased chance of achieving remission. In one questionnaire-based study of owners of diabetic

cats treated with glargine insulin participating in an Internet forum, strict glycemic control, administration of corticosteroids before diagnosis, and absence of polyneuropathy were more likely in cats that achieved remission. Factors that were not useful predictors of remission included age, sex, body weight, and presence of chronic renal disease or hyperthyroidism. Cats that achieved remission had a lower mean maximum insulin dose (0.43 U/kg, every 12 hours) than cats that did not achieve remission (0.66 U/kg, every 12 hours).104 In another study of 90 cats with newly diagnosed diabetes, 50% of cats achieved remission after a median time of 48 days. The maintenance insulin was glargine for 47% of cats and protamine zinc insulin (PZI) for 53% of cats. The median duration of remission was 151 days for cats still alive at the end of the study. Insulin was resumed in 29% of cats that had achieved remission, but six of the cats achieving remission did not require insulin again for more than 1000 days. In this study age and cholesterol levels were predictive of remission in multivariate analysis. Increased serum cholesterol decreased the chance of remission by about 65%. For each year of age, the chance of remission increased by approximately 25%. Duration of remission was longer with higher body weight and shorter with higher serum glucose. Cats treated with glargine insulin had an increased chance of remission based on univariate analysis.135

Specifics of Treatment in the “Well” Cat with Diabetes Mellitus Insulin therapy and dietary management are the mainstays for management of the basically “well” cat with DM that is not anorexic. The importance of weaning off corticosteroids when possible and management of any underlying infections or concurrent diseases should not be underestimated, but they are not specific to diabetic management. Insulin Therapy Insulin therapy provides the most effective and reliable means of achieving glycemic control in diabetic cats. The sooner glycemic control is reached, the higher the likelihood that diabetic remission can be achieved. A variety of insulin types can be used in cats for maintenance insulin therapy. It is difficult to predict in advance which cats will do better with which insulin, so the clinician must be knowledgeable about the insulin choices for treatment of feline diabetes. Although there are guidelines for choosing the starting dose of insulin for cats, the appropriate maintenance dose for each patient will be the dose that controls clinical signs and hyperglycemia. Most cats require twice-daily administration, regardless of the type of insulin selected. Because of the


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TABLE 24-2 Characteristics of Insulins Commonly Used to Treat Feline Diabetes Mellitus Insulin

Licensed in Cats

ProZinc

Manufacturer

Formulation

Action

Dose*

Yes

Boehringer Ingelheim Vetmedica

U40 recombinant PZI

Nadir 5-7 hours Duration 8-9 hours

Start 0.25-0.5U/kg, every 12 hours; Median maintenance dose 0.6 U/kg, every 12 hours

Vetsulin, Caninsulin

Yes

Intervet/Schering Plough

U40 Porcine zinc

Nadir 4 hours Duration 8-12 hours

Start 0.25-0.5 U/kg, every 12 hours; Median maintenance dose 0.5 U/kg, every 12 hours

Lantus

No

Sanofi Aventis

U100 Insulin glargine (recombinant human analog)

Nadir and duration not determined in diabetic cats

Start 0.25-0.50 U/kg, every 12 hours Median maintenance dose 2.5 U/cat, every 12 hours

Levemir

No

Novo Nordisk

U100 Insulin detemir (recombinant human analog)

Nadir and duration not determined in diabetic cats

Start 0.25-0.50 U/kg, every 12 hours Median maintenance dose 1.75 U/cat, every 12 hours

*Based on lean body weight.

unpredictability of the individual response to different insulins, it is important to be conservative when selecting insulin doses, either initially or when switching a cat from one type of insulin to another. It is critical for veterinary staff and owners to be aware of the concentration of the insulin being used for a given patient and to use the correct syringes for the insulin to prevent dosing error. Most human insulins are 100 units/mL (U100), and micro-fine or ultra-fine U100 syringes should be used. Because cats often require very small doses of insulin, many owners find it helpful to use 3/10 cc (0.3 mL) syringes for U100 insulins. However, Caninsulin/Vetsulin and ProZinc are U40 insulin, and U40 syringes must be used. U40 insulins are often more suitable than U100 insulins for administration of the small doses that diabetic cats require. The types of insulins most commonly used in cats can be summarized as follows (Table 24-2): Long-acting insulins: • Glargine (Lantus, Sanofi Aventis) • Detemir (Levemir, Novo Nordisk) • Protamine Zinc Insulin (ProZinc, Boehringer Ingelheim Vetmedica) Intermediate-duration insulins: • Porcine Lente (Vetsulin or Caninsulin, Intervet Schering Plough) • Neutral Protamine Hagedorn (NPH; e.g., Humulin-N, Eli Lilly or Novolin-N, Novo Nordisk) Rapidly acting, soluble insulin will be discussed below with therapy of diabetic ketoacidosis.

PZI-Vet (IDEXX Pharmaceuticals, Inc.), a 90% beef/10% pork U40 insulin, was commonly used in cats but is no longer commercially available because of the lack of a U.S. Food and Drug Administration–approved source of bovine pancreas. Compounded PZI cannot be recommended because the potency varies from batch to batch, making long-term regulation difficult. A replacement product based on recombinant human PZI insulin was developed and approved for cats as ProZinc (Boehringer Ingelheim Vetmedica) in 2009. One study that compared recombinant PZI (PZI-R, now sold as ProZinc) to PZI-Vet was conducted in six private feline specialty clinics. A total of 50 cats with DM and stable glycemic control on PZI-Vet (for at least 90 days) were switched to PZI-R for 30 days at the same dose rate and interval. In the 47 cats completing the study, there were no significant differences in body weight or serum fructosamine concentrations at days 15 or 30 compared with day 0. The researchers concluded that PZI-R provides glycemic control that is comparable to that of PZI-Vet when used at the same dose and dosing interval.87 A prospective, uncontrolled 45-day clinical trial evaluating the efficacy of PZI-R (ProZinc) for controlling glycemia in cats with newly diagnosed, untreated diabetes (n = 120) and cats with previously treated, poorly controlled diabetes (n = 13) was also published recently. Treatment was started at 1 to 3 U/cat every 12 hours (0.22 to 0.66 U/kg every 12 hours), and the dose was adjusted at re-evaluations on the basis of the history and results of physical examination, body weight, and BG curves. Feeding the same diet to all cats was not attempted, although most cats were fed a high-protein/ low-carbohydrate diet. The mean time of BG nadir was

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between 5 and 7 hours, and subsequent BG concentrations were rising in most cats by 9 hours after administration. By day 45 the owner’s subjective assessment of polyuria and polydipsia had improved in 79% of cats; 89% of cats had good body weight; and 9-hour mean BG concentration, serum fructosamine concentration, or both had improved in 84% of the cats compared with day 0. Biochemical hypoglycemia (BG less than 4.4 mmol/L [80 mg/dL]) occurred at least once in 64% of cats, and clinical signs of hypoglycemia were confirmed in two cats.83 Vetsulin/Caninsulin, a porcine lente insulin, is a mixed insulin zinc suspension containing 30% amorphous zinc insulin (which is rapidly absorbed and has a short duration of activity) and 70% crystalline zinc insulin (which is absorbed more slowly and has a longer duration of activity). The onset and duration of action are shorter than that of PZI in cats, with a BG nadir at about 4 hours after injection, and a duration of about 8 to 12 hours.72,74 A 12-month prospective study of Vetsulin/Caninsulin was conducted with 25 cats, most of which were newly diagnosed (n = 15), whereas the remainder were poorly controlled on other therapies. Cats with BG over 19 mmol/L (over 342 mg/dL) were started at 0.5 U/kg every 12 hours and cats with BG less than 19 mmol/L (less than 342 mg/dL) were started at 0.25 U/kg every 12 hours. No specific diet was fed. After an initial 6-day examination period, the cats were re-examined at 4, 8, 12, 26, and 52 weeks. Increases in insulin dose were made as needed, with a target BG nadir of 5 to 9 mmol/L (90 to 162 mg/dL). The median insulin dose was 0.5 U/ kg every 12 hours (range 0.1 to 1.9 U/kg every 12 hours), and only two cats required doses higher than 1 U/kg every 12 hours. During the study period seven cats went into remission within 15 weeks, and none relapsed during the 12 months. Of the 18 cats that did not go into remission, 13 reached the water intake target established for ideal diabetic control (less than 20 mL/kg per day for canned diets, less than 70 mL/kg per day for dry diets). The control of clinical signs in the cats that did not achieve remission was deemed either excellent or good. It took approximately 3 months for significant resolution of clinical signs.75 Another recent prospective, multicenter, nonblinded, open study followed 46 cats with diabetes (either newly diagnosed [n = 39], or previously treated but poorly controlled [n = 7]) during treatment with Vetsulin/ Caninsulin. The cats were monitored for about 16 weeks (stabilization phase), with additional monitoring of some cats (n = 23) for a variable period. The starting dose for each cat was based on the initial BG concentration: 0.25 U/kg if the BG was less than 20 mmol/L (360 mg/ dL), and 0.5 U/kg if greater than 20 mmol/L (360 mg/dL). The maximum starting dose did not exceed 2 U/dose, and dose rates greater than 0.5 U/kg twice daily were

not recommended during the first 3 weeks of treatment. No specific diet was used for all cats. At the end of the stabilization phase, 15% of cats achieved clinical remission. None of these cats had been treated previously for diabetes. Approximately 60% of the remaining cats were clinically stable after 3 to 4 months of treatment, a finding in line with studies published previously using a variety of insulins. Clinical signs of hypoglycemia were observed in nine cats during the stabilization period and were significantly associated with a dose of 3 U/cat or over 0.5 U/kg administered every 12 hours.79 PZI and lente insulins, when administered twice daily, resulted in marked hyperglycemia (>18 mmol/L, 324 mg/dL) for several hours before each insulin injection in one study using nine healthy cats.72 The continued (though intermittent) hyperglycemia of such therapy most likely contributes to continued glucotoxic effects of permanently damaging beta islet cells and would explain why higher remission rates have been seen with glargine73,104 and detemir.106 Glargine is a genetically engineered human insulin analog that has hormonal action identical to native insulin. When glargine is injected, it precipitates because of a pH change and forms microcrystals, which cause sustained release of the product. In humans glargine achieves long-lasting glycemic control and minimizes fluctuations in BG concentrations. The recommended starting dose of glargine is 0.25 U/ kg every 12 hours for cats with BG less than 20 mmol/L (less than 360 mg/dL), and 0.50 U/kg every 12 hours when the BG is over 20 mmol/L (over 360 mg/dL). One study in nine healthy cats showed that the nadir with glargine occurs approximately 12 to 16 hours after injection,72 whereas another study in five healthy cats using a euglycemic clamp showed the peak effect occurred between 2 and 9.75 hours.33 Although it may appear that there is a discrepancy in reported time to peak action for glargine, it is likely a result of the very different study designs and different parameters each study used to define time to peak insulin action (nadir versus maximal glucose infusion rate). Put simply, the first study reported the time that nadir glucose occurred (based on actual BG concentration), whereas the second study reported the time of peak glucose infusion rate (to maintain normoglycemia). Further, these studies were performed with small numbers of healthy cats, and whether a similar response would be seen in diabetic cats is unknown. Individual cats with a glargine nadir after 12 hours may achieve adequate glycemic control with once-daily dosing, but twice-daily dosing is associated with better glycemic control and higher remission rates.73,124 Hence twice-daily dosing is recommended for most cats. Detemir is an insulin analog that binds to albumin and is released slowly for a long duration of action. On the basis of studies by the manufacturer in humans, variations in BG with detemir may be even less

pronounced than with glargine. The duration of action and peak effect of detemir and glargine were evaluated in a study of five healthy cats. Definitive conclusions are hard to reach with small numbers of healthy cats, but the authors assessed that although glargine has a more rapid peak effect than detemir, it was more variable from cat to cat than detemir (glargine: 120 to 585 minutes; detemir: 370 to 575 minutes). The duration of action was longer for detemir in three cats but longer for glargine in two cats.33 It is important not to mix or dilute detemir or glargine insulin because the duration of action depends on the pH of the product. Glargine (Lantus) is available in 10-mL vials and a 3-mL SoloSTAR pen that measures in 1-unit increments. However, the pen is expensive, cannot be refrigerated, and expires in 1 month. The cartridges for the pen can be dispensed to be used as individual 3-mL vials. If refrigerated, open vials of glargine or detemir can be used for approximately 6 months.96 Detemir is available in 10-mL vials and a 3-mL FlexPen that measures in 1-unit increments. Once in use, the FlexPen is stored at room temperature and expires in 42 days. These insulins should be clear and colorless; if cloudiness, discoloration, or clumping is noted, the product should be discarded. It is not necessary to shake or rotate the vial before use. Glargine and detemir are not licensed for use in veterinary patients. Two studies with the same protocols, except varying insulin type, found similar remission rates for glargine (84%)104 and detemir (81%)106 in diabetic cats starting therapy within 6 months of diagnosis. Remission rates were much lower if insulin therapy was started more than 6 months after diagnosis. The insulins were administered twice daily, and a low-carbohydrate diet was fed. Median time to remission was 1.7 months for cats receiving detemir and 1.9 months for cats receiving glargine. Most of the cats achieving remission were able to stay off insulin, and the median duration of remission was 10.8 months for glargine and 1 year for detemir. Although biochemical hypoglycemia was common, clinical hypoglycemia was rare, with only a single event with mild signs in one cat on each insulin. The median detemir dose was 1.75 U/cat every 12 hours, and the median glargine dose was 2.5 U/cat every 12 hours. A direct comparison of insulin therapies in 24 newly diagnosed diabetic cats found remission rates were higher in those cats receiving glargine (100%) than PZI (38%) and lente insulin (25%) during the 16-week study period.73 The initial dose of insulin was 0.5 U/kg ideal body weight if the BG on admission was greater than or equal to 360 mg/dL (20 mmol/L), and 0.25 U/kg if BG was less than 20 mmol/L (360 mg/dL). BG was measured every 2 hours for 12 hours for each cat for the first 3 days of treatment to ensure that cats did not become hypoglycemic. No increase in insulin dose was made during the first 3 days, even if persistent hyperglycemia


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was present. During the study two cats treated with lente insulin and one cat treated with PZI had severe clinical hypoglycemia requiring intravenous glucose therapy. None of the glargine-treated cats exhibited signs of hypoglycemia, although many had biochemical hypoglycemia (BG less than 3 mmol/L [less than 54 mg/ dL]) without clinical signs. By 16 weeks all eight cats in the glargine group had achieved remission, whereas two of eight cats in the porcine lente group and three of eight cats in the PZI group had achieved remission. The probability of remission in newly diagnosed patients fed a low-carbohydrate/high-protein diet was significantly greater for cats treated with glargine than cats treated with PZI or lente in this study. One 12-week study of 13 diabetic cats found no significant difference in remission rates in cats receiving lente insulin (three of seven, 43%) compared to glargine (one of six, 17%). However, approximately half the cats enrolled in this study were not newly diagnosed with diabetes, cats received glargine only once daily but lente insulin twice daily, and monitoring was only every 4 weeks (after the initial 4 weeks).124 The findings of these studies indicate that the greatest chance of achieving diabetic remission is prompt initiation of therapy with glargine or detemir insulin twice daily combined with dietary therapy and intensive monitoring to enable dose adjustments. However, remission has been achieved with all of the insulin types previously listed, and clinicians should become familiar with the usage of more than one type of insulin for feline patients. In countries where a legal obligation exists to use a product with a veterinary license first, PZI would be the first choice, if available, and porcine lente would be the second choice. Many factors must be considered when choosing insulin, such as product availability and affordability, convenience and ease of dosing, legal and licensing issues, and product support. In general, clinicians can expect good product support when using veterinary-licensed products in cats but no product support when using products licensed for use in human medicine. INSULIN DOSING AND MONITORING PROTOCOLS

Managing diabetic cats with insulin with the objective of diabetic remission is a balancing act requiring sufficient insulin for glycemic control without causing hypoglycemia. The recommended starting dose for most insulins is 0.25 U/kg to 0.5 U/kg, with higher doses preferred for those cats with higher BG (more than 20 mmol/L [360mg/dL]) recognized at diagnosis.71,104,106 Frequent re-evaluations are required during the initial stabilization period, as outlined later and in Box 24-1. Typically, most cats first go through a phase where insulin dose is increasing, then stabilize when insulin dose is consistent, and then for cats achieving remission, a phase of decreasing insulin dose.

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BOX 24-1 Suggested Treatment and Management Protocol for Cats with Nonketotic Diabetes Mellitus At diagnosis • Evaluate for concurrent diseases with minimum database (complete blood count, serum biochemistry profile, urinalysis, urine culture, total T4, feline pancreatic lipase immunoreactivity). • Hospitalize for 1 day to begin insulin therapy; measure blood glucose every 3-4 hours, monitor for hypoglycemia. • Consultation with owner to demonstrate insulin handling and injection techniques, discharge with written instructions on diet, monitoring for hypoglycemia, monitoring appetite and water intake, and so on. Introduce the concept of home blood glucose monitoring. Three days later (this step not necessary for Lente insulin). • Hospitalize for 1 day; measure blood glucose every 3-4 hours, and monitor for hypoglycemia. • Consult with owner to confirm insulin handling and injection techniques. One week later • Re-evaluate body weight and condition, and perform full physical examination. • Hospitalize to perform blood glucose curve, and adjust insulin dose as needed; preferably use the same portable blood glucose meter that the owners would eventually use at home, and validate by comparison to in-hospital chemistry analyzer. • Consult with owner on home management of diet, and identify and correct any problems with insulin administration.

In human medicine, specialized educators provide most of the information on disease management, insulin injection and handling, BG monitoring, and so forth. In the veterinary setting this function is performed by the veterinarian or often by the veterinary nurse/technician. Owners must be properly trained to give insulin injections and educated on the important aspects of the disease in cats. For example, if some of the insulin dose is spilled during injection, the owner should be warned not to give additional insulin to avoid overdose. Whenever there is uncertainty about whether a dose has been administered, it is safest to wait until the next scheduled dose, because the consequences of missing one dose are negligible. Close contact with owners during the initial weeks of insulin therapy can help identify and correct any problems or misconceptions. The owner and all members of the household should be aware of the clinical signs of hypoglycemia, which include lethargy, trembling, ataxia, altered mentation, seizures, and coma. If signs suspected to be caused by hypoglycemia are noted at home, the owner should be

Repeat weekly in hospital blood glucose curves. • Until owner feels confident to perform at home (can show owner each week) • Or until appropriate nadir is achieved • Confirm appropriate nadir 1 month later. One month later • Re-evaluate body weight and condition, and perform full physical examination. • Hospitalize to perform blood glucose curve, and adjust insulin dose as needed. • Consult with owner on any problems encountered with home care or monitoring. • Discuss home blood glucose monitoring; demonstrate techniques, and provide supplies and written instructions. Home monitoring • Owner performs 12-hour blood glucose curve weekly until stabilized and telephones hospital to provide results. Three months later and every 3 months subsequently • Re-evaluate body weight and condition, and perform full physical examination. • Evaluate home monitoring, including blood glucose measurements. • Hospitalize for blood glucose curve. • Compare hospital blood glucose curve and home blood glucose curve. • Make insulin dose adjustments as required. • Make adjustments to dietary therapy as required. • Owner performs home blood glucose curve once monthly. • Periodically repeat minimum database.

instructed to give high glucose syrup orally. Suitable products are marketed for use by human diabetics. If the cat is unable to swallow, the syrup can be rubbed on the oral mucosa. When an episode of hypoglycemia occurs or is suspected, the owner should also seek veterinary care and discontinue insulin dosing in the meantime. It is the authors’ experience that hypoglycemia is rare initially, and if it is recognized biochemically within the first few days of therapy, there is a very low probability of clinical signs. Starting most diabetic cats at 0.5 U/kg increases the chance of establishing timely glycemic control. However, starting a cat on this dose of insulin requires close monitoring from day 1. When glargine was first introduced to management of feline diabetes, initial protocols called for BG testing every 4 hours for each of the first 3 days and then weekly.71 It is usually more practical to perform BG curves on day 1 and day 3. Long-acting insulins are marketed in human medicine as being peakless; this is not the case (at the very least in cats),72 and “spot” checks of BG are not adequate or appropriate to maintain glycemic control of diabetic cats. Serial BG

Long-acting insulins (see also Box 24-1): • Day 1 (to monitor for early hypoglycemia) • Day 3 • Day 10 (1 week later) • Weekly until appropriate nadir (can be twice a week if monitored at home) • Then confirm 1 week later • 1 month later • If monitored at home, once monthly • In-hospital evaluation every 3 months for all cats (including those monitored at home) BG can be evaluated every 3 to 4 hours. After an owner obtains a BG curve at home, especially during the stabilization period, the results should be reported to the clinician or veterinary nurse/technician. An appropriate BG curve for a stable diabetic cat being treating with long-acting insulin (e.g., glargine or detemir) is shown in Figure 24-5. A cat with a curve similar to the one illustrated needs no dose adjustment. However, cats can have such a curve yet need a dosage reduction (or increase) at a subsequent evaluation. In the early stages of treatment with long-acting insulins, the BG curve may resemble a curve obtained with lente insulin (Figure 24-6) with more distinct peaks but will usually flatten within 2 to 3 weeks. The slow absorption of glargine and detemir can result in atypical shaped curves with elevations of BG in the middle of the day (but this usually only occurs when there is minimal change in BG). Any dose adjustment decisions should be based on the lowest BG level of the day and should always take into account

8 7 6 5 4 3 2 1 0

8:00 AM

12:00 PM

4:00 PM

8:00 PM

557 144 126 108 90 72 54 36 18 0

Blood glucose (mg/dL)

measurements (BG curves) are the most effective monitoring technique to establish what is happening with the cat’s glucose homeostasis. Fructosamine assays are a crude measure reflecting the mean BG concentration for approximately the past week (compared with longer time periods in other species)64 and are not an effective measure for tight management of glycemic control. High serum fructosamine concentrations indicate poor glycemic control but give no information about the nadir BG concentration and cannot be used to determine whether the insulin dose must be increased or decreased. In addition, some disease states, such as hyperthyroidism, affect fructosamine concentrations. Cats with overt, uncontrolled hyperthyroidism may have fructosamine concentrations below the normal range, probably as a result of metabolic changes.101 There is no uniformly recognized BG monitoring protocol for diabetic cats. High remission rates have been achieved with weekly in-hospital monitoring of BG curves (stretching to every 2 weeks after 4 weeks)73 as well as with home monitoring up to daily and insulin dose changes instituted as often as every 3 days.104,106 The following schedule is suggested for BG monitoring either at home or in the hospital (serial measurements are taken on each day):


Blood glucose (mmol/L)

Time

FIGURE 24-5 Ideal blood glucose curve for stable diabetic cat using long-acting insulin (e.g., glargine, detemir). Note that there typically is a nadir, but the variation from preinsulin blood glucose to nadir is not great.

the patient’s clinical assessment (e.g., body weight, body condition score, appetite, water intake, and urine output). Intermediate-acting insulins (e.g., lente) (see Box 24-1): • Day 1 (to monitor for early hypoglycemia) • Day 7 • Weekly until appropriate nadir (can be twice a week if monitored at home) • Then confirm 1 week later • 1 month later • Every 3 months An appropriate curve for a stable diabetic cat being treating with an intermediate-acting insulin (e.g., Vetsulin/Caninsulin or Humulin-N) is shown in Figure 24-6. Note the extended periods of time that BG remains above 15 mmol/L (above 260 mg/dL). Common sense should be used when making any insulin dose adjustments. Suggested guidelines for dosage adjustments are shown in Table 24-3. Some guidelines for long-acting insulin dose adjustments also include recommendations based on the pre-insulin BG. The reason for monitoring is to assess the effect that particular dose of insulin has had, so changing the dose on the morning of testing defeats that purpose. The exception to this rule is when BG concentration is low before administration of insulin, in which case that dose should be skipped and the dose administered 12 hours later should be lower. As for long-acting insulins, dose adjustments should always take into account the patient’s clinical assessment (e.g., body weight, body condition score, appetite, water intake, and urine output). Once a cat achieves remission, ongoing BG monitoring should continue for the first month. Over the long term, urine glucose, body condition, appetite, and water intake can be monitored to detect loss of euglycemia. If hyperglycemia is detected, insulin therapy should be restarted promptly to avoid further damage to pancreatic beta cells. A low-carbohydrate, calorie-controlled diet often helps prevent obesity, minimize the demand on beta cells, and lower the risk of relapse.

25

450

20

360

15

270

10

180

5

90

0

8:00 AM 10:00 AM 12:00 PM 1:00 PM

2:00 PM

4:00 PM

6:00 PM

8:00 PM

Blood glucose (mg/dL)


Blood glucose (mmol/L)

558

0

Time

FIGURE 24-6 Ideal blood glucose curve for stable diabetic cat using intermediate-acting insulin (e.g., lente). Note the extended periods of time that blood glucose remains above the renal threshold.

TABLE 24-3 Suggested Guidelines for Insulin Dose Adjustment Based on Blood Glucose Curve Results Insulin Type

Glucose Concentration

Insulin Dose Recommendation

Vetsulin Caninsulin

Nadir 13 mmol/L (234 mg/dL) Pre-insulin 100% increase

>100% increase

Hyperthyroidism

5 years) and dying from causes likely unrelated to the disease. If left untreated, most cats eventually die or are euthanized because of the development of severe congestive heart failure, renal failure, respiratory distress, or the neurologic effects of an expanding pituitary tumor.

Diabetes Insipidus DI is an uncommon condition characterized by marked polyuria and secondary polydipsia. The disorder may be classified as either neurogenic (central) or nephrogenic in origin. Central DI results from a complete or partial failure of the neurohypophysis to secrete vasopressin (also called ADH), whereas nephrogenic DI is related to a lack of renal responsiveness to the antidiuretic actions of vasopressin.31,79 Cause of Diabetes Insipidus in Cats DI is an extremely rare disorder in cats, with only 18 reported cases.* All cats have had central DI; a primary nephrogenic form of DI (congenital DI) has not yet been described in cats. As in dogs, cats can develop either partial or complete forms of central DI.58,86,94 In most cats the exact cause of the disorder cannot be determined (idiopathic DI) but is thought to be a congenital defect in vasopressin secretion. Head trauma, however, is a relatively common identifiable cause of DI in cats, with about a third of the reported cases having such a history.4,16,56,86,94 Other less common causes of DI in cats include pituitary macrotumors31 or pituitary malformation.99 Clinical Features of Diabetes Insipidus All 18 reported cats with DI have been kittens or young adults, with an average age at diagnosis of 16 months (range, 2 months to 5 years).† Of the 18 cats, 12 (67%) have been males. There is no breed predilection. The major clinical signs of feline DI are marked polydipsia (generally above 100 mL/kg daily; normal, 40 to 70 mL/kg daily) and polyuria, usually of several months’ duration.79 The severity of clinical signs varies because DI may result from a partial to complete defect in either arginine vasopressin secretion or action. Other clinical signs affected cats show less consistently include weight loss (resulting from a preoccupation with drinking) and dehydration (if access to water has been restricted). Physical examination findings are usually unremarkable.

*References 4, 14-16, 23, 36, 43, 49, 56, 58, 81, 86, 94, 99. †

References 4, 14-16, 23, 36, 43, 49, 56, 58, 81, 86, 94, 99.

Diagnostic Workup for Polyuria and Polydipsia The first step for any cat presented with the owner complaint of polyuria and polydipsia is to establish that the problem actually exists, preferably by a combination of history; random USG determinations; and, if necessary, home measurement of water consumption over several days. The diagnosis of DI requires that it be differentiated from other medical diseases that cause polyuria and polydipsia in cats.64,79 The most important ones to rule out for polyuria and polydipsia in cats include primary renal disease, DM, and hyperthyroidism, all of which are much more common that DI. Although primary (psychogenic) polydipsia, a rare disorder associated with compulsive water drinking, has not been welldocumented in the cat, it may play a role in the polyuria and polydipsia that develops in more than a third of cats with hyperthyroidism.71,83 In general, routine hematologic and serum biochemical testing in cats with central DI are either normal or show evidence of mild dehydration (e.g., mild increases in packed cell volume, total protein, and sodium). In contrast, most of the other differential disorders for polyuria and polydipsia result in marked abnormalities in these screening tests (e.g., elevated serum urea nitrogen, creatinine, glucose, or T4). In central DI complete urinalysis is unremarkable except for the finding of persistently dilute urine. In cats the finding of USGs consistently below 1.008 is usually associated with either DI or hyperthyroidism.71,79 Obviously, hyperthyroidism should be ruled out before initiating testing procedures for DI. It is important to realize that the finding of a USG below 1.008 in a cat excludes mild (occult) renal disease, so further workup for renal disease or precautions associated with the water deprivation test are not necessary. The workup for polyuric cats with USGs about 1.008 is more complicated. Finding a USG of 1.008 to 1.012 or greater (but less than 1.030) can be associated with hyperthyroidism, stage 1 (occult) renal insufficiency, or pyelonephritis, as well as partial forms of central DI.71,79 The first step in workup of this group of cats is to exclude hyperthyroidism. If the serum T4 concentration is normal, pyelonephritis and early renal insufficiency should next be ruled out. The veterinarian should never perform a water deprivation test in a cat until renal disease is excluded, inasmuch as water deprivation could induce overt renal failure or urosepsis in a cat with unsuspected renal insufficiency.31,79 For the workup of pyelonephritis and early renal insufficiency, the following stepwise diagnostic approach is recommended. First, the veterinarian should perform a urine culture to help exclude pyelonephritis and associated urinary tract infection. If the urine culture is


619

negative, renal size and architecture are evaluated by abdominal radiography or, preferably, renal ultrasonography.42,79 If urine culture results are negative and radiographic or ultrasonographic findings are equivocal, determination of GFR40 or renal biopsy97 may be indicated. Because the urine culture can sometimes be negative in cats with pyelonephritis, a therapeutic trial with an appropriate antibiotic (e.g., enrofloxacin) should be instituted, especially if clinical or ultrasonographic findings suggest occult pyelonephritis. Confirming the Diagnosis of Diabetes Insipidus Several different diagnostic approaches can be used to confirm central DI, nephrogenic DI, and primary (psychogenic) polydipsia. The water deprivation test is generally considered by most authorities to be the best diagnostic test to differentiate these disorders. However, the water deprivation test is labor intensive, is difficult to perform correctly, is unpleasant for the cat, relies heavily on repeated emptying of the bladder, and can lead to untoward complications and misdiagnosis in some cats.31,64,79 A simpler and more practical method of diagnosis that can be recommended as an alternative to water deprivation testing is evaluation of the clinical response to a closely monitored therapeutic trial with the vasopressin analog, desmopressin.31,64,79 This approach is less complicated and time consuming than the water deprivation test and is certainly easier on the cat. The cost of the two approaches varies according to circumstances but is often comparable. Again, before a desmopressin trial is initiated, it is extremely important to rule out all other common causes of polyuria and polydipsia, limiting the differential diagnosis to central DI, primary nephrogenic DI, and primary (psychogenic) polydipsia. To perform the test, the owner should first measure the cat’s 24-hour water intake for 2 to 3 days before desmopressin is initiated, allowing free-choice water intake. The cat is then treated with therapeutic dosages of desmopressin (see the section on the treatment of diabetes insipidus later in this chapter), which ideally are administered subcutaneously at the dosage of 1.0 µg twice daily for a period of 5 to 7 days. If subcutaneous injections cannot be given, administration of desmopressin by the conjunctival (1 drop twice daily) or oral routes (75 mg twice daily) can be used (Tables 24-13 and 24-14). During this treatment period the owner should continue to measure the cat’s daily water intake and monitor the degree of urine output. A dramatic reduction in water intake (more than 50% of pretreatment measurements) and polyuria strongly suggests a diagnosis of central DI, whereas a lack of any reduction in polydipsia and polyuria is most consistent with primary nephrogenic DI. With more prolonged treatment, water consumption and urine output should completely normalize in cats with central DI.

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TABLE 24-13 Desmopressin Formulations Available in the United States Formulation

Concentration

How Supplied

Storage

Trade Name

Manufacturer

Nasal solution and sprays

0.1 mg/mL (100 µg/mL) 0.1 mg/mL (100 µg/mL) 0.1 mg/mL (100 µg/mL)

2.5-mL bottle 5-mL bottle 2.5-mL bottle

Refrigerate Room temp Room temp

1.5 mg/mL (1,500 µg/mL) 0.1 mg/mL (100 µg/mL)

2.5-mL bottle 5-mL bottle

Room temp Refrigerate

Sanofi Aventis Sanofi Aventis Ferring Pharmaceuticals CSL Behring Bausch and Lomb

0.1 mg/mL (100 µg/mL)

5-mL bottle

Room temp

DDAVP Rhinal Tube DDAVP Nasal Spray Minirin (DDAVP) Nasal Spray Stimate Nasal Spray Desmopressin Acetate Nasal Soln (generic) Desmopressin Acetate Nasal Soln (generic)

4 µg/mL

Refrigerate

DDAVP Injection

Sanofi Aventis

4 µg/mL

1-mL single-dose vial 10-mL multiuse vial 1-mL vial

Refrigerate

Minirin injection

4 µg/mL

1-mL vial

Refrigerate

4 µg/mL

1-mL vial

Refrigerate

Desmopressin Acetate Injection (generic) DDAVP injection (generic)

Ferring Pharmaceuticals Hospira

0.1 mg; 0.2 mg 0.1 mg; 0.2 mg

Bottle of 100 tabs Bottle of 30 tabs

Room temp Room temp

DDAVP Tablets Minirin Tablets

0.1 mg; 0.2 mg 0.1 mg; 0.2 mg

Bottle of 100 tabs Bottle of 100 tabs

Room temp Room temp

DDAVP Tablets (generic) Desmopressin Acetate Tablets (generic)

60 mg; 120 mg; 240 mg

10, 20, or 100 wafers

Refrigerate

Minirin Melt®

Injectable

Tablets

Melt

Apotex Corporation

Teva Pharmaceuticals Sanofi Aventis Ferring Pharmaceuticals Teva Pharmaceuticals Apotex Corporation Ferring Pharmaceuticals

Company websites for more information: Sanofi Aventis: http://www.sanofi-aventis.us/live/us/en/layout.jsp?scat=BD0DB735-32D7-41C4-898F-74F67D343145 Ferring Pharmaceuticals: http://www.ferring.com/en/therapeutic/urology/Products.htm http://www.mims.com/Page.aspx?menuid=mng&name=Minirin+(DDAVP)+nasal+spray&CTRY=TW&brief=false CSL Behring: http://www.stimate.com/ Bausch and Lomb: http://www.bausch.com/en_us/msds/msds_listing.aspx Hospira: http://www.hospira.com/default.aspx Teva Pharmaceuticals: http://www.tevausa.com/ Apotex Corporation: http://www.apotex.com/us/en/ Desmopressin acetate is also available generically (many companies) and may also be known by the following synonyms and internationally registered trade names: Concentraid, D-Void, Defirin, Desmogalen, Desmospray, Desmotabs, Emosint, Minurin, Nocutil, Octim, Octostim, or Presinex.

TABLE 24-14 Treatment with Desmopressin in Cats Expected Daily Dose

Frequency of Administration

Cost of Generic Product

Conjunctival drops

2-4 medium to large drops

Once daily or given every 8 or 12 hours

Intermediate ($1.50-$3.00/day)

0.1 mg/mL (100 µg/mL)

Subcutaneous

2-4 µg/day

Once daily or given every 12 hours

Cheapest ($0.60-$1.20/day)

Injectable solution

4 µg/mL

Subcutaneous

2-4 µg/day

Once daily or given every 12 hours

Most expensive ($12-$24/day)

Oral tablet

0.1 mg or 0.2 mg (100 µg and 200 µg)

Oral

50-150 µg/day

Given every 8 or 12 hours

Expensive ($3.50-7.50/day)

Formulation

Concentration

Nasal spray or solution

0.1 mg/mL (100 µg/mL)

Nasal spray or solution

Route of Administration

In any older cat that develops DI, the veterinarian should consider pituitary imaging with CT or MRI to exclude a pituitary mass. This is especially true if the affected cat has associated neurologic signs. Treatment of Diabetes Insipidus Treatment with arginine vasopressin (the cat’s ADH) or its analogs restores medullary hypertonicity and a normal urinary concentrating ability in cats with central DI. Historically, ADH tannate in oil, an extract of arginine vasopressin prepared from bovine and porcine pituitary glands, was administered every 2 to 3 days as needed to control polyuria and polydipsia. Because this product is no longer available, desmopressin acetate, a synthetic analog of arginine vasopressin with prolonged and enhanced antidiuretic activity, has become the drug of choice for the treatment of central DI in cats. Desmopressin acetate is available in preparations for intranasal, parenteral (injectable), or oral administration (see Table 24-13). NASAL SPRAYS OR SOLUTIONS OF DESMOPRESSIN

The nasal formulations are supplied with two different delivery systems: either a spray pump or a rhinal tube delivery system (see Table 24-13) in which the desmopressin is “sprayed” or “blown” into the nose, respectively. Obviously, most cats will not tolerate either of these intranasal delivery methods. Drops placed in the conjunctival sac provide a more suitable alternative for cats. With the rhinal tube delivery formulation (DDAVP Rhinal Tube, Sanofi Aventis), the desmopressin is packaged with a small, calibrated plastic catheter so that exact amounts of the drug can be measured and administered. The calibrated rhinal tube has four graduation marks that measure amounts of 0.05 mL, 0.1 mL, 0.1 mL, and 0.2 mL and thereby can deliver doses of 5 to 20 µg of desmopressin. Although this system allows for accurate dosing, it is awkward to use. In addition, because this rhinal tube delivery system is not available as a generic product, this formulation is quite expensive. The most common intranasal formulations of desmopressin are marketed as nasal sprays or solutions equipped with a compression pump that delivers 10 µg of drug with each spray. For use in cats this spray bottle should be opened and the desmopressin solution transferred to a sterile vial; this dispensing vial then allows the user to place the desmopressin drops within the cat’s conjunctival sac. These intranasal preparations of desmopressin are generally supplied as a concentration of 100 µg/mL; depending on the size of the drop, 1 drop of nasal solution corresponds to 1.5 to 4 µg of desmopressin. One highly concentrated nasal solution (1.5 mg/ mL) is marketed for use in hemophilia (see Table 24-13), but it should not be used to treat cats with DI because of the strong likelihood of overdosage.


621

In most cats 1 to 2 drops of the intranasal preparation administered once or twice daily are sufficient to control polyuria and polydipsia (see Table 24-14). Use of a tuberculin or insulin syringe allows for more accurate dosing. Application of desmopressin into the conjunctival sac may cause local irritation because the solution is acidic. Some cats may object to the daily eye drops, making this route of administration ineffective.4,81 ORAL DESMOPRESSIN TABLETS

The oral preparation of desmopressin is available both as a sublingual dissolve melt tablet (not suitable for treating cats) and as 0.1-mg and 0.2-mg tablets. Each 0.1-mg (100-µg) tablet is roughly comparable to 5 to 10 µg (1 or 2 large drops) of the nasal solution (see Table 24-13). In one report of five cats with DI,4 all were treated successfully with oral desmopressin. Doses were variable, but most were well-controlled using oral dosages of 50 µg administered twice or three times daily.4 The tablet form of desmopressin is a more costprohibitive alternative than the conjunctival or subcutaneous routes of administration. The cost of daily oral desmopressin in cats is roughly 2.5 times that of the cost of conjunctival drops and roughly 6 times the cost of subcutaneous injections of desmopressin. For some cat owners, however, the use of a tablet form may prove to be a more convenient, or the only possible, route of administration. INJECTABLE DESMOPRESSIN SOLUTIONS FOR SUBCUTANEOUS OR INTRAVENOUS USE

An injectable sterile solution of desmopressin acetate (4 µg/mL) marketed for intravenous use is available (see Table 24-13) and can be used in cats with DI. However, the cost of the injectable desmopressin is approximately 7 to 15 times higher per µg than the intranasal preparation, making this formulation cost prohibitive for use in most cats. To circumvent this cost issue, the intranasal form of desmopressin—although not designed for parenteral use—can be given subcutaneously to cats with excellent results.14,16,43,81 Because the nasal forms of desmopressin are not considered to be sterile, however, it is best to first sterilize the product by passing the nasal solution through a 0.2-micron bacteriostatic syringe filter31,63 (see www.whatman.com/ GDXSyringeFilters.aspx for more information). Clinically the nasal and injectable preparations of desmopressin induce indistinguishable responses when administered subcutaneously. To make dosing easier, the desmopressin is best administered with an U-100 low-dose insulin syringe. The solution can be diluted in sterile physiologic saline to make dosing easier. The subcutaneous route of desmopressin adminis tration has many advantages over the other routes of

622


administration. following:

These

advantages

include

the

• First, drug appears to be most effective when administered via the subcutaneous route. • Second, the duration of action is longer after subcutaneous injection than when administered orally or through the conjunctival sac. • Third, because of the smaller subcutaneous doses required to control signs (about 15% and 40% of the oral and conjunctival doses, respectively), the cost of treatment is greatly reduced. • Fourth, many cats seem to prefer long-term subcutaneous injections to the chronic use of eye drops or oral medication. DOSE ADJUSTMENTS FOR DESMOPRESSIN

Recommended initial doses of desmopressin vary depending on the route by which it is being administered. If the conjunctival route is employed, 1 or 2 drops of the intranasal preparation administered once or twice daily is usually sufficient to control polyuria (see Table 24-14). With the subcutaneous route of administration, the initial recommended dose is 1 to 2 µg once or twice daily. If the nasal solution (100 µg/mL) were used for this purpose, the veterinarian would inject only 0.01 to 0.02 mL (or 1 to 2 U with a U-100 insulin syringe). With the oral tablets a starting dose of 0.05 µg to 0.075 µg (50 to 75 µg) once or twice daily is initiated. In cats with central DI, daily administration of desmopressin may completely eliminate polyuria and polydipsia. However, because of individual differences in absorption and metabolism, the dose required to achieve complete, around-the-clock control varies from patient to patient. The maximal effect of desmopressin occurs from 2 to 8 hours after administration, and the duration of action varies from 8 to 24 hours.31,63 Larger doses of the drug appear to both increase its antidiuretic effects and prolong its duration of action; however, expense can become a limiting factor for some owners. No matter what route of administration is used, the daily dose should be gradually adjusted as needed to control signs of polydipsia and polyuria. The morning and evening doses can be adjusted separately if needed. ADVERSE EFFECTS OF DESMOPRESSIN

Desmopressin is relatively safe for use in cats with central DI. Adverse effects of desmopressin are uncommon, but overdosage can lead to fluid retention, hyponatremia, and decreased plasma osmolality.31,63 Although extremely rare, fluid intoxication associated with desmopressin overdosage can lead to central nervous system disturbances, including depression, increased salivation, vomiting, ataxia, muscle tremors, coma, and convulsions.31,41 In such instances furosemide can be given to induce diuresis.

To avoid the potential problem of overdosage, cats should not be allowed free access to water immediately after each dose of desmopressin, especially if severe polydipsia and polyuria have redeveloped. Without such short-term (1 to 2 hours) water restriction, the cat many consume excessive amounts of water that cannot be subsequently excreted, insofar as the desmopressin is absorbed and has its peak antidiuretic effects on the renal tubules. COST OF DESMOPRESSIN

The principle drawback with the use of any of the desmopressin preparations in the treatment of central DI is the drug’s considerable expense. The oral route of administration is the most expensive, and the subcutaneous route of administration (using the sterilized nasal solutions) is generally the most cost-effective. Prognosis of Diabetes Insipidus In some cats with DI, the owner may elect not to treat the cat because of financial concerns. Because polyuria and polydipsia do not pose a serious health hazard in these cats (as long as adequate access to water is available), treatment is not essential or mandatory. In cats with untreated DI, however, it is imperative that the water never be restricted because the inability to concentrate urine may lead to dehydration and possibly even death from neurologic complications. Cats with idiopathic, traumatic, or congenital DI usually respond well to treatment with desmopressin, with near complete resolution of clinical signs of polyuria and polydipsia. With proper care these cats have an excellent prognosis and a normal life expectancy. In contrast, cats with DI caused by large or aggressive hypothalamic masses or pituitary macrotumors have a grave prognosis. External radiation therapy in combination with desmopressin medical treatment offers the best chance for decreasing tumor size while controlling signs of polyuria in such cats.50,91 Fortunately, this appears to be an extremely rare cause of DI in cats.

References 1. Abraham LA, Helmond SE, Mitten RW et al: Treatment of an acromegalic cat with the dopamine agonist L-deprenyl, Aust Vet J 80:479, 2002. 2. Abrams-Ogg A, Holmberg DL, Stewart WA et al: Acromegaly in a cat: diagnosis by magnetic resonance imaging and treatment by cryohypophysectomy, Can Vet J 34:682, 1993. 3. Abrams-Ogg A, Holmberg DL, Quinn RF et al: Blindness now attributed to enrofloxacin therapy in a previously reported case of a cat with acromegaly treated by cryohypophysectomy, Can Vet J 43:53, 2002. 4. Aroch I, Mazaki-Tovi M, Shemesh O et al: Central diabetes insipidus in five cats: clinical presentation, diagnosis and oral desmopressin therapy, J Feline Med Surg 7:333, 2005. 5. Auriemma RS, Galdiero M, De Martino MC et al: The kidney in acromegaly: renal structure and function in patients with


6.

7.

8.

9.

10. 11.

12. 13.

14.

15. 16. 17.

18. 19. 20.

21.

22. 23. 24.

25.

26.

27.

28.

acromegaly during active disease and 1 year after disease remission, Eur J Endocrinol 162:1035, 2010. Berg RI, Nelson RW, Feldman EC et al: Serum insulin-like growth factor-I concentration in cats with diabetes mellitus and acromegaly, J Vet Intern Med 21:892, 2007. Biering H, Knappe G, Gerl H et al: [Prevalence of diabetes in acromegaly and Cushing syndrome], Acta Med Austriaca 27:27, 2000. Bishop JS, Steele R, Altszuler N et al: Diminished responsiveness to insulin in the growth hormone-treated normal dog, Amer J Physiol 2l2:272, 1967. Blois SL, Holmberg DL: Cryohypophysectomy used in the treatment of a case of feline acromegaly, J Small Anim Pract 49:596, 2008. Bluestone R, Bywaters EG, Hartog M et al: Acromegalic arthropathy, Ann Rheum Dis 30:243, 1971. Bondanelli M, Ambrosio MR, degli Uberti EC: Pathogenesis and prevalence of hypertension in acromegaly, Pituitary 4:239, 2001. Brahms S: The development of the hypophysis of the cat (felis domestica), Am J Anat 50:251, 1932. Brearley MJ, Polton GA, Littler RM et al: Coarse fractionated radiation therapy for pituitary tumours in cats: a retrospective study of 12 cases, Vet Comp Oncol 4:209, 2006. Brown B, Peterson ME, Robertson GL: Evaluation of the plasma vasopressin, plasma sodium and urine osmolality response to water restriction in normal cats and a cat with diabetes insipidus, J Vet Intern Med 7:113, 1993. Burnie AG, Dunn JK: A case of central diabetes insipidus in the cat: Diagnosis and treatment, J Small Anim Pract 23:237, 1982. Campbell FE, Bredhauer B: Trauma-induced central diabetes insipidus in a cat, Aust Vet J 86:102, 2008. Carpenter JL, Andrews LK, Holzworth J: Tumors and tumor-like lesions. In Holzworth J, editor: Diseases of the cat: medicine and surgery, Philadelphia, 1987, Saunders, p 406. Chanson P: Emerging drugs for acromegaly, Expert Opin Emerg Drugs 13:273, 2008. Chanson P, Salenave S, Kamenicky P et al: Pituitary tumours: acromegaly, Best Pract Res Clin Endocrinol Metab 23:555, 2009. Chastain CB, Ganjam VK: The endocrine brain and clinical tests of its function In: Chastain CB, Ganjam VK, editors, Clinical endocrinology of companion animals, Philadelphia, 1986, Lea & Febiger, p 37. Clemmons DR: Roles of insulin-like growth factor-I and growth hormone in mediating insulin resistance in acromegaly, Pituitary 5:181, 2002. Colao A, Pivonello R, Scarpa R et al: The acromegalic arthropathy, J Endocrinol Invest 28:24, 2005. Court MH, Watson AD: Idiopathic neurogenic diabetes insipidus in a cat, Aust Vet J 60:245, 1983. Daminet S: Feline hypothyroidism In Mooney CT, Peterson ME, editors: BSAVA manual of canine and feline endocrinology. ed 4, Shurdington, Cheltenham, 2011, British Small Animal Veterinary Association (in press). Dellmann HD: The endocrine system In Dellmann HD, Brown EM, editors: Textbook of veterinary histology, Philadelphia, 1976, Lea & Febiger, p 373. Dominici FP, Argentino DP, Munoz MC et al: Influence of the crosstalk between growth hormone and insulin signalling on the modulation of insulin sensitivity, Growth Horm IGF Res 15:324, 2005. Dunning MD, Lowrie CS, Bexfield NH et al: Exogenous insulin treatment after hypofractionated radiotherapy in cats with diabetes mellitus and acromegaly, J Vet Intern Med 23:243, 2009. Eigenmann JE, Wortman JA, Haskins ME: Elevated growth hormone levels and diabetes mellitus in a cat with acromegalic features, J Am Anim Hosp Assoc 20:747, 1984.

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29. Elliott DA, Feldman EC, Koblik PD et al: Prevalence of pituitary tumors among diabetic cats with insulin resistance, J Am Vet Med Assoc 216:1765, 2000. 30. Feldman EC, Nelson RW: Disorders of growth hormone. In Feldman EC, Nelson RW, editors: Canine and feline endocrinology and reproduction, Philadelphia, 2004, Elsevier, p 69. 31. Feldman EC, Nelson RW: Water metabolism and diabetes insipidus In Feldman EC, Nelson RW, editors: Canine and feline endocrinology and reproduction, ed 3, Philadelphia, 2004, Saunders, p 2. 32. Fracassi F, Mandrioli L, Diana A et al: Pituitary macroadenoma in a cat with diabetes mellitus, hypercortisolism and neurologicsigns, J Vet Med A Physiol Pathol Clin Med 54:359, 2007. 33. Gembardt C, Loppnow H: Pathogenesis of spontaneous diabetes mellitus in the cat. II. Acidophilic adenoma of the pituitary gland and diabetes mellitus in 2 cases, Berl Munch Tierarztl Wochenschr 89:336, 1976. 34. Goossens MM, Feldman EC, Nelson RW et al: Cobalt 60 irradiation of pituitary gland tumors in three cats with acromegaly, J Am Vet Med Assoc 213:374, 1998. 35. Greco DS: Pediatric endocrinology, Vet Clin North Am Small Anim Pract 36:549, 2006. 36. Green RA, Farrow CS: Diabetes insipidus in a cat, J Am Vet Med Assoc 164:524, 1974. 37. Heinrichs M, Baumgartner W, Krug-Manntz S: Immunocytochemical demonstration of growth hormone in an acidophilic adenoma of the adenohypophysis in a cat, Vet Pathol 26:179, 1989. 38. Hurty CA, Flatland B: Feline acromegaly: a review of the syndrome, J Am Anim Hosp Assoc 41:292, 2005. 39. Hurxthal LM: The serum phosphorus level as an index of pituitary growth hormone activity in acromegaly; a preliminary report, Lahey Clin Bull 5:194, 1948. 40. Kerl ME, Cook CR: Glomerular filtration rate and renal scintigraphy, Clin Tech Small Anim Pract 20:31, 2005. 41. Kim RJ, Malattia C, Allen M et al: Vasopressin and desmopressin in central diabetes insipidus: adverse effects and clinical considerations, Pediatr Endocrinol Rev 2(Suppl 1):115, 2004. 42. Konde LJ: Sonography of the kidney, Vet Clin North Am Small Anim Pract 15:1149, 1985. 43. Kraus KH: The use of desmopressin in diagnosis and treatment of diabetes insipidus in cats, Compend Cont Ed Prac Vet 9:752, 1987. 44. Latimer HB: The weights of the hypophysis, thyroid, and supradrenals in the adult cat, Growth 3:435, 1939. 45. Lewitt MS, Hazel SJ, Church DB et al: Regulation of insulin-like growth factor-binding protein-3 ternary complex in feline diabetes mellitus, J Endocrinol 166:21, 2000. 46. Lichtensteiger CA, Wortman JA, Eigenmann JE: Functional pituitary acidophil adenoma in a cat with diabetes mellitus and acromegalic features, Vet Pathol 23:518, 1986. 47. Littler RM, Polton GA, Brearley MJ: Resolution of diabetes mellitus but not acromegaly in a cat with a pituitary macroadenoma treated with hypofractionated radiation, J Small Anim Pract 47:392, 2006. 48. Macri B, Marino F, Mazzullo G et al: Mucopolysaccharidosis VI in a Siamese/short-haired European cat, J Vet Med A Physiol Pathol Clin Med 49:438, 2002. 49. Mason KV, Burren VS: Successful management of a case of feline diabetes insipidus with occular instilation of desmoporessin, Aust Vet Practitioner 15:156, 1985. 50. Mayer MN, Greco DS, LaRue SM: Outcomes of pituitary tumor irradiation in cats, J Vet Intern Med 20:1151, 2006. 51. Meij BP: Hypophysectomy as a treatment for canine and feline Cushing’s disease, Vet Clin North Am Small Anim Pract 31:1015, 2001. 52. Meij BP, Voorhout G, Van Den Ingh TS et al: Transsphenoidal hypophysectomy for treatment of pituitary-dependent hyperadrenocorticism in 7 cats, Vet Surg 30:72, 2001.

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53. Meij BP, van der Vlugt-Meijer RH, van den Ingh TS et al: Somatotroph and corticotroph pituitary adenoma (double adenoma) in a cat with diabetes mellitus and hyperadrenocorticism, J Comp Pathol 130:209, 2004. 54. Meij BP, van der Vlugt-Meijer RH, van den Ingh TS et al: Melanotroph pituitary adenoma in a cat with diabetes mellitus, Vet Pathol 42:92, 2005. 55. Meij BP, Auriemma E, Grinwis G et al: Successful treatment of acromegaly in a diabetic cat with transsphenoidal hypophysectomy, J Feline Med Surg 12:406, 2010. 56. Mellanby RJ, Jeffery ND, Gopal MS et al: Secondary hypothyroidism following head trauma in a cat, J Feline Med Surg 7:135, 2005. 57. Melmed S: Acromegaly pathogenesis and treatment, J Clin Invest 119:3189, 2009. 58. Miller MS: Diagnosis of partial central diabetes insipidus in a kitten, Pulse 33:19, 1991. 59. Mol JA, van Garderen E, Rutteman GR et al: New insights in the molecular mechanism of progestin-induced proliferation of mammary epithelium: induction of the local biosynthesis of growth hormone (GH) in the mammary glands of dogs, cats and humans, J Steroid Biochem Mol Biol 57:67, 1996. 60. Moller N, Jorgensen JO: Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects, Endocr Rev 30:152, 2009. 61. Morrison SA, Randolph J, Lothrop CD, Jr.: Hypersomatotropism and insulin-resistant diabetes mellitus in a cat, J Am Vet Med Assoc 194:91, 1989. 62. Muggeo M, Bar RS, Roth J et al: The insulin resistance of acromegaly: evidence for two alterations in the insulin receptor on circulating monocytes, J Clin Endocrinol Metab 48:17, 1979. 63. Nichols R, Hohenhaus AE: Use of the vasopressin analogue desmopressin for polyuria and bleeding disorders, J Am Vet Med Assoc 205:168, 1994. 64. Nichols R: Polyuria and polydipsia. Diagnostic approach and problems associated with patient evaluation, Vet Clin North Am Small Anim Pract 31:833, 2001. 65. Niessen SJ, Khalid M, Petrie G et al: Validation and application of a radioimmunoassay for ovine growth hormone in the diagnosis of acromegaly in cats, Vet Rec 160:902, 2007. 66. Niessen SJ, Petrie G, Gaudiano F et al: Feline acromegaly: an underdiagnosed endocrinopathy? J Vet Intern Med 21:899, 2007. 67. Niessen SJ: Feline acromegaly: an essential differential diagnosis for the difficult diabetic, J Feline Med Surg 12:15, 2010. 68. Norman EJ, Mooney CT: Diagnosis and management of diabetes mellitus in five cats with somatotrophic abnormalities, J Feline Med Surg 2:183, 2000. 69. O’Shea MH, Layish DT: Growth hormone and the kidney: a case presentation and review of the literature, J Am Soc Nephrol 3:157, 1992. 70. Patnaik AK, Liu SK, Hurvitz AI et al: Nonhematopoietic neoplasms in cats, J Natl Cancer Inst 54:855, 1975. 71. Peterson ME, Kintzer PP, Cavanagh PG et al: Feline hyperthyroidism: pretreatment clinical and laboratory evaluation of 131 cases, J Am Vet Med Assoc 183:103, 1983. 72. Peterson ME: Effects of megestrol acetate on glucose tolerance and growth hormone secretion in the cat, Res Vet Sci 42:354, 1987. 73. Peterson ME, Kemppainen RJ: Pituitary intermediate lobe in cats: active secretion of alpha-MSH and in vivo evidence for dopaminergic and beta-adrenergic regulation. Program of the 72nd Annual Meeting of The Endocrine Society 1990;121 (Abstract). 74. Peterson ME, Taylor RS, Greco DS et al: Acromegaly in 14 cats, J Vet Intern Med 4:192, 1990. 75. Peterson ME, Kemppainen RJ, Orth DN: Plasma concentrations of immunoreactive proopiomelanocortin peptides and cortisol in clinically normal cats, Am J Vet Res 55:295, 1994.

76. Peterson ME, Randolph JF, Mooney CT: Endocrine diseases. In Sherding RG, editor: The cat: diagnosis and clinical management, ed 2, New York, 1994, Churchill Livingstone, p 1404. 77. Peterson ME: Feline hyperadrenocorticism. In Mooney CT, Peterson ME, editors: BSAVA manual of canine and feline endocrinology, ed 3, Gloucester, 2004, British Small Animal Veterinary Association, p 205. 78. Peterson ME: Acromegaly. In Mooney CT, Peterson ME, editors: BSAVA manual of canine and feline endocrinology, ed 3, Gloucester, 2004, British Small Animal Veterinary Association, p 187. 79. Peterson ME, Nichols R: Investigation of polyuria and polydipsia. In Mooney CT, Peterson ME, editors: BSAVA manual of canine and feline endocrinology, ed 3, Gloucester, 2004, British Small Animal Veterinary Association, p 16. 80. Peterson ME: Acromegaly in cats: are we only diagnosing the tip of the iceberg? J Vet Intern Med 21:889, 2007. 81. Pittari JM: Central diabetes insipidus in a cat, Feline Practice 24:18, 1996. 82. Quante S, Fracassi F, Gorgas D et al: Congenital hypothyroidism in a kitten resulting in decreased IGF-I concentration and abnormal liver function tests, J Feline Med Surg 12:487, 2010. 83. Radcliffe CE: Observations on the relationship of the thyroid to the polyuria of experimental diabetes insipidus, Endocrinology 415, 1943. 84. Reaves TA, Liu HM, Qasim MM et al: Osmotic regulation of vasopressin in the cat, Am J Physiol 240:E108, 1981. 85. Reusch CE, Kley S, Casella M et al: Measurements of growth hormone and insulin-like growth factor 1 in cats with diabetes mellitus, Vet Rec 158:195, 2006. 86. Rogers WA, Valdez H, Anderson BC et al: Partial deficiency of antidiuretic hormone in a cat, J Am Vet Med Assoc 170:545, 1977. 87. Romeis B: Innersekretorische drüsen II: Hypophyse (Dritter Teil) In: Möllendorff WV, ed. Handbuch der Mikroskopischen Anatomie des Menschen, Sechster Band, Blutgefäss-Und Lymphgefässappart Innerskretorische Drüsen, Berlin, 1940, Verlag Von Julius Springer, p 280. 88. Sacca L, Cittadini A, Fazio S: Growth hormone and the heart, Endocr Rev 15:555, 1994. 89. Sande RD, Bingel SA: Animal models of dwarfism, Vet Clin North Am Small Anim Pract 13:71, 1983. 90. Scott-Moncrieff JC: Insulin resistance in cats, Vet Clin North Am Small Anim Pract 40:241, 2010. 91. Sellon RK, Fidel J, Houston R et al: Linear-accelerator-based modified radiosurgical treatment of pituitary tumors in cats: 11 cases (1997-2008), J Vet Intern Med 23:1038, 2009. 92. Slatopolsky E, Rutherford WE, Rosenbaum R et al: Hyperphosphatemia, Clin Nephrol 7:138, 1977. 93. Slingerland LI, Voorhout G, Rijnberk A et al: Growth hormone excess and the effect of octreotide in cats with diabetes mellitus, Domest Anim Endocrinol 35:352, 2008. 94. Smith JR, Elwood CM: Traumatic partial hypopituitarism in a cat, J Small Anim Pract 45:405, 2004. 95. Starkey SR, Tan K, Church DB: Investigation of serum IGF-I levels amongst diabetic and non-diabetic cats, J Feline Med Surg 6:149, 2004. 96. Troxel MT, Vite CH, Van Winkle TJ et al: Feline intracranial neoplasia: retrospective review of 160 cases (1985-2001), J Vet Intern Med 17:850, 2003. 97. Vaden SL: Renal biopsy of dogs and cats, Clin Tech Small Anim Pract 20:11, 2005. 98. Vitale G, Pivonello R, Auriemma RS et al: Hypertension in acromegaly and in the normal population: prevalence and determinants, Clin Endocrinol (Oxf) 63:470, 2005. 99. Winterbotham J, Mason KV: Congenital diabetes insipidus in a kitten, J Small Anim Pract 24:569, 1983.


100. Young FG: Growth hormone and diabetes, Rec Progr Horm Res 8:471, 1953. 101. Zaki F, Harris J, Budzilovich G: Cystic pituicytoma of the neurohypophysis in a Siamese cat, J Comp Path 85:467, 1975. 102. Zaki FA, Liu SK: Pituitary chromophobe adenoma in a cat, Vet Pathol 10:232, 1973.

DISORDERS OF CALCIUM METABOLISM Randolph M. Baral

CALCIUM HOMEOSTASIS Calcium plays a key role in many physiologic processes. In addition to skeletal support, these include muscle contractions (skeletal, smooth, and cardiac muscle), transmission of nerve impulses, and blood clotting.41 In most cases plasma or serum biochemistry analytes are assessed by determining where the analyte is produced and excreted, as well as taking into account other influences. For example, albumin is produced by the liver and excretion is by way of renal or gastrointestinal routes. This means that in most cases a decrease in albumin is due to decreased production (indicating hepatopathy) or increased loss (due to renal or gastrointestinal causes). A further influence is dehydration, which can increase albumin results. In contrast to albumin, calcium regulation is exceedingly complex. In the first instance routine measurements of plasma or serum calcium are of total calcium (tCa), but calcium exists in three forms83: 1. Ionized (free) calcium (iCa), which is the only physiologically active form and makes up 50% to 60% of tCa 2. Protein-bound calcium that accounts for approximately 10% of tCa 3. Complexed calcium (bound to e.g., phosphate, bicarbonate, lactate), which makes up 30% to 40% of tCa Ionized calcium (iCa) must be measured immediately in-house or collected and separated anaerobically and measured within 2 hours (at room temperature) or 6 hours (if kept refrigerated).7 Our measurements of calcium are a reflection of extracellular fluid (ECF) calcium levels. The influences on ECF calcium are shown in Figure 24-30. Not only is ECF calcium increased by absorption from the gastrointestinal tract and decreased by secretion back to the gastrointestinal tract for excretion (90%), but filtration occurs through the kidneys for urinary excretion (10%). The kidneys also reabsorb 99% of this filtered calcium. Further, approximately 99% of total body calcium is stored in bones, which act as reservoirs, releasing calcium when ECF calcium reduces.41

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Parathyroid gland PTH

PTH

Ca

Pi, Ca

1,25(OH)2D3

Ca

Ca

Ca ECF

Ca

FIGURE 24-30 Influences on calcium concentrations. Extracellular fluid calcium is increased by absorption from the gastrointestinal tract, released from bone (where 99% of body calcium is stored) and reabsorbed by the kidneys. Extracellular fluid calcium reduces by secretion back to the gastrointestinal tract for excretion (90%) and filtration through the kidneys for urinary excretion (10%). These interactions are mediated by parathyroid hormone and calcitriol (activated vitamin D). Parathyroid hormone responds to decreased ionized calcium. Parathyroid hormone release results in increased calcitriol production by the kidneys. (From Schenck PA, Chew DJ, Behrend EN: Update on hypercalcemic disorders. In August JR, editor: Consultations in feline internal medicine, ed 5, St Louis, 2006, Elsevier Saunders, p 157.)

These interactions between the gastrointestinal tract, kidneys, and bone to maintain ECF calcium within a relatively narrow range are predominantly mediated by the following41: 1. Parathyroid hormone (PTH) • Produced by “chief cells” within the parathyroid gland 2. Calcitriol, or 1,25-dihydroxycholecalciferol, the most active form of vitamin D • The final stage of the conversion of vitamin D to calcitriol occurs within the kidneys 3. Calcitonin • Secreted by the thyroid gland • Has only a minor role in decreasing plasma calcium concentration PTH acts to increase ECF calcium, and in a normal cat PTH is secreted in response to decreased levels of ECF calcium (or increased phosphate) and results in the following41: 1. Increased calcium (and phosphate) absorption from bone 2. Decreased calcium excretion from the kidneys (and increased phosphate excretion) 3. Increased calcitriol formation by the kidneys

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Increased calcitriol levels result in the following41: 1. Increased intestinal absorption of calcium (and phosphate) 2. Enhancement of the ability of PTH to resorb bone 3. Decreased renal calcium and phosphate excretion (minor effect) All these interactions are also influenced by plasma phosphate (PO4) concentrations.41

APPROACH TO THE CAT WITH HYPERCALCEMIA The clinical signs of hypercalcemia are very nonspecific. Mild hypercalcemia may not result in any signs. More severe clinical signs are usually associated with a concurrent problem (e.g., malignancy). Extreme hypercalcemia can cause depression of the nervous system, polyuria and polydipsia may be seen, and uroliths can form. A list of the clinical signs of hypercalcemia is shown with the pathophysiologic reason in Table 24-15. Mostly, however, hypercalcemia is detected by plasma biochemistry screening of a generally unwell cat with nonspecific signs such as lethargy or inappetence. The following approaches to a cat with hypercalcemia must take into account physical examination and other laboratory findings as well as the cat’s signalment (e.g., neoplasia is much less likely to occur in a kitten) and clinical history (e.g., possible exposure to rodenticide). The main diagnostic steps are as follows: 1. Confirm finding of elevated tCa. 2. Measure iCa. 3. Measure PTH. 4. Measure parathyroid hormone-related protein (PTHrP) and vitamin D metabolites. 5. Assess results and relationships of tCa, iCa, and PTH concentrations. Assessment of the results of these tests narrows down the potential causes of hypercalcemia considerably, particularly when the cat’s age, clinical history, and physical examination findings are taken into account. Step 4, testing for vitamin D metabolites (calcidiol and calcitriol) and PTHrP should be considered as an optional step. The results of these tests are sometimes helpful, but a diagnosis can often be reached without testing for these. Together with further diagnostics, these will be discussed under the specific conditions where their testing is appropriate.

Step 1: Confirm Finding of Elevated Total Calcium The tCa is usually measured by a colorimetric assessment and so is susceptible to spurious increases caused

TABLE 24-15 Clinical Signs of Hypercalcemia Clinical Sign

Pathophysiology

Polyuria and polydipsia

Impaired response of renal tubules to antidiuretic hormone Impaired renal tubular resorption of sodium and chloride Secondary to renal damage

Weakness, depression, mental dullness

Depressed excitability of muscular and nervous tissue

Anorexia, vomiting, constipation

Decreased contractility of the smooth muscle of the gastrointestinal tract

Muscle twitching, shivering, seizures

Direct effect on central nervous system

Cardiac arrhythmias

Direct neurologic effect

Lower urinary tract signs

Presence of uroliths

Modified from Barber PJ: Disorders of calcium homeostasis in small animals, In Pract 23:262, 2001

by lipemia or hemolysis. Additionally, mild hypercalcemia may be transient. A second sample should be taken after a 12-hour fast because food intake can sometimes cause mild hypercalcemia, as well as lipemia. If the finding of hypercalcemia is repeatable, then iCa should be measured. Further, iCa can be increased when tCa is normal. In these cases tCa will be at the high end of the normal reference range, so it is appropriate to test iCa concentrations in those cats with repeatable high normal tCa concentrations.85 It is prudent to collect a sample with the special handling required for iCa (discussed later) at the time of sampling for confirmation of elevated tCa. Correction equations that take into account total protein or albumin levels have been devised for people and dogs to improve diagnostic interpretation of tCa values.55,62 These equations are controversial in these two species. In cats the equations are even less reliable because the relationship between tCa and albumin is too variable.37

Step 2: Measure Ionized Calcium The iCa should be measured in all cases where tCa is elevated or on the high side of the normal reference range. iCa values can be artefactually increased by exposure to air because pH and temperature affect the equilibrium between the three fractions of ionized, protein-bound, and complex-bound calcium.7,85 Therefore samples should be tested immediately with an in-house analyzer or collected anaerobically and sent chilled (4° C) to a commercial laboratory. When heparinized whole blood is used for in-house iCa sampling, it results in a lower iCa concentration than

serum samples.40 These differences should be taken into account by using different reference ranges. Commercial laboratories measure iCa from serum. Ethylenediaminetetraacetic acid (EDTA) plasma must never be used for either in-house or commercial laboratory assessment of ionized calcium because EDTA chelates calcium, which falsely reduces the concentration.85 Anaerobic collection of serum requires two serum vacutainer tubes, a centrifuge, and a spinal needle. Silicon separator vacutainer tubes should not be used because calcium is released from the silicone gel, falsely elevating the calcium level. The needle of the syringe used to collect the blood sample from the cat should placed directly through the stopper of the first vacutainer tube (without opening the tube) to transfer the sample from syringe to blood tube. The blood should be allowed to clot (approximately 20 minutes), then separated by centrifugation. The spinal needle (attached to a syringe that does not contain air) is used to withdraw serum from this tube without opening it. This serum is then transferred to the second vacutainer tube (again, without opening the tube). The sample is refrigerated and then sent to the reference laboratory with an ice pack.83

Step 3: Measure Parathyroid Hormone PTH is an 84-chain amino acid. The amino acid sequence of PTH is known for the dog, cow, pig, rat, chicken, and human, and most mammals appear to have very similar amino-terminal portions of the molecule.87 Mature feline PTH is 84% identical to human PTH.97 At least two PTH assays have been validated for use in the cat. Both are two-site immunoradiometric assays (IRMA) for human intact PTH. Two-site means using antibodies that bind with epitopes at the two terminals of the molecule and therefore avoids measuring the PTH fragments that can be present in blood and would otherwise potentially be detected by a one-site assay (rendering it less accurate).10,77 Serum or plasma can be assayed but should be separated with minimal exposure of samples to room temperature (less than 2 hours). The samples then should be refrigerated or frozen before analysis to prevent degradation.6,85,87 The serum sample for iCa requires similar handling. It is therefore practical to use the same serum for both iCa and PTH at a reference laboratory.

Step 4: Measure PTH-Related Protein and Vitamin D Metabolites PTHrP is secreted by some malignant neoplasms and mimics the action of PTH by binding to PTH receptors. It is elevated in some cases of hypercalcemia of malignancy, but not all. One study of 322 cats with elevated iCa found PTH in the lower half of the normal reference range in 263 cats (81.7%), yet PTHrP was elevated in


627

only 31 cats (9.6%). Clinical records were not available for all cats, and only seven cats had confirmed malignancy.77 It is highly likely that a large number of cats with normal PTHrP had hypercalcemia caused by malignancy. Two-site assays for human PTHrP have been validated for cats.77 PTHrP is best measured from fresh or frozen EDTA plasma.84 Vitamin D metabolites are identical in all species, so radioimmunoassays used for humans are appropriate for cats.84 Human endocrinology laboratories often offer this testing, and developing a relationship with such a laboratory at a local human hospital can be beneficial for practitioners. The different vitamin metabolites should be considered. Calcidiol (25-hydroxyvitamin D) increases with ingestion of cholecalciferol-containing rodenticides. Calcitriol (1,25-dihydroxyvitamin D) increases with ingestion of calcitriol-containing plants (such as Cestrum diurnum [day-blooming jessamine]) and granulomatous inflammation. Calcidiol and calcitriol are best measured from chilled serum. Neither analyte is increased with hypercalcemia caused by ingestion of calcipotriene, a vitamin D analog found in psoriasis cream.84

Step 5: Assess tCa, iCa, and Parathyroid Hormone Relationships Table 24-16 outlines common conditions that result in hypercalcemia together with the tCa, iCa, PO4, and PTH results. Broadly, disorders resulting in hypercalcemia should be classified as those for which PTH is typically increased, those for which PTH is typically reduced, and those for which PTH is normal. Exceptions to these findings do occur, and these are addressed under the specific conditions. The most common causes of hypercalcemia in cats, with the most common iCa and PTH findings, are as follows: 1. Neoplasia: • iCa often very high • PTH often undetectable, may be in lower half of reference range 2. Renal disease: • iCa often normal • PTH elevated 3. Idiopathic hypercalcemia • iCa often mildly elevated • PTH in lower half of normal range Mnemonics, such as “GOSH DARN IT”85 for all causes of hypercalcemia and “SHIRT”24 for common causes of hypercalcemia have been devised. These are listed in Boxes 24-5 and 24-6. Veterinarians are advised to remember the causes of hypercalcemia in terms of PTH results because this gives a better understanding of the underlying processes.

628


TABLE 24-16 Common Conditions That Result in Hypercalcemia with Expected Calcium (Total and Ionized), Albumin, Phosphate, Parathyroid Hormone, and Other Calcemic Indices* tCa

iCa

Alb

PO4

PTH

PTHrP

25-OH vit D

1,25(OH)2 vit D

Primary hyperparathyroidism

↑

↑

N

↓ or N

↑

N

N

N or ↑

Renal secondary hyperparathyroidism

↑

N or ↓

N

↑

↑

N

N or ↓

N or ↓

Tertiary hyperparathyroidism

↑

↑

N

↑

↑

N

N or ↓

↓ or N

Neoplasia Humoral hypercalcemia

↑

↑

N or ↓

↓ or N

↓ or N

↑ or N

N

↓ or N or ↑

Neoplasia Local osteolytic

↑

↑

N or ↓

N or ↑

↓ or N

N or ↑

N

N

Hypervitaminosis D Calcitriol (including granulomatous inflammation)

↑

↑

N

N or ↑

↓

N

N

↑

Hypervitaminosis D Cholecalciferol (rodenticide)

↑

↑

N

↑ or N

↓

N

↑

N or ↑

↑

↑

N

N or ↑

N or ↓

N

N

N or ↓ or ↑

Dehydration

↑

N or ↑

↑ or N

N or ↑

N or ↓

N

N

N

Hypoadrenocorticism

↑

↑

N or ↓

↑ or N

↓ or N

N

N

↓ or N

N or ↑ or ↓

↑ or ↓

N

N or ↑

↑ or N or ↓

N

N

N or ↓

INCREASED PTH

REDUCED PTH

NORMAL PTH Idiopathic MISCELLANEOUS CAUSES

Hyperthyroidism

tCa, Total calcium; iCa, ionized calcium; alb, albumin; PO4, phosphate; PTH, parathyroid hormone; PTHrP, PTH-related peptide; 25-OH vit D, calcidiol; 1,25(OH)2 vit D, calcitriol; N, normal. *Note that the most common conditions are highlighted yellow. Variations in expected results are indicated with the more common result noted first.

BOX 24-5 “GOSH DARN IT” Mnemonic to Help Remember Causes of Hypercalcemia

BOX 24-6 “SHIRT” Mnemonic to Help Remember Common Causes of Hypercalcemia

Granulomatous disease Osteolysis Spurious (e.g., laboratory error; presence of lipemia, hemolysis) Hyperparathyroidism, House plant ingestion, Hyperthyroidism D toxicosis (i.e., vitamin D toxicosis), Dehydration Addison’s disease (hypoadrenocorticism), Aluminum toxicity Renal disease Neoplasia, Nutritional Idiopathic Temperature (hyperthermia)

Spurious (lipemia, hemolysis; always verify before proceeding) Hyperparathyroidism Idiopathic Renal disease (mostly normal iCa despite elevated tCa) Tumors (lymphoma, carcinoma, multiple myeloma)

Modified from Schenck PA, Chew DJ, Behrend EN: Update on hypercalcemic disorders. In August JR, editor: Consultations in feline internal medicine, ed 5, St Louis, 2006, Elsevier Saunders, p 157.

Modified from Cook AK: Guidelines for evaluating hypercalcemic cats, Vet Med 103:392, 2008.


INCREASED PARATHYROID HORMONE WITH HYPERCALCEMIA Hypercalcemia with increased PTH may be due to primary hyperparathyroidism or renal secondary hyperparathyroidism. Tertiary hyperparathyroidism is a rare consequence of renal secondary hyperparathyroidism. Renal disease is a far more common cause of hypercalcemia than primary hyperparathyroidism. Hypercalcemia from renal disease usually results in increased tCa but normal iCa.

Primary Hyperparathyroidism Primary hyperparathyroidism is relatively rare in cats. One case series of 71 hypercalcemic cats recognized only four cats with this condition.82 One small cases series of seven hyperparathyroid cats has been reported,50 but all other publications have been case reports.* One case was reported in a cat with multiple endocrine neoplasia.78 Further, nonfunctional parathyroid adenomas were removed from two cats, having been recognized by cervical palpation.69 The underlying cause is commonly benign, such as adenoma, cystadenoma, or hyperplasia17,28,50,82,93 but can be malignant adenocarcinoma.50,57,75 The age range of affected cats was 8 to 20 years, with no sex predisposition. There are no definitive breed predispositions; five of the seven initial cases were Siamese,50 most subsequent cases have been mixed-breed cats, but two recent cases were Persian.2,19 Presenting clinical signs are generally nonspecific and consistent with hypercalcemia of any cause (see Table 24-15); polydipsia and polyuria do not seem to be commonly reported. Physical examination findings are generally nonspecific; however, a palpable parathyroid (that may be mistaken for an enlarged thyroid gland) may be present in approximately 40% of cases. One cat with probable primary hyperparathyroidism had lytic changes and disruption of normal bone architecture, affecting mainly the femoral diaphyses.39 Laboratory results show elevations of tCa and iCa with an inappropriately elevated PTH concentration; phosphate is suppressed by PTH and so should initially be low but may rise with impaired renal function caused by ongoing hypercalcemia. In a physiologically normal cat, hypercalcemia should suppress PTH, so a PTH concentration at the high end of the normal reference range may still suggest primary hyperparathyroidism. Further, PTH concentrations vary with time. In one case five of seven PTH measurements from the same cat were normal; the other two were notably increased.28

*References 2, 17, 19, 28, 39, 51, 57, 75, 93.

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Ultrasound has been used as a diagnostic aid in some cases.75,93 In one report parathyroid adenomas in two cats measured greater than 1 cm in diameter and contained hypoechoic regions with distal acoustic enhancement, compared to the hyperechoic homogenous masses.93 In another case fluid retrieved by fineneedle aspiration from a cystic cervical mass had higher concentrations of PTH than serum from the same cat.75 Surgical resection of the abnormal parathyroid tissue is the treatment of choice. Before surgery, it is advisable to use fluid therapy to rehydrate the animal and attempt to reduce the severity of the hypercalcemia. Surgical approaches are as for thyroidectomy (see the section on Thyroid Gland Disorders). During surgery, the ventral and dorsal surfaces of both thyroid and parathyroid complexes should be examined. Any enlarged or discolored parathyroid tissue should be removed. Parathyroid adenomas are usually single nodules, and the remaining normal tissue is typically atrophied and can be difficult to see. However, in some cases, adenomas may be as small as 2 mm in diameter. External parathyroid adenomas are easily removed, but excision of adenomas of internal parathyroid glands may require removal of the entire thyroid and parathyroid complex on that side. It is imperative that at least one parathyroid gland is left intact to prevent permanent hypoparathyroidism. If no abnormal parathyroid gland tissue can be visualized, it is possible that an ectopic parathyroid gland is responsible. A thorough inspection of the ventral neck should be made, although an ectopic gland may be located in the cranial mediastinum. In most cases the abnormal parathyroid gland will be palpated before surgery, making the procedure relatively straightforward.7 Because chronic hypercalcemia leads to atrophy of normal parathyroid glands, surgical removal of the autonomously secreting gland will lead to a rapid decline in PTH levels and relative hypoparathyroidism.6 It is therefore crucial to monitor closely for signs of hypocalcemia. Hypocalcemia that is sufficiently severe to require treatment is likely to develop within 24 to 48 hours, with clinical signs of hypocalcemia occurring 3 to 6 days after surgical removal of a parathyroid gland tumor.87 Most reported cases have been treated preventively with calcitriol and calcium to reduce this risk, but hypocalcemia has not been a commonly recognized sequela.28,50,51 Initiating treatment for hypocalcemia before the onset of clinical signs is not recommended because it removes the hypocalcemic stimulus to reverse parathyroid atrophy by actively inhibiting PTH secretion.6 If hypoparathyroidism does result after surgery, it is usually transient, and treatment can be gradually withdrawn over a few months. In some cases the postoperative stabilization of serum calcium can present a major challenge.7

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Renal Disease Chronic renal disease (CRD) is one of the more common underlying causes of hypercalcemia in cats.82,85 The frequency of hypercalcemia among cats with CRD has been reported from 11.5%29 to 58%,9 but the author recognizes far fewer than even this lower number. The degree of hypercalcemia correlates with the severity of renal disease; in one study of 73 cats with CRD, the frequency of hypercalcemia was 8% in cats with compensated renal disease, 18% in those with uremic renal disease, and 32% in cats with end-stage renal disease (that died within 21 days of sampling).9 Hypercalcemia caused by CRD often results in normal to low iCa, but occasionally iCa can be elevated.9,85 Therefore normal to low iCa concentrations make underlying CRD more likely, but an elevated iCa concentration does not rule out CRD. Insofar as hypercalcemia can cause CRD, the presence of both concomitantly creates a diagnostic challenge. Hypercalcemia caused by renal failure is usually quite mild. The primary cause is phosphate retention resulting from the failing kidneys’ inability to secrete sufficient phosphate, leading to PTH secretion. Other mechanisms are also responsible, including alterations to serum protein binding and decreased GFR.41 In most cases tCa will be increased but iCa will be normal or low (the increase in tCa being related to altered protein binding)— if this is the case, it is easier to resolve the etiology (renal failure causing the hypercalcemia), and the lack of ionized hypercalcemia means that specific therapy is not required. Deleterious effects of hypercalcemia occur in patients with CRD only if it is associated with increases in serum iCa concentration. Consequently, clinical signs of hypercalcemia are uncommon in CRD patients, and measurement of serum iCa concentration to assess calcium status in CRD patients is important. Tertiary hyperparathyroidism has been recognized for some time in humans. The term refers to the emergence of ionized hypercalcemia over months to years as a result of progression from renal secondary hyperparathyroidism. Consequently, the patient has elevated tCa, iCa, and PTH because of an alteration in the calcium set point to stimulate release of PTH (i.e., higher concentrations of iCa are necessary to inhibit PTH secretion).26 As already noted, elevated iCa is sometimes recognized in cats with hypercalcemia caused by CRD9; however, tertiary hyperparathyroidism has not specifically been described in cats. Prevention of phosphate retention is central to the management of CRD and has been shown to reduce renal secondary hyperparathyroidism.11 Treatment consists primarily of dietary phosphate restriction using phosphate-restricted diets or intestinal phosphatebinding agents (or a combination of the two, if required).

There is a small chance that phosphate-restricted diets or phosphate binders can actually cause hypercalcemia. In one study 2 of 15 cats with CRD developed hypercalcemia while eating a phosphate-restricted veterinary diet designed for treatment of CRD. Hypercalcemia in these cats was associated with a decrease in serum phosphorus and low or undetectable PTH concentrations. Hypercalcemia resulted in clinical signs for one cat. In this cat the dietary therapy was stopped for 6 months. The phosphate-restricted diet was then reintroduced such that the cat was fed two thirds of its energy intake as phosphate-restricted diet and one third as ordinary commercial canned cat food, which halted the rise in plasma phosphate and PTH. The proportion of phosphate-restricted diet was subsequently increased and this reduced plasma phosphate and PTH concentrations to below pretreatment values without recurrence of the hypercalcemia. The other cat showed no clinical signs of hypercalcemia, and calcium returned to normal on cessation of the phosphate-reduced diet.11 Theoretically, the agents in phosphate binders could cause hypercalcemia. The most commonly used phosphate binders for cats with CRD contain aluminum phosphate. Aluminum has been shown to experimentally cause hypercalcemia and renal disease in dogs.43 Alternative phosphate binders for cats contain calcium carbonate. Calcium carbonate is also an ingredient of many antacids used for humans, and hypercalcemia has been recognized as a result of consumption of large amounts of such antacids.42 Hypercalcemia as a result of ingestion of aluminum hydroxide or calcium carbonate as phosphate binders has not been described in cats but is theoretically possible. Therapy with low-dose calcitriol has been recommended as preventive management of renal secondary hyperparathyroidism in textbooks and review articles.21,67,68 One study of 10 cats showed that PTH concentrations were not significantly different after 14 days of calcitriol administration.47 It is possible that a longer duration of therapy is required to note benefits. An unpublished 1-year-duration randomized, controlled clinical trial failed to show any benefit in cats with varying severity of CKD; the possibility that calcitriol was of benefit was not excluded by the study.76 Of course, overdosing a cat with calcitriol used for this purpose can, in itself, result in hypercalcemia.

DECREASED PARATHYROID HORMONE WITH HYPERCALCEMIA The most common reason for hypercalcemia associated with suppressed levels of PTH is neoplasia. In most cases PTH is suppressed to undetectable or very low concentrations (i.e., zero or approaching zero). On some occasions cats with hypercalcemia of malignancy may

have PTH concentrations in the middle of the normal reference range,77 thus creating overlap with idiopathic hypercalcemic cats and potential diagnostic difficulties. An alternative diagnosis for suppressed PTH concentration is hypervitaminosis D, which can result from vitamin D ingestion or granulomatous inflammation. In many cases there will be a clinical history of toxic ingestion, or potential neoplasia will be recognized at physical examination (e.g., palpation of an abdominal mass), and these overt signs should be investigated in the first instance. Further investigations of hypercalcemia are appropriate in cases when no such toxin exposure or indicative physical examination findings are present. Distinctions may be found by measuring PTHrP or vitamin D metabolites. However, malignancy-associated hypercalcemia does not necessarily cause an increase in PTHrP, and the different forms of vitamin D create different responses depending on what the toxic agent is. PTHrP and vitamin D metabolite measurements may be considered relatively specific (false-positive results are unlikely) but not very sensitive (false-negative results are a strong possibility).

Neoplasia Malignancy-associated hypercalcemia may result from two mechanisms: 1. Humoral hypercalcemia of malignancy (HHM) • Neoplastic tissues can elaborate numerous cytokines that act like PTH to stimulate bone resorption, thus elevating serum calcium • PTHrP is a principal mediator of this effect, but others are possible 2. Local osteolytic hypercalcemia • Subsequent to local invasion and dissolution of bone by the tumor Numerous types of malignancies have been associated with hypercalcemia of malignancy. Most commonly reported is lymphosarcoma32,33,82 (in various locations) or squamous cell carcinoma48,54,82 (e.g., in the mandible or ear canal); hypercalcemia of malignancy has also been recognized with multiple myeloma,14,44,90 osteosarcoma,82 fibrosarcoma,82 bronchogenic carcinoma,82 leukemia,60 renal carcinoma, and thyroid carcinoma.77 The author has recently recognized hypercalcemia in a cat with intestinal small cell lymphoma. In many cases neoplasia will be apparent on physical examination. When hypercalcemia is recognized in a generally unwell cat and iCa is increased and PTH is very low or even unrecordable, investigations for neoplasia should take place. Increased concentrations of PTHrP indicate malignancy is present, but failure to detect increased PTHrP does not rule it out; calcidiol and calcitriol concentrations will be normal in most cases.


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FIGURE 24-31 Lateral thoracic radiograph of a cat with hypercalcemia of malignancy caused by bronchogenic carcinoma. Note that there is not only pleural effusion and a consolidated caudal lung lobe but also osteolysis of the ninth rib. The tumor was also adhered to the diaphragm, so one diaphragmatic crus is farther cranial than the other.

Thoracic radiographs (Figure 24-31), abdominal ultrasonography, and bone marrow aspiration are all appropriate investigations. The order in which these are undertaken will depend on the clinical signs, but sometimes all three are necessary. Treatment of malignancy-associated hypercalcemia requires treatment of the underlying malignancy; however, therapies to reduce the magnitude of hypercalcemia (discussed later) may be necessary. There are no data in cats to compare survival times of cats with neoplasia with and without hypercalcemia.

Hypervitaminosis D Hypervitaminosis D is not very common in cats but is an important differential diagnosis for hypercalcemia of malignancy. As with malignancy, hypervitaminosis D results in elevated iCa and suppressed PTH. It is important to obtain a thorough clinical history with potential of ingestion of, or access to, known toxins (discussed later). Presence of an abdominal mass or intrathoracic lesions may indicate that the hypercalcemia is associated with granulomatous inflammation and not neoplasia. Serum calcitriol will be elevated in most cases of hypervitaminosis D (exceptions are noted later). Granulomatous Inflammation Hypercalcemia can result from granulomatous inflammation because macrophages can synthesize calcitriol from calcidiol without negative feedback regulation. Hypercalcemia has been recognized in cats with mycobacteriosis,5,61 nocardiosis,61 histoplasmosis,45 toxoplasmosis, pulmonary cryptococcosis, Actinomyces rhinitis, and feline infectious peritonitis.82 A direct

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association between granulomatous inflammation and hypercalcemia was not made in most reported cases, but elevated calcitriol concentrations were recognized in one cat with both nocardiosis and atypical mycobacterial infection.61 In most cases investigations will proceed to diagnose abnormalities found on physical examination and include thoracic radiographs and abdominal ultrasonography. Hypercalcemia may, in such cases, be wrongly considered to be due to neoplasia. An elevated calcitriol concentration can help distinguish such cases as being due to granulomatous inflammation rather than neoplasia. It is, however, theoretically possible for neoplasia to cause a granulomatous response sufficient to cause hypercalcemia; a definitive diagnosis of the cause of hypercalcemia requires cytologic or histologic assessment with culture required to identify the causative agent. Toxic Exposures Vitamin D toxicity is not commonly reported in cats because they seem to be resistant to cholecalciferol toxicosis if their diet is otherwise complete and balanced.91 However, several reports from Japan in the early 1990s documented significant hypercalcemia with clinical signs resulting from hypervitaminosis D associated with commercial diets consisting of fish that contained over 100 times the minimal requirement of cholecalciferol (50 IU/100 g of diet for growing cats).66,81 Toxicity can occur from ingestion of vitamin D–containing plants such as C. diurnum (known as dayblooming cestrum, or day-blooming jessamine, or dayblooming jasmine).31 Calcitriol may be used to treat hypoparathyroidism and potentially renal secondary hyperparathyroidism, and overdosing (perhaps after an error by a compounding pharmacist) is another potential source of toxicity.85 All these toxicities will result in an elevation of calcitriol (1,25-dihydroxyvitamin D) with normal calcidiol (25-hydroxyvitamin D). Ingestion of cholecalciferol-containing rodenticides such as Quintox or Rampage65,72 can also cause hypervitaminosis D. In these circumstances calcidiol will be elevated, and calcitriol is often normal but may be elevated. Calcidiol can remain elevated for weeks to months because of lipid storage and slow release.85 Calcipotriol or calcipotriene is a calcitriol analog formulated as a topical dermatologic agent to treat psoriasis in people. There are anecdotal reports of cats licking this ointment from their owners’ skin85 and documented cases of toxicity in dogs.18,34,80,98 With calcipotriol toxicity, calcidiol concentrations remain normal; calcitriol concentrations would be expected to remain normal (or perhaps be suppressed), but this is undetermined.85

NORMAL PARATHYROID HORMONE WITH HYPERCALCEMIA The main consideration for a cat with hypercalcemia and normal PTH concentration is idiopathic hypercalcemia. Because cats with hypercalcemia of malignancy may have PTH levels in the lower half of the normal reference range, there can be considerable overlap with cats with idiopathic hypercalcemia. Cats for which this diagnostic dilemma occurs (but in which occult neoplasia is not detected after thoracic auscultation, abdominal ultrasonography, and bone marrow analysis) should be managed as if they had idiopathic hypercalcemia. These cats also should be serially monitored (every 3 months is appropriate for a stable cat), not only for calcium concentrations but with a thorough examination on each visit with a clinical suspicion of neoplasia. Repeat ancillary testing to look for occult neoplasia is appropriate if clinical signs arise, but after a period of time (1 year can be considered a good yardstick), idiopathic hypercalcemia becomes more likely and the need for repeat diagnostics decreases.

Idiopathic Hypercalcemia Idiopathic hypercalcemia refers to abnormally elevated serum iCa concentration of unknown cause after extensive medical evaluation to rule out known causes of hypercalcemia.23 It may now be the most common type of hypercalcemia and has been anecdotally recognized in North America, Europe,23 and Australia despite being reported only in the United States.63,88 With idiopathic hypercalcemia serum calcium concentrations can be increased for months to years without overt clinical signs. Hypercalcemia may initially be recognized as a fortuitous discovery from a blood sample taken in a well cat (e.g., for preanesthetic screening) or a cat with an unrelated condition. One study reported as an abstract assessed 427 cats with idiopathic hypercalcemia recognized at a single diagnostic laboratory; no clinical signs were noted in 46% of cases, 18% had mild weight loss only, chronic constipation was noted in 5% of cats, and inflammatory bowel disease was seen in 6% (although it was not noted how this was diagnosed). Uroliths or renoliths were observed in 15% of cats, and calcium oxalate stones were specifically noted in 10% of cases.88 Similarly, in an earlier series of 20 cases, 35% of cats had urolithiasis, as well as signs normally attributable to the gastrointestinal tract, such as vomiting and diarrhea.63 The recognition of intestinal signs is interesting insofar as an association has been made between inflammatory bowel disease and renal urolith formation in humans (possibly because of poor absorption of magnesium and citrate, which are considered stone inhibitors).59 No such association has been made in cats.

Cats with idiopathic hypercalcemia can be any age; the clinical cases series of 20 cats found an age range of 2 to 13 years (with a mean of 5.8 years)63 compared with the larger set of 427 cats, which found a mean of 9.8 years (range 0.5 to 20 years).88 No gender predispositions are recognized, but longhaired cats seem to be overrepresented, including both domestic longhaired cats and purebreds, such as Persians and Himalayans.63,88 In most cases elevations of both tCa and iCa concentrations are mild to moderate (10% to 20% above the upper limit of the reference range), but some cats can have markedly high elevations. PTH concentrations are typically normal but at the low end of the reference range, with the mean value equaling 1.1 pmol/L (range 0 to 4) in both series.63,88 PTHrP was negative in 301 cats tested in one series88 but increased in 1 of 11 cats in the other. The reason for the abnormally high concentration of PTHrP in this cat could not be determined, but the cat survived more than 3 years after the onset of hypercalcemia, making underlying malignancy an unlikely explanation for the high PTHrP concentration.63 Calcitriol was normal in 12 cats in one series88 but increased in one of seven cats in the other. Similar to the cat with increased PTH, this cat lived a further 2 years after the onset of hypercalcemia, and at postmortem examination neither neoplasia nor granulomatous disease was identified.63 The relationship between renal disease and idiopathic hypercalcemia is not clear-cut. Renal disease can occur secondary to longstanding idiopathic hypercalcemia (Figure 24-32); some cats with renal disease can have idiopathic hypercalcemia recognized after protracted


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periods of normocalcemia; in yet other cats, renal disease may be recognized concurrently with recognition of idiopathic hypercalcemia.85 Multiple factors have been considered in relation to the underlying cause of idiopathic hypercalcemia. It is unknown whether increased intestinal calcium absorption, increased bone resorption, or decreased renal calcium excretion (or some combination thereof) is the key factor leading to the development of this condition. Three of five cats in one series58 and all 14 cats for which diet history was available in another63 had been fed acidifying diets designed to minimize struvite crystalluria and urolithiasis. Of course, not all cats on acidifying diets develop hypercalcemia, so these patients must have had an additional underlying factor that predisposed them to hypercalcemia. All five cats in that first series58 had reduced serum calcium when the diet was changed to a high-fiber diet, and two of four cats that could be assessed had a partial response in the second study.63 Genetics is another consideration, given the overrepresentation of longhaired cats. Management of idiopathic hypercalcemia is discussed in the following section.

OTHER CAUSES OF HYPERCALCEMIA Some causes of hypercalcemia are not appropriate for assessment in relation to PTH levels—chiefly, hypercalcemia caused by endocrinopathies. In these cases the underlying condition dictates the clinical investigations and findings, and hypercalcemia is relatively mild and resolves as the underlying disease is managed.

Hyperthyroidism One study has recognized increased tCa, but normal iCa, in 2 of 26 hyperthyroid cats,8 and a study of 71 hypercalcemic cats recognized 2 hyperthyroid cats.82 Conversely, decreased iCa concentrations can be seen, and increased PTH concentration was recognized in 77% of hyperthyroid cats in one of these reports.8 The reasons for and importance of these changes are not entirely clear. Hypercalcemia almost invariably resolves on treatment of hyperthyroidism.

Hypoadrenocorticism

FIGURE 24-32 Small, misshapen kidneys as a consequence of idiopathic hypercalcemia. Note the small urolith (arrow). This cat’s hypercalcemia with elevated ionized calcium and midrange parathyroid hormone was recognized more than 12 months before the development of azotemia.

Naturally occurring primary hypoadrenocorticism has been well documented in 18 cats (see the section on Adrenal Gland Disorders); of these, three cats (17%) were hypercalcemic. Additionally, one cat with iatrogenic hypoadrenocorticism and DM was hypercalcemic,92 and in a series of 71 hypercalcemic cats, one was hypoadrenocorticoid.82 The hypercalcemia in these

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patients is usually mild and has little effect on the outcome of hypoadrenocorticism. The magnitude of hypercalcemia usually parallels the severity of hyperkalemia and hypovolemia. The mechanism of hypercalcemia is unknown and typically resolves with treatment of hypoadrenocorticism.86

TREATMENT OF HYPERCALCEMIA Acute Therapy The principle treatment aim for a hypercalcemic cat is to identify and manage the underlying condition. Treatment to specifically reduce hypercalcemia may be necessary based on the degree of hypercalcemia or severity of clinical signs resulting from hypercalcemia. There is no absolute serum calcium concentration that can be used as a guideline for the decision to treat hypercalcemia aggressively, but a serum calcium concentration of 4 mmol/L (16 mg/dL) or greater has been recommended as a rule of thumb.87 In practice, hypercalcemia of this magnitude can be expected to be accompanied by clinical signs such as depression, anorexia, vomiting, or dysrhythmia. Concurrent hyperphosphatemia potentiates soft tissue mineralization, and the result of multiplying serum calcium by serum phosphate (calcium × phosphate product) has been used to judge the risk of nephrotoxicity and thus help determine whether immediate treatment is required.85 When using U.S. units (mg/dL), a calcium × phosphate product of 60 to 80 has been used as the level at which to consider treatment; this correlates to a calcium × phosphate product of approximately 5 to 6.5 when using SI units. The principles of emergency treatment of severe hypercalcemia are summarized in sequential order in Box 24-7. Intravenous fluid therapy is the first step in symptomatic treatment of hypercalcemia. The initial aim is to correct fluid deficits, but the volume expansion not only dilutes the circulating calcium concentration but also increases renal calcium excretion. Normal (0.9%) saline is the fluid of choice and should be infused at approximately 2 to 3 times the maintenance requirements, which for most cats means 20 to 30 mL per hour. Potassium supplementation is usually required, and maintenance potassium requirements can be calculated as 5 mEq/cat every 24 hours (with additional potassium required if hypokalemia is present). Diuretic therapy with frusemide (furosemide) can be added after rehydration and after any other electrolyte abnormalities are corrected. Diuretics are appropriate only if intravenous fluid therapy alone is not adequate to correct hypercalcemia. Bolus doses of 1 to 2 mg/kg can be used every 8 to 12 hours, or a constant-rate infusion of 2 to 6 mg/kg every 24 hours can be used. Care must be taken to ensure that the intravenous fluid

BOX 24-7 Acute Medical Management of Hypercalcemia 1. Identify and treat underlying cause. 2. Fluid therapy (0.9% saline) at 2-3 times maintenance rates. • Volume expansion to correct dehydration. • Diuresis increases renal calcium excretion. • Potassium supplementation usually required. 3. Diuretic therapy with frusemide (furosemide). • Use when fluids alone do not resolve hypercalcemia. • Ensure hydration–electrolyte balance has been corrected and is maintained. • Administer 1-2 mg/kg every 8-12 hours. 4. Calcitonin therapy • Use when fluid and diuretic therapy are not successful. • Administer 4-6 IU/kg subcutaneously every 8-12 hours. • May result in anorexia. 5. Bisphosphonates • There are few reports of use in cats. • Oral agents can result in esophagitis in humans. 6. Glucocorticoids • They should not be used until all diagnostic testing is complete. • They may decrease effectiveness of chemotherapy.

rates overcome the volume loss induced by diuretic therapy. Calcitonin has not been frequently used in cats. It can be tried if fluid diuresis and diuretic treatment do not resolve hypercalcemia. Calcitonin is administered subcutaneously at 4 to 6 IU/kg every 8 to 12 hours. The magnitude and duration of effect are limited, although there is a fast onset of action. Calcitonin causes anorexia in dogs.85 Intravenous bisphosphonates have been reported to reduce hypercalcemia in two cats (pamidronate disodium)46 and have also been used for slowing of tumor growth and pathologic bone turnover associated with oral squamous cell carcinoma (zoledronate).101 Bisphosphonates reduce the activity and number of osteoclasts after binding to hydroxyapatite. Pamidronate was administered at 1.5 to 2 mg/kg given as a slow (approximately 4-hour) intravenous infusion diluted in normal saline; ionized calcium concentration returned to normal within 48 hours. One cat with idiopathic hypercalcemia remained normocalcemic for 9 weeks; the other cat had nocardiosis, which was successfully treated, and no recurrence was reported.46 Adequate hydration is required before bisphosphonates should be considered insofar as nephrotoxicity is a potential risk factor.


Glucocorticoids should not be administered to hypercalcemic cats until a diagnosis has been confirmed because they can interfere with the ability to reach a diagnosis, affect chemotherapy efficacy, and reduce immunity against infectious agents (that can cause hypercalcemia associated with granulomatous inflammation). The beneficial effects of glucocorticoids to manage hypercalcemia include reducing bone resorption of calcium, decreasing intestinal calcium absorption, and increasing renal calcium excretion; they are also cytotoxic to neoplastic lymphocytes (and therefore used as part of most chemotherapeutic protocols for these types of neoplasia). The previously noted therapies are rarely unsuccessful in managing hypercalcemia acutely. It is the author’s opinion that glucocorticoids should be reserved to manage hypercalcemia in chronic cases when other therapy is unsuccessful.

Chronic Therapy The key principle for chronic therapy of hypercalcemia is the same for acute management—that is, manage the underlying cause. In most cases, management of the underlying cause will be sufficient to reduce hypercalcemia. Consequently, the key condition for which chronic management must be instituted is when the diagnosis is idiopathic hypercalcemia—those instances when thorough investigation fails to uncover an underlying cause. The treatment options for chronic management of hypercalcemia are summarized in Box 24-8.

BOX 24-8 Chronic Medical Management of Hypercalcemia 1. Identify and treat underlying cause. 2. Dietary therapy • High-fiber diets • Renal disease diets • Calcium oxalate–preventive diets • Canned diets 3. Subcutaneous fluids (0.9% saline) • Not assessed • Unlikely to be harmful 4. Low-dose diuretics such as frusemide (furosemide). • Not assessed in chronic situation • Potential for dehydration • Must evaluate for azotemia serially 5. Glucocorticoids • Should not be used until all diagnostic testing complete • Can decrease efficacy of chemotherapy • Prolonged use can increase risk of diabetes mellitus in susceptible cats 6. Bisphosphonates • Few reports in cats • Oral agents can result in esophagitis in humans

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There have been mixed reports of the efficacy of dietary therapy in reducing hypercalcemia. One report noted a return to normocalcemia in all five cats fed a high-fiber diet.58 In another study three cats were fed a high-fiber diet, three were fed an oxalate urolith– preventive diet, and three were fed a diet for management of CRD; there was minimal response to dietary therapy in any of these cats.63 An oxalate urolith– preventive diet had no effect on ionized calcium concentrations in three cats with apparent idiopathic hypercalcemia in another study.56 High-fiber diets may increase intestinal transit time of calcium; foods designed for cats with renal disease are lower in calcium and phosphorus; oxalate urolith– preventive diets are also calcium restricted; canned diets of any description are generally calcium restricted. There is no firm evidence for the benefits of dietary therapy, but insofar as this management is very unlikely to be harmful and many cats with idiopathic hypercalcemia do not show clinical signs for years, it is appropriate to try dietary therapy in the first instance. The author recommends starting with canned highfiber diets (e.g., Hill’s Prescription Diet w/d Feline) or adding psyllium fiber (e.g., Metamucil, Procter & Gamble) to a maintenance canned diet and rechecking calcium values at 2- to 4-week intervals. If normocalcemia is not restored after 6 to 8 weeks, alternative diets can be tried similarly. Further therapy is warranted if no benefit is noted from any diet. Subcutaneous fluid administration at home, as is often recommended for cats with renal insufficiency, is a potential management strategy for hypercalcemic cats. It is important to note that this treatment modality has not been critically assessed for this condition. However, there are few contraindications—namely, congestive heart failure, hypoalbuminemia, and edema or other evidence of fluid overload. Fluid overloading is difficult to achieve with subcutaneous therapy but is a potential issue in a cat with, for example, an unrecognized cardiomyopathy. Certainly, subcutaneous fluid administration is a sensible approach in a hypercalcemic cat that is azotemic because the treatment will, in most cases, manage the two conditions concurrently. Diuretic therapy with low-dose frusemide (furosemide) has also not been critically assessed as management for chronic hypercalcemia. It is imperative to use extreme caution with diuretics in an already dehydrated (azotemic) cat, including cats with renal disease. Anecdotally, the author has found that cats vary immensely in their sensitivity to frusemide (furosemide). As little as 0.5 mg/kg (or 2.5 mg/cat) frusemide (furosemide) can reduce mild hypercalcemia in many cats and usually does not result in azotemia but can cause severe azotemia in some susceptible individuals. If a low dose is not effective in reducing hypercalcemia and is not causing azotemia, the dose can slowly be titrated upward with

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weekly rechecks to assess calcium and azotemia. Other potential consequences of chronic diuretic administration are metabolic alkalosis with hypokalemia and reduction of sodium and chloride. Glucocorticoids, in the form of prednisone (5 to 12.5 mg/cat daily) were effective in resolving hypercalcemia completely in four of six treated cats in one study.63 Uncited textbook references note that 50% of cats respond to 5 to 10 mg/cat daily of prednisone or prednisolone, but some cats require up to 20 mg/cat daily to restore normocalcemia; some cats escape the effect of glucocorticoid treatment, and hypercalcemia can return despite maximal prednisone doses.23,85 Glucocorticoid therapy must not be initiated until neoplasia and granulomatous inflammation have been conclusively ruled out. In these circumstances, when other therapies have been unsuccessful, prednisone (or prednisolone) can be attempted at 5 mg/cat daily for 1 month before reassessment. If iCa remains increased, the dose can be titrated upward (with reassessments). Chronic administration of corticosteroids can induce DM in susceptible individuals (see Endocrine Pancreatic Disorders). Because of the concern that increased renal excretion of calcium induced by corticosteroids has the potential to aggravate hypercalciuria and calcium oxalate urolithiasis, appropriate monitoring should be instituted.63 Bisphosphonates have not been thoroughly assessed but may become a routine alternative for management of hypercalcemia. Intravenous pamidronate was reported to result in normocalcemia for 9 weeks after a single dose of 1.5 to 2 mg/kg in one cat with idiopathic hypercalcemia.46 The duration of effect is likely to vary from cat to cat and may vary with dose, but it is not unreasonable to suggest that intravenous pamidronate therapy approximately every 2 months may be appropriate management for a cat with idiopathic hypercalcemia. Further, an uncited textbook reference notes that a small number of cats have been treated successfully with 10 mg of alendronate orally once weekly for up to 1 year.23 Erosive esophagitis is noted as a possibility in humans receiving bisphosphonates, but this risk is most associated with swallowing the medication with little or no water, lying down during or after ingestion of the tablet, continuing to take alendronate after the onset of symptoms, and having preexisting esophageal disorders.27 These risks may be reduced in cats by following the medication with 5 mL of water syringed into the cat’s mouth; dabbing butter on the cat’s lips to promote licking and salivation has also been recommended.23

HYPOCALCEMIA Hypocalcemia is not a common clinical finding in cats. When present, signalment and history, with other clinical and routine laboratory findings, usually give

an indication of the underlying cause.7 For example, hypocalcemia in a queen in the first few weeks after delivery is most likely due to eclampsia; low calcium after thyroidectomy is most likely due to iatrogenic hypoparathyroidism; taking a thorough dietary history will help the clinician recognize nutritional secondary hyperparathyroidism. As with hypercalcemia, serum PTH and calcitriol concentrations can help confirm a diagnosis. Calcidiol and PTHrP concentrations are not usually helpful to distinguish causes of hypocalcemia.

Clinical Signs The clinical signs due to hypocalcemia vary depending on the severity and rate of change of iCa concentrations; mild decreases in iCa concentration may not result in obvious clinical signs.7 Low plasma iCa increases the excitability of neuromuscular tissue. Typical signs seen are muscle tremors, stiff gait, and even generalized seizures; anorexia and lethargy are noted in cats with primary hypoparathyroidism. In severe cases circulatory effects (hypotension and decreased myocardial contractility) and paralysis of respiratory muscles can result in death.22,73

Underlying Causes Hypocalcemia develops when bone mobilization of calcium is reduced, skeletal calcium accretion is enhanced, urinary losses of calcium are increased, gastrointestinal absorption of calcium is reduced, calcium is translocated intracellularly, or a combination of these mechanisms occurs.87 Common potential underlying causes of hypocalcemia, with associated biochemistry and calcemic hormone changes, are shown in Table 24-17. It should be noted that renal disease can cause hypocalcemia as well as hypercalcemia. Hypocalcemia has also been recognized in cats with acute pancreatitis and is associated with a poorer prognosis.53 Primary Hypoparathyroidism Primary hypoparathyroidism has been reported in the literature in cats on nine occasions. Aside from one small case series of five cats,73 other descriptions have been single case reports.12,38,71,79 This appears to be a disorder of young cats with a mean reported age of 1.8 years (range 0.5 to 6.7 years), with four cats being 1 year old or less. Approximately equal numbers of male and female cases have been reported. All but two cats were domestic shorthairs (one Himalayan and one Siamese). Clinical signs were mostly those expected with prolonged hypocalcemia, such as seizures, tremors, and tetany. Cataracts were noted in five of the nine cases; bilateral protrusion of the nictitating membrane was noted in two cats.

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TABLE 24-17 Anticipated Changes in Calcemic Hormones and Serum Biochemistry Associated with Common Disorders of Hypocalcemia tCa

iCa

Alb

↓

↓

N

↑ or N

N or ↓

N or ↓

N

Eclampsia

↓

↓

Ethylene glycol toxicity

↓

Phosphate enema Septic peritonitis

Hypoparathyroidism Idiopathic Iatrogenic Secondary hyperparathyroidism Nutritional Renal

Hypoalbuminemia

PO4

PTH

PTHrP

25-OH vit D

1,25(OH)2 vit D

↓or N

N

N

N or ↓

N or ↑

↑

N

↓ or N

N or ↓

N

↓

Mild ↑ or N

N

N

N or ↓

↓

N

↑ or N

↑

N

N

↓ or N

↓

↓

N

↑

↑

N

N

Nor ↓ or ↑

↓ or N

↓

↓ or N

N

↑ or N

N

N

N

↓

N

↓

N

N or ↑

N

N

N or ↑

tCa, Total calcium; iCa, ionized calcium; Alb, albumin; PO4, phosphate; PTH, parathyroid hormone; PTHrP, PTH-related peptide; 25-OH vit D, calcidiol; 1,25(OH)2 vit D, calcitriol; N, normal.

Eight of nine hypocalcemic cats were also hyperphosphatemic (without azotemia). Some cats had elevated ALT values. PTH concentration was normal in the two cats in which it was measured. In physiologically normal cats, PTH should increase in the face of hypocalcemia. Histopathology of the parathyroid gland was assessed in three cases, and no parathyroid tissue was found in any. In one case a lymphocytic plasmacytic infiltrate was recognized adjacent to the cranial pole of a thyroparathyroid lobe,38 suggesting an immune-mediated mechanism. Affected cats may initially require emergency therapy with intravenous calcium gluconate but subsequently require lifelong supplementation with oral calcium and calcitriol supplementation; phosphate binders have been used to reduce high phosphate concentrations. Approaches for therapeutic requirements are the same as for all causes of hypocalcemia and will be covered later in this chapter. When appropriate therapy is instituted, the prognosis is excellent. Iatrogenic Hypoparathyroidism Iatrogenic hypoparathyroidism can occur subsequent to parathyroidectomy (as discussed in the section on hyperparathyroidism), bilateral thyroidectomy, sudden correction of chronic hypercalcemia of malignancy, or alkali administration. The sudden correction of chronic hypercalcemia can lead to hypocalcemia as a result of parathyroid gland atrophy and inadequate ability to synthesize and secrete PTH. This can be a consequence of surgical excision of the affected parathyroid gland on account of primary hyperparathyroidism caused by parathyroid gland adenoma. The degree of parathyroid gland atrophy depends on the magnitude of hypercalcemia and its duration before correction. Rapid correction of

hypercalcemia of malignancy after chemotherapy often results in mild hypocalcemia that is usually not associated with clinical signs, but clinical signs of hypocalcemia may occur in some cases.87 Postoperative hypocalcemia is reported in 6% to 82% of cats undergoing bilateral thyroidectomy, depending on the surgical method.15,36 Hypoparathyroidism and associated hypocalcemia result from accidental removal of the external parathyroid glands or disruption of the vascular supply. This consequence becomes transient when parathyroid autotransplantation is used as outlined in the section on Thyroid Gland Disorders; in one study seven of eight cats regained normocalcemia within 20 days of bilateral thyroparathyroidectomy with parathyroid autotransplantation.70 Hypocalcemia is a rare consequence of unilateral thyroidectomy. The administration of alkaline agents may result in hypocalcemia. This has been recognized in a cat treated for salicylate intoxication with sodium bicarbonate.1 Muscle fasciculations increased during treatment with sodium bicarbonate, and serum tCa was low. A single dose of intravenous sodium bicarbonate at 4 mEq/L to cats resulted in a maximal decrease of iCa 10 minutes after infusion; iCa remained below baseline for 3 hours.20 Nutritional Secondary Hyperparathyroidism Nutritional secondary hyperparathyroidism was once a common nutritional disease in small animals,13 being most frequently encountered in puppies and kittens fed exclusively all-meat diets.89 More recent reports are sporadic,95,100 but two very recent papers30,64 demonstrate the continuing importance of this entity. Theoretically, nutritional secondary hyperparathyroidism may also occur when severe gastrointestinal disease is present (as has been reported in dogs and people), limiting the absorption of calcium and vitamin D.87

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The two major forms of clinical signs reflect either complications of severe osteopenia or typical signs of hypocalcemia. Typical radiographic findings include an extensive decrease in bone opacity (osteopenia) with decreased contrast between bones and soft tissue. Cortices are thin and diaphyseal, and metaphyseal trabeculation is coarse. Longitudinal limb growth and physeal appearance are normal. Pathologic fractures are a notuncommon consequence. In contrast, the skull tends to be predominantly affected in osteodystrophy as a result of renal secondary hyperparathyroidism. Hypocalcemia signs can include muscle twitching, excitation, or generalized seizures.95 The prognosis for uncomplicated cases is good, and dietary correction alone results in normalized mineralization in 4 to 8 weeks.30,95 Supplementing diets with additional calcium may accelerate osteoid mineralization but may represent a risk for hypercalcemia when calcitriol levels are markedly increased. Vitamin D administration may also be contraindicated because of its potentiating effect, in concert with PTH, on bone resorption.95 Renal Secondary Hyperparathyroidism The most likely causes of hypocalcemia in renal disease are decreased calcitriol synthesis by diseased kidneys and the response to markedly increased serum phosphorus concentration.87 One study found that 15% of 74 cats with clinical renal disease were hypocalcemic on the basis of serum tCa.29 Another found that hypocalcemia was underappreciated when based on results of only tCa measurement (and not iCa), especially with advancing azotemia. In that study 56% of 47 cats with advanced renal disease had ionized hypocalcemia. Only 14% of cats with moderate renal disease had ionized hypocalcemia, and no cats with “compensated” renal disease were hypocalcemic.8 Prevention of phosphate retention is central to the management of chronic renal disease, primarily using phosphate-restricted diets. Intestinal phosphate-binding agents can be used for additional phosphate restriction.7 Low-dose calcitriol therapy has been recommended but is clinically unproven.47,76 Eclampsia Puerperal tetany (eclampsia) is rare in cats but when present typically occurs between 1 and 3 weeks post partum and has been attributed to loss of calcium into milk during lactation.16,99 Eclampsia was described in four cats in which hypocalcemia developed 3 to 17 days before parturition. Signs of depression, weakness, tachypnea, and mild muscle tremors were most common; vomiting and anorexia were less common, and prolapse of the third eyelid occurred in some cats. Hypothermia, instead of hyperthermia as seen in dogs, was observed. All cats responded to parenteral calcium

gluconate initially and to oral calcium supplementation throughout gestation and lactation.35 Calcium supplementation before parturition is not recommended for queens at risk of eclampsia because it may downregulate PTH secretion and actually increases the risk of eclampsia.99 Toxic Exposures PHOSPHATE ENEMAS

Phosphate enemas (e.g., Fleet enema, Johnson & Johnson) should not be used in cats because the rapid absorption of phosphate results in hyperphosphatemia that can be greater than five times the upper limit of normal. Such significant hyperphosphatemia results in hypocalcemia, with serum tCa decreasing within 45 minutes and persisting for 4 hours.4,49,96 ETHYLENE GLYCOL

Ethylene glycol ingestion can result in hypocalcemia. This is due to chelation of calcium by a metabolite and calcium deposition in soft tissues. Hypocalcemia is recognized along with acute renal failure and hyperphosphatemia.94 Septic Peritonitis Hypocalcemia has been recognized with septic peritonitis in 59% of cats (20 of 34) in one study25 and 89% of cats (49 of 55) in another.52 No specific signs of hypocalcemia were recognized in any cat in the latter study; although 10 cats in this study received calcium supplementation, no treatment benefit could be demonstrated. Treatment could potentially result in subclinical deleterious effects such as precipitation of calcium in soft tissues or excessive intracellular calcium accumulation, leading to cell death. Therefore routine treatment of hypocalcemia in the septic patient is not recommended. Failure of iCa concentration to normalize during hospitalization may be a negative prognostic indicator.52 Hypoalbuminemia Hypoalbuminemia may result in hypocalcemia because of a decrease in the protein-bound fraction of calcium. Ionized calcium should be evaluated in these circumstances but is usually normal, so clinical signs do not result. Correction formulae based on albumin concentration do not improve the prediction of actual iCa concentration and should not be used.87

Treatment of Hypocalcemia Treatment of hypocalcemia must take into account the underlying cause. Treatment of acute signs of hypocalcemia such as tetany or seizures is identical regardless of cause. However, some causes of hypocalcemia, such as nutritional secondary hyperparathyroidism,

eclampsia, and toxicities, will not require supplemental treatment beyond the acute phase. Conversely, conditions such as primary hypoparathyroidism and bilateral thyroparathyroidectomy (without parathyroid autotransplantation) will require lifelong treatment. Hypocalcemia should be anticipated in cats that undergo bilateral thyroidectomy (even with parathyroid autotransplantation) because transiently lowered serum calcium concentrations can still occur. In humans, assessing PTH as well as calcium concentrations 24 hours after surgery has proved a useful predictor of postoperative hypoparathyroidism.3 Those cats undergoing parathyroidectomy for primary hyperparathyroidism should be monitored similarly to cats undergoing thyroidectomy. Preemptive therapy to increase serum calcium concentration is appropriate for cats with marked hypocalcemia that do not yet show clinical signs. Acute Management of Tetany or Seizures Tetany or seizures caused by hypocalcemia are an indication for an immediate infusion of intravenous calcium gluconate, administered to effect. Ten percent calcium gluconate at a dosage of 10 to 15 mg/kg (1 to 1.5 mL/ kg) is slowly infused over a 10- to 20-minute period.22,74 Calcium gluconate is the calcium salt of choice because it is nonirritating if the solution is inadvertently injected perivascularly.22 Heart rate and, ideally, electrocardiogram should be monitored during this infusion; bradycardia and shortening of the Q-T interval are indicators of cardiotoxicity and, if recognized, the infusion should be slowed or temporarily discontinued. Not all clinical signs abate immediately after acute correction of hypocalcemia; there may be a lag of 30 to 60 minutes before signs such as nervousness, panting, and behavioral changes abate, despite attainment of normocalcemia. This may reflect a lag in equilibration between cerebrospinal fluid and extracellular fluid calcium concentrations.22 Subacute Management The initial bolus injection of elemental calcium can be expected to decrease signs of hypocalcemia for as little as 1 hour to as long as 12 hours if the underlying cause of hypocalcemia is still present. Consequently, a constantrate infusion of calcium gluconate administered with intravenous fluids is required at 60 to 90 mg/kg per day (2.5 to 3.75 mg/kg per hour) of elemental calcium until oral medications provide control of serum calcium concentration. Note that 10 mL of 10% calcium gluconate provides 93 mg of elemental calcium. For a 4-kg cat maintenance fluid rates are approximately 10 mL per hour, so approximately 2.5 mg/kg per hour (or 10 mg/ 4-kg cat per hour) of calcium is provided by adding 100 mL of calcium gluconate per 1 L fluids (as long as the fluid rate is maintained at 10 mL per hour). Calcium salts should not be added to fluids that contain lactate,


639

acetate, bicarbonate, or phosphates because calcium salt precipitates can occur.22,86 Subcutaneous administration of calcium gluconate can result in iatrogenic calcinosis cutis, skin necrosis, and scarring at the injection site79 and should be avoided. Oral calcium and calcitriol should be started as soon as possible while the cat is receiving intravenous calcium. The intravenous dose of calcium is reduced as oral calcium salts and calcitriol become effective at maintaining serum calcium.22,74,87 Chronic Maintenance Therapy Maintenance therapy is required for conditions (e.g., primary or iatrogenic hypoparathyroidism) for which parathyroid function is lost permanently so that PTH cannot be produced. PTH cannot be supplemented, although supplementing with calcitriol (the secretion of which is stimulated by PTH in a physiologically normal cat) suffices in most cases. Initially, calcium also must be supplemented. However, in most patients a complete and balanced diet supplies a normal dietary intake of calcium and is sufficient to maintain adequate serum calcium concentrations as long as calcitriol treatment is continued. Consequently, oral calcium salt supplementation can be tapered and, for most cats, discontinued after calcitriol reaches adequate levels.7,87 Calcium carbonate is the most widely used oral preparation of the calcium salts because it contains the greatest percentage of elemental calcium. Any given volume of calcium carbonate contains 40% of that volume of elemental calcium. Oral calcium is usually administered at 25 to 50 mg/kg per day by way of elemental calcium in divided doses (divided into three or four doses over a day). A 4-kg cat will require 100 to 200 mg daily of elemental calcium, which is equivalent to 250 to 500 mg daily of calcium carbonate. If serum phosphorus concentrations remain increased, oral calcium carbonate can be continued for its intestinal phosphate-binding effects.74,87 Calcitriol is the vitamin D metabolite of choice to provide calcemic actions because it has the most rapid onset of maximal action and the shortest biologic halflife. The dose of calcitriol can be adjusted frequently because of its short half-life and rapid effects on serum calcium concentration. If hypercalcemia occurs, it abates quickly after dose reduction. A loading dose of 20 to 30 ng/kg daily has been recommended when more rapid correction of serum calcium concentration is desirable. A maintenance dose of 10 to 20 ng/kg daily divided and given twice daily ensures sustained priming effects on intestinal epithelium for calcium absorption.87 Dose recommendations should be taken as guidelines, and individual doses should be determined for each cat on the basis of frequent evaluation of calcium concentrations.

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Commercially available calcitriol capsules (Rocaltrol, Hoffman-LaRoche) of 0.25- and 0.50-µg (250 and 500 ng) per capsule are not appropriate for cats because the doses are too high to be useful. Furthermore, it is difficult to divide capsules because active calcitriol within the capsule is in a liquid form. Fortunately, there is also a commercial liquid formulation of Rocaltrol with a concentration of 1 µg/mL that can be used to dose cats appropriately. Compounding pharmacists are also able to make up appropriate doses of calcitriol for cats. Periods of hypocalcemia and hypercalcemia occur sporadically in patients during initial efforts to manage serum calcium concentration. During the stabilization period, serum tCa should be assessed daily. Subsequently, until target serum calcium concentration has been achieved and maintained, serum calcium should be assessed weekly. Measurement of serum tCa concentration is recommended every 3 months thereafter in animals with permanent hypoparathyroidism. Serum calcium concentration should be adjusted to just below the normal reference range. This not only lessens the likelihood that hypercalcemia will develop but also reduces the magnitude of hypercalciuria that occurs in patients with PTH deficiency. Maintaining a mildly decreased serum calcium concentration also ensures a continued stimulus for hypertrophy of the remaining parathyroid tissue in patients with postoperative hypoparathyroidism.87

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12. Bassett J: Hypocalcemia and hyperphosphatemia due to primary hypoparathyroidism in a six-month-old kitten, J Am Anim Hosp Assoc 34:503, 1998. 13. Bennett D: Nutrition and bone disease in the dog and cat, Vet Rec 98:313, 1976. 14. Bienzle D, Silverstein D, Chaffin K: Multiple myeloma in cats: variable presentation with different immunoglobulin isotypes in two cats, Vet Pathol 37:370, 2000. 15. Birchard SJ, Peterson ME, Jacobson A: Surgical treatment of feline hyperthyroidism: results of 85 cases, J Am Anim Hosp Assoc 20:705, 1984. 16. Bjerkas E: Eclampsia in the cat, J Small Anim Pract 15:411, 1974. 17. Blunden AS, Wheeler SJ, Davies JV: Hyperparathyroidism in the cat of probable primary origin, J Small Anim Pract 27:791, 1986. 18. Campbell A: Calcipotriol poisoning in dogs, Vet Rec 141:27, 1997. 19. Cavana P, Vittone V, Capucchio MT et al: Parathyroid adenocarcinoma in a nephropathic Persian cat, J Feline Med Surg 8:340, 2006. 20. Chew DJ, Leonard M, Muir W, 3rd: Effect of sodium bicarbonate infusions on ionized calcium and total calcium concentrations in serum of clinically normal cats, Am J Vet Res 50:145, 1989. 21. Chew DJ, Nagode LA: Calcitriol in treatment of chronic renal failure. In Kirk RW, Bonagura JD, editors: Current veterinary therapy XI, Philadelphia, 1992, Saunders, p 857. 22. Chew DJ, Nagode LA: Treatment of hypoparathyroidism. In Bonagura JD, editor: Current veterinary therapy XIII small animal practice, Philadelphia, 2000, Saunders, p 340. 23. Chew DJ, Schenck PA: Idiopathic Feline Hypercalcemia. In Bonagura JD, Twedt DC, editors: Kirk’s current veterinary therapy XIV, St Louis, 2009, Saunders Elsevier, p 236. 24. Cook AK: Guidelines for evaluating hypercalcemic cats, Vet Med 103:392, 2008. 25. Costello MF, Drobatz KJ, Aronson LR et al: Underlying cause, pathophysiologic abnormalities, and response to treatment in cats with septic peritonitis: 51 cases (1990-2001), J Am Vet Med Assoc 225:897, 2004. 26. Davies DR, Dent CE, Watson L: Tertiary hyperparathyroidism, Br Med J 3:395, 1968. 27. de Groen PC, Lubbe DF, Hirsch LJ et al: Esophagitis associated with the use of alendronate, N Engl J Med 335:1016, 1996. 28. den Hertog E, Goossens MM, van der Linde-Sipman JS et al: Primary hyperparathyroidism in two cats, Vet Q 19:81, 1997. 29. DiBartola SP, Rutgers HC, Zack PM et al: Clinicopathologic findings associated with chronic renal disease in cats: 74 cases (19731984), J Am Vet Med Assoc 190:1196, 1987. 30. Dimopoulou M, Kirpensteijn J, Nielsen DH et al: Nutritional secondary hyperparathyroidism in two cats, Vet Comp Orthop Traumatol 23:56, 2010. 31. Drazner FH: Hypercalcemia in the dog and cat, J Am Vet Med Assoc 178:1252, 1981. 32. Dust A, Norris AM, Valli VE: Cutaneous lymphosarcoma with igg monoclonal gammopathy, serum hyperviscosity and hypercalcemia in a cat, Can Vet J 23:235, 1982. 33. Engelman RW, Tyler RD, Good RA et al: Hypercalcemia in cats with feline-leukemia-virus-associated leukemia-lymphoma, Cancer 56:777, 1985. 34. Fan TM, Simpson KW, Trasti S et al: Calcipotriol toxicity in a dog, J Small Anim Pract 39:581, 1998. 35. Fascetti A, Hickman M: Preparturient hypocalcemia in four cats, J Am Vet Med Assoc 215:1127, 1999. 36. Flanders JA, Harvey HJ, Erb HN: Feline thyroidectomy a comparison of postoperative hypocalcemia associated with three different surgical techniques, Vet Surg 16:362, 1987. 37. Flanders JA, Scarlett JM, Blue JT et al: Adjustment of total serum calcium concentration for binding to albumin and protein in cats: 291 cases (1986-1987), J Am Vet Med Assoc 194:1609, 1989.

CHAPTER 24 Endocrinology 38. Forbes S, Nelson RW, Guptill L: Primary hypoparathyroidism in a cat, J Am Vet Med Assoc 196:1285, 1990. 39. Gnudi G, Bertoni G, Luppi A et al: Unusual hyperparathyroidism in a cat, Vet Radiol Ultrasound 42:250, 2001. 40. Grosenbaugh DA, Gadawski JE, Muir WW: Evaluation of a portable clinical analyzer in a veterinary hospital setting, J Am Vet Med Assoc 213:691, 1998. 41. Guyton AC, Hall JE: Parathyroid hormone, calcitonin, calcium and phosphate metabolism, vitamin d, bone, and teeth. In Guyton AC, Hall JE, editors: Textbook of medical physiology, ed 11, Philadelphia, 2006, Elsevier-Saunders, p 978. 42. Hakim R, Tolis G, Goltzman D et al: Severe hypercalcemia associated with hydrochlorothiazide and calcium carbonate therapy, Can Med Assoc J 121:591, 1979. 43. Henry DA, Goodman WG, Nudelman RK et al: Parenteral aluminum administration in the dog: I. Plasma kinetics, tissue levels, calcium metabolism, and parathyroid hormone, Kidney Int 25:362, 1984. 44. Hickford F, Stokol T, vanGessel Y et al: Monoclonal immunoglobulin G cryoglobulinemia and multiple myeloma in a domestic shorthair cat, J Am Vet Med Assoc 217:1029, 2000. 45. Hodges R, Legendre A, Adams L et al: Itraconazole for the treatment of histoplasmosis in cats, J Vet Intern Med 8:409, 1994. 46. Hostutler R, Chew D, Jaeger J et al: Uses and effectiveness of pamidronate disodium for treatment of dogs and cats with hypercalcemia, J Vet Intern Med 19:29, 2005. 47. Hostutler RA, DiBartola SP, Chew DJ et al: Comparison of the effects of daily and intermittent-dose calcitriol on serum parathyroid hormone and ionized calcium concentrations in normal cats and cats with chronic renal failure, J Vet Intern Med 20:1307, 2006. 48. Hutson CA, Willauer CC, Walder EJ et al: Treatment of mandibular squamous cell carcinoma in cats by use of mandibulectomy and radiotherapy: seven cases (1987-1989), J Am Vet Med Assoc 201:777, 1992. 49. Jorgensen LS, Center SA, Randolph JF et al: Electrolyte abnormalities induced by hypertonic phosphate enemas in two cats, J Am Vet Med Assoc 187:1367, 1985. 50. Kallet AJ, Richter KP, Feldman EC et al: Primary hyperparathyroidism in cats: seven cases (1984-1989), J Am Vet Med Assoc 199:1767, 1991. 51. Kaplan E: Primary hyperparathyroidism and concurrent hyperthyroidism in a cat, Can Vet J 43:117, 2002. 52. Kellett-Gregory LM, Mittleman Boller E, Brown DC et al: Retrospective Study: Ionized calcium concentrations in cats with septic peritonitis: 55 cases (1990-2008), J Vet Emerg Crit Care 20:398, 2010. 53. Kimmel S, Washabau R, Drobatz K: Incidence and prognostic value of low plasma ionized calcium concentrations in cats with acute pancreatitis: 46 cases (1996-1998), J Am Vet Med Assoc 219:1105, 2001. 54. Klausner JS, Bell FW, Hayden DW et al: Hypercalcemia in two cats with squamous cell carcinomas, J Am Vet Med Assoc 196:103, 1990. 55. Labriola L, Wallemacq P, Gulbis B et al: The impact of the assay for measuring albumin on corrected (“adjusted”) calcium concentrations, Nephrol Dial Transplant 24:1834, 2009. 56. Lulich J, Osborne C, Lekcharoensuk C et al: Effects of diet on urine composition of cats with calcium oxalate urolithiasis, J Am Anim Hosp Assoc 40:185, 2004. 57. Marquez GA, Klausner JS, Osborne CA: Calcium oxalate urolithiasis in a cat with a functional parathyroid adenocarcinoma, J Am Vet Med Assoc 206:817, 1995. 58. McClain H, Barsanti J, Bartges J: Hypercalcemia and calcium oxalate urolithiasis in cats: a report of five cases, J Am Anim Hosp Assoc 35:297, 1999.

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59. McConnell N, Campbell S, Gillanders I et al: Risk factors for developing renal stones in inflammatory bowel disease, BJU International 89:835, 2002. 60. McMillan FD: Hypercalcemia associated with lymphoid neoplasia in two cats, Feline Pract 15:31, 1985. 61. Mealey K, Willard M, Nagode L et al: Hypercalcemia associated with granulomatous disease in a cat, J Am Vet Med Assoc 215:959, 1999. 62. Meuten DJ, Chew DJ, Capen CC et al: Relationship of serum total calcium to albumin and total protein in dogs, J Am Vet Med Assoc 180:63, 1982. 63. Midkiff AM, Chew DJ, Randolph JF et al: Idiopathic hypercalcemia in cats, J Vet Intern Med 14:619, 2000. 64. Moarrabi A, Mosallanejad B, Khadjeh G et al: Nutritional secondary hyperparathyroidism in cats under six-month-old of Ahvaz, Iranian J Vet Surg 3:59, 2008. 65. Moore FM, Kudisch M, Richter K et al: Hypercalcemia associated with rodenticide poisoning in three cats, J Am Vet Med Assoc 193:1099, 1988. 66. Morita T, Awakura T, Shimada A et al: Vitamin D toxicosis in cats: natural outbreak and experimental study, J Vet Med Sci 57:831, 1995. 67. Nagode L, Chew D, Podell M: Benefits of calcitriol therapy and serum phosphorus control in dogs and cats with chronic renal failure: both are essential to prevent or suppress toxic hyperparathyroidism, Vet Clin North Am Small Anim Pract 26:1293, 1996. 68. Nagode LA, Chew DJ: Nephrocalcinosis caused by hyperparathyroidism in progression of renal failure: treatment with calcitriol, Semin Vet Med Surg (Small Anim) 7:202, 1992. 69. Norsworthy G, Adams V, McElhaney M et al: Palpable thyroid and parathyroid nodules in asymptomatic cats, J Feline Med Surg 4:145, 2002. 70. Padgett S, Tobias K, Leathers C et al: Efficacy of parathyroid gland autotransplantation in maintaining serum calcium concentrations after bilateral thyroparathyroidectomy in cats, J Am Anim Hosp Assoc 34:219, 1998. 71. Parker JSL: A probable case of hypoparathyroidism in a cat, J Small Anim Pract 32:470, 1991. 72. Peterson EN, Kirby R, Sommer M et al: Cholecalciferol rodenticide intoxication in a cat, J Am Vet Med Assoc 199:904, 1991. 73. Peterson ME, James KM, Wallace M et al: Idiopathic hypoparathyroidism in five cats, J Vet Intern Med 5:47, 1991. 74. Peterson ME, Randolph JF, Mooney CT: Endocrine Diseases. In Sherding RG, editor: The cat: diseases and clinical management, ed 2, New York, 1994, Churchill Livingstone, p 1403. 75. Phillips D, Radlinsky M, Fischer J et al: Cystic thyroid and parathyroid lesions in cats, J Am Anim Hosp Assoc 39:349, 2003. 76. Polzin DJ, Ross S, Osborne CA: Calcitriol. In Bonagura JD, editor: Kirk’s current veterinary therapy XIV, Philadelphia, 2008, Saunders Elsevier, p 892. 77. Provencher Bolliger A, Graham PA, Richard V et al: Detection of parathyroid hormone-related protein in cats with humoral hypercalcemia of malignancy, Vet Clin Pathol 31:3, 2002. 78. Reimer S, Pelosi A, Frank J et al: Multiple endocrine neoplasia type I in a cat, J Am Vet Med Assoc 227:101, 2005. 79. Ruopp J: Primary hypoparathyroidism in a cat complicated by suspect iatrogenic calcinosis cutis, J Am Anim Hosp Assoc 37:370, 2001. 80. Saedi N, Horn R, Muffoletto B et al: Death of a dog caused by calcipotriene toxicity, J Am Acad Dermatol 56:712, 2007. 81. Sato R, Yamagishi H, Naito Y et al: Feline vitamin D toxicosis caused by a commercially available cat food, J Japan Vet Med Assoc 46:577, 1993. 82. Savary K, Price G, Vaden S: Hypercalcemia in cats: a retrospective study of 71 cases (1991-1997), J Vet Intern Med 14:184, 2000. 83. Schenck PA, Chew DJ: What’s new in assessing calcium disorders Part 1, Proc 21st ACVIM Forum 2003;517.

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84. Schenck PA, Chew DJ: What’s new in assessing calcium disorders Part 2, Proc 21st ACVIM Forum 2003;519. 85. Schenck PA, Chew DJ, Behrend EN: Update on hypercalcemic disorders. In August JR, editor: Consultations in feline internal medicine, ed 5, St Louis, 2006, Elsevier Saunders, p 157. 86. Schenck PA, Chew DJ, Jaeger JQ. Clinical disorders of hypercalcemia and hypocalcemia in dogs and cats, Proc 21st ACVIM Forum 2003, p 521. 87. Schenck PA, Chew DJ, Nagode LA et al: Disorders of calcium: hypercalcemia and hypocalcemia. In DiBartola SP, editor: Fluid, electrolyte and acid-base disorders in small animal practice, ed 3, St Louis, 2006, Saunders Elsevier, p 122. 88. Schenck PA, Chew DJ, Refsal K et al: Calcium metabolic hormones in feline idiopathic hypercalcemia [abstract], J Vet Intern Med 18:442, 2004. 89. Scott PP: Nutritional secondary hyperparathyroidism in the cat, Vet Med Small Anim Clin 62:42, 1967. 90. Sheafor S, Gamblin R, Couto C: Hypercalcemia in two cats with multiple myeloma, J Am Anim Hosp Assoc 32:503, 1996. 91. Sih T, Morris J, Hickman M: Chronic ingestion of high concentrations of cholecalciferol in cats, Am J Vet Res 62:1500, 2001. 92. Smith S, Freeman L, Bagladi-Swanson M: Hypercalcemia due to iatrogenic secondary hypoadrenocorticism and diabetes mellitus, J Am Anim Hosp Assoc 38:41, 2002.

93. Sueda MT, Stefanacci JD: Ultrasound evaluation of the parathyroid glands in two hypercalcemic cats, Vet Radiol Ultrasound 41:448, 2000. 94. Thrall MA, Grauer GF, Mero KN: Clinicopathologic findings in dogs and cats with ethylene glycol intoxication, J Am Vet Med Assoc 184:37, 1984. 95. Tomsa K, Glaus T, Hauser B et al: Nutritional secondary hyperparathyroidism in six cats, J Small Anim Pract 40:533, 1999. 96. Tomsa K, Steffen F, Glaus T: [Life threatening metabolic disorders after application of a sodium phosphate containing enema in the dog and cat], Schweiz Arch Tierheilkunde 143:257, 2001. 97. Toribio R, Kohn C, Chew D et al: Cloning and sequence analysis of the complementary DNA for feline preproparathyroid hormone, Am J Vet Res 63:194, 2002. 98. Torley D, Drummond A, Bilsland DJ: Calcipotriol toxicity in dogs, Br J Dermatol 147:1270, 2002. 99. Waters CB, Scott-Moncrieff JCR: Hypocalcemia in cats, Comp Contin Educ Vet 14:497, 1992. 100. Watson ADJ: Treatment of nutritional secondary hyperparathyroidism in the cat, Can Vet J 24:107, 1983. 101. Wypij JM, Fan TM, Fredrickson RL et al: In vivo and in vitro efficacy of zoledronate for treating oral squamous cell carcinoma in cats, J Vet Intern Med 22:158, 2008.

C H A P T E R

25

Hematology and Immune-Related Disorders Edward Javinsky O U T L I N E Diagnostic Techniques, 643 Erythrocyte Physiology and Diagnostic Evaluation, 647 Supportive Care for Cats with Anemia, 653 Erythrocyte Disorders, 656 Selected Leukocyte Disorders, 675 Disorders of Hemostasis, 679

Disorders of the Spleen, 685 Lymphadenopathy, 688 Cytokines, 692 Systemic Lupus Erythematosus, 696 Systemic Anaphylaxis, 698

Blood and immune diseases are relatively common in cats and often caused by infectious agents. Many of the presenting signs are nonspecific, requiring a detailed and logical investigation into their cause. Understanding normal physiology is important in recognizing disease. This chapter covers some diagnostic techniques useful in evaluating cats with blood disease. Important, non-neoplastic blood and systemic immune dysfunction is discussed, with an emphasis on diagnosis and treatment. Specific immune disorders of the skin and joints are covered in Chapters 22 and 26, and neoplastic diseases are discussed in Chapter 28.

DIAGNOSTIC TECHNIQUES

used to stage neoplasia or determine the etiology of hypercalcemia or hypergammaglobulinemia that may be caused by lymphosarcoma or multiple myeloma. Although most healthy cats do not have visible iron stores in the bone marrow, the presence of iron here will eliminate iron deficiency as a cause of anemia.34 Additional indications for collecting bone marrow include the inappropriate presence of immature hematopoietic cells in the circulation, unexplained leukocytosis or thrombocytosis, and dysplastic changes in the circulating blood cells. Routine evaluation of the bone marrow is not helpful in sorting out the causes of absolute erythrocytosis (polycythemia) because the erythroid morphology of the marrow appears the same in all cases (erythroid hyperplasia).47

Bone marrow evaluation is an underutilized technique in veterinary medicine. Any veterinarian with the easily obtained proper supplies can collect bone marrow. For a diagnostic technique so full of potential rewards, the risks are minimal. As with any other diagnostic test, proper patient selection is important to avoid performing an unnecessary procedure.

Contraindications There are few contraindications for collecting a sample of bone marrow when it is warranted. Most of these relate to the severity of the cat’s condition and its ability to tolerate sedation or general anesthesia. Hemorrhage as a result of the bone marrow collection is uncommon even in situations of severe thrombocytopenia. The veterinarian should not hesitate to collect bone marrow when it is indicated.

Indications Indications for obtaining a sample of bone marrow include the presence of an unexplained nonregenerative anemia, neutropenia, thrombocytopenia, or combination of cytopenias (Box 25-1). Bone marrow collection can be

Equipment and Supplies Most hospitals will have, or can easily obtain, the supplies required to collect a bone marrow sample. These supplies include a bone marrow biopsy needle, chemical restraint, surgical scrub, sterile fenestrated surgical

Bone Marrow Collection


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BOX 25-1 Indications for Sampling Bone Marrow Abnormal Peripheral Blood Findings • Unexplained anemia, leukopenia, or thrombocytopenia • Unexplained leukocytosis or thrombocytosis • Myeloproliferative disease • Lymphoproliferative disease • Abnormal blood cell morphology • Rubricytosis (increased nucleated erythrocytes) without polychromasia • Neutrophilic left shift without inflammatory disease

Historical or Physical Findings • • • • •

Fever of unknown origin Occult disease Unexplained lymphadenopathy Drug toxicity Neoplasia

Therapeutic Monitoring • Hematopoietic disorders • Neoplasia

Abnormal Serum Biochemical Changes • • • •

Unexplained hypercalcemia Monoclonal gammopathy Polyclonal gammopathy Proof of adequate iron stores (normal cats may have no identifiable stored iron)

drape, slides, anticoagulant, a 12-mL syringe, a dozen glass microscope slides, sterile gloves, and a scalpel blade. If a core biopsy will be performed, tissue fixative such as 10% formalin will be required. Local anesthesia will be used for patients in which chemical restraint is contraindicated. Other supplies that may be useful, but are not required, include pipettes and microhematocrit tubes. Several types of bone marrow needles are available (Figure 25-1). An 18-gauge needle is an appropriate size for collecting marrow from a cat. The Jamshidi and Rosenthal needles are made of stainless steel and can be heat sterilized. The Illinois needle contains plastic and requires gas or cold sterilization. The presence of a stylet in the needle keeps the lumen from becoming plugged with a core of cortical bone at the beginning of the procedure. The stylet must be completely in place until the actual sample is collected, or a frustrating obstruction of the needle will occur. For hospitals without a bone marrow needle, an 18-gauge venipuncture needle may

FIGURE 25-1 Bone marrow biopsy needles. Left to right, Jamshidi disposable core-aspiration biopsy needle (11-gauge, 4 inches), stylet for the Jamshidi biopsy needle, Rosenthal reusable core-aspiration biopsy needle (16-gauge, 1 5 16 inches), stylet for the Rosenthal needle.

be substituted. Because there is no stylet to keep the lumen open, an obstruction of the venipuncture needle is likely. This means a second needle will be needed, and dexterity will be required to find the hole in the cortical bone made by the first needle. Bone marrow collection is a painful procedure. The struggling of an uncooperative and anxious patient makes collecting a diagnostic sample difficult. It may also be unethical to put a cat through unnecessary pain and anxiety when chemical restraint is available; trauma to assistants can also be avoided. If chemical restraint is not appropriate, a local anesthetic can be used to minimize the pain of passing the needle through the skin to the periosteum. Cortical bone itself has no pain receptors. Unfortunately, the endosteum cannot be anesthetized, and most of the pain of this procedure occurs when the endosteum is torn during sample collection. Bone marrow clots readily when collected. The use of an anticoagulant is recommended so that there is no rush to process the sample after collection. A 2.5% solution of ethylenediaminetetraacetic acid (EDTA) can be made by injecting 0.35 mL of sterile saline into a 3-mL lavender-top EDTA blood collection tube. The contents are withdrawn and injected into a second EDTA tube.71 The resulting 0.5 mL volume is placed in a 12-mL syringe and should be adequate for preventing coagulation of the collected marrow sample. Collection Sites Bone marrow can be collected from one of three sites: the proximal humerus (Figure 25-2), the iliac crest, or the femur (Figure 25-3). The proximal humerus is easily accessible, has little overlying tissue, and offers a large

CHAPTER 25 Hematology and Immune-Related Disorders

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The iliac crest may be wide enough only in large cats and is difficult to palpate in obese patients. The needle is directed ventrally and slightly medially into the most dorsally palpable portion of the ilium, where the bone is widest. Occasionally, the needle will come to rest against the opposing cortical wall. If aspirating a sample from the iliac crest is difficult, the clinician should withdraw the needle slightly before concluding that the procedure is a failure. The proximal femur is an easily accessed site for collecting marrow from cats. The greater trochanter is palpated and the needle inserted into the trochanteric fossa medial to the trochanter. The needle is directed parallel to the long axis of the femur. A potential, but uncommon, complication with using this site is damage to the sciatic nerve running medial and caudal to the greater trochanter. There should be plenty of room, however, to obtain the sample while leaving the nerve untouched.

FIGURE 25-2 Bone marrow collection site from the proximal humerus. (Redrawn from Grindem CB: Bone marrow biopsy and evaluation, Vet Clin North Am 19:674, 1989.)

FIGURE 25-3 Bone marrow collection sites from the iliac crest and the proximal femur. (Redrawn from Grindem CB: Bone marrow biopsy and evaluation, Vet Clin North Am 19:673, 1989.)

surface for needle placement. The greater tubercle is palpated, and the needle inserted into the flat surface of the craniolateral humerus just distal to the tubercle. The needle is inserted in a craniomedial direction perpendicular to the long axis of the bone.

Aspiration Biopsy Before preparing the patient, the veterinarian should place all the materials in easy reach. A surgical tray is an excellent choice. Once the cat is anesthetized, it is placed in lateral recumbency with the side to be sampled facing up. The area is shaved, surgically prepared, and draped. While wearing sterile gloves, the veterinarian makes a small incision in the skin and superficial subcutaneous tissue. The incision need only be large enough for the needle to pass through. The veterinarian holds the needle between the thumb and middle finger with the index finger along the shaft for stabilization. The top of the stylet should rest against the palm of the hand so that it does not become displaced during the passage through the cortical bone. The grip is more like holding a screwdriver than a pen and allows for more force to be placed on the needle during the procedure. The veterinarian firmly holds the limb with one hand while advancing the needle through the incision down to the bone. After ensuring the proper orientation of the needle, the veterinarian begins advancing through the cortical bone with firm clockwise and counterclockwise rotations while maintaining proper orientation. When the needle is properly placed, it will feel solidly seated. For example, if the veterinarian is collecting from the proximal femur, the cat’s whole leg should move when the needle is fanned. If the seating does not feel proper or the needle slides down the side of the bone into the soft tissue, the veterinarian should withdraw it to the level of the cortical bone, reposition if necessary, and try again. When the needle is in the soft tissue, it is freely movable. Once the needle is firmly in the bone, the stylet is removed. If an 18-gauge blood collection needle is being used, it should be removed and a second needle placed in the same hole in the cortical bone. The anticoagulated 12-mL syringe is placed on the end of the needle, and

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the plunger of the syringe is pulled rigorously to aspirate the marrow. A sample may be obtained with the first aspiration, or several attempts may be required. If no marrow is aspirated, the stylet is replaced. If it does not go all the way in, there may be a bony plug at the end of the needle. If the stylet resumes its normal position, the veterinarian should continue advancing the needle for a short distance and try again. Once a sample appears in the syringe, no more than 1 or 2 mL of marrow is required. The syringe is removed from the needle and rocked gently to mix the sample with the anticoagulant. The marrow is then expelled onto a glass microscope slide. It should look like blood with small particles in it. The slide is then tilted to allow blood to run off onto a paper towel. What remains on the slide are the whitish to gray bone marrow spicules. These can be collected with a pipette, a microhematocrit tube, or the end of another glass slide. The sample is transferred to a slide and covered with a second slide. The sample is allowed to spread a small amount, and then the two slides are rapidly but gently slid apart. Little, if any, pressure should be applied because this may damage the cells. If a sufficiently large sample is collected, about 12 slides should be made in this manner; if not, as many slides should be made as the sample allows. These slides should be air dried and submitted to the laboratory along with a sample of peripheral blood in a lavender-top tube. The interpretation of a bone marrow sample should always be made in the light of a complete blood cell count (CBC). If the patient suffers from severe thrombocytopenia, direct pressure should be applied to the wound once the needle is removed. Aspiration of marrow allows for a cytologic evaluation, but architecture cannot be assessed. It is recommended to perform both an aspiration and a core biopsy of the bone marrow so that the procedure does not have to be repeated at a later date. A core biopsy is also recommended if there is a dry tap. Potential causes for a dry tap include myelofibrosis, myelophthisis, marrow necrosis or aplasia, and operator error. The only additional supply required for a core biopsy is tissue fixative. The veterinarian must remember to remove any cytology preparations away from the area when working with formalin. The fumes released when the vial is opened can fix the prepared slides, preventing proper staining of the cells. Core Biopsy If an aspiration of the bone marrow has been performed, the needle should still be in place. If not, the veterinarian should follow the instructions for performing an aspiration of bone marrow without aspirating any bone marrow. Collecting a core sample of bone marrow from a separate site may increase the likelihood of identifying metastatic neoplasia.71

Once the needle is seated firmly in the bone, or if it is still in place after aspiration, it is advanced another 1 to 1.5 cm, with the stylet removed, using the same rotational pressure as before. This maneuver should cut a core out of the marrow. At this point the needle need no longer be advanced. The core is broken off by several clockwise revolutions of the needle followed by several counterclockwise twists. The needle is withdrawn a short distance and advanced slightly again, this time at an angle slightly off axis. It should be twisted in both directions several times so that the bevel of the needle cuts the core off at the endosteum. The needle is removed by again rotating in both directions. The core sample should be gently pushed out of the top of the needle using the stylet. Bone marrow biopsy needles are tapered at the beveled end, and forcing the core sample through the tip will damage the sample. Once removed, the core can be rolled on a glass microscope slide for cytology if an aspirate has not been obtained. The veterinarian then places the sample into tissue fixative, remembering to remove any cytology preparations from the area before opening a jar of formalin to avoid having the fumes fix the cells on the slide. Direct pressure is placed on the wound to prevent hematoma formation in cats with severe thrombocytopenia. With a little practice and the proper supplies, which all clinics can obtain easily, the cause of unexplained changes in circulating cells may be elucidated. More specific therapy may then be possible. Other than the risks involved with an anesthetic, there are few, if any, contraindications to the procedure.

Cross-Match A crossmatch test can identify compatibility or incompatibility between the blood donor and transfusion recipient. It tests for the presence of alloantibodies, induced or naturally occurring, for which blood typing does not test. At the present time, typing for the Mik erythrocyte antigen is not readily available. Other, unknown erythrocyte antigens may be present and cause blood incompatibility. Because of the potential presence of unknown alloantibodies in feline blood, a cross-match should be performed before any transfusion, even if both donor and recipient are blood typed and a prior cross-match has indicated compatibility. The major cross-match tests for alloantibodies in the plasma of the recipient that may hemolyze the donor’s red cells. The minor cross-match tests for alloantibodies in the plasma of the donor that may attack the recipient’s erythrocytes. Autoagglutination in the major crossmatch predicts that antibodies in the recipient’s plasma will attack the donor’s red cells, likely eliciting a transfusion reaction. A minor cross-match incompatibility suggests that antibodies in the donor’s blood will attack the


recipient’s red cells. Incompatible blood should not be used for transfusions. A quick means of performing a major cross-match is to mix 2 drops of plasma from the recipient with 1 drop of anticoagulated blood from the donor on a slide at room temperature.35 The opposite will be a minor crossmatch. Development of macroscopic agglutination within a minute suggests the presence of anti-A alloantibodies in the plasma sample of the recipient (major cross-match) or donor (minor cross-match). In either case the blood is incompatible. Autoagglutination can make interpretation of the test difficult. Running a control test using saline instead of plasma may help with interpretation. For hospitals performing frequent transfusions, a standardized gel agglutination test is available for in-hospital use. Although more time consuming than the previously described method, the gel test is less vulnerable to operator interpretation error. Because it is stable, the test result can be saved and reviewed at a later time if needed.118 Two commercially available products include the DiaMed-ID cross-match gel (DiaMed, Switzerland) and the Rapid Vet-H companion animal crossmatch gel (DMS Laboratories, Flemington, New Jersey). More rigorous and time-consuming methods involving washing, centrifuging, and incubating samples have been published.25,42

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FIGURE 25-4 The “stack of coins” arrangement associated with rouleaux formation. (Courtesy Rick Cowell.)

Slide Agglutination Test A positive, properly performed slide agglutination test suggests the presence of antibody-coated erythrocytes and negates the need for performing a direct Coombs’ test. It is important to differentiate erythrocyte clumping caused by autoagglutination from that caused by rouleaux formation. These types of erythrocyte clumping are differentiated by washing the cells with saline, which will reliably break up clumps formed by rouleaux. A quick method of performing the test is to mix a drop of EDTA anticoagulated blood on a slide with 2 to 5 drops of 0.9% NaCl followed by a gross and microscopic examination of the sample.54 The “stacked coins” appearance characteristic of rouleaux formation (Figure 25-4) will disperse, whereas the random or rosette clumping of autoagglutination will not (Figure 25-5). If the test is negative, a direct Coombs’ test should be requested. An important limitation to this test is its inability to separate primary from secondary immune-mediated disease.

ERYTHROCYTE PHYSIOLOGY AND DIAGNOSTIC EVALUATION The erythrocyte is a unique cell with a singular function: to carry oxygen to the tissues. Decreased numbers of red blood cells results in decreased tissue oxygenation;

FIGURE 25-5 Macroscopic agglutination is apparent on the slide. If clumping remains after proper washing, autoagglutination would be the conclusion. (From Fry MM, McGavin MD: Bone marrow, blood cells, and lymphatic system. In McGavin MD, Zachary JF, editors: Pathologic basis of veterinary disease, ed 4, St Louis, 2007, Mosby.)

however, an excessive number of erythrocytes make blood more viscous, potentially resulting in less than optimal oxygenation. Changes in the visual appearance of erythrocytes yield clues as to the underlying disease. A change in red blood cell numbers is a sign of disease, not a disease itself. Therefore a change in erythrocyte numbers or appearance requires investigation of the etiology. The production of erythrocytes by the bone marrow is influenced by the hormone erythropoietin (EPO),

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Metarubricyte

12 Hours

10 Days

Aggregate

Punctate

Mature cell

FIGURE 25-6 Diagram depicting the progressive maturation of feline reticulocytes. Aggregate reticulocytes lose their inclusions and mature into punctate reticulocytes in approximately 12 hours. The punctate reticulocytes slowly lose their inclusions over a period of around 10 days. (From Weiser MG: Disorders of erythrocytes and erythropoiesis. In Sherding RG, editor: The cat: diseases and clinical management, ed 2, Philadelphia, 1994, Saunders.)

which is produced by fibroblasts adjacent to the renal tubules near the corticomedullary junction in response to decreased local oxygen tension.129 Increased EPO production begins within minutes of onset of hypoxia, with maximal production occurring 24 hours later. Colonyforming-unit erythrocytes in the bone marrow respond to increased concentrations of EPO by increasing production, maturation, and release into circulation of new red cells. Increasing numbers of new circulating erythrocytes will not be apparent for at least 2 or 3 days. When hypoxia is caused by anemia, immature erythrocytes are released early to the circulation. The immaturity of the released cells is proportional to the severity of the anemia. Reticulocytes are immature erythrocytes that still contain ribosomes, are larger than mature red cells, and have lower concentrations of hemoglobin. The ribosomes stain a bluish color, giving reticulocytes their characteristic blue-gray color. Their presence in circulation is responsible for the variation in cell size and color observed on a blood smear examination in regenerative anemias. Two types of feline reticulocytes are recognized: aggregate and punctate. Aggregate reticulocytes have long, linear chains of ribosomes; are larger and bluer than mature red cells; and are the less mature of the two types of reticulocytes. The ribosomes appear dark blue after staining with new methylene blue. Most of the ribosomes are removed within 12 hours as the cell matures into a punctate reticulocyte. Punctate reticulocytes have a few small dots representing the remaining ribosomes and are the color of a mature red cell. It takes up to 10 to 14 days for the remaining ribosomes to be removed and the cell to become a mature erythrocyte. Some punctate reticulocytes are present in healthy cats, and punctate reticulocytes may be present in the circulation for up to 1 month after an anemic event. It is important to realize that these two types of reticulocytes are not different cells but rather a progression in the maturation of the erythrocyte (Figure 25-6). As the anemia becomes more severe, younger reticulocytes are released in an attempt to increase the number of oxygencarrying red cells. The result is an increase in the number of aggregate reticulocytes in the circulation. Because

they mature so quickly to punctate reticulocytes, the presence of increased numbers of circulating aggregate reticulocytes suggests ongoing hypoxia. An important concept regarding feline anemia is that an increase in the numbers of aggregate reticulocytes (above the reference range for the laboratory) is required before a moderate to severe anemia is considered regenerative. Unless the anemia is mild, and the more immature aggregate reticulocytes are not required, the presence of punctate reticulocytes alone is not evidence of regeneration. In cats the absolute number of aggregate reticulocytes is a more reliable indicator of regeneration than the corrected reticulocyte percentage or the reticulocyte production index.54 EPO also stimulates hemoglobin synthesis. Feline hemoglobin is unique in that it has less affinity for oxygen than the hemoglobin found in other species; consequently, oxygen is more easily released to the tissues. This may be one explanation for why the packed cell volume (PCV) and hemoglobin concentration in the normal cat are lower than those of normal dogs.54 In a healthy cat the production and removal of erythrocytes is balanced. The life span of the normal, mature feline erythrocyte is approximately 73 days, after which they are removed from circulation by macrophages in the spleen, and the heme and iron recycled.

Quantitative Erythrocyte Parameters Erythrocytes can be classified by their size and hemoglobin concentration on the basis of quantitative parameters such as the mean corpuscular volume (MCV, the average cell size), the red cell distribution width (RDW), and the mean corpuscular hemoglobin concentration (MCHC). Macrocytosis, normocytosis, and microcytosis refer to cell size above, within, or below the reference range, respectively. The RDW is derived from the cell numbers versus cell volume histogram (Figure 25-7); an increase in RDW indicates a greater than normal variation in cell size. The RDW may be artifactually affected by the overlap in size between feline platelets and red cells. Normochromia and hypochromia refer to MCHC within or below the reference range, respectively. Hemoglobin makes up


Relative number of cells

approximately 33% of the volume of the cell. Erythrocytes cannot carry more hemoglobin in their cytoplasm than normal, so they cannot be hyperchromic. An increased MCHC is usually associated with hemolysis, either a result of disease or of improper venipuncture or sample handling. A change in any of these parameters requires a review of a blood smear for an explanation.126

MCV

Cell volume (fl)

FIGURE 25-7 The erythrocyte volume distribution histogram. The mean cell volume is represented by the vertical bar. Increased variation in cell volume (anisocytosis) causes the curve to widen, increasing the red cell distribution width (RDW). (From Weiser MG: Disorders of erythrocytes and erythropoiesis. In Sherding RG, editor: The cat: diseases and clinical management, ed 2, Philadelphia, 1994, Saunders.)

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Qualitative Erythrocyte Parameters Qualitative erythrocyte parameters are based on a blood smear evaluation. Increased variations in cell size, color, and shape are known as anisocytosis, polychromasia, and poikilocytosis, respectively. Anisocytosis is present if there is a combination of normal-size cells along with an appreciable number of larger or smaller cells. Anisocytosis may result in an increased RDW. The larger cells are often reticulocytes, although infection with the feline leukemia virus (FeLV) can result in larger cells without increased reticulocyte numbers. Polychromasia is usually due to the presence of increased numbers of aggregate reticulocytes and indicates regeneration.126 Lack of polychromasia, however, does not rule out regeneration.18 Variations in cell shape may be artifactual or due to disease (Figure 25-8). Echinocytes are crenated red cells with uniform, often pointy, projections. They are usually artifacts but are important to recognize; when the projections are viewed end on, they may appear as small rings and mimic the ring form of hemoplasmosis (e.g., Mycoplasma haemofelis). Acanthocytes are similar to echinocytes but have fewer and more rounded projections. They are frequently present in cats with hepatic disease. Erythrocyte fragments, such as schistocytes or keratocytes, are the result of cell trauma. When there are many fragments, the presence of turbulent blood flow or microangiopathic disorders such as hemangiosarcoma or disseminated intravascular coagulation (DIC) should be considered. Iron deficiency may also cause increased fragmentation.18 Spherocytes are smaller cells that are

FIGURE 25-8 Some common terms and synonyms are given beneath a drawing of selected morphologic changes in red blood cells. These illustrations are of the cell as it appears on a Wright-stained smear, except for reticulocytes and Heinz bodies, which are preferentially stained with new methylene blue. A canine erythrocyte is included for comparison purposes. (From Weiss D, Tvedten H: The complete blood cell count and bone marrow examination: general comments and selected techniques. In Willard MD, Tvedten H, editors: Small animal diagnosis by laboratory methods, ed 4, St Louis, 2004, Saunders.)

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the product of immune-mediated removal of antibodycoated parts of the erythrocyte membrane, after which the cell is reconfigured into a sphere. Because normal feline erythrocytes are small and lack central pallor, spherocytosis in this species is difficult or impossible to appreciate and identification is best left to an experienced veterinary hemocytologist. Microagglutination and rouleaux formation may be visible on blood smears. Agglutination appears as a random, disorganized clumping of cells not dispersed by the addition of saline. True autoagglutination indicates an immune-mediated disease affecting the erythrocyte. Rouleaux formation looks similar to a stack of coins (see Figure 25-4) and will disperse after the addition of saline (see Figure 25-5). Circulating monocytes may phagocytose antibody-covered red cells; this is called erythrophagocytosis. Although not observed very often, erythrophagocytosis also suggests the presence of immune-mediated red cell damage. Heinz bodies are areas of oxidatively denatured hemoglobin within the cell (discussed later). The altered hemoglobin is pushed off to one side and often seen as a projection off the surface of the cell membrane. Heinz bodies stain dark with new methylene blue stain, somewhat clear with Diff-Quik, and the same as the cytoplasm with Wright’s stain18 (Figures 25-9 and 25-10). Howell–Jolly bodies are intracytoplasmic remnants of nuclear material found in erythrocytes that may mimic red cell parasites. Blood smear examination is an essential part of a CBC, particularly when it comes to evaluating the erythron. There is no other way to identify the morphologic changes in red cells that can yield clues to the etiology of erythrocyte disease. Without a blood smear evaluation, a CBC is incomplete.

FIGURE 25-9 Heinz bodies appear as dark-stained structures in this new methylene blue–stained smear of feline blood. (Courtesy Rick Cowell.)

Blood Types

FIGURE 25-10 Heinz bodies stain pale on a Wright-stained feline

There are three well-known, clinically important blood groups in cats: A, B, and AB. Another potentially important group called Mik has recently been identified.124 The blood groups are genetically determined erythrocyte surface antigens. The A-allele is dominant over the b-allele so that cats with genotypes A/A and A/b will be type A, whereas only the homozygous b/b will have the type B phenotype. A third allele, Ab, occurs rarely and is said to be recessive to the A-allele and dominant to the b-allele, although controversy exists regarding the exact inheritance. A and B antigens are produced on the same red cell only in cats with the genotypes Ab/b or Ab/Ab.35 A more in-depth discussion of feline blood types has recently been published.7 Blood typing can be performed by a diagnostic laboratory using various methods or in the hospital with a card typing system (DMS RapidVet-H [feline], DMS Laboratories). If the card-typing system is used, type AB and type B results should be confirmed by a referral laboratory because some cross-reactions

have been known to occur.104 A recently introduced option for patient-side blood typing is the gel column agglutination test (DiaMed-Vet feline typing gel, DiaMed, Switzerland). This test is easier to interpret than the card method, although it requires a specially designed centrifuge that may be cost prohibitive in some settings.118 An evaluation of various blood typing methods for the cat concluded that the gel column test is reliable compared with the gold standard, the Penn tube assay.104 Genetic blood typing using buccal mucosal swabs is available from certain labs and may allow breeders to identify heterozygous type A cats (A/b). Breeding two of these cats together would be expected to produce 25% type B kittens (b/b) and 50% heterozygous type A kittens (A/b). However, genetic typing cannot distinguish between type A and type AB.

blood smear. They may be seen projecting from some erythrocytes, whereas others appear as pale areas in the erythrocyte, as shown by the arrows. (Courtesy Rick Cowell.)

Understanding feline blood groups is important because, unlike other mammals, cats produce naturally occurring antibodies, called alloantibodies, against the erythrocyte antigens not present on their own cells. The kitten produces these alloantibodies at approximately 2 to 3 months of age, as a result of exposure to antigens on plants, bacteria, or protozoa that are structurally similar to red cell antigens. No alloantibodies are produced against antigens that are similar to self-antigens, and no previous exposure to blood products (transfusions) is necessary to produce the alloantibodies. Knowledge of this system is important in the prevention of transfusion reactions and neonatal isoerythrolysis. Cats with type B blood have anti-A antibodies with strong hemolytic potential. Even a small volume of type A or AB blood administered to a type B cat can cause potentially life-threatening hemolysis within minutes of the transfusion.36 Hemolysis of type B blood administered to a type A cat will result in a reduced life span of the transfused erythrocytes, but severe reactions are uncommon.42 Ingestion of colostrum from a type B queen by a type A newborn results in absorption of anti-A alloantibodies and subsequent rapid hemolysis of the kitten’s erythrocytes. This is known as neonatal isoerythrolysis and occurs only when type A or AB kittens are born to a type B queen. The distribution of blood types varies by geographic region and breed (Tables 25-1 and 25-2). Type A is the most common type among cats. There is, however, a geographic variation in the number of type B domestic shorthair cats. More than 10% of the domestic shorthair cats in Australia, France, Greece, India, Italy, Japan, Turkey, and some regions of England are type B. Distribution of blood types among pedigreed breeds does not vary as much by location because of the international exchange of breeding cats. More than 30% of British Shorthair cats, Cornish and Devon Rex cats, and Turkish Angora or Vans have type B blood. In contrast, Siamese and related breeds are almost exclusively type A. Ragdoll cats appear to be unique with regard to blood types. Approximately 3% of Ragdoll cats are discordant when genotyping is compared to serology, necessitating further investigation in this breed.7 The AB blood type is very rare, and the frequency of the Mik blood type is unknown. The presence of erythrocyte antigens in addition to the A and B groups may explain why transfusion compatibility is not guaranteed by blood typing; cross-matching is recommended before any transfusion.124 Breeding queens, along with blood donors and, if possible, blood recipients, should be blood typed.

Clinical Evaluation of Cats with Anemia Anemia is defined as a decrease in the number of circulating red blood cells, the PCV, or the hemoglobin concentration. Because anemia is a sign of disease, making


651

TABLE 25-1 Geographic Distribution of Blood Type Frequencies in Domestic Cats Region US (British Virgin Island)

Number of Cats 32

A%

B%

100

0

AB% 0

US (New England)

69

100

0

0

Finland

61

100

0

0

Hungary (Budapest area)

73

100

0

0

432

99.77

0.23

0

US (82% Philadelphia area)

US

1072

99.72

0.28

0

Switzerland

1014

99.6

0.4

0

Japan US (Northeast)

238

89.9

0.9

9.2

1450

99.7

0.3

0

US (North Central)

506

99.4

0.4

0.2

US (Southeast)

812

98.5

1.5

0

US (Southwest)

483

97.5

2.5

0

US (West Coast)

812

94.8

4.7

0

Germany (Berlin and Brandenburg area)

372

98.7

1.1

0.3

Denmark (Copenhagen area)

105

98.1

1.9

0

Argentina (Buenos Aires area)

76

96.1

2.6

1.3

172

94.8

2.9

2.3

Scotland

Brazil (Rio de Janeiro area)

70

97.1

2.9

0

Austria

101

97

3

0

England (Manchester)

477

97

3

0

Portugal (North)

147

89.1

4.1

6.8

Netherlands

95

Spain (Barcelona area)

100

Germany (Gieben area)

404 97

Gran Canaria

94.8

4.2

0.1

94

5

1

94.1

5.9

0

88.7

7.2

4.1

Italy (Piedmont region)

122

86.9

7.4

5.7

UK (Edinburgh area)

139

87.1

7.9

5

Italy (Lombardy region) Japan (Tokyo)

57 207

89.5 90

8.8 10

1.7 0

Italy (Tuscany region)

363

87.1

12.9

0

France (Paris area)

350

85

15

0

Greece

207

78.3

20.3

1.4

Turkey

301

73.1

24.6

2.3

1895

73.3

26.3

0.4

Australia (Brisbane area) England (Southeast)

105

67.6

30.5

1.9

Australia (Sydney region)

187

62

36

1.6

US, United States; UK, United Kingdom. From Bighignoli B, Owens S, Froenicke L, et al: Blood types of the domestic cat. In August JR: Consultations in feline internal medicine, ed 6, St Louis, 2010, Elsevier.

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TABLE 25-2 Worldwide Frequencies of Blood Types A, B, and AB in Different Breeds Breed

Country

Number of Cats

A%

B%

AB%

Abyssinian

US

230

86.5

13.5

0

Abyssinian

US

194

79.9

20.1

0

Birman

US

216

82.4

17.6

0

British Shorthair

UK

121

39.7

58.7

1.6

British Shorthair

US

85

41.2

58.8

0

British Shorthair

Germany

33

54.5

45.5

0

British Shorthair

Germany

35

71.4

28.6

0

British Shorthair

Denmark

30

66.7

33.3

0

Burmese

Australia

30

93

3

3

Burmese

US

25

100

0

0

Chartreux (Kartäuser)

Germany

27

77.8

18.5

3.7

Devon Rex

US

288

50.3

49.7

0

Devon Rex

US

100

57

43

0

Devon Rex*

Australia

71

45

54

1.4

Himalayan

US

35

80

20

0

Maine Coon

Germany

25

96

4

0

Persian

US

230

90.4

9.6

0

Persian

US

170

75.9

24.1

0

Persian

Germany

157

91.7

7.6

0.6

Persian

Denmark

56

96.4

3.6

0

Persian

Italy

38

97.4

2.6

0

Ragdoll

Italy

36

72.2

8.3

19.4

Scottish Fold

US

27

85.2

14.8

0

Siamese

US

99

100

0

0

Siamese

Germany

46

100

0

0

Siamese

Italy

26

96.2

3.8

0

Somali

US

27

77.8

22.2

0

Tonkinese

US

31

0

0

Turkish Angora

Turkey

28

53.6

46.4

0

Turkish Van

Turkey

85

40

60

0

100

US, United States; UK, United Kingdom. *Also includes hybrids. From Bighignoli B, Owens S, Froenicke L, et al: Blood types of the domestic cat. In August JR: Consultations in feline internal medicine, ed 6, St Louis, 2010, Elsevier.

appropriate therapeutic decisions depends on identifying the underlying etiology. As with any disease, the first, most important steps include taking a thorough history and performing a detailed physical examination. The signs associated with anemia are often nonspecific. They are the result of decreased oxygencarrying capacity of the blood, decreased blood volume, or the underlying disease. The severity of the signs is related to the rate of onset of the disease and

the severity of the anemia. Most anemic cats are presented for evaluation of weakness, lethargy, or anorexia. Bleeding may or may not be obvious, depending on its location. The owner should be asked about previous illnesses in addition to the duration and course of the present illness. Exposure to drugs or toxins, such as acetaminophen or onions, as well as the outdoors is important to ascertain. Cats that go outside have a greater risk of trauma and increased exposure

to other cats and thus infectious diseases such as retroviral infections. Outdoor cats are also more likely to be exposed to fleas or ticks, possible vectors for important infectious causes of anemia. Discolored urine from hemoglobinuria must be distinguished from hematuria. The geographic location of the cat and its travel history may provide clues as to the cause of the disease. The blood type of a neonate’s parents may be critical information if an ill day-old kitten exhibits signs of neonatal isoerythrolysis. Other signs, such as polyuria and polydipsia, can indicate the presence of chronic diseases. Gastrointestinal signs may lead to the consideration of chronic blood loss or inflammatory disease. Recent surgery or trauma may result in blood loss anemia. Mucous membrane pallor is a common physical finding. If hemolysis is present, the mucous membrane color may be icteric. Decreased peripheral perfusion from causes such as shock or congestive heart failure may also cause pallor, whereas hepatic failure can result in icterus. Evidence of volume contraction, such as tacky mucous membranes or prolonged skin tenting, may be present. Remember that older cats lack skin elasticity and may have a prolonged skin tent even if well hydrated. A moderate decrease in erythrocyte numbers leads to decreased blood viscosity and tissue hypoxia. A soft murmur may be present because turbulent blood flow is directly related to decreased blood viscosity. Hypoxia leads to vasodilation, resulting in an increased heart rate in an attempt to increase cardiac output and oxygen delivery to the tissues. Tachypnea is also a common finding. Fleas or ticks may be found during a detailed examination of the skin, particularly in young animals. Fever may be present in cats with infectious causes of anemia, and splenomegaly is a common finding in cats with hemolysis of any etiology. Small kidneys may be appreciated in a cat with chronic renal disease. Any abdominal mass should be noted for further evaluation. Petechial or ecchymotic hemorrhages indicate bleeding from hemostatic disorders, whereas bleeding wounds may be evidence of recent trauma. Discolored urine may stain the perineum of a longhaired white cat. The severity of the clinical signs shown by anemic cats is more often related to the chronicity than degree of anemia. Chronic anemia allows the cat to adapt physiologically and behaviorally to decreased tissue oxygenation, whereas acute anemia does not allow this adaptation to take place. When presented with a pale cat, the first diagnostic step is to measure the PCV and total plasma protein concentration. If the PCV is normal, the veterinarian should look for other causes of pallor. If the PCV is low, the next step is to determine if the anemia is regenerative or nonregenerative (Figure 25-11). The single, best indicator of regeneration is an increase in the absolute aggregate reticulocyte count.126 The severity of anemia should


653

not be assessed until any volume deficits have been corrected. A CBC with a platelet and aggregate reticulocyte count and a blood smear examination will provide evidence of regeneration as long as sufficient time has elapsed since the initial insult. If the protein content is low, acute bleeding should be suspected. Additional tests to consider include a slide agglutination test, a direct Coombs’ test, testing for retroviral infection, and a polymerase chain reaction (PCR) test for hemotrophic Mycoplasma. Other tests to consider include thoracic and abdominal radiography and abdominal ultrasonography, a serum biochemical profile, urinalysis, and coagulation profile. If the anemia is nonregenerative, evaluation of the bone marrow may be required to make an etiologic diagnosis. An attempt should be made to biopsy any masses identified during the evaluation. Examination and sampling of the gastrointestinal mucosa may be required to diagnose causes of blood loss from this system. To differentiate anemia of inflammatory disease from iron deficiency anemia, serum iron, ferritin, and transferrin (total iron-binding capacity) will have to be measured. By following a logical, ordered diagnostic approach to anemia, the veterinarian can often make an etiologic diagnosis, allowing specific therapy to be instituted.

SUPPORTIVE CARE FOR CATS WITH ANEMIA Specific treatment for an anemic cat can be attempted only after the cause has been identified. Until that time, supportive care is essential. Bleeding should be controlled to prevent further blood loss. Home care while awaiting test results may be adequate if the anemia is mild. Avoiding stressful situations, such as excessive handling, barking dogs, or fractious cats, will help reduce oxygen requirements. Correction of volume contraction may improve the patient’s attitude and appetite. Intravenous fluids may be necessary if volume depletion is significant. Concerns regarding reduction of oxygencarrying capacity by reducing the PCV with fluid therapy are probably unfounded. The total body hemoglobin and oxygen-carrying ability remains unchanged. However, cats with low plasma protein levels are at risk of edema formation as a result of dilution by aggressive fluid administration. Cats with severe signs related to the anemia, such as respiratory distress or extreme weakness, may require a transfusion. Oxygen administration adds little to the ability to improve tissue hypoxia in anemic patients.35 The low solubility of oxygen in plasma results in a very small increase in the dissolved oxygen content when 100% oxygen is inhaled. In addition, the stress a cat may experience during oxygen administration may be deleterious.

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Anemia

Adequate reticulocytosis

Yes

No

MCV

MCV, MCHC

High or normal

Low

Low MCV and MCHC

Low MCV Normal MCHC

Likely hemolysis

Possible iron deficiency (look for red cell fragments)

Blood smear examination

Serum iron Ferritin TIBC

Normal MCV and MCHC

High MCV Normal MCHC

Acute anemia Chronic renal failure Anemia of inflammatory disease FeLV infection Myelophthisis Histoplasmosis Immune-mediated aplastic anemia Idiopathic aplastic anemia

FeLV infection Agglutination artifact

Bone marrow exam Red cell fragments

Microangiopathic hemolysis or iron deficiency

Erythrophagocytosis

Autoagglutination

Immune-mediated hemolysis

Heinz bodies

Mycoplasma or cytauxzoon

No obvious cause found

Possible occult mycoplasma, immune-mediated hemolysis, or acute hemorrhage

FIGURE 25-11 An algorithm that may be useful in evaluating a cat with anemia. Clinical judgment should be used when following any algorithm because an individual cat may not follow the rules. Further testing should be performed as needed.

Basic Feline Transfusion Medicine The indications for the use of blood products are many and include hemorrhage, anemia, hemostatic defects, and hypoproteinemia.42 Many blood products are available or may be prepared, although most veterinary hospitals have hospital cats to use as needed for whole blood donation. Many blood products are available and have specific uses. Fresh, whole blood contains erythrocytes, platelets, clotting factors, and serum proteins. Storage of whole blood results in the loss of platelets in 2 to 4 hours and clotting factors V and VIII within 24 hours of collection.42 Packed red cells maintain the oxygen-carrying capacity of whole blood in a smaller volume. This product may be used when volume expansion is unwanted, such as anemic cats with heart disease. Fresh frozen plasma

contains albumin and all the clotting factors and is used in cats hemorrhaging from coagulation disorders such as liver failure, DIC, or anticoagulant rodenticide toxicity. The use of plasma products to treat hypoalbuminemia is beneficial only in the short-term because transfused albumin rapidly equilibrates with the extravascular space.25 The addition of synthetic colloids may prolong the oncotic effects of a plasma transfusion in these cats.42 Platelet-rich plasma is indicated for cats bleeding from platelet deficiency or dysfunction. Sources for products other than fresh whole blood include a local emergency or referral hospital or a regional veterinary blood bank. Oxyglobin (Biopure, Cambridge, Mass.) is a bovine hemoglobin product containing 130 g/L of hemoglobin that has been licensed for use in dogs. Because no cell membranes are present, there is no antigenicity and the product can be used when compatible

blood is unavailable. However, availability of the product has been erratic, and at the time of this writing, it is not available. Donor cats should be healthy larger cats with a PCV above 35% and fully vaccinated.42 Donors should be blood typed before blood is collected. No abnormal morphologic cell types should be present, and platelet numbers should be in the reference range. The American College of Veterinary Internal Medicine (ACVIM) consensus statement on screening blood donors recommends testing donor cats for M. haemofelis; Candidatus Mycoplasma haemominutum; FeLV antigen; feline immunodeficiency virus (FIV) antibody; and, possibly, Bartonella infections.122 Cats that test positive for FIV antibody should be excluded even if vaccinated against the disease because development of reliable tests to discriminate between antibodies present from a natural infection versus vaccination has been difficult. Heartworm disease cannot be transmitted by blood donation, insofar as the larvae require passage through the mosquito to become infective. Screening for cytauxzoonosis is unnecessary because most cats with the disease are ill. Toxoplasmosis and feline infectious peritonitis have not been documented to be transmitted by transfusion.122 Donor cats should be kept indoors to reduce the risk of exposure to infectious diseases. Healthy cats can donate 10% to 20% of their total blood volume without adverse effects. A cat’s total blood volume is approximately 66 mL/kg. For example, approximately 50 mL of blood (10 mL/kg) can be collected from a 5-kg cat no more often than every 4 to 6 weeks. Subcutaneous fluids should be administered at 2 to 3 times the volume of donated blood. Collection of more than 70 mL of blood from a 5-kg cat can lead to hypovolemia, and the volume should be replaced with intravenous fluids. Many donors resent sitting still long enough to have this volume of blood removed and may require sedation or general anesthesia. For the treatment of anemia, there are no established levels of PCV below which a cat requires a blood transfusion. The decision to transfuse is instead based on the condition of the patient and assessment of the potential benefits weighed against the risks. Indications that an anemic cat may require a transfusion include respiratory distress, weak pulses, or severe weakness.126 Both the donor and recipient should be blood typed. Even if the blood types are known, cross-matching should be performed before blood administration to prevent incompatible transfusions caused by untested or unknown erythrocyte antigens such as Mik. The half-life of appropriately matched red blood cells in the cat is 29 to 39 days, but for mismatched transfusions the half-life may be a matter of hours. When type B blood is transfused to a type A cat, the life span of transfused red blood cells is only 2 days. When type A blood is transfused to a type B cat, in addition to a potentially severe and fatal


655

reaction, the life span of the transfused cells is only a few hours. A cross-match should be performed again if more than 4 days have elapsed since the last transfusion from the same donor or if another donor is used. Blood collected for immediate use can be anticoagulated with heparin. Heparin has no preservative properties, and heparinized blood should be used within 8 hours.42 If blood is to be stored for a longer period, citrated anticoagulants should be used. The required blood volume can be collected into a large syringe. If stored blood is used, it should be warmed to room temperature. Blood is administered through a filter connected to a dedicated intravenous line or a line without the presence of calcium-containing fluids. The transfusion is usually administered using gravity flow, although an infusion pump can be used if the manufacturer has stated that it can be used for this purpose. Bacterial contamination is a potential risk, and aseptic techniques for blood collection should be followed. Blood products can be administered intravenously or intraosseously in small patients. For severely anemic cats the goal of transfusing whole blood is to ameliorate life-threatening decreases in PCV. This can be accomplished by attempting to raise the PCV to over 20%.42 The volume of whole blood required to increase the PCV to a desired level can be calculated by using the following formula: 70 × recipient’s body  desired PCV − recipient PCV  ×  weight in kg onor PCV do  The volume to be delivered is equal to 70 times the recipient cat’s weight in kilograms times the difference between the desired and the patient’s PCV divided by the donor’s PCV. Administer 2 to 3 mL of typed and cross-matched blood over 5 minutes and watch for evidence of adverse reaction, such as an increased body temperature, increased heart or respiratory rate, or a prolongation of the capillary refill time. Whole blood can be administered at 10 mL/kg/hour in a normovolemic cat or 2 to 4 mL/kg/hour in a cat with heart disease. The recipient should be constantly monitored for increased heart and respiratory rate, fever, and any signs of adverse reaction (e.g., vomiting) until the transfusion is complete. The transfusion should be completed within 4 hours to avoid bacterial contamination and the PCV measured 1 to 2 hours after completion. For cats with incompatible cross-matches or in cases when blood products are unavailable, Oxyglobin (Biopure, Cambridge, Mass.) may be administered at a dose of 5 to 15 mL/kg at a rate of 5 mL/kg/h. Because the product contains no red cells, the hemoglobin concentration is measured to assess the effectiveness of the treatment. Oxyglobin has high colloidal properties, and cats are prone to volume overload with its use. Adverse reactions in cats included vomiting, pulmonary edema,

656


and pleural effusion. In one study of cats receiving Oxyglobin, 20% of cats developing respiratory signs required furosemide or supplemental oxygen during or after treatment. Most of these cats had preexisting heart disease.32 The lower dose should be used cautiously in cats with cardiac disease. The oxygen-carrying effects of Oxyglobin last up to 3 days in circulation.42 Adverse effects of blood transfusions can be immunologic reactions to incompatible blood or nonimmune events and may occur within 1 or 2 hours after the transfusion begins. Occasionally, they may be seen up to 48 hours later.42 In a study of 126 cats that received blood transfusions, 11 cats (8.7%) suffered acute reactions.53 Multiple red blood cell transfusions (either whole blood or packed red blood cells) are also well tolerated in cats and may be critical for survival of some severely ill patients.98 Immune-mediated reactions can include hemolysis, allergic reactions, fever, or graft-versus-host reactions. Bacterial contamination of the blood product, hemolysis, hypocalcemia (from citrate toxicity), hypothermia, hyperammonemia, and volume overload are examples of nonimmune adverse reactions. In either case, the life span of the transfused erythrocytes may be shortened. Some reactions are severe enough to cause death. Despite the best efforts to prevent them, transfusion reactions may still occur. Depending on the severity, therapy may include glucocorticoids, epinephrine, crystalloid intravenous fluids, and discontinuation of the transfusion. Fever is usually mild, requiring no treatment. Furosemide should be administered if volume overload occurs. To prevent hypothermia, the blood product can be warmed to no more than 37° C. If the reaction is relatively mild, the transfusion can be restarted at a slower rate. Cross-matching blood is the best means of preventing immune-mediated transfusion reactions even if the blood type is known for both cats. It is also imperative that blood be collected and administered as aseptically as possible and that cats receiving blood products be carefully monitored.

ERYTHROCYTE DISORDERS Regenerative (Responsive) Anemia Definition Regenerative anemia is recognized by a decrease in the PCV, erythrocyte count, and hemoglobin concentration, along with evidence of bone marrow production of new erythrocytes. The presence of polychromasia or increased reticulocyte numbers (or both) is evidence that the bone marrow has increased production of new cells. Regenerative anemia is recognized in a cat with blood loss of longer than 4 to 7 days or with destruction (hemolysis) of erythrocytes faster than they can be replaced. Blood loss anemia can be caused by gastrointestinal bleeding;

bleeding secondary to vessel damage from trauma or surgery; bleeding associated with hemostatic defects such as platelet or coagulation disorders; or the early stages of flea or tick infestations. Red cell destruction has myriad potential causes, including primary immunemediated mechanisms; immune-mediated destruction secondary to infectious disease or drug administration; direct damage from hemoglobin oxidation or blood parasites; congenital defects resulting in erythrocyte membrane fragility; or exposure to alloantibodies from incompatible transfusions or neonatal isoerythrolysis. An anemia is regenerative if there are adequate numbers of circulating aggregate reticulocytes for the degree of anemia. An anemia may not appear regenerative for 4 to 7 days, the time it takes the bone marrow to produce and release new aggregate reticulocytes. History and Physical Examination The signs associated with anemia are often nonspecific and have been covered in a previous section of this chapter (Clinical Evaluation of Cats with Anemia). Diagnostic Plans A regenerative anemia of greater than 5 days’ duration would be expected to show specific changes in a CBC. All cats suspected of being anemic on the basis of the history and clinical signs should have blood drawn for a CBC to include erythrocyte indices, a reticulocyte count, and a blood smear evaluation. The presence of pinpoint hemorrhages (petechiae) should prompt a platelet count. A CBC from a cat with a regenerative anemia should reveal evidence of a reduced erythrocyte mass such as a decreased PCV, red blood cell count, and hemoglobin concentration. The presence of reticulocytes, which are larger and have less hemoglobin than mature erythrocytes, should result in an increased MCV and decreased MCHC. This is why regenerative anemias are classified as macrocytic (increased MCV) and hypochromic (decreased MCHC). Examining a properly made blood smear is very important. The blood smear evaluation may reveal populations of cells of different sizes (anisocytosis) and colors (polychromasia). Morphologic changes may also be present that may give clues as to the cause of the anemia. Blood parasites and Heinz bodies may be seen on a blood smear. Because of the small size of feline erythrocytes, recognizing spherocytes in this species is difficult and is best left to an experienced veterinary cytopathologist. Microscopic agglutination and rouleaux formation can be appreciated when looking at a blood smear. The presence of a population of immature erythrocytes will increase the RDW, and a histogram of cell size versus numbers may contain two peaks representing two populations of cells—mature and immature. If the anemia has not been present long enough, few reticulocytes will be in the circulation and the red cell indices are likely to be within

the reference range for the laboratory. It may be necessary to repeat a CBC at a later date to reveal regeneration. After recognizing a regenerative anemia, the veterinarian must decide if the anemia is due to hemorrhage or to hemolysis. Coagulation parameters and, if not part of the initial CBC, a platelet count may illuminate the cause of unknown bleeding. Endoscopic examination may be required to identify causes of gastrointestinal blood loss. Radiography of the thorax and an abdominal ultrasound examination should be performed to look for the presence of an effusion or mass. Congenital or acquired coagulopathy or trauma may result in a hemorrhagic effusion. A mass lesion may indicate the presence of neoplasia that could result in a secondary immunemediated event. An abdominal radiograph may reveal the presence of a metallic foreign body in the gastrointestinal tract. Such a foreign body may be a zinccontaining coin, suggesting a possible nonimmune cause for the hemolytic anemia. A slide agglutination test should be performed on a washed or saline diluted EDTA blood sample. If there is no obvious agglutination on gross examination of the slide, a microscopic exam should be performed. Because both test for the presence of antibodies coating the erythrocyte, a direct Coombs’ test is unnecessary if the slide agglutination test is positive. If the slide agglutination test is negative, a direct Coombs’ test should be performed. Occasionally, FeLV will cause immune-mediated hemolysis. Testing for FeLV antigen is recommended in cats with a regenerative anemia, as is a PCR test for hemotrophic mycoplasma DNA. Acute Blood Loss Early in the course of blood loss, before reticulocytes can be produced and released, the anemia may appear nonregenerative. The physiologic response to volume loss is to shunt blood away from the skin and spleen to protect the heart, brain, and viscera.34 Pallor seen in this situation is not due to anemia but to decreased blood flow to the mucosa. During and immediately after significant blood loss, the PCV may remain normal, insofar as there is loss of both erythrocytes and plasma. A shift of fluid from the interstitial to intravascular space occurs within 12 to 24 hours, diluting the erythrocytes.129 The result is a decrease in the PCV and total protein concentration. These decreases occur earlier if intravenous fluids have been administered. Erythrocyte morphology at this point will be normal, as will the MCV and MCHC. For 3 to 5 days, the anemia will appear nonregenerative and the diagnosis of a blood loss anemia is made on the basis of suspicion, history, physical findings, and a decreased total protein concentration. Once sufficient time has elapsed, reticulocytes appear and the anemia becomes regenerative. If the bleeding is controlled, the transient increase in aggregate reticulocyte numbers is followed by a rise in the number of punctate reticulocytes as


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the aggregate ones mature.34 If clinical signs are sufficiently severe, a whole blood transfusion should be considered. If the cause of the bleeding is not determined or controlled, loss of iron stores will lead to an iron deficiency anemia. Gastrointestinal bleeding should be considered if a cause for the blood loss is not obvious. Bleeding gastrointestinal tumors, inflammatory bowel disease, gastric ulcers from overzealous use of nonsteroidal antiinflammatory drugs (NSAIDs), and gastrointestinal parasitism are all potential causes of external blood loss.34 Urinary blood loss is unlikely to cause depletion of iron stores.129 Young kittens infested with fleas can experience significant blood loss, insofar as 100 fleas can consume approximately 1 mL of blood daily.34 This represents about 10% of a 1-kg kitten’s blood volume over a 1-week period. Immune-Mediated Hemolysis Immune-mediated hemolytic anemia (IMHA) occurs when an immune response is directed against antigens on erythrocytes, leading to their removal by the mononuclear phagocyte system of the spleen (extravascular hemolysis) or complement-mediated lysis (intravascular hemolysis). If the immune-mediated event is associated with another disease, it is a secondary IMHA. Infectious or inflammatory disease may lead to secondary IMHA, as might neoplasia or drug administration. When no underlying cause can be discerned, it is termed primary IMHA. Dysregulation of the immune system results in a loss of self-tolerance. Antibodies may be formed against erythrocyte antigens (type II hypersensitivity), against a non-erythrocyte antigen attached to the red cell surface (type III hypersensitivity), or an antibody may be produced against an unassociated antigen that is similar to an erythrocyte antigen. Alloantibodies present in transfused blood or in colostrum from a type B queen ingested by a type A kitten may lead to immune-mediated hemolysis. Some erythrocyte antigens are hidden and exposed to the immune system only after the cell membrane has been damaged. New antigens that cross-react with red cell antigens or attach to the red cell membrane may be released into circulation by infection or inflammation.34 The antibodies involved in the immune process are usually IgG, although IgM can be present alone or with IgG. Macrophages of the mononuclear phagocyte system have receptors for the Fc portion of the IgG antibody but not for IgM. Fc receptors are proteins on the surfaces of cells such as macrophages and neutrophils that contribute to the protective functions of the immune system. Fc receptors bind to the Fc portion of antibodies attached to pathogens or infected cells and stimulate the activity of phagocytic or cytotoxic cells. The antibody-coated cells are removed after antibody binds to the receptor on the macrophage, mostly in the red

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pulp of the spleen. The result is extravascular hemolysis. Complete phagocytosis may not occur, and only a portion of the membrane may be removed. The cell’s volume-to-surface-area ratio is reduced, and the cell becomes spherical. Spherocytes are less able to deform, making passage through the spleen more difficult. Because of the nonsinusoidal nature of the feline spleen (see the section on splenic diseases later in this chapter), less cell deformability is required for cells to pass through, and decreased numbers of spherocytes are trapped and destroyed than in dogs. Splenic macrophages also have receptors for complement. If a sufficient quantity of IgG antibodies coat the cell membrane, complement may also bind to the erythrocyte. The presence of complement on the cell membrane increases the efficiency of erythrocyte removal. If a sufficient number of the antibodies are IgM, complement-mediated lysis can occur, resulting in intravascular hemolysis. However, none of the 19 cats with primary IMHA in one study had intravascular hemolysis despite the presence of IgM in 8 of the cats.57 Cats with IMHA, whether primary or secondary, will exhibit signs related to the anemia. These can include anorexia, lethargy, weakness, or respiratory difficulties. Additional signs as a result of the underlying disease may be present in cats with secondary IMHA. Most of the cats with primary IMHA are young adults. In the previously mentioned report of 19 cats with primary disease, six were younger than 2 years old; the median age for all 19 cats was 2 years.57 Eleven of the cats were male, and eight female. Cats with secondary disease will have a signalment related to the underlying disease. Physical changes that might be present include pale or icteric mucous membranes, tachycardia, tachypnea, or splenomegaly as a consequence of increased processing of damaged erythrocytes. Tachypnea and tachycardia are attempts at compensating for the decreased oxygencarrying capacity of the anemic patient; pulmonary thromboembolism, so common in dogs with IMHA, is rare in cats.57 Splenomegaly occurs in many nonimmune disorders causing hemolysis as the organ attempts to deal with the increased numbers of damaged red cells. Body temperature is likely to be normal unless the patient is moribund, in which case hypothermia may be noted. A systolic murmur may be heard during auscultation of the thorax. Diagnosis of IMHA can be frustrating. There are many mechanisms causing hemolysis that do not involve the immune system. Distinguishing primary from secondary IMHA is important because therapy may be different. With aggressive diagnostic investigation, an underlying cause is often found. Two sources state that primary IMHA is rare in cats.34,75 However, Kohn and coworkers57 found that of 23 anemic cats with a positive Coombs’ test or persistent erythrocyte agglutination, an underlying cause was identified in only four patients

after an extensive workup. Put another way, 19 of the 23 Coombs’-positive cats had primary IMHA. To make a diagnosis of primary IMHA, other causes of hemolysis must be eliminated. A CBC with reticulocyte and platelet counts, serum biochemical profile, and urinalysis should be performed. The cat’s retroviral status should be ascertained and a PCR test for M. haemofelis DNA should be run. Thoracic radiography and an abdominal ultrasound examination should be performed to rule out the presence of potential bronchial infections, or thoracic or abdominal masses. A bone marrow evaluation may be useful when a regenerative response to the anemia is equivocal. Specific immunodiagnostic tests such as a slide agglutination test and a direct Coombs’ test should be performed. If the hemolysis is severe enough and the anemia is not peracute, there should be evidence of regeneration in the CBC report. Increased numbers of aggregate reticulocytes should be present. Polychromasia and rubricytosis (nucleated red blood cells) may be present. The hallmark of IMHA in dogs, spherocytosis, is unlikely to be identified. The PCV may be surprisingly low for the condition of the patient; cats seem to tolerate a lower PCV than dogs.57 The lower the PCV, the higher the aggregate reticulocyte count should be. If the reticulocyte count is not appropriate for the degree of anemia, it may be nonregenerative. In this case an immune response directed at erythrocyte precursors in the bone marrow might be considered. Another difference from dogs is the lack of leukocytosis or neutrophilia with left shift in cats with primary IMHA. In the aforementioned study by Kohn and coworkers57 17 of the 19 cats with primary IMHA had a white cell count within the reference range. The platelet count should be within the reference range, too. Evans syndrome, a combination of immune-mediated damage to both erythrocytes and platelets, is rare in cats. Although evidence of DIC is common in dogs with IMHA, it is uncommon in cats. Before convicting a cat with anemia of also having thrombocytopenia on the basis of an automated cell count, a blood smear should be examined to determine whether platelet clumping is present. The smear examination will also allow identification of intraerythrocytic parasites or morphologic changes in the erythrocyte that may suggest causes of anemia other than IMHA. There are no pathognomic changes for IMHA in the biochemical profile. Anemia may cause hepatic centrilobular hypoxia, hepatocyte injury, and subsequent increases in serum alanine transferase (ALT) activity. Hyperbilirubinemia and hyperproteinemia may be present. Volume contraction may be reflected by azotemia, which is likely prerenal in cats with primary IMHA. Other changes may be present if there is an underlying disease (secondary IMHA). Any thoracic or abdominal masses should be biopsied. An airway wash with


cytology and culture might be attempted in cats with peribronchial thickening. The direct Coombs’ test detects the presence of antibodies or complement on the red cell surface. A positive test is consistent with, but not necessarily diagnostic for, IMHA. However, a diagnosis of IMHA should include a positive direct Coombs’ test.34 False-negative tests are unlikely. In the study by Kohn and coworkers, 78 cats with anemia had a direct Coombs’ test performed and 55 were negative, all of which had nonimmune etiologies identified as causing the anemia; an additional 14 cats without anemia were also direct Coombs’ test negative.57 The direct Coombs’ test may become negative after a patient with IMHA enters remission, although a few days of immunosuppressive therapy is unlikely to cause a negative test.34 A limitation of the test is the inability to differentiate between primary and secondary IMHA. A properly performed slide agglutination test may detect anti-erythrocyte IgM or large quantities of anti-erythrocyte IgG coating the erythrocytes. Autoagglutination must be distinguished from rouleaux formation by proper washing or dilution of the blood on the slide. A direct Coombs’ test is unnecessary if the slide agglutination test is positive because they both test for anti-erythrocyte antibodies; autoagglutination is considered indicative of IMHA.57 Autoagglutination may artifactually increase the MCV because clumps of cells are counted as one. Therapy for IMHA depends on the cause and severity of the anemia and must be tailored to the individual. Removal of an underlying cause or trigger will help bring secondary IMHA under control. If an infection, such as M. haemofelis, is thought to be contributing to the disorder, use of appropriate antibiotics is required. Surgical drainage of any fight-wound abscesses or removal of potentially neoplastic masses may be necessary. Removal of nonessential drugs, particularly those known to induce an immune response, may eliminate a potential trigger for the immunemediated process. Supportive measures should not be forgotten. Volume expansion in a severely ill cat will improve organ

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perfusion. Concerns regarding exacerbating hypoxia by decreasing the PCV with intravenous fluids are unwarranted. Although the PCV may decrease, the total amount of hemoglobin in the body does not. However, rehydration will reveal the true severity of the anemia. Depending on the cat’s condition and PCV, a blood transfusion may be required. A major cross-match before collecting and administering blood is imperative, even if the blood type of the donor and recipient is known. Unfortunately, autoagglutination may make interpretation of the cross-match difficult. Alternatively, a hemoglobin-containing solution, Oxyglobin, may be used to improve oxygen-carrying capacity. Stressful situations while in hospital, such as frequent handling or exposure to barking dogs, should be minimized in severely ill cats. Reduction of the immune-mediated destruction of erythrocytes is the goal of drug therapy. The optimal drug protocol will decrease phagocytosis of antibody or complement coated red cells, reduce complement activation, and eliminate the production of anti-erythrocyte antibodies (Table 25-3). Glucocorticoids are the initial drug of choice. These drugs are both antiinflammatory and immunosuppressive, although higher doses are required to accomplish the latter. Oral prednisone is the most commonly used glucocorticoid, but it requires conversion by the liver to the active form, prednisolone.100 There is some evidence that intestinal absorption or hepatic conversion of prednisone to prednisolone may be poor in cats,119 thus prednisolone is thought by some to be a better initial choice in this species. The pharmacologic effects are due to interference with cellular communication and interaction among cells of the immune system. Glucocorticoids also inhibit production of cytokines used to amplify the immune response.75 Decreased production of IL-2 leads to decreased Th1 helper cell proliferation and cytotoxicity.27 Glucocorticoids stimulate maturation of T-suppressor cells and inhibit antibody-dependent cytotoxicity by natural killer cells,27 resulting in inhibition of the cellular arm of the immune system. They are beneficial in reducing binding of the Fc component of the attached IgG to the Fc receptors on

TABLE 25-3 Immunosuppressive Drugs Drug

Trade Name

Dose

Prednisone/prednisolone

2-4 mg/kg/day

Dexamethasone

0.25-1 mg/kg/day

Preparation

Chlorambucil

Leukeran

0.1-0.2 mg/kg q24h or 2 mg/cat q48-72h

2-mg tablets

Cyclophosphamide

Cytoxan

2-4 mg/kg q24h 4 days/week

25- and 50-mg tablets

Cyclosporine

Atopica, Neoral

1-5 mg/kg q12-24h use ideal body weight for obese cats

10-, 25-, 50-, and 100-mg capsules (Atopica) 25- and 100-mg capsules, 100-mg/mL oral suspension (Neoral)

Leflunomide

Arava

2-4 mg/kg q24h

10- and 20-mg tablets

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splenic macrophages. In addition, they may decrease antibody binding to the red cell membrane and complement activation.34 There are few direct effects on B-lymphocytes, and therefore there is little effect on antibody production.27,90 Cats have fewer and less sensitive cytoplasmic glucocorticoid receptors than dogs.16 This may explain why cats typically have less pronounced side effects; for instance, polyuria and polydipsia and steroid hepatopathy are not typical side effects of glucocorticoid use in cats.27 Cats receiving immunosup pressive doses of glucocorticoids may have difficulty eliminating infections on their own, and some infections may be inapparent because the inflammation associated with the infection may be blunted by the antiinflammatory effect of the glucocorticoid. An initial immunosuppressive dose of prednisone or prednisolone is 2 to 4 mg/kg orally every 24 hours. The biological duration of action of these drugs is 24 to 36 hours, which is longer than the plasma half-life. Therefore there is little advantage in dividing the daily dose in two other than to reduce the gastric irritation some patients experience at very high doses.16 If oral medication is contraindicated because of vomiting or severe oral cavity or esophageal disease, injectable dexamethasone may be substituted at 0.25 to 1 mg/kg every 24 hours subcutaneously, intramuscularly, or intravenously. Repository glucocorticoids such as methylprednisolone acetate (Depo-Medrol, Pfizer) prevent accurate titrating of the dose, and their use is not recommended.16 Response is indicated by a stable or rising PCV and can be expected within a week. Appropriately treated secondary IMHA may respond more quickly. The Coombs’ test will remain positive, possibly for months, despite a normal PCV. Once the PCV has reached and remains in the low part of the reference range for at least 1 week, consideration may be given to slowly decreasing the glucocorticoid dose. A rapid response may allow for a more rapid reduction in dose. The dose may be reduced by 25% to 50% every 2 to 4 weeks. Once the dose of prednisolone has reached 0.5 mg/kg, alternate-day therapy may begin. It is imperative to ensure the maintenance of remission before each dose reduction. There is no sense in reducing the dose in a cat that is deteriorating. Once a physiologic dose (0.25 mg/kg) of prednisolone has been reached, an attempt can be made to discontinue the drug. Whether this is possible depends on the individual cat. Relapses are to be expected and should be treated by increasing to the last effective dose. Additional immunosuppressive drugs may be required if the response to prednisolone is inadequate, if control occurs only at high doses of prednisolone, or if side effects are unacceptable. Chlorambucil is an acceptable additional drug to use in cats. Although not as potent as cyclophosphamide, it is well tolerated by cats and is the preferred first choice when an additional drug is required. Dosages range from 2 mg/cat orally

every 48 to 72 hours119 to 0.1 to 0.2 mg/kg orally every 24 hours.88 Hemorrhagic cystitis has not been reported in cats, and myelosuppression is uncommon119; however, myelotoxicity may result in neutropenia, with a nadir occurring 7 to 14 days after starting the drug. A white blood cell count should be performed at that time. If the neutrophil count is less than 0.5 × 109/L, the veterinarian should administer prophylactic antibiotics and reduce the dose by 25%.85 Other immunosuppressive drugs include cyclophosphamide, cyclosporine, and leflunomide. An alkylating agent similar to chlorambucil, cyclophosphamide may have a more rapid onset of action.87 Cats seem more resistant to the adverse effects of this medication than dogs87; however, gastrointestinal signs such as vomiting, diarrhea, nausea, and anorexia are possible. Although it is metabolized in the liver to active metabolites, production of substances toxic to the bladder epithelium do not seem to be produced as they are in dogs,87 and sterile hemorrhagic cystitis has not been reported in cats receiving cyclophosphamide. The drug is cytotoxic and decreases the production of white blood cells and antibodies. As with chlorambucil, a white blood cell count should be performed 7 to 14 days after starting the drug. The dose is 2 to 4 mg/kg orally every 24 hours for 4 consecutive days per week.29 The tablet is not homogeneous and therefore should not be split; compounding may be required to enable accurate dosing. Cyclosporine acts by suppressing cytokine release from T cells, particularly IL-2.119 This, in turn, prevents early activation of Th1 helper cells and cytotoxic T cells. Cyclosporine has little effect on nonstimulated T cells, is not cytotoxic or myelosuppressive,58 and spares other rapidly dividing cells.40 Common adverse effects include anorexia and vomiting, which respond to a decrease in the dose. It has a bitter taste that may cause refusal to eat if mixed with food.87 Hepatotoxicity is not a problem except at extremely high blood levels,40 but reversible nephrotoxicity, although not as common as in people, can occur in cats at any blood level.40 Monitoring of renal function in cats receiving cyclosporine is warranted. The gingival lesions seen in dogs receiving cyclosporine have not been reported in cats.119 Patients receiving cyclosporine may also have an increased risk of developing neoplasia, particularly lymphosarcoma.40 This effect may be due to decreased surveillance for neoplastic cells by the cellular arm of the immune system. Only the modified formulations of cyclosporine are recommended. A veterinary preparation of the emulsified form, Atopica (Novartis Animal Health), is available in capsules, allowing more accurate dosing in cats. This formulation is administered orally at 1 to 5 mg/kg of ideal body weight every 12 to 24 hours, and routine drug monitoring is generally unnecessary87 unless the patient is not responding as expected. Measuring 2-hour postadministration cyclosporine concentrations is more

closely correlated with the drug’s area under the curve than trough blood levels and more accurately predicts clinical response.87 Because cyclosporine is extensively bound to erythrocytes, whole blood levels are higher than plasma concentrations.58 Leflunomide (Arava, Sanofi Aventis) is a prodrug that is metabolized into the active form by the intestinal mucosa.40 The active form inhibits a lymphocyte growth factor receptor40 and mitochondrial enzymes, leading to inhibition of T cell proliferation.40,92 It is particularly effective in inhibiting B cell proliferation and antibody production. The drug is metabolized by the liver and excreted in the urine.92 The gastrointestinal problems experienced by dogs do not seem to occur in cats,40 insofar as the metabolite causing the gastrointestinal distress is less toxic to cats.130 Cats with inadequate renal function may, however, accumulate enough of the metabolite to cause gastrointestinal upset.130 Leflunomide is administered orally at 2 to 4 mg/kg every 24 hours. Once remission is achieved, the dose can be reduced to once or twice weekly to maintain adequate blood levels.40 Leflunomide orally at 10 mg per day has been used along with methotrexate to induce remission of refractory rheumatoid arthritis in cats. Once control is achieved, the dose is reduced to 10 mg twice weekly. Because of the severe myelosuppression that occurs in cats, azathioprine is not recommended. When weaning off treatment using multiple drugs, the veterinarian should start by reducing the cytotoxic drugs. Once they are discontinued, reduction in glucocorticoid doses can begin. In the rare instance that combination therapy is ineffective, splenectomy may be required. The prognosis for cats with IMHA depends on response to therapy, the prognosis associated with any underlying disease, and the occurrence of complications. The mortality rate for cats with primary IMHA is thought to be much lower than in dogs. Kohn and coworkers57 reported a mortality rate of 23.5% compared with much higher rates in dogs. Life-threatening complications such as DIC or pulmonary thromboembolism also occur at a much lower rate in cats. In summary, primary IMHA may be more common in cats than previously thought. Diagnosis remains an exclusionary one; elimination of other disorders by comprehensive investigation is required before making a diagnosis of primary IMHA. Therapy depends on whether an underlying condition exists but usually involves the use of immunosuppressive drugs. Fortunately, the prognosis for cats with primary IMHA is better than for dogs. Inherited Erythrocyte Abnormalities Causing Hemolysis The erythrocyte membrane is composed of a lipid bilayer attached to the membrane skeleton. Numerous glycoproteins act as receptors or transporters. The membrane


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sodium/potassium (Na/K) ATPase is lost during maturation, and, subsequently, the cytoplasmic sodium and potassium concentrations are similar to plasma. Because erythrocytes lack mitochondria, energy generation is exclusively anaerobic. Pyruvate kinase (PK) is involved in the last step in energy production and catalyzes the production of pyruvate from phosphoenolpyruvate, yielding a high-energy ATP molecule.55 Some of this energy is responsible for maintaining the pliability of the cell membrane, which allows the cell to squeeze through small capillaries. Two inherited defects in the feline erythrocyte occur in the related Abyssinian and Somali breeds of cat. Both defects affect erythrocyte survival time. One involves a PK deficiency; the other an idiopathic increase in red cell osmotic fragility. Both are inherited in an autosomal recessive manner and are identified in young cats with Coombs’-negative hemolytic anemia. Other, more common causes of hemolysis must be eliminated as possible causes of anemia before considering inherited defects. This requires an exhaustive effort to find other causes of regenerative anemia. A CBC, including an aggregate reticulocyte count and measurement of red cell indices, serum biochemical profile, and a urinalysis, should be performed. The patient should be screened for retroviral and hemoplasma infection and have a direct Coombs’ test run. Abyssinian and Somali cats with PK deficiency are usually young adults when presented for evaluation, although cats younger than 1 year old may be affected. These cats exhibit the common signs associated with anemia, including lethargy, weakness, pale mucous membranes, and anorexia. The signs are often intermittent and mild, even in cats with severe anemia. Physical findings are not specific for PK deficiency and may include pallor, lethargy, icterus, or weight loss. Mild to moderate splenomegaly is common. At presentation, most, but not all, cats are anemic, with a PCV between 13% and 29% (median of 25%) reported in one study.55 The anemia in most is regenerative with macrocytosis, polychromasia, and an aggregate reticulocytosis. Some cats have a lymphocytosis and a polyclonal hyperglobulinemia, possibly as a result of nonspecific immune system stimulation. A genetic test is available for PK deficiency and might be useful in all breeding Abyssinian and Somali cats, particularly those related to cats with anemia. Affected cats are homozygous for the causative mutation and have very low PK activity.33 Heterozygotes have intermediate PK activity and, because they are asymptomatic carriers, can transmit the defect unknowingly. Therapy is limited for cats with PK deficiency. They are often misdiagnosed with IMHA or hemoplasmosis and receive prednisolone, doxycycline, or both. Prednisolone may be beneficial in reducing the number of hemolytic crises by delaying phagocytosis by macrophages in the spleen. Splenectomy should be considered when recurrent hemolytic episodes occur or if

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the spleen becomes so large that it restricts expansion of the stomach, leading to anorexia.55 Stressful events can lead to a life-threatening hemolytic crisis and should be avoided. The prognosis for a cat with PK deficiency is variable. Most cats that die do so during a hemolytic crisis. In contrast to dogs, cats do not develop progressive osteosclerosis.33 Some cats can live to an older age; according to one source,34 the oldest PK-deficient cat lived to 13 years of age. A population of Somali and Abyssinian cats has been identified with increased fragility of the erythrocyte membrane.56 The cause for the increased fragility has not been elucidated, but an inherited defect in the cell membrane is suspected with a likely autosomal recessive mode of inheritance. The disorder has also been identified in Siamese and domestic shorthair cats.34 All of the cats had normal PK activity. The age at the initial visit was between 6 months and 5 years (mean of 2 years). The most common presenting complaints included lethargy, anorexia, weight loss, and pale mucous membranes—signs typical of anemia. In some cats the signs were episodic. Physical examination revealed the presence of pallor and splenomegaly. As these cats age, the splenomegaly appears to become more profound. As with PK deficiency, the initial presentation may be misinterpreted for some other cause of hemolysis. Most blood samples were severely hemolyzed after an overnight stay in refrigeration. Although the PCV was most often in the range of 15% to 25%, during a hemolytic crisis it dropped to as low as 5%. The anemia was usually mildly to moderately regenerative with macrocytosis, anisocytosis, polychromasia, and an aggregate reticulocytosis. Macroscopic agglutination was present in 50% of the cats but disappeared after proper washing. The agglutination may have artifactually increased the MCV as aggregates of cells passed through the cell counter. Many cats had a lymphocytosis and polyclonal hyperglobulinemia. Retroviral tests were negative, as was a direct Coombs’ test. Microscopic examination for hemoplasma infection was negative; because of the insensitivity of this test in detecting the bacteria, cats were treated with doxycycline anyway. Osmotic fragility testing is performed by placing the patient’s red cells in serial dilutions of a saline solution. Because mature erythrocytes have no Na/K ATPase, the amount of water inside the cell rapidly equilibrates with that of the solution and the cell increases in volume. Hemolysis of patient erythrocytes occurs at much higher concentrations of saline than control samples. Affected erythrocytes are osmotically fragile even when there are no clinical signs. Whereas some of the cats responded to glucocorticoid administration, others improved without treatment. Splenectomy was performed in cats that did not respond or had recurrent hemolytic events. This effectively removed the organ responsible for phagocytosis of the damaged erythrocytes.

In summary, cats with PK deficiency and increased erythrocyte fragility have many clinical and hematologic similarities, such as the young age of onset, character and chronicity of the hemolytic anemia, splenomegaly, and treatments available. Because of the similarity of the two diseases, testing for both in a patient in whom the disease is suspected may be wise. A DNA test for PK deficiency is available for Abyssinian and Somali cats. Osmotic fragility testing requires an EDTA blood sample from both the patient and a control. Cats with PK deficiency have relatively normal osmotic fragility, and those with severe osmotic fragility have normal PK activities. Neonatal Isoerythrolysis The strong hemolytic characteristics of the anti-A alloantibodies found in the serum of type B cats is responsible for the often fatal hemolysis that occurs in very young kittens. When the pathologic basis for neonatal isoe rythrolysis is understood, it is easy to see how it can be prevented. Treatment of the disorder is often unrewarding. The A and Ab alleles in cats are dominant to the b allele. Type B queens mated to type A or AB toms may have kittens that have expressed type A (or AB) antigens on their erythrocytes. Because the placenta in cats is impermeable to the passage of immunoglobulins, in utero hemolysis does not occur. Once the kitten is born, however, passive absorption of proteins from colostrum, including anti-A antibodies, occurs for the first 12 to 24 hours. Exposure to the strongly hemolyzing anti-A antibodies leads to massive, often fatal erythrocyte destruction in type A and AB kittens. The severity of signs is related to the amount of colostral antibody absorbed before closure of the kitten’s intestinal tract to passive immune transfer. Once gut closure occurs, the kitten is no longer at risk for neonatal isoerythrolysis. The time at which this occurs varies among individuals. Kittens at risk are born healthy and become ill only after consuming anti-A antibodies in the colostrum. Clinical signs appear within the first few hours to days of life and may range in severity from sudden death to development of tail-tip necrosis from vessel obstruction by agglutinating erythrocytes. Some kittens develop dark-colored urine. These kittens may also stop nursing, fail to thrive or gain weight, and develop anemia and icterus; they usually die within the first week after birth. The diagnosis is confirmed by blood typing the queen and affected kittens. Because of the acute nature of the disease, therapy is usually unsuccessful. The kitten should be removed from the queen for the first 24 hours after birth, and the body temperature should be well controlled. Between 2 and 3 mL of type B blood may be transfused through an intraosseous catheter. Type B blood is used because the only alloantibodies present in the sick newborn kitten

are the anti-A antibodies from the queen’s colostrum; the kitten has not yet made any of its own alloantibodies. Ideally, the blood would come from the queen because she has no antibodies directed against her own red cells. Kittens start to produce their own anti-B alloantibodies soon after birth. If a further transfusion is necessary 3 days after birth, type A blood should be used. Preventing the disorder, however, is much more successful than treating it. Blood typing of breeding individuals in breeds known to have a high percentage of type B cats will identify matings at risk of producing neonatal isoerythrolysis (see Tables 25-1 and 25-2). If mating a type B queen with a type A or AB tom is desired, plans should be made to foster the kittens to a type A queen for the first 24 hours of life. Alternatively, these kittens can be fed with kitten milk replacer for the first 24 hours. If there is concern about lack of passive transfer of maternal immunity in kittens fed milk replacer, 5 mL of serum from a type A cat can be administered subcutaneously or intraperitoneally every 8 hours for the first 24 hours.60 Type B kittens receiving anti-B antibodies from the colostrum of type A queens are not known to be at risk of developing isoerythrolysis. Because blood typing is readily available, preventing kitten death from neonatal isoerythrolysis is rather easy. It is recommended that cats of breeds with high frequency of type B blood, whether intended for breeding or as pets, have their blood typed at the earliest opportunity in case the information is needed in an urgent situation in the future. Cytauxzoonosis Cytauxzoonosis is a tick-borne blood disease of cats caused by the protozoal organism Cytauxzoon felis. The reservoir for the organism is the North American bobcat (Lynx rufus). Infection in domestic cats is usually rapidly fatal, insofar as they are a terminal host.9 The only proven vector for the organism is the tick Dermacentor variabilis. Cytauxzoonosis presently has a limited geographic distribution in the central, south-central, southeastern, and mid-Atlantic areas of the United States. This is also the geographical area where D. variabilis is encountered. After the tick ingests parasitized erythrocytes from an infected host, the parasite is released into the gut, undergoes reproduction, and migrates to the salivary glands. When the tick feeds on a domestic cat, the parasite enters the circulation and infects mononuclear phagocytes. Massive replication in the phagocytes (tissue phase) causes the cells to swell and burst. Freed parasites are found in erythrocytes 1 to 3 days later (erythrocyte phase).39 Interestingly, inoculation of infected red cells results in a chronic erythrocyte parasitemia without the severe illness normally seen in domestic cats. In order for the parasite to cause virulent disease, it must develop


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in the tick.9 There is no evidence the parasite can infect humans. The prepatent period for the disease is between 2 and 3 weeks. The tissue phase is responsible for many of the clinical signs because the swollen macrophages obstruct vessels, resulting in decreased organ perfusion. Damage to the lungs, liver, spleen, bone marrow, and brain account for many of the clinical signs. Erythrocyte infection and destruction occur 2 to 3 days before death, not enough time for the hemolytic anemia to become regenerative. Surviving cats may have a regenerative anemia if a sufficient number of erythrocytes are destroyed. If the hemolysis is severe enough, the resulting hypoxia will exacerbate organ damage. By-products of the parasite may be cytotoxic, pyrogenic, and vasoactive.39 Once clinical signs are present, death follows in less than 1 week. There is no age or gender predilection, although younger cats seem to represent many of the cases. Cats that go outside have an increased the risk of tick exposure. Most infections are identified during early spring to early fall, when the ticks are most active. Cats infected with C. felis exhibit vague, nonspecific signs such as lethargy, anorexia, pallor, icterus, or respiratory distress. Physical examination of an infected cat may reveal fever, hepatosplenomegaly, tachycardia, tachypnea, and pale or icteric mucous membranes. Alterations in mentation, seizures, and vocalizing may be seen in cats in the later stages of the disease. Recumbency, hypothermia, and coma are seen in terminally ill cats. Death usually occurs a few days after the temperature peaks. Diagnostic plans entail a CBC, including a platelet and aggregate reticulocyte count and blood smear evaluation; serum biochemical profile, and urinalysis. The cat’s retrovirus status should be determined. If hepatosplenomegaly is palpated, an abdominal ultrasound examination is warranted. The goal of testing is to logically eliminate potential causes of the clinical signs. Diagnosing a C. felis infection requires an index of suspicion for the disease. Cats in an endemic area with acute onset of vague signs of disease should be considered candidates for this infection. Finding a tick on the cat’s body can be an enormous clue. Anemia is not present until later in the course of illness and is usually normocytic and normochromic, with no increase in the number of aggregate reticulocytes. A neutrophilic leukocytosis may be present; however, if parasite-laden macrophages fill up the bone marrow, myelophthisis may lead to neutropenia. Thrombocytopenia may be present as a result of consumption, possibly from DIC. Hepatic infiltration with parasite-loaded macrophages may cause hyperbilirubinemia and increases in liver enzyme activities. A definitive diagnosis involves identifying the parasite in macrophages or red blood cells. Because erythrocyte infection takes place later in the course of disease, aspiration of liver, spleen, lymph nodes, lung or bone

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marrow is more likely to produce a diagnosis. Infected monocytes may be identified at the feathered edge of a blood smear. The organism is recognized as a basophilic, possibly lobulated area taking up much of the cytoplasm of the phagocyte (Figure 25-12). The parasite can be demonstrated in the erythrocyte as a characteristic round signet ring form (Figure 25-13). Other forms found in the

10 m

FIGURE 25-12 A macrophage from a feline liver contains a developing Cytauxzoon schizont. The early schizont is outlined by arrowheads and appears as a lobulated basophilic area within the cytoplasm of the cell. A large prominent nucleolus in the host nucleus is indicated by the long arrow (Wright-Giemsa, ×165). (From Greene CE, Meinkoth J, Kocan A: Cytauxzoonosis. In Greene CE, editor: Infectious diseases of the dog and cat, ed 3, St Louis, 2006, Saunders/Elsevier.)

FIGURE 25-13 Feline erythrocytes infected with the characteristic signet-ring shaped Cytauxzoon piroplasms. The clear nuclear area in the parasite allows the organism to be differentiated from hemotropic Mycoplasma organisms (Wright-Giemsa, ×330). (From Greene CE, Meinkoth J, Kocan A: Cytauxzoonosis. In Greene CE, editor: Infectious diseases of the dog and cat, ed 3, St Louis, 2006, Saunders/Elsevier.)

red cells include small dots and an ovoid safety-pin shape. There is usually only one parasite per red cell, but pairs and tetrads are seen occasionally.39 Because erythrocyte infection occurs later in the disease, parasitemia may not be present early; a repeated smear examination should reveal the parasite. Even though infection with C. felis is usually fatal, cats have survived, including some that received only aggressive supportive care. A population of 18 cats from the Arkansas–Oklahoma border area survived, suggesting the presence of a less virulent strain of the parasite.72 Goals of therapy include preventing DIC and bacterial septicemia, promoting perfusion, and improving tissue oxygenation. Aggressive intravenous fluid administration will help preserve intravascular volume, maintain tissue perfusion, and consequently improve tissue oxygenation and help prevent DIC. The prophylactic use of heparin to prevent DIC has been suggested.9 Even though antibiotics are not able to directly control the protozoa, they have been used in most cats that have survived.9 Effective drugs able to eradicate C. felis are not yet available. In fact, many cats that survived infection did so without the benefit of antiprotozoal drugs. Therapy is often unrewarding; most cats die despite aggressive treatment. Until effective protocols for treating C. felis infections are developed, prevention of the initial infection should be the goal of the veterinarian and owner. Tick control is mandatory in preventing infection, as is confinement indoors during the tick season to minimize exposure to the protozoal parasite. Daily grooming to remove ticks is also helpful. Preliminary data have been published regarding the use of oral atovaquone 15 mg/kg every 8 hours in combination with oral azithromycin 10 mg/kg every 24 hours for 10 days along with aggressive supportive care. The protocol resulted in the survival of 14 of 22 infected cats.8 It is possible that some of these cats were infected with the less virulent strain of C. felis. Heinz Body Anemia Heinz bodies are indicative of oxidative injury to the erythrocyte. They are clumps of irreversibly denatured hemoglobin attached to the erythrocyte cell membrane (see Figures 25-9 and 25-10). Feline hemoglobin is quite sensitive to oxidative injury because there are more targets on the molecule to oxidize than in other mammals and cats have reduced capacity for scavenging oxidative substances. Feline hemoglobin also dissociates more readily than other species.14 Because of the nonsinusoidal nature of the feline spleen, rigid bodies such as erythrocytes with Heinz bodies are not forced to squeeze their way through the red pulp. Therefore the feline spleen is inefficient in removing Heinz bodies, and they accumulate. Still, the result is decreased erythrocyte survival time. Oxidation of the iron in the hemoglobin can occur without denaturing the hemoglobin. The Fe+2 is oxidized


BOX 25-2 Substances and Diseases Associated with Oxidative Damage to Erythrocytes Foods • • • • •

Onions Propylene glycol Broccoli Garlic Salmon-based food

Drugs • • • • •

Acetaminophen Benzocaine Propofol DL-methionine Vitamin K3

Metals • Zinc • Copper

Disease • • • •

Diabetes mellitus (especially with ketoacidosis) Hyperthyroidism Hepatic lipidosis Lymphosarcoma

to Fe+3, which is unable to bind oxygen. The result is methemoglobinemia. Oxidative substances are free radicals that damage cell structures. They may accumulate when there is increased production or decreased detoxification of the free radical, which can be produced spontaneously from oxygen. They may also be the result of drugs, plants, or chemicals with oxidative properties.14 Many substances or diseases can produce Heinz bodies (Box 25-2). Heinz bodies are reported as the percentage of red cells containing Heinz bodies. Because of the nature of the feline spleen, up to 10% of erythrocytes in healthy cats may have Heinz bodies.126 Any amount over this percentage should generate questions for the owner regarding diet and drug exposure. Owners who give their cats homemade diets or meat-based baby food may be inadvertently feeding enough onion powder to cause up to 50% Heinz bodies.14 Cats ingesting an oxidative diet may be more susceptible to oxidative drugs. Cats with diseases generating increased numbers of Heinz bodies should not be given foods with Heinz body– producing potential insofar as the effects can be additive.

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Cats are more susceptible to damage from oxidative drugs than other species. A number of drugs can produce oxidative damage to the red blood cell. In cats acetaminophen is particularly dangerous. Cats cannot metabolize the drug through glucuronidation, and oxidative metabolites are formed that damage the erythrocyte and the hemoglobin. Several diseases can produce substances that cause oxidative injury. Ketoacidotic cats may have up to 70% large Heinz bodies.14 Diabetic cats without ketosis have a lesser degree of Heinz bodies. Owners should refrain from feeding onion-containing baby food to diabetic cats. Signs of Heinz body anemia are similar to those found in most anemic cats: lethargy, anorexia, pale mucous membranes, tachycardia, and tachypnea. The addition of the lowered oxygen-carrying capacity of methemoglobin caused by iron oxidation can make the signs of hypoxia appear worse than the lowered PCV would suggest. If over 15% of the hemoglobin is in the form of methemoglobin, the color of the mucosa and blood can be altered to appear darker red or brownish in color. Significant methemoglobin is rarely associated with diet or diseases that produce Heinz bodies.14 The development and degree of anemia depends on the size, number, and rate of formation of Heinz bodies. Heinz bodies are produced at a slower rate by diet or disease compared with oxidative drugs and are less likely to be associated with acute hemolysis. Anemia is more likely when the Heinz bodies are large and affect over 30% of the erythrocytes. Heinz bodies appear dark when stained with new methylene blue stain. Ghost cells may appear on the slide if the erythrocytes are seen to be extruding the Heinz body. These cells look like empty circular rims with an attached Heinz body. As opposed to dogs, cats often have single, large Heinz bodies. The presence of many large Heinz bodies can artifactually increase the MCHC and automated leukocyte count. Once Heinz body anemia has been discovered, the veterinarian should carefully evaluate the cat for drug or onion ingestion or diabetes mellitus. It is important to search for an underlying cause for anemia even if Heinz bodies are present; they are a sign of disease, not the disease itself. Thoracic and abdominal radiography and abdominal ultrasonography may help identify any malignancies or metallic foreign bodies. Offending dietary substances may be identified on the food’s package label. Owners sometimes unwittingly administer acetaminophen to cats that seem to be in pain. Therapy for Heinz body anemia should first be directed at removing the cause of the oxidative damage (e.g., eliminating onion-containing foods or treating the underlying disease). As with any anemia-causing disease, supportive care based on the cat’s condition is important. Intravenous fluid therapy to correct volume contraction is always important in dehydrated cats. If the clinical signs warrant, a blood transfusion may

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become necessary. Lastly, antioxidant therapy may be required if the disorder is severe. N-acetylcysteine is used to treat acetaminophen toxicity (see Chapter 31). Methylene blue can be administered intravenously to cats at 1 to 1.5 mg/kg once; however, additional doses may exacerbate the Heinz body anemia. Once the oxidative substance is removed from the cat, the Heinz bodies should disappear over the next 1 to 4 weeks. Acute Hemolysis Secondary to Severe Hypophosphatemia Phosphorus exists in the body as organic and inorganic phosphates. Organic phosphate is an important component of many cellular structures and molecules in the cat such as adenosine-5′-triphosphate (ATP), cyclic adenosine monophosphate (cAMP), the electron transport chain, and cell membranes. These, in turn, are important in maintaining the integrity of the cell. Inorganic phosphate is present mostly in the extracellular space and is an important substrate for oxidative phosphorylation and glycogenolysis.74 Acute hemolysis due to hypophosphatemia has been recognized in cats treated for diabetes mellitus and hepatic lipidosis.1 Cats with these diseases may already have low serum phosphate concentrations; treatment of the disease may result in a further decrease as exogenous insulin is administered to diabetic patients or endogenous insulin increases when chronically anorexic cats are refed. Insulin results in an intracellular shift of phosphate as it follows glucose into cells. The intraerythrocytic phosphate concentration is dependent on the serum phosphate concentration. Severe hypophosphatemia leads to decreased erythrocyte phosphate and consequently depletion of ATP. The resultant loss of the high-energy phosphate leads to an inability to maintain the cell’s biconcave shape,1 a reduction in membrane deformability, increased osmotic fragility, and increased susceptibility to oxidative stress.34 The result is a rigid, oxidatively stressed, fragile cell. The macrophages in the spleen remove these cells, and anemia develops. The presence of Heinz bodies in diabetic cats can exacerbate the anemia caused by hypophosphatemia. Anemia caused by acute hemolysis develops within 1 to 2 days of documentation of a serum phosphate concentration less than 0.65 mmol/L. Because of the acute nature of the hemolysis, the anemia will be normocytic and normochromic and appear nonregenerative. In one report the PCV dropped between 9 and 18 percentage points.1 Increased numbers of Heinz bodies may be found when examining a blood film. Cats that survive are expected to develop an aggregate reticulocytosis during recovery. Supplementation is recommended when the serum phosphate is less than 0.65 mmol/L. Intravenous sodium phosphate or potassium phosphate is administered at 0.01 to 0.06 mmol/kg per hour in calcium-free

solutions.49 Serum calcium and phosphate concentrations should be monitored every 6 hours because hypocalcemia is a common complication (it is treated with intravenous calcium gluconate).34 Once serum phosphate is over 0.65 mmol/L, the dosage can be decreased by half and discontinued shortly thereafter. Oral supplementation is started at this time. Hypophosphatemia-associated acute hemolytic anemia is a complication of treating a diabetic cat or can result from refeeding syndrome. It is important to remember to evaluate the serum phosphate levels in these cats because the development of anemia can complicate recovery. Prophylactic use of phosphate supplementation for these patients may be considered if proper monitoring is available. Feline Hemoplasmosis (Hemobartonellosis) Feline hemoplasmas are epicellular gram-negative organisms causing anemia and illness in cats around the world. In one study 27% of 310 cats with acute or regenerative anemia tested positive for hemoplasmosis.109 Another investigation found that 14% of all anemic cats were positive for hemoplasmosis.83 Four distinct hemoplasmas have been detected in cats by PCR testing: M. haemofelis, Candidatus Mycoplasma haemominutum, Candidatus Mycoplasma turicensis, and Candidatus Mycoplasma haematoparvum. The most common hemoplasma found in cats is Candidatus M. haemominutum; mixed infections are not unusual.109 M. haemofelis is the most pathogenic of the hemoplasmas and can cause potentially fatal hemolytic anemia. Candidatus M. haemominutum usually causes little to no illness in cats,31 unless there is FeLV co-infection or co-infection with another hemoplasma. Candidatus M. turicensis has caused anemia when inoculated into specific-pathogen free cats.108 The pathogenicity of Candidatus M. haematoparvum is as yet undetermined. Erythrocyte cell membrane damage occurs as a result of attachment of the organism. Consequently, cell survival time is affected. The damaged membrane can also reveal antigens previously hidden from the immune system. Antibodies directed against these antigens (type II immune reaction) as well as the organism itself (type III immune reaction) can lead to Coombs’-positive immune-mediated hemolysis. The spleen removes these damaged cells, leading to a reduction in the PCV. Macrophages in the spleen may also remove the bacteria from the surface of the red cell and, if it is not too severely damaged, return the erythrocyte back into the circulation.111 Despite appropriate therapy, cats that recover can remain subclinically infected for a period of time. PCR remains positive in these cats while the bacteria disappears from the erythrocytes and the PCV reaches the reference range. Cats that become carriers have reached a steady state between organism replication and macrophage phagocytosis and removal of

erythrocytes. Carriers are more likely to occur after infection with Candidatus M. haemominutum than with M. haemofelis.111 The mode of transmission is poorly understood. Traditionally, it was thought that transmission of hemoplasmas occurred by fleas (Ctenocephalides felis). Although PCR tests have documented the presence of hemoplasma DNA in flea larvae, feces, and eggs, ingestion of these did not result in transmission to cats under experimental conditions.133 Transmission of infection has been found after fleas infected with hemoplasma fed on cats in an experimental setting. Experimental ingestion of infected blood, but not infected feline saliva,79 also resulted in transmission of infection. Whether these results translate to the clinical setting is unknown, but this research leads to speculation that aggressive interactions between cats may also play a role in the transmission of the organism.83 Cats infected with hemoplasmas can be males or females of any age and are brought to the veterinarian for reasons similar to those of most other cats with anemia. They are often lethargic, pale, not eating well, and losing weight. The course may be waxing and waning as circulating parasite numbers fluctuates. The severity of the clinical signs depends on the species involved, the rate of development, and the degree of anemia. Cats infected with M. haemofelis or Candidatus M. turicensis are more likely to become anemic than cats infected with Candidatus M. haemominutum. The presence of FeLV co-infection results in a more severe illness; however, concurrent infection with FIV is not associated with more severe disease.108 Physical findings include fever, pale mucous membranes, splenomegaly, and icterus. Cats infected with Candidatus M. haemominutum may have no physical abnormalities at all.108 An ill cat infected with Candidatus M. haemominutum and no co-infection should be evaluated for other causes of anemia. Evaluation of a cat experiencing the aforementioned clinical signs should include a CBC with a blood smear examination, an aggregate reticulocyte, and a platelet count; a Coombs’ test; and retroviral testing. The anemia caused by feline hemoplasma infection should be macrocytic, normochromic to hypochromic and regenerative if enough time has elapsed to allow production of new erythrocytes. Increases in aggregate reticulocyte numbers should be present if the anemia is moderate to severe. If the anemia is mild, only punctate reticulocytes may be observed. The Coombs’ test is often positive.111 The cat should be evaluated for other causes of regenerative anemia as warranted by other clinical signs, such as bleeding. Specific tests for hemoplasmosis include close inspection of erythrocytes on the blood smear for evidence of the organism and PCR tests for organism DNA. Occasionally, the organisms may appear on the blood smear


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FIGURE 25-14 Giemsa-stained blood smear form a cat with Mycoplasma haemofelis infection. The organisms are attached to the surface of the erythrocytes. Anisocytosis (variation in cell size) is present on the slide. (From Tasker S, Lappin MR: Update on hemoplasmosis. In August JR, editor: Consultations in feline internal medicine, ed 5, St Louis, 2006, Elsevier.)

(Figure 25-14). The likelihood of finding organisms in this manner is affected by the cyclic nature of the parasitemia and, possibly, by sample handling issues. Slides should be made within 1 hour of collection to prevent the unlikely possibility that the organism will dislodge from the red cells.111 Infected erythrocytes must be differentiated from Howell–Jolly bodies, stain precipitate, and ribosomecontaining reticulocytes. PCR is a more sensitive test and is considered the test of choice for the infection. Cats undergoing antibiotic treatment are often PCR negative and should not be tested with this technique. A positive test result indicates the presence of organism DNA and may not correlate with clinical disease. Carriers of the infection are identified with this test. Traditionally, cats with hemoplasma infections have been treated with tetracycline. Oral doxycycline at 10 mg/kg every 24 hours can be effective in treating the illness caused by hemoplasmosis. Courses longer than 21 days may be required for elimination of the organism. Esophageal strictures are a possible complication of doxycycline administration in tablet or capsule form and can be prevented by ensuring passage of the drug into the stomach by syringing a small amount of food or water after administering the pill to the cat. Doxycycline can also be compounded into a suspension. Applying a small amount of butter or margarine to the nose may accomplish the same thing. Fluoroquinolone antibiotics have been shown to be effective in treating cats with hemoplasma infections. Enrofloxacin (Baytril, Bayer HealthCare) at 5 mg/kg orally every 24 hours was associated with improvement in clinical signs, although elimination of the infection was uncommon.21 Daily doses higher than this may cause retinal degeneration in cats. Other fluoroquinolones may be effective.

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Marbofloxacin (Zeniquin, Pfizer Animal Health) at 2 mg/kg orally every 24 hours is effective at treating illness but may not result in clearance of the infection.110 Retinal toxicity has not yet been identified in cats receiving marbofloxacin. Pradofloxacin (Veraflox, Bayer AG) at 5 mg/kg orally every 24 hours appears to be safe and effective in treating illness caused by hemoplasma infections. It also appears to be more effective in clearing the organism than doxycycline.22 Prednisolone, initially dosed at 2 mg/kg orally every 24 hours, before dose tapering has been used to control the immune-mediated component of the disease. However, this drug may be unnecessary because some cats recover without the use of glucocorticoids.111 If the illness and anemia are severe, a transfusion may be required. Cats with anemia caused by hemoplasmosis have an excellent prognosis for recovery.83 The prognosis may not be as good for cats with concurrent disease, such as co-infection with FeLV. Prevention of the disease may include flea control and preventing aggressive interactions with other cats. The efficacy of these tactics is unknown insofar as the mode of transmission of the infection is still not clear. Cats with a positive PCR test should not be used as blood donors.

Nonregenerative (Nonresponsive) Anemia Definition Nonregenerative anemia is defined as a decreased erythrocyte mass (decreased PCV, red cell count, and hemoglobin concentration) without evidence of increased bone marrow production of new red blood cells. Lack of regeneration can be caused by decreased EPO production, decreased responsiveness of the bone marrow to EPO, decreased erythroid precursors in the bone marrow, or iron deficiency. Numerous disorders can lead to a nonregenerative anemia, including chronic renal disease, liver disease, inflammatory disease, FeLV infection, immune-mediated destruction of erythrocyte precursors, and primary bone marrow disease such as neoplasia and myelodysplasia. An anemia is nonregenerative if there are inadequate numbers of circulating aggregate reticulocytes for the degree of anemia. It is important to remember that an acute onset of anemia may also appear nonregenerative if there has not been enough time (4 to 7 days) for the bone marrow to produce and release aggregate reticulocytes. History and Physical Examination The signs associated with anemia are often nonspecific and have been covered in a previous section of this chapter (Clinical Evaluation of Cats with Anemia). Diagnostic Plans A CBC, along with measurement of erythrocyte indices, a blood smear evaluation, and a reticulocyte count,

should be performed in all cats in which anemia is a suspected cause of the clinical signs. Nonregenerative anemias are most often normocytic and normochromic. As with regenerative anemias, the PCV, erythrocyte count, and hemoglobin concentration are all decreased. However, because there is no increase in reticulocyte production, the MCV is usually within the reference range. The RDW is also in the reference range because most of the erythrocytes are similar in size. These parameters may lie outside the reference range in disorders such as iron deficiency and infection with FeLV. Most of the erythrocytes will have their normal allotment of hemoglobin, so the MCHC is also in the reference range. Once a nonregenerative anemia has been identified, the goal of further diagnostic procedures is to identify extramarrow causes of the anemia before pursuing intramarrow disorders. A serum biochemical profile, urinalysis, and retroviral tests should be performed.18 If the duration of illness is shorter than 5 days, the cat’s bone marrow may not have had enough time to increase erythrocyte production. Another CBC and reticulocyte count should be performed to ensure that the anemia is nonregenerative. Other diagnostic procedures that may be useful include thoracic radiographs and abdominal imaging. If these steps have not identified a cause for the anemia, evaluation of the bone marrow should be performed. Iron Deficiency Iron exists in the body in the form of hemoglobin, myoglobin, labile iron, tissue iron, and transported iron.129 Hemoglobin concentrations inside the maturing erythrocyte help determine when cell division stops; erythrocytes undergo extra divisions, resulting in smaller cells when decreased hemoglobin is available. In most species the anemia of iron deficiency is microcytic (decreased MCV) and hypochromic (decreased MCHC), but cats are less likely to develop these changes.18 Early in the course of iron deficiency, the anemia is likely to be regenerative. Sufficient polychromasia and reticulocytosis may be present.18 As iron stores are depleted, polychromasia and reticulocytosis decrease and the anemia becomes nonregenerative. The degree of anemia ranges from mild to life threatening.129 Variations in red cell shape (poikilocytosis)129 and fragmented erythrocytes (schistocytosis)18 are commonly observed on the blood smear. Poikilocytosis is also common in cats with liver disease.126 Kittens are at risk of developing iron deficiency anemia as a result of endoparasitism or ectoparasitism. Repeated blood sampling from kittens can also lead to iron depletion. Severe flea-bite anemia occurs in young kittens as a result of iron loss.129 Anemia from total body iron depletion is unusual in adult cats.129 Chronic blood loss caused by gastrointestinal ulceration or neoplasia may result in an iron deficiency anemia. If the amount of blood lost at any one time is small, there will not be


TABLE 25-4 Anemia of Inflammatory Disease Versus Iron-Deficiency Anemia Anemia of Inflammatory Disease

Iron-Deficiency Anemia

Erythrocyte indices

Normocytic, normochromic

Microcytic, hypochromic

Serum iron concentration

Low

Low

Total iron-binding capacity (transferrin)

Often decreased

Often normal

Bone marrow iron

May be increased

Absent (also a finding in normal cats)

Serum ferritin

High

Low

Inflammatory disease

Present

Need not be present

evidence of regeneration; the anemia will be caused by chronic iron loss. Careful evaluation of the gastrointestinal tract may be required insofar as there may be no overt evidence of gastrointestinal disease (e.g., vomiting, melena).93 Loss through the urinary tract from bleeding transitional cell carcinoma or cystitis is unlikely to lead to iron loss sufficient to cause anemia.129 Diagnosis of an iron deficiency anemia can be difficult. The changes in the erythron can be similar to anemia of inflammatory disease (AID; see later discussion). Sometimes the diagnosis can be made on the basis of the history and physical examination because there will be evidence of blood loss or active inflammation. Often, more information is required. Healthy cats typically do not have visible iron stores in their bone marrow. Although the presence of iron in the bone marrow rules out iron deficiency, its absence does not prove it.34,128 An iron profile can prove useful (Table 25-4). Serum iron concentrations alone are too nonspecific.128 Assessing the total iron-binding capacity (TIBC) and serum ferritin concentrations can be helpful. The TIBC is a measure of the concentration of transferrin, a plasma protein that functions in iron transport. In an iron-deficient cat, transferrin (and TIBC) would be expected to be normal to slightly increased34 in an attempt to offer more capacity for transport of iron to the cells. Because serum iron is low, the saturation of transferrin is decreased. Iron sequestration and decreased iron transport are a consequence of inflammatory disease so that transferrin concentrations (and TIBC) are decreased.126 Ferritin is a cytoplasmic protein that stores iron in a soluble phase inside the cell.34 In states of iron deficiency, cytoplasmic iron stores are decreased, resulting in decreased ferritin requirements and decreased plasma concentrations. Ferritin also

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happens to be an acute phase inflammatory protein. In conditions involving inflammation, ferritin concentrations are expected to be elevated.128 In summary, transferrin (TIBC) is increased and ferritin decreased in iron deficiency, whereas the reverse may be true for AID. When a cat with iron deficiency is being treated, it is imperative that the cause of blood loss be identified and addressed. If the cat’s clinical signs warrant it, a transfusion may be required. Iron replacement therapy involves administering ferrous sulfate at 50 to 100 mg/ cat orally every 24 hours. If gastrointestinal upset occurs, the dose may be divided. The dose should be decreased by 50% once the PCV is in the reference range. If intestinal absorption is questionable, iron dextran should be administered intramuscularly at 50 mg every 3 to 4 weeks until the gastrointestinal disease is under control. Occasionally, hypersensitivity reactions will occur with iron dextran injections. Evidence of regeneration, such as polychromasia and reticulocytosis, should be apparent within several days18 as hemoglobin synthesis and erythropoiesis accelerate. Anemia of Inflammatory Disease Inflammatory conditions cause mild to moderate nonregenerative anemia.43,126 The PCV is often greater than 20% and is generally associated with an inflammatory leukogram18 and fever.126 Cytokines released by inflammatory cells in response to infection, cell damage, or malignancy cause iron sequestration by macrophages. Because iron is an essential growth factor for microorganisms,86 this is thought to be a protective mechanism against infection. It also leaves less iron for erythropoiesis. The inflammatory environment leads to decreased erythrocyte survival, decreased EPO secretion in response to anemia, and decreased bone marrow response to existing EPO.86 This process has been known as anemia of chronic disease; however, cats in one study had a decreased PCV within 2 days of onset of an inflammatory disease.86 Many of the cats developed hyperglobulinemia as a result of the inflammation. The diagnosis of AID is one of exclusion. Other causes of nonregenerative anemia must first be eliminated.86 Evidence for this mechanism of anemia may be found in the history or physical examination. Decreases in serum iron concentrations may mimic iron deficiency and are not confirmatory for either disease. Measuring serum ferritin concentrations may be helpful. In addition to being an iron-carrying protein, it is also an acute phase protein and may be elevated in inflammatory disorders.128 Bone marrow cytology is nonspecific because changes such as myeloid hyperplasia and erythroid hypoplasia are common. This results in an increased myeloid to erythroid (M : E) ratio.18 Therapy for AID involves treating the underlying disease. When treated successfully, the anemia should resolve within several weeks.86 Because the anemia is

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usually mild to moderate, specific therapy, such as blood transfusions, is usually not required. Supplementation with iron products is not recommended because the increased iron may promote the growth of pathogenic bacteria or tumor cells.86 Occasionally, the anemia is severe, and a blood transfusion is needed. In a retros pective study, only 3 of 21 cats with nonregenerative anemia associated with inflammatory disease required a transfusion.86 Chronic Renal Disease Anemia is an expected consequence of chronic renal disease (CRD) in cats and contributes significantly to their lack of well-being.91 Marked azotemia and an inappropriate urine specific gravity are usually present by the time CRD causes a significant anemia.18 The cause of anemia is multifactorial and may be exacerbated by concurrent illness.93 There are four major causes of the anemia: 1. Uremic toxins may suppress the maturation of erythroid precursors in the bone marrow. 2. Erythrocyte life span may be shortened in animals with CRD. 3. Blood loss is often overlooked as a cause of anemia in CRD patients. Uremia can lead to platelet dysfunction and to gastrointestinal ulceration.129 Evidence of gastrointestinal blood loss can be difficult to find because melena may not be present.93 4. The most important contributing factor to the anemia of CRD is EPO deficiency. EPO is produced in the peritubular fibroblasts deep in the renal cortex in response to hypoxia. Decreasing renal mass results in decreased numbers of EPOproducing cells. The anemia of CRD is normocytic, normochromic, and hypoproliferative.97 Poikilocytes may be noted during examination of a blood smear.93 Initially, the anemia is mild, but as renal disease progresses, the anemia becomes correspondingly more severe.129 Occasionally, a transfusion becomes necessary. Bone marrow cytology may reveal erythroid hypoplasia and an increased myeloid to erythroid (M : E) ratio. Specific therapy directed at treating anemia of CRD includes EPO replacement and minimizing blood loss. An overlooked but obvious consideration is minimizing the number and volume of blood samples obtained when a patient is hospitalized. Repeated blood monitoring should be limited to that which is essential to manage the patient.93 Occult gastrointestinal blood loss can lead to significant anemia in patients that would otherwise have enough EPO to maintain the PCV in an acceptable range. Because of the difficulty in proving gastrointestinal blood loss, empirical use of H2 receptor blockers along with sucralfate should be considered.93

Recombinant human EPO (rhEPO) is a genetically engineered protein used to treat anemia in humans.19 The structure of EPO is relatively well conserved across species, allowing for biological activity of rhEPO in cats.128 Hormone replacement using rhEPO is the treatment of choice for anemia associated with erythropoietic failure in cats with chronic renal failure.93 Consideration for use of rhEPO should be limited to patients with severe anemia that affects quality of life. The initial dose is 100 units/kg subcutaneously three times weekly. This dose may be modified if the anemia is particularly severe without requiring a transfusion. If the PCV is less than 14%, 150 U/kg may be administered subcutaneously three times weekly. Should the patient be hypertensive or if the anemia is not particularly severe (yet still causing clinical signs), a dose of 50 U/kg may be effective in increasing the PCV while preventing a further increase in blood pressure.93 The initial dose is continued for 8 to 12 weeks until the target PCV of 30% is reached.19 The PCV should be measured weekly so the dose can be altered when the target is reached.70 At that point, dosing frequency is reduced to once or twice weekly to maintain the PCV above 30%. The dosage and dosing interval must be individualized for each patient.128 Changes in dose should be made infrequently because there is a lag between a dosage change and its effect on the PCV. Generally, the dose should not be changed more than once monthly.93 If iatrogenic erythrocytosis occurs, the dose or dosing interval (or both) should be decreased. A cat that does not respond should be evaluated for iron deficiency, external blood loss, AID, or the development of antibodies directed against rhEPO.19 Improper storage, handling, or administration by the owner should also be considered.93 The drug vial should be refrigerated, and care should be taken not to vigorously shake the vial to prevent protein denaturation. Potential adverse effects of rhEPO administration include iron deficiency, hypertension, erythrocytosis, anaphylaxis, local reactions to the injection,94 and most important the development of anti-EPO antibodies.128 The rapid increase in erythropoiesis can lead to the use of large amounts of iron. If iron is not supplemented, iron deficiency will develop. All cats receiving rhEPO should also receive ferrous sulfate at 50 to 100 mg/cat per day orally. Chronic anemia leads to vasodilation19 to facilitate delivery of blood to the tissues. Once the anemia is corrected by using rhEPO, total peripheral resistance increases, although clinical hypertension is uncommon. In a study of cats receiving recombinant feline EPO (rfEPO), only 2 of 26 cats that responded developed hypertension requiring antihypertensive therapy.94 Although the rhEPO molecule is very similar to the cat’s endogenous EPO, it is not identical. There is enough structural variation for the immune system of some cats to recognize rhEPO as a foreign protein and mount an

immune response against it.94 Approximately 20% to 50% of cats receiving rhEPO will develop antibodies against the protein.91,128 These antibodies usually develop in cats receiving rhEPO for longer than 4 weeks.128 Unfortunately, these antibodies block the biological effects not only of rhEPO but also of the cat’s endogenous EPO.94 This can lead to a life-threatening red cell aplasia as the patient’s PCV drops to below pretreatment levels. This condition is reversible with cessation of the drug, but it may be months before the PCV recovers.70 Until that time transfusions may be necessary to support the cat. After developing antibodies against rhEPO, its use is contraindicated. Because of the development of these antibodies, rhEPO should be reserved for patients most in need. Proper client education and communication are important when making decisions regarding the use of this therapy. Evaluation of an rfEPO has been reported. Although the product is not available, it seems to be effective in reversing the anemia of chronic renal failure.94 It also reversed the red cell aplasia caused by antibodies against rhEPO in some cats. Unexpectedly, 8 of the 26 cats receiving rfEPO redeveloped a nonregenerative anemia after an initial response. It was postulated that perhaps there are variations in the endogenous EPO in the cat population, allowing immune response against the molecule. Other possible targets of an immune reaction are the carbohydrate moiety on the molecule or some additive in the rfEPO preparation.94 Darbepoietin is a longer acting form of rhEPO. Anecdotally, it seems to have similar efficacy and safety as rhEPO.97 It can be administered as a weekly injection and may be less immunogenic in animals, but this has not been documented. Darbepoietin acts similarly to EPO by stimulating erythropoiesis in the bone marrow. Adverse effects in animals are unknown but are likely similar to rhEPO because darbepoietin causes increased erythropoiesis and improved oxygen delivery to tissues. This may result in hypertension, erythrocytosis, and iron deficiency. Until proven otherwise, darbepoietin should be considered potentially immunogenic. With the availability of rhEPO, the ability to control anemia caused by chronic renal failure has improved. Careful patient selection, proper patient monitoring, and constant client communications are crucial to successful management of these patients. Supplementation with ferrous sulfate and control of gastrointestinal bleeding are also essential. Feline Leukemia Virus Infection Various hematologic abnormalities are common in cats infected with FeLV. Anemia can be caused by bone marrow suppression, myelodysplasia, myelophthisis due to lymphosarcoma or leukemia, or immunemediated hemolysis.129 Most of the anemias caused by FeLV are nonregenerative. The anemia can be


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normocytic, normochromic, and nonregenerative or macrocytic, normochromic, and nonregenerative. If there is immune-mediated hemolysis, a regenerative anemia may occur.18 Hemolysis may be a direct result of the virus or due to co-infection with M. haemofelis. The virus causes nonregenerative anemia by infecting erythroid precursors in the bone marrow and the stromal cells supporting the marrow.59 Integration of proviral DNA into the marrow cell may cause marrow dysfunction by altering regulatory mechanisms or inducing the expression of an unknown antigen on the surface of the erythrocyte precursor or stromal fibroblast, leading to immune-mediated destruction of these cells.107 The result is depletion and maturation arrest of erythrocyte precursors in the bone marrow.59 Granulocyte precursors and megakaryocytes may also be affected, causing leukopenia and thrombocytopenia or thrombocytosis.125 Cats with macrocytic nonregenerative anemias are often FeLV antigen positive.18 Macrocytosis is thought to result from a skipped mitosis during erythropoiesis; reticulocyte numbers are not increased.129 Some FeLV-infected cats will have normocytic nonregenerative anemias with anisocytosis but no polychromasia. Anisocytosis results from a subpopulation of mature cells that are larger than the others but are not reticulocytes.26 These cats may have an increased RDW reported on a hemogram. If a histogram of red cell size is provided, two peaks may be present, reflecting the two populations of cells: one of normal size and one a bit larger. Macrocytosis without anemia may be seen in some cats with hyperthyroidism.14 A spurious macrocytosis may result from the agglutination of erythrocytes as they pass through automated cell counters. A cat with hematologic changes that is negative for circulating FeLV antigen may still be infected with the virus. Latent FeLV infections are defined as circulating antigen negative and bone marrow positive. The provirus is present in a nonreplicating form in myelomonocytic precursors in the marrow.107 The viral particles may be identified by performing an indirect fluorescent antibody test on marrow smear or by using a PCR test. A study of a population of cats with various types of nonregenerative cytopenias of unknown origin was performed to assess the role of latent FeLV infections. All the cats had a negative test for circulating FeLV antigen. Only 2 of the 37 cats had a positive PCR test for FeLV proviral DNA in the bone marrow. The researchers concluded that FeLV latency does not play an important role in cats with nonregenerative cytopenias.107 Any cat with anemia without obvious cause (e.g., trauma, blood loss) should be checked for the presence of FeLV antigen. If the anemia is regenerative, additional testing for blood parasites such as M. haemofelis is indicated. Therapy for cats with FeLV-associated anemia is supportive. Concurrent infection with blood parasites should be treated appropriately. Immunosuppressive

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doses of prednisolone should be used if immunemediated hemolysis is a factor.128 Blood transfusions will be useful in ameliorating clinical signs of anemia. Some cats may respond to the administration of rhEPO, although most cats already have high circulating concentrations of EPO.59 Pure Red Cell Aplasia Pure red cell aplasia (PRCA) is characterized by a severe normocytic, normochromic, nonregenerative anemia along with erythroid hypoplasia and increased lymphocyte numbers in the bone marrow.125 Granulocytes and megakaryocytes are left intact. This is a rare syndrome129 thought to be caused by immune-mediated response against erythrocyte precursors in the marrow. Infection with FeLV subgroup C has also been implicated in the pathogenesis of the disease. It appears to be a disease of younger cats.125 A Coombs’ test may be positive, and other causes of anemia are absent. The PCV is often lower than 20%.26 Aggressive combination immunosuppressive therapy with prednisolone and another drug (such as chlorambucil) is often required to control the immune-mediated damage (see the previous section on treating immune-mediated hemolytic anemia). Response to treatment may not be apparent for several weeks. Acute Blood Loss or Hemolysis Acute loss of sufficient erythrocytes either by hemorrhage or hemolysis leads to hypoxia and increased production of EPO by the kidneys. If the cat is evaluated before aggregate reticulocytes are released by the bone marrow, the circulating red cell morphology will appear nonregenerative. Immediately upon bleeding, both red cells and plasma are lost and no decrease in PCV is detected. Within 12 to 24 hours of acute hemorrhage, interstitial fluid shifts into the intravascular space. The increase in plasma volume dilutes the red cells and is recognized as anemia. Acute hemolysis will also lead to decreased erythrocyte numbers. In both situations the anemia may be evaluated before the appearance of aggregate reticulocytes in the circulation. A CBC performed at this time will reveal the presence of a normocytic, normochromic, nonregenerative anemia without polychromasia or increased aggregate reticulocyte numbers. The anemia will not be recognized as regenerative until aggregate reticulocytes are released 4 or 5 days after the initial event. A second CBC should be performed 5 days after onset of illness before the conclusion is reached that an anemia is nonregenerative. Bone Marrow Disease Numerous types of bone marrow disorders can cause nonregenerative anemia in cats, although they are very uncommon. Disorders include aplastic anemia, myelofibrosis, myelodysplasia, and myelophthisis secondary to inflammatory diseases or neoplasia. Many are associated

with FeLV. The etiologic diagnosis of bone marrow disease requires a cytologic or histopathologic evaluation of a bone marrow sample. Aplastic anemia is defined as the presence of bicytopenia or pancytopenia. Most of the hematopoietic space of the marrow is replaced by adipose tissue. Cats most commonly have a nonregenerative anemia along with leukopenia, thrombocytopenia, or both. Although it may be idiopathic in cats, aplastic anemia is also associated with chronic renal disease, FeLV infections, and methimazole and griseofulvin toxicity.125 Starvation and emaciation appear to have a role in the pathogenesis of the disorder in association with chronic renal disease and those with idiopathic aplastic anemia.127 Some cats may survive for prolonged periods despite the presence of hypocellular bone marrow.127 Myelofibrosis is defined as proliferation of fibroblasts or collagen in the bone marrow. It can be primary or secondary. Primary or idiopathic myelofibrosis is a disorder of dysplastic megakaryocytes, which produce cytokines that induce proliferation of fibroblasts.52 Secondary myelofibrosis in cats is associated with immunemediated anemia, myelodysplasia, acute myelogenous leukemia, CRD,125 and FeLV infection.52 Most commonly, a moderate to severe nonregenerative anemia is found in cats.125 Myelofibrosis should be suspected when repeated bone marrow aspirates are unsuccessful, and definitive diagnosis is based on finding excessive fibroblasts on histopathologic examination of a bone marrow core biopsy.52 Myelodysplastic syndrome (MDS) comprises a group of proliferative hematologic disorders originating from a mutation in a hematopoietic stem cell.125 Most cats are anemic, and many have other cytopenias. The anemia is commonly macrocytic, normochromic, and nonregenerative. Almost 80% of cats with MDS are FeLV positive.129 MDS is thought to be a preneoplastic condition and may be lethal without progression to leukemia.129 Therapy for cats with MDS is supportive and may include blood transfusions, antibiotics for those with severe leukopenia, and corticosteroids. Survival time for a cat with MDS is likely to be measured in days to weeks from the time of diagnosis. However, some cats may survive for longer than 1 year. By definition, myelophthisis is the replacement of hematopoietic space of the bone marrow by neoplastic, inflammatory, or collagen-producing cells.52 Acute and chronic leukemia may infiltrate the bone marrow, leading to a nonregenerative anemia. Acute inflammatory lesions in the marrow have been associated with immunemediated hemolytic anemia, bacterial sepsis, and infection with the coronavirus responsible for feline infectious peritonitis. Pyogranulomatous inflammation has been observed in cats with disseminated histoplasmosis. The anemia in cats with myelophthisis is often moderate to severe.125

Unfortunately, nonregenerative anemia can be a frustrating problem to solve and sometimes unrewarding to treat. A lack of increased numbers of aggregate reticulocytes in the face of a decreased PCV is indicative of this type of anemia. Extensive testing is often required to achieve a diagnosis. Some cats remain a diagnostic dilemma and must be treated symptomatically with blood transfusions, antibiotics, and corticosteroids. Frequent monitoring is often required to detect changes that may affect the cat’s well-being.

Feline Erythrocytosis Definition Erythrocytosis, also known as polycythemia, is defined as an increase in the red blood cell mass as measured by an increase in the PCV, red blood cell count, and hemoglobin concentration. Like anemia, erythrocytosis is a sign of disease, not a disease in itself. Erythrocytosis is an uncommon finding in cats. EPO is a hormone produced by fibroblasts adjacent to proximal convoluted tubules deep in the renal cortex.47 These cells are subject to negative feedback based on systemic or local oxygen tension. They respond to hypoxia by increasing the production of EPO. Red blood cell precursors in the bone marrow respond to EPO by dividing and maturing into cells capable of carrying oxygen to the tissues. Optimal oxygen delivery in normovolemic cats occurs at a PCV between 35% and 45%.84 When hypoxia resolves, EPO production decreases, and production of new erythrocytes slows. Clinical Signs and Physical Findings The signs associated with erythrocytosis are due to increased blood viscosity. This leads to a decrease in the rate of blood flow in the microcirculation followed by distention and possibly thrombosis of these vessels. Hyperemia, bleeding, and central nervous system signs are the result of these changes. With increased hemoglobin concentration comes a greater chance of exceeding the 50 g/L level of deoxygenated hemoglobin, above which cyanosis becomes evident, making the detection of hyperemia difficult. Bleeding occurs because of rupture of the distended small vessels. Vessel obstruction and bleeding may result in central nervous system hypoxia and subsequent alterations in mentation, seizures, weakness, ataxia, and blindness. Approximately 25% of cats will have splenomegaly.47 Other clinical signs may be present if there is an underlying disease. Classification and Pathophysiology Erythrocytosis can be classified into categories, each with its own unique underlying pathophysiology (Figure 25-15). The disorder can be relative or absolute. Relative erythrocytosis is caused by decreased plasma volume


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and a “relative” increase in the red blood cell volume as measured by the PCV. Whereas the PCV is mildly increased, the total erythrocyte mass is not. Any disease leading to fluid loss and volume contraction may result in a relative erythrocytosis. Common causes include diarrhea and burns. EPO concentrations and reticulocyte numbers would be expected to be low to normal. Splenic contraction does not significantly elevate erythrocyte numbers in cats.84 Absolute erythrocytosis, characterized by an actual increase in the red blood cell mass, is further categorized into primary and secondary absolute erythrocytosis. Primary erythrocytosis is a neoplastic disease seen in young to middle-aged cats in which autonomous erythrocyte precursors in the bone marrow divide and mature in the absence of EPO.84 The other cell lines in the bone marrow remain unaffected. Secondary absolute erythrocytosis is associated with increased EPO production and is divided further into physiologically appropriate or inappropriate. Appropriate secondary erythrocytosis occurs as a normal response to systemic hypoxia and is an appropriate, compensatory response. The most common causes include congenital cardiac disease with right-to-left shunting of blood, a high-altitude environment, chronic pulmonary parenchymal disease, and severe obesity (Pickwickian syndrome).47,84 Serum EPO would be expected to be normal to high. Inappropriate secondary erythrocytosis is defined as increased erythrocyte mass without evidence of systemic hypoxia. The most common cause in cats is renal disease, including solid tumors or diffusely infiltrative neoplasia, polycystic kidney disease, amyloidosis, or pyelonephritis.47 Locally reduced renal parenchymal blood flow due to compression or infiltration leads to focal hypoxia in the cortex, resulting in increased production of EPO.84 Tumors of other body systems may produce EPO or EPO-like substances as a paraneoplastic syndrome. As with appropriate secondary erythrocytosis, EPO levels would be expected to be normal to high. Diagnostic Plans A logical approach to the diagnosis of erythrocytosis is important, insofar as treatment depends on the underlying cause. A thorough history and detailed physical examination, along with a CBC with a reticulocyte count, serum biochemical profile, and urinalysis is the recommended minimum database.84 Relative erythrocytosis should be evident at this phase of the workup; the history and physical examination should reveal evidence of disease causing volume contraction. Along with an elevated PCV, the reticulocyte count should be low because erythropoiesis is not increased. The total plasma protein concentration should be elevated, along with the presence of azotemia and an appropriate increase in urine specific gravity. A

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Polycythemia (PCV 59%) Repeat PCV PCV remains high

PCV returns to normal

Fluid therapy

Relative polycythemia splenic contraction

Remains polycythemic

PCV returns to normal

Absolute polycythemia

Relative polycythemia from hypovolemia

Blood gas analysis

Hypoxia

Secondary polycythemia appropriate response to hypoxia

Renal neoplasia or pyelonephritis

Secondary inappropriate absolute polycythemia inappropriate erythropoietin release

Normal PO2 Evaluate kidneys

No detectable cause

Primary absolute polycythemia polycythemia vera, myeloproliferative disease

FIGURE 25-15 An algorithm that may be useful in deciding the classification of erythrocytosis. A diagnosis of primary erythrocytosis is made only when all other potential causes have been eliminated. The veterinarian should use clinical judgment when following an algorithm because an individual cat may not follow the rules. PCV, Packed cell volume. (Modified from Figure 3-6; Weiss D, Tvedten H: Erythrocyte disorders. In Willard MD, Tvedten H, editors: Small animal diagnosis by laboratory methods, ed 4, St Louis, 2004, Saunders.)

reduction in PCV after volume expansion confirms the diagnosis. If the erythrocytosis is not relative, the next step is to look for evidence of hypoxia and accelerated erythropoiesis. An increased reticulocyte count in the face of an increased PCV suggests increased erythropoietic activity.47 Severe obesity causing decreased pulmonary function may be present.84 Cats with hypoxia often show evidence of respiratory distress and possibly cyanosis. Pulse oximetry and arterial blood gas assessment should confirm hypoxia. An etiologic diagnosis should be pursued by obtaining thoracic radiographs and performing an echocardiogram. Mild bronchointerstitial changes in the lungs and mild left ventricular hypertrophy may be found in cats with hyperviscosity from any cause.47 Rarely, methemoglobinemia in cats can lead to erythrocytosis. If no evidence of hypoxia is found, a diligent search for disorders causing an inappropriate production of

EPO should be performed. Because renal neoplasia (both carcinoma and lymphosarcoma) is the most common cause, imaging of the kidneys is prudent.84 Abdominal radiography, intravenous pyelography, and abdominal ultrasonography may identify structural abnormalities of the kidneys. These procedures may also reveal tumors of other organs that may be producing EPO or EPO-like substances. Primary erythrocytosis is a diagnosis made by exclusion.84 Most cats with this disease will have normal laboratory parameters, other than the hemogram, and normal imaging results. EPO concentrations would be expected to be low to normal84; if not, the veterinarian should reconsider the likelihood of inappropriate secondary erythrocytosis. Bone marrow examination is not helpful in the diagnosis, insofar as there are no markers for abnormal erythrocyte precursors, and absolute erythrocytosis leads to marrow erythroid hyperplasia, no matter the cause.47

Therapeutic Plans Phlebotomy should be the initial treatment for symptomatic cats with absolute erythrocytosis from any cause. The goal is to maintain the PCV such that clinical signs are alleviated. This is usually in the range of 50% for cats, unless they have hypoxia causing an appropriate secondary erythrocytosis.47 No more than 10 to 20 mL/kg should be removed daily to reduce the PCV to the target level, and when it is safe to do so, the veterinarian should administer an equal volume of intravenous fluids or re-infuse the patient’s removed plasma to further reduce viscosity. This should be repeated as needed to maintain the PCV at that range. Phlebotomy is a generally safe procedure. However, phlebotomy is more physically demanding for the operator when dealing with erythrocytosis because of the increased viscosity of the blood being removed. Potential unwanted sequelae include hypovolemia and hypoproteinemia.84 Frequent blood removal may also lead to iron deficiency, and iron supplementation may be required. Therapy for relative erythrocytosis involves volume expansion with appropriate intravenous fluids or blood products and correction of the underlying cause. Successful treatment of inappropriate secondary erythrocytosis resulting from EPO-secreting tumors involves surgical removal of the offending neoplasm after stabilization of the cat’s clinical status and PCV.84 Presurgical phlebotomy may reduce the risk of bleeding or thrombosis during surgery. Drainage of large cysts and antimicrobial therapy may be useful in cats with polycystic kidney disease or pyelonephritis, respectively. Appropriate secondary erythrocytosis is a compensatory mechanism to combat hypoxia; therefore removing too much blood by phlebotomy may exacerbate the hypoxia experienced by the cat. Systemic oxygenation declines with a PCV over 60%, so the veterinarian should attempt to maintain a PCV in the range of 55% to 60%.47,84 Treating the underlying cause is imperative. Severely obese cats should have a proper weight loss program instituted, and cats with heart disease and those with chronic bronchial disease should be treated appropriately. Because cats with cardiac disease may already be volume expanded, crystalloid replacement of the volume of blood removed by phlebotomy may result in volume overload and pulmonary edema. Cats with primary absolute erythrocytosis will require phlebotomy for the rest of their lives. If the procedure needs to be performed too frequently or is ineffective in maintaining the PCV at an appropriate level, the addition of hydroxyurea should be considered. Hydroxyurea is an alkylating chemotherapeutic agent that suppresses production of erythrocytes. The dose should be individualized to maintain an acceptable PCV. The regimen begins with 10 to 15 mg/kg orally every 12 hours until


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the target PCV is met, then continues every other day at the lowest dose needed to maintain that PCV. The dose is increased if the PCV starts to climb.120 Hydroxyurea may cause reversible myelosuppression,47 so a CBC with platelet count should be performed periodically to assess white blood cell and platelet numbers. If cell numbers decrease significantly, the medications should be discontinued until cell counts become normal, and the drug is restarted at a lower dose. Other potential side effects include vomiting, anorexia, and methemoglobinemia at high doses. Prognosis The prognosis for cats with erythrocytosis depends on the underlying cause. Removal of a renal tumor in a patient with secondary inappropriate erythrocytosis may be curative as long as metastasis has not occurred. Animals with primary erythrocytosis have lived for many years with appropriate treatment.47

SELECTED LEUKOCYTE DISORDERS Evaluation of White Blood Cell Changes Interpretation of the leukogram seems straightforward, and often it is. As with investigating any other body system, evaluation of white blood cells involves integration of the signalment, history, and physical findings with the numbers reported on the CBC. Abnormal cell numbers in a healthy cat may be normal for that particular cat. A thorough white blood cell evaluation is both quantitative (cell numbers) and qualitative (smear examination). Interpretation of absolute cell numbers for each of the different cell types is essential; relative cell percentages are often inaccurate and should be ignored. It is also important to look at the value reported for each cell, not just those flagged as abnormal. An important aspect of a CBC is examining a well-made smear for changes in cell appearance. White blood cells are short lived in the circulation, and changes can be rapid. It is important to remember a CBC is an evaluation at a set point in time, and repeated CBCs may be necessary to identify important trends.

Neutrophilia Physiologic Leukogram This increase in leukocyte count is transient and nonpathologic (Box 25-3). The fear or excitement a cat experiences during a trip to the veterinarian results in an increase in epinephrine secretion with subsequent increases in heart rate, blood pressure, and blood flow. Neutrophils and lymphocytes are mobilized out of the marginated pool next to the vessel wall and into the

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BOX 25-3 Some Causes of Neutrophilia in Cats Physiologic Leukocytosis • Stress • Illness • Glucocorticoid administration

Inflammatory • • • • •

Tissue trauma Pancreatitis Surgery Burns Immune-mediated tissue injury

Infection • • • • •

Pyothorax Pyometra Abscesses Peritonitis Mycotic

Metabolic • Uremia • Diabetic ketoacidosis

Acute Hemolysis • Drug induced • Immune-mediated (uncommon) • Hemoplasmosis

Neoplasia • • • •

Lymphosarcoma Granulocytic leukemia Adenocarcinomas Ulcerated or necrotic masses

circulating pool. Because many of the neutrophils in cats are in the marginated pool, the increase in neutrophil numbers can be significant, up to three to four times the upper level of the reference range. The same degree of increase may be expected in the lymphocyte count.10 The changes are immediate and usually last 20 to 30 minutes. A physiologic leukocytosis is, then, mature neutrophilia with lymphocytosis. There should not be an increase in immature neutrophils. Stress Leukogram Chronic pain and illness cause secretion of glucocorticoids, leading to a change in the leukocyte count known as a stress leukogram, which is also recognized in cats receiving exogenous glucocorticoids for disease

management. The increased glucocorticoid concentration results in decreased diapedesis of neutrophils into the tissues, increased mobilization of neutrophils out of the marginated pool and into the circulating pool, and increased production and release of neutrophils by the bone marrow. The stress leukogram is characterized by a mature neutrophilia (no bands), lymphopenia, and eosinopenia. Unlike in dogs, monocytosis is an uncommon finding in cats with a stress leukogram. Resolution of a stress leukogram may take days after cessation of glucocorticoid administration. Inflammatory Leukogram The number of neutrophils in the blood represents balances among bone marrow production and release, physiologic changes in blood flow, diapedesis, and tissue demands. Inflammation from many different causes increases demands for neutrophils, and the bone marrow responds through increased release of stored mature neutrophils and accelerated production of new neutrophils. If the bone marrow can supply enough neutrophils to meet the needs of the inflamed tissue, there should be increases in the number of mature and immature neutrophils in the circulation. This is called a regenerative left shift and is characterized by a neutrophilia with an increased number of band neutrophils. A left shift should not be thought of as just the result of a bacterial infection, although this is a common cause. Immature neutrophils representing greater than 10% of the neutrophils in a cat with neutropenia is also called a regenerative left shift. When tissue requirements for neutrophils outpaces the bone marrow’s ability to replace them, most of the mature neutrophils will be in the tissues and the circulating neutrophils will be composed mostly of immature cells. If the number of bands (or other immature neutrophils) is greater than the number of mature neutrophils, a degenerative left shift is present and is often associated with a guarded to poor prognosis. Severe inflammation can cause changes in the morphology of the maturing neutrophil, leading to the presence of what are known as toxic changes. Döhle bodies are small, retained accumulations of grey-staining cytoplasmic endoplasmic reticulum. They represent mild toxic changes. Retention of ribosomes in the cytoplasm causes basophilia and, along with vacuolization, suggests more severe inflammation. In one study the presence of toxic neutrophils was associated with longer hospitalization.102 This same study also found that, unlike dogs, toxicity was not associated with increased mortality in cats. Toxic granules represent severe inflammation and, in Birman cats, must be differentiated from the nonpathologic neutrophil granulation anomaly seen in this breed. Extreme neutrophilic leukocytosis is defined as a white blood cell count over 50 × 109/L with more than 50% of


the cells identified as neutrophils.64 This finding is associated with a grave prognosis; 76 of the 104 cats in a study of extreme neutrophilic leukocytosis died as a result of the underlying disease.64 Surprisingly, only 29 of the cats were febrile. Categories of disease causing this extreme white blood cell count included various types of infections, malignancies, immune-mediated diseases, and severe tissue necrosis. The highest risk of death associated with extreme neutrophilic leukocytosis was in cats with neoplasia.64

Neutropenia A neutrophil count below the reference range for the laboratory may be caused by overwhelming tissue needs, decreased production or abnormal release of neutrophils by the bone marrow, or immune-mediated destruction (Box 25-4). Deficient neutrophil production

BOX 25-4 Some Causes of Neutropenia in Cats 1. Increased tissue demand or destruction a) Severe bacterial infections b) Drug induced c) Immune mediated d) Paraneoplastic 2. Neutrophil shift from circulating to marginated pool a) Endotoxic shock 3. Decreased bone marrow production a) Myelophthisis i. Neoplasia ii. Myelofibrosis b) Drug-induced (idiosyncratic) i. Chloramphenicol ii. Trimethoprim–sulfa iii. Griseofulvin (especially in FIV-positive cats) iv. Methimazole v. Propylthiouracil vi. Albendazole vii. Anticancer drugs viii. Immunosuppressive drugs (e.g., azathioprine) c) Infectious disease i. FeLV ii. FIV iii. Feline parvovirus (panleukopenia) iv. Histoplasmosis d) Idiopathic 4. Defects in neutrophil precursor maturation and release from bone marrow a) Drug-induced (as above) b) FeLV/FIV infection c) Myelodysplasia d) Cyclic neutropenia FIV, Feline immunodeficiency virus; FeLV, feline leukemia virus.

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is caused by infection with FeLV, FIV, or feline parvovirus (panleukopenia); drug administration; or myelophthisis. Because the half-life of circulating neutrophils, at 7 to 10 hours, is shorter than that for erythrocytes or platelets, neutropenia is often the first evidence of bone marrow disease. Approximately half of cats with FeLV-related disease have neutropenia.43 Mild neutropenia appears to be the most common change and is associated with mild lymphopenia and normal hematopoiesis. Moderate neutropenia is associated with hypoplastic bone marrow and must be differentiated from infection with feline parvovirus.43 Severe neutropenia is caused by ineffective maturation and release of neutrophils by the bone marrow and is associated with a paradoxical marrow granulocyte hyperplasia because the cells produced are not released to the circulation effectively. FeLV can also cause a cyclic neutropenia, with the lowest neutrophil count occurring every 8 to 18 days.43 Occasionally, a healthy cat will be identified with neutropenia after a CBC is performed as part of wellness or preanesthestic testing. It is often difficult to know how aggressively this finding should be pursued. The history and physical examination should be revisited in a more thorough manner. The veterinarian should ensure that a blood smear has been examined to confirm the neutropenia. A new blood sample of adequate volume should be collected for a repeated CBC to eliminate laboratory or blood collection errors.13 If the cat is easygoing, the sample may be collected after exposure to a mild stressful event such as running tap water. Epinephrine secretion will mobilize neutrophils from the marginated pool into the circulating pool for sampling. If the neutrophil count is over 2 × 109/L, monitoring the cat’s temperature and attitude at home is probably sufficient.85 Another reason for an apparently healthy cat to have a mild neutropenia is the manner in which laboratory reference ranges are determined. The reference range is designed to catch 90% of normal patients, meaning that 5% of normal cats will fall below the reference range for neutrophil counts and be considered neutropenic despite being normal for that individual. Sometimes the neutrophil count will persist below 1 × 109/L, necessitating further investigation. A serum biochemical profile and urinalysis should be performed if not already done. Urine can also be collected for culture. The cat’s retroviral status should be ascertained and imaging of the chest and abdomen performed to look for abnormalities. If the neutropenia persists for more than 1 week, the veterinarian should consider performing a bone marrow examination in an attempt to catch bone marrow disease early.13 An afebrile cat with a neutrophil count below 0.5 × 109/L has an increased risk of infection with normal gastrointestinal, nasal cavity, or skin bacteria. Broadspectrum antibiotics should be administered when

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neutrophil counts drop below 0.5 × 109 cells/L and continued until the neutrophil count is over 2 × 109/L.85 These cats should be isolated at home to decrease the risk of infection. They should be kept indoors, and the owner should monitor the cat’s appetite, attitude, and temperature. The owner should refrain from giving the cat table scraps.13 Constant communication between the veterinarian and owner is essential. A cat with a neutrophil count below 0.5 × 109/L, fever, and an unconfirmed bacterial infection should be hospitalized, preferably in isolation, for investigation into the cause of the neutropenia and supportive care. The evaluation would be similar to the workup mentioned previously. Additional tests, depending on physical findings, might include arthrocentesis, cerebrospinal fluid collection, airway wash, echocardiography, and blood cultures.13 The cat should be closely monitored while hospitalized. Parameters to monitor include temperature, respiratory rate, body weight, urine output, blood pressure, and central venous pressure. Hands should be thoroughly washed and laboratory coats changed before handling these cats. One thermometer should be designated for use in this particular cat. Broad-spectrum bactericidal antibiotics should be administered through an aseptically maintained intravenous catheter. Antibiotic administration should continue for 1 to 7 days past the return of the neutrophil count to above 1 × 109/L and resolution of the fever.85 Cats with confirmed pulmonary, urinary tract, or soft tissue infections require antibiotics for a minimum of 7 days past return of the neutrophil count to above 1 × 109/L and resolution of clinical signs and radiographic changes.85 A reduction in fever would be expected 72 hours after appropriate antibiotic administration.85 Potential causes for apparent treatment failure include infection with something other than bacteria, a bacteria not sensitive to the chosen drug, or poor host defenses.

Changes in the Numbers of Other Leukocytes A significant eosinophilia may be seen in cats with endoparasitism or ectoparasitism, certain neoplasms such as mast cell tumors, hypersensitivity reactions such as asthma and eosinophilic gastritis, hypereosinophilic syndrome, or hyperthyroidism.43 An increased eosinophil count by itself should not be used to confirm eosinophilic disease, and the degree of eosinophilia is not helpful in differentiating among the various eosinophilic disorders. Non-neoplastic lymphocytosis in cats can be seen along with a mature neutrophilia in a physiologic leukocytosis or after antigenic stimulation. Lymphopenia is a nonspecific finding in many ill cats. Monocytosis is also a nonspecific finding in cats and has little diagnostic value. A decreased number of monocytes is insignificant. Basophilia is interpreted in a manner similar to eosinophilia.

Hypereosinophilic Syndrome Hypereosinophilic syndrome is a disease characterized by a mature eosinophilia and eosinophilic infiltration into many organs and is usually fatal. Clonal expansion of type 2 helper T (Th2) cells secreting eosinopoietic factors such as interleukin-5 (IL-5) result in increased eosinophil survival.134 The eosinophils infiltrate the liver, spleen, lymph nodes, bone marrow, and the gastrointestinal tract and result in organ failure. Almost three times as many female cats are affected as male cats.11 Clinical signs depend on the organ affected. Vomiting, diarrhea, anorexia, fever, weight loss, and pruritus have been reported. Diagnosis depends on demonstrating excessive eosinophilic infiltration into numerous organs. Often, a fine-needle aspiration biopsy of the liver, spleen, or an affected lymph node will suffice. Although glucocorticoids have been used, no therapy has proved effective in cats. Imatinib mesylate (Gleevec, Novartis), a signal inhibitor, has been used successfully in humans.10 Other promising treatments include the use of anti-IL-5 antibodies, IL-5 receptor blockers, and eosinophil chemotaxis inhibitors.134

Birman Hypotrichosis and Thymic Atrophy A severe combined immunodeficiency has been identified in Birman kittens born hairless. These kittens are T cell deficient as a result of thymic atrophy and die within a few days of birth. Necropsy findings include a lack of a thymus and aplastic lymph nodes. The disorder has an autosomal recessive mode of inheritance.28

Birman Neutrophil Granulation Anomaly Birman neutrophil granulation anomaly is a hereditary trait in Birman cats. The trait is transmitted in an autosomal recessive manner. Neutrophil function is unaffected, and no treatment is necessary. The increased granularity of the cytoplasm of the abnormal neutrophils resembles the cytoplasm of immature cells. The main concern is to differentiate the anomaly from toxic granulation found in severely ill cats.10

Chédiak–Higashi Syndrome Although light blue smoke-colored Persian cats with yellow-green eyes may be attractive, they also may have Chédiak–Higashi syndrome (CHS). Homozygous cats affected by CHS are prone to bleeding and infections and usually die at an early age. They also tend to have abnormal brain stem auditory evoked responses.11 The disease is an autosomal recessive inherited trait. Decreased bone marrow release of neutrophils leads to neutropenia. The neutrophils that do make their way into circulation have defects of intracellular killing and


motility.10 The large granules found in the neutrophils are friable and rupture spontaneously, causing tissue damage such as cataracts noted in cats with this disease.115 Impaired natural killer (NK) cell and cytotoxic lymphocyte function has also been identified. Abnormal platelet granule release results in impaired platelet aggregation and an increased buccal mucosal bleeding time. Diagnosis is based on signalment, history, and physical findings. A few large, eosinophilic granules can be found in the neutrophils, and comparison of the hair shafts of affected animals to those of normal cats reveals large melanin granules in the affected cat.10 At present, there is no cure for the disease. Care should be taken to avoid and control hemorrhage in affected cats. Use of drugs known to cause platelet dysfunction is contraindicated. Administration of recombinant canine granulocyte colony-stimulating factor (rcG-CSF) or IL-2 has been shown temporarily to improve neutrophil function. A bone marrow transplant may resolve the neutrophil and platelet dysfunction, but the neurologic and renal changes will remain.10 Affected cats should not be bred, and their unaffected parents, who are obligate carriers, should be removed from breeding programs.

Pelger–Huët Anomaly Pelger–Huët anomaly is an uncommon, benign congenital defect of leukocyte development found in domestic shorthair cats that is transmitted in an autosomal dominant manner.10 Affected cats are heterozygous because the homozygous defect is lethal in utero. The disorder is characterized by hyposegmentation of granulocytes and monocytes. Cell function is normal, and no treatment is necessary. Affected neutrophils resemble immature band cells; affected cells, however, have mature, clumped chromatin. A healthy cat with this anomaly may be reported as having a degenerative left shift without toxic change. It is important to differentiate a true left shift associated with sick cats from healthy cats with this anomaly to avoid unnecessary, potentially expensive, and possibly invasive testing and treatment. Pseudo Pelger–Huët anomaly is a transient condition caused by various illnesses and administration of drugs such as ibuprofen or anticancer agents.10 The changes resolve after resolution of the disease or withdrawal of the offending drug. Drug-associated changes are idiosyncratic.

DISORDERS OF HEMOSTASIS Hemostasis is a complex and coordinated system, with a balance between clot formation and dissolution. Its sole purpose is to seal the defects in vessel walls that occur in health and disease until they can be mended. Disorders of this system can lead to clinically significant

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bleeding. Fortunately, abnormalities of hemostasis are rare in cats, and spontaneous bleeding is uncommon in patients with these abnormalities. Normal hemostasis comprises primary and secondary hemostasis and fibrinolysis. Primary hemostasis involves interactions among the vessel wall, platelets, and von Willebrand factor (vWf), whereas secondary hemostasis results in the formation of a fibrin mesh. Fibrinolysis is the process of dissolving previously formed clots. It is important to realize that hemostasis (primary and secondary) and fibrinolysis, along with the various inhibitory and amplification steps, are all happening at the site of vascular injury simultaneously, and not in a stepwise fashion.

Primary Hemostasis Platelets are small anucleate cells formed in the bone marrow by fragmentation of megakaryocytes. A single megakaryocyte may produce thousands of platelets, with thrombopoiesis taking approximately 4 days. The survival time of platelets in circulation is 1 to 2 days, after which they are removed by macrophages of the mononuclear phagocyte system in the spleen. Vascular damage leads to local vasoconstriction and exposes subendothelial collagen, to which platelets adhere by way of a membrane receptor. Adhesion to collagen is made more efficient by the presence of vWf. After adhesion platelets undergo shape change (to increase their surface area) and activation (release of granular contents), with the subsequent recruitment of more platelets that adhere to the wound and one another. Platelet-to-platelet adhesion is known as aggregation. Platelet adhesion to the vessel wall and aggregation to one another form a temporary and unstable plug in the damaged vessel that is sufficient to stem bleeding from the minor defects associated with daily life.

Secondary Hemostasis Mediators of secondary hemostasis are produced in the liver (clotting factors) and cells in and surrounding the vessel wall (tissue factor). Clotting factors are released into circulation in inactive form and require activation to become functional. For the hepatocyte to produce factors II, VII, IX, and X, vitamin K1 must be present in adequate quantities. Vascular damage exposes tissue factor to the circulation, which combines with circulating activated factor VII (VIIa) to activate factor X (Xa), the extrinsic pathway of coagulation. Factor Xa activates and combines with factor V (Va). Factors Xa and Va combine with ionized calcium (Ca2+) and phospholipid on the platelet membrane, which localizes the formation of thrombin from prothrombin to the area of the platelet plug. The formation of thrombin is the beginning of the common pathway. Thrombin catalyzes the conversion of

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fibrinogen to soluble fibrin and amplifies the coagulation process by activating other procoagulant factors, particularly those of the intrinsic pathway. Finally, after activation by thrombin, factor XIIIa catalyzes the crosslinking of the fibrin strands into an insoluble mesh that stabilizes the platelet plug produced by primary hemostasis. Classically, the intrinsic and extrinsic pathways were thought to be equally important in initiating the coagulation process. However, in live animals the beginning of the intrinsic pathway, activation of factor XI, is catalyzed by thrombin generated by the extrinsic pathway. Therefore it is more appropriate to consider the extrinsic pathway as the initiator of coagulation and the intrinsic pathway as the sustainer or amplifier of coagulation.103 Inhibition of coagulation prevents excessive and uncontrolled clot formation. Antithrombin (AT), previously known as antithrombin 3, is produced by the liver and inhibits the actions of thrombin, IXa, Xa, and XIa. The presence of heparin on the surface of the vascular endothelial cell augments the function of AT and helps control clot formation at the edges of the damaged vessel localizing the clot to the damaged area.103 Like factors II, VII, IX and X, synthesis of protein C and protein S is vitamin K1 dependent, and they are released in inactive form by the liver. After binding to thrombomodulin on the endothelial cell, thrombin loses its coagulant activity and activates protein C, which combines with protein S to inactivate factors V and VIII.103

thrombocytopenia as the platelets are consumed in an attempt to control the bleeding. However, the decrease is usually mild insofar as thrombopoiesis ramps up quickly and the spleen releases sequestered platelets. Very low platelet counts in bleeding cats are usually the cause of the bleeding, not caused by bleeding.66 Reduced activity or concentrations of clotting factors can be congenital or acquired and result in secondary hemostatic disorders (Table 25-5). Factor XII deficiency is the most common congenital coagulopathy in cats.89 This is an autosomal recessive disorder resulting in prolongation of the partial thromboplastin time (PTT) or activated clotting time (ACT). Because in vivo generation of fibrin does not require activated factor XII, no spontaneous bleeding is associated with this defect. It is most often identified in the course of a preoperative evaluation before an elective surgery or invasive diagnostic procedure such as a liver biopsy.12 Factor IX deficiency (hemophilia B) also results in prolongation of the PTT and ACT.38 This is an X-linked recessive disorder that may lead to bleeding in severely affected male cats. As with all bleeding from factor deficiencies, hematomas and cavitary bleeding are most likely. A definitive diagnosis is based on identification of decreased factor IX activity. Once the gene encoding the feline factor IX protein is sequenced, a genetic test may become

Fibrinolysis

Inherited Factor Deficiency

Comments

Clot dissolution is mediated by plasmin produced by the liver as plasminogen. Tissue plasminogen activator (tPA) is produced by endothelial cells and, as its name suggests, activates plasminogen. Plasmin degrades fibrinogen and soluble and insoluble fibrin into fibrin degradation products (FDPs), which also have inhibitory actions on platelets and various clotting factors. Degradation of cross-linked or insoluble fibrin also results in the production of D-dimers. Inhibition of fibrinolysis occurs by way of inhibition of tPA or plasmin by various proteins.

Factor I (fibrinogen)

DSH, DLH

Factor VII

DSH

Factor VIII (hemophilia A)

DSH, DLH, Persian, Havana brown, Siamese, Himalayan

Factor IX (hemophilia B)

DSH, DLH, British Shorthair, Siamese

Factor X

DSH

Factor XII

DSH, DLH (does not cause bleeding)

Etiology of Hemostatic Disorders Primary hemostatic defects result from vasculopathy, thrombocytopenia, platelet dysfunction, or a combination of these (Box 25-5). They may be congenital or acquired. Ehlers–Danlos syndrome is an uncommon inherited defect of collagen. Cats with this condition typically have hyperelastic skin. Because normal subendothelial collagen is required for platelet adhesion to the damaged vessel, cats with Ehlers–Danlos syndrome have a propensity to bleed, similar to cats with platelet dysfunction. Acute, traumatic bleeding may result in

TABLE 25-5 Secondary Hemostatic Defects

Acquired Factor Deficiency Hepatic disease

Factors II, VII, IX, and X

DIC

FDPs also inhibit the function of multiple factors Vitamin K1 Antagonism or Deficiency

Anticoagulant rodenticide Severe cholestasis

Decreased bile-associated fat-soluble vitamin absorption

Phenobarbital

Decreased activities of factors II and VII

DSH, Domestic shorthair; DLH, domestic longhair; FDPs, fibrin degradation products.


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BOX 25-5 Selected Primary Hemostatic Disorders Thrombocytopenia

Platelet Functional Defects

A—Decreased Bone Marrow Production

A—Inherited

Infection • Retroviral infections • Systemic mycosis involving the marrow • Feline infectious peritonitis • Cytauxzoonosis Neoplasia Drugs • Methimazole • Propylthiouracil • Griseofulvin • Cytotoxic drugs such as chlorambucil • Chloramphenicol • Trimethoprim–sulfa • Albendazole Myelodysplasia

von Willebrand disease Chédiak–Higashi syndrome

B—Increased Destruction Immune mediated Primary Secondary • Drugs • Penicillins • Cephalosporins • Sulfonamides • Methimazole • Propylthiouracil • Infection • Retroviral infections • Mycoplasma haemofelis • Bacterial • Neoplasia • Modified-live vaccines • Inflammatory disorders such as pancreatitis

B—Acquired Drugs • NSAIDs • Clopidogrel • Penicillins • Diazepam • Acepromazine • Ketamine • Propofol Uremia Antiplatelet antibodies from IMTP Fibrin degradation products from DIC Liver disease Myeloproliferative disease

Vessel (Endothelial) Disorders Ehlers–Danlos syndrome Vasculitis • FIP

C—Increased Use/Consumption DIC • Liver disease • Neoplasia • Sepsis • FIP • Shock Hemorrhage (mild decrease only)

D—Sequestration in the Spleen Infiltrative disease Splenitis NSAIDs, Nonsteroidal antiinflammatory drugs; IMTP, immune-mediate thrombocytopenia; DIC, disseminated intravascular coagulation; FIP, feline infectious peritonitis.

available. Cats with less than 1% of the normal activity often die at birth from umbilical bleeding. Cats with greater than 5% activity may have no clinical signs until challenged by trauma or surgery.38 Clinically affected cats are treated with appropriately typed and

cross-matched fresh frozen plasma or, if sufficiently anemic, whole blood transfusions. It must be remembered that hemostatic abnormalities in cats are very uncommon, and spontaneous bleeding associated with them is even more unusual.89

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A combination of primary and secondary disorders may be found in cats with DIC. In one retrospective study, 21 of 69 cats with hemostatic abnormalities had laboratory evidence of DIC, the most common hemostatic abnormality. Most of these cats did not have clinically significant bleeding. Neoplasia, feline infectious peritonitis, and hepatic disease were the most common causes of DIC in this study.89 Another study identified neoplasia and pancreatitis as the most common diseases associated with DIC.24 Only 7 of the 46 cats with DIC in this study had evidence of hemorrhage. DIC consists of excessive thrombin formation combined with the loss of inhibitory control and stimulation of inflammation.105 Normally kept out of circulation by the vascular endothelium, intravascular production of tissue factor by neoplastic cells or inflammatory cytokine-stimulated monocytes initiates DIC.105 The initial phase of DIC is hypercoagulable, with inhibitors counterbalancing the formation of thrombin. This is the non-overt or compensated stage of DIC. Although difficult to detect clinically, treatment at this stage may prevent progression to the next stage. When coagulation inhibitors are overwhelmed, widespread microthrombosis occurs, leading to tissue hypoxia and death. This overt or decompensated phase is clinically important in the deterioration of the patient’s condition. In the study by Estrin and coworkers,24 43 of 46 cats with DIC died or were euthanized. The thrombotic stage is much more common than the hemorrhagic stage of DIC, as demonstrated by the few cats in DIC that bleed.24 The late stage occurs when there is consumption of clotting factors and platelets. Neoplasms can also cause hemostatic abnormalities by causing thrombocytopenia or platelet dysfunction or by producing procoagulants. Inhibition of clotting factors and intrinsic anticoagulants are also potential mechanisms by which substances produced by neoplasms can affect the clotting system. A multifactorial clotting factor defect has been identified in Devon Rex cats involving a decrease in the vitamin K1–dependent activity of the enzyme gammaglutamyl carboxylase.62 Without the function of this enzyme, vitamin K1 is not properly recycled, resulting in decreased activation of clotting factors II, VII, IX, and X. An autosomal recessive mode of inheritance is suspected.62,67 Affected cats may present for spontaneous intracavitary bleeding or uncontrolled postoperative hemorrhage. There may be a history of similar episodes in related cats. Both the prothrombin and activated partial thromboplastin times are significantly prolonged.67 Severe liver failure, intestinal malabsorption, and exposure to anticoagulant rodenticide toxins must be ruled out. Treatment involves transfusion with appropriately typed and cross-matched blood because there are many individuals with blood type B in this breed. Intravenous or subcutaneous administration of vitamin K1 at 5 mg/cat every 24 hours is also required.

Long-term normalization of the laboratory and clinical abnormalities is accomplished by using oral vitamin K1 at 2.5 to 5 mg/cat every 24 hours.62,67 Treatment may be required for the life of the patient. This disorder should be suspected in any Devon Rex cat presenting with a history of unexpected bleeding.

Clinical Evaluation Cats with hemostatic abnormalities are often brought to see the veterinarian for reasons other than spontaneous bleeding. Unlike dogs, cats with hemophilia rarely develop detectable spontaneous bleeding; the disease is suspected after prolonged intraoperative bleeding is noted, often during elective surgery such as ovariohysterectomy or castration. Cats tolerate thrombocytopenia and lower concentrations of clotting factors better than dogs do.66,89 This may be partially due to a cat’s more sedentary lifestyle. Many platelet disorders are secondary to other diseases, and the patient may exhibit signs related to that disease. The patient may be volume contracted or have signs of anemia such as weakness, lethargy, pallor, or respiratory distress. Cats with severe hereditary hemostatic disorders may exhibit bleeding at a young age before elective surgery. Owners should be questioned about potential exposure to anticoagulant rodenticides or drugs known to cause platelet dysfunction. Evidence of hemostatic problems such as melena, bruising, or petechiation may not be recognized by the owner as bleeding. Excessive or prolonged bleeding from previous traumatic events, surgery, dental procedures, or nail trims should be queried. Spontaneous bleeding resulting from severe thrombocytopenia or platelet dysfunction usually arises from small breaks in capillaries that cannot be plugged by platelets. These pinpoint hemorrhages in the skin, mucosa, or conjunctiva are known as petechiae. Coalescence of petechiae into a larger area of bruising is known as ecchymosis. A cat presenting with either of these two abnormalities likely suffers from severe platelet disease. However, cats with platelet disorders may also have epistaxis, hematemesis, melena, hyphema, or hematuria, signs often associated with clotting factor abnormalities. Cats with congenital factor XII deficiency rarely bleed spontaneously. A palpably enlarged spleen may be present if there is excessive immune-mediated destruction of platelets.132

Diagnostic Plans Most hemostatic abnormalities in cats are identified unexpectedly because they are usually subclinical. Once trauma has been ruled out, diagnostic evaluation of a bleeding cat revolves around deciding if the abnormality is with primary or secondary hemostasis or both. The initial step is to perform a CBC with a platelet count


and blood smear examination. Additional tests to consider, depending on clinical signs and results of the CBC, include a serum biochemical profile and urinalysis to identify potential systemic diseases (e.g., hepatic or renal failure) that may result in bleeding diathesis. Retroviral testing is imperative because FeLV is a common cause of thrombocytopenia. Thoracic radiography and abdominal ultrasonography might identify evidence of bacterial bronchitis or abdominal masses or organomegaly that may be responsible for immunemediated thrombocytopenia or DIC. Sampling the bone marrow may yield clues as to the cause of unidentified thrombocytopenia. Because M. haemofelis infection occasionally causes thrombocytopenia, PCR testing for hemoplasmosis is suggested. If anemia is present, a positive Coombs’ test may help prove the presence of Evans syndrome (primary immune-mediated anemia and thrombocytopenia).

Laboratory Evaluation of Primary Hemostasis Primary hemostasis consists of interactions between vascular endothelial cells, platelets, and vWf. A buccal mucosa bleeding time (BMBT), along with a platelet count, is performed before evaluating the levels of vWf. A BMBT should be performed using a standardized stylet rather than a scalpel blade or a hypodermic needle; however, the latter instruments will suffice if the stylet is unavailable. The BMBT is difficult to perform in nonsedated cats and should be less than 4 minutes.66 Longer times suggest an abnormality in any of the components of primary hemostasis. A normal BMBT eliminates primary hemostatic defects as a cause of the bleeding.103 Platelet counting can be performed by an automated cell counter or manually using a hemacytometer, or it can be estimated by examination of the blood smear. The most common cause of thrombocytopenia when reported from a laboratory is artifact caused by platelet clumping. Clumped platelets cannot be counted separately by automated cell counters, which also have difficulty differentiating between the rather large feline platelet and the small feline erythrocyte. The following handling factors are among those that predispose feline platelets to clump: • • • • •

Traumatic venipuncture Slow sampling from a peripheral vein Refrigeration Use of EDTA for anticoagulation Sampling from a recently used vein or through catheters

A smear made from fresh blood should accompany any sample to the laboratory in case it is needed for estimation of platelet numbers. Smears made by the laboratory will be from blood refrigerated before making

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the smear. Using sodium citrate as an anticoagulant can reduce, but not eliminate, the amount of clumping. A normal platelet count reported by the laboratory is probably normal and can be trusted. A low platelet count reported by an automated cell counter should always be confirmed by a manual count or by examination of a fresh blood smear. Estimation of platelet numbers is performed by examining the monolayer of a smear (which is an essential part of a CBC anyway) under oil immersion and counting the number of platelets in 5 to 10 fields. The average number of platelets per oil field is multiplied by 20 to get the number of platelets × 109/L.66 Many clumps suggest a normal number of platelets. A smear examination also allows for identification of shift platelets, evidence of increased marrow production of platelets. The presence of shift platelets precludes the necessity for collecting bone marrow. FeLV infection, a common cause of thrombocytopenia, is also associated with increased platelet volume.44 Spontaneous bleeding caused by thrombocytopenia in cats usually occurs only when the platelet count is lower than 30 × 109/L.51 If bleeding occurs in a cat with a platelet count above this, the veterinarian should consider a concurrent platelet function defect or a secondary hemostatic problem. Because the BMBT evaluates hemostatic abnormalities resulting from platelet disorders in addition to problems with the vascular endothelium, it is unnecessary to perform this test when platelet counts are severely depressed. A prolonged BMBT in a cat with a platelet count over 30 × 109/L suggests a vessel problem such as vasculitis or an inherited collagen defect, congenital or acquired platelet dysfunction, or von Willebrand disease. A detailed history should eliminate the possible exposure to drugs that can cause platelet dysfunction. Platelet function testing is usually performed only by special hemostasis laboratories and often requires freshly drawn blood samples.

Laboratory Evaluation of Secondary Hemostasis Tests evaluating secondary hemostasis include those that test the extrinsic, intrinsic, and common pathways of secondary hemostasis and tests of fibrinolysis. The prothrombin time (PT) evaluates the extrinsic (the initiating pathway) and the common pathway by using tissue factor to activate factor VII and initiate clot formation. The test is rather insensitive insofar as it will be normal until more than 65% of the factor activity is lost103 and is not affected by thrombocytopenia. The activated partial thromboplastin time (aPTT) evaluates the intrinsic (amplification pathway) and common pathways by activating factor XII to initiate clotting. Prolongation of this test also occurs only when over 65% of factor activity is lost. Thrombocytopenia does not affect the test results. The ACT essentially mimics the aPTT in that it also initiates clotting by activating factor XII. Accuracy is affected

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by variations in the temperature at which the test is performed and by the experience of the operator in recognizing the endpoint of the test, which is the formation of a clot. The ACT is very insensitive insofar as it is not prolonged until more than 90% of the factor activity is lost. Severe thrombocytopenia will erroneously prolong the test as platelet cell membranes provide the phospholipids required by the test. An abnormal PT in the face of a normal aPTT suggests an abnormality in factor VII activity, because of either an inherited deficiency or early vitamin K1 antagonism. An abnormal aPTT with a normal PT will occur if there are abnormalities in factors VIII (hemophilia A), IX (hemophilia B), XI, or XII. A patient with a prolonged aPTT is not predisposed to spontaneous bleeding.103 If both the PT and aPTT are prolonged, a common pathway defect, multiple factor involvement, or late vitamin K1 antagonism should be considered. Testing for hepatic failure would be appropriate in this situation. Specific factor activities can be assessed depending on the test results. A low platelet count in association with a prolonged PT and aPTT is consistent with DIC, and an evaluation of fibrinolysis is warranted.

Laboratory Evaluation of Fibrinogen and Fibrinolysis Measurement of the thrombin time evaluates the conversion of fibrinogen to fibrin, and prolongation is suggestive of fibrinogen deficiency, abnormal fibrinogen structure, or inhibition of thrombin by FDPs or heparin. Low fibrinogen concentrations are due to an inherited deficiency, decreased production by the liver, or increased utilization from DIC. FDPs are formed by the plasminmediated dissolution of fibrinogen, soluble (not crosslinked) fibrin or insoluble (cross-linked) fibrin. Increased FDPs are indicative only of plasmin activation because they can be produced by breakdown of fibrinogen without the presence of a clot. D-dimers are the result of plasmin dissolution of cross-linked fibrin found in clots, and increases in this substance truly represent active thrombosis and fibrinolysis. Controversy exists regarding the sensitivity of the D-dimers test for the detection of DIC in cats.105,112 A combination of prolonged PT and aPTT, thrombocytopenia, and elevations in D-dimers is consistent with a diagnosis of consumptive coagulopathy, particularly if there are signs compatible with DIC or a disease known to cause DIC (e.g., neoplasia) is present.

Supportive Care for Cats with Hemostatic Disorders Although most cats with hemostatic disorders do not present with spontaneous bleeding, supportive care for those that do is important in preventing serious

consequences. It is important to identify and control underlying disease; this may remove any triggers for secondary thrombocytopenia, platelet dysfunction, or DIC. Gentle handling is essential in preventing further damage to vessels. Cage rest in the hospital or at home, if possible, is imperative until the cause of the bleeding is isolated and brought under control. Pressure bandages may be required to control bleeding from surgical sites. Fractious cats may require sedation. Offering soft food may prevent gingival bleeding.132 Unnecessary trauma such as elective surgery or intramuscular injections should be avoided. However, should collection of bone marrow be required, the veterinarian should not hesitate to perform the procedure because bleeding is rarely a problem. Drugs that affect platelet function, particularly NSAIDs, should be avoided. If the cat is thrombocytopenic, interfering with function of the remaining platelets will make the situation worse. Blood should be collected as atraumatically and infrequently as possible using small bore needles and preferably sampling from the jugular vein. Several minutes of compression after blood collection may be necessary to prevent hematoma formation. Cats requiring additional fluid support should receive fluids intravenously through a smallgauge catheter. Thoracocentesis or abdominocentesis is not recommended unless respiratory distress is present. Cats suspected of ingesting anticoagulant rodenticides should receive vitamin K1. Cats with bleeding disorders related to biliary obstruction may also benefit from parenteral vitamin K1. A blood transfusion using fresh whole blood may supply needed clotting factors; platelets; and, if the patient is anemic, erythrocytes to cats with DIC. Blood administered to patients with DIC is more effective in controlling clotting factor consumption if heparin is used at the same time. Because cats usually tolerate thrombocytopenia without excessive bleeding, platelet transfusion should be considered when the count is less than 5 × 109/L, which is rarely encountered in this species. However, the veterinarian should always use clinical judgment and not base treatment solely on a number. Administration of platelets to cats with destructive or consumptive causes of thrombocytopenia is usually ineffective because the transfused platelets are quickly lost. Platelets administered to cats with bone marrow failure will last a few days, the normal life span of a platelet.

Thrombocytopenia A genuine decrease in platelet numbers is an uncommon finding in cats. The most common cause of thrombocytopenia is clumping of platelets. If it is determined that the low platelet count is real, a concerted effort should be made to identify the underlying cause. One study of

41 cats with thrombocytopenia identified only one cat with primary immune-mediated platelet destruction.51 Even in cats with documented presence of plateletbound antibodies, 17 of the 19 cats had identifiable underlying causes for the immune-mediated disease.132 The most commonly identified causes of feline thrombocytopenia are infectious. In the previously mentioned study of 41 cats with thrombocytopenia, 19 (46%) had infectious diseases identified as the cause of the thrombocytopenia. Of those 41 cats, 37 were tested for FeLV antigen and 11 (30%) of them were positive. The next most common cause was various types of malignancy, which affected 16 (39%) of the cats.51 Immune-mediated thrombocytopenia (IMTP) is caused by the removal of antibody-coated platelets by macrophages in the spleen. Similar to IMHA, these antibodies may be directed against antigens on the surface of the platelet or against antigens similar in structure to platelet antigens. Disease may reveal hidden antigens on the platelet surface. Antigen–antibody complexes may deposit on the platelet membrane and elicit a type 3 hypersensitivity response (innocent bystander destruction). Platelets also have Fc receptors on their surface and may bind the Fc portion of an antibody to these receptors. Antiplatelet antibodies may also contribute to platelet dysfunction.132 Because primary IMTP is rare in cats, it is important not to immediately administer immunosuppressive doses of glucocorticoids to cats with thrombocytopenia. Laboratory proof of the presence of antiplatelet antibodies is difficult to obtain. Specialized laboratories may be able to perform a flow cytometric assay for platelet-bound antibodies. In most veterinary hospitals the diagnosis of primary IMTP is made by the elimination of secondary etiologies of platelet destruction and response to immunosuppressive therapy. Once secondary causes of IMTP have been eliminated, primary IMTP may respond well to oral prednisolone at 2 to 4 mg/kg every 24 hours.66 In a report of four cats with presumed primary IMTP, two of the three survivors required either administration of a different glucocorticoid or the addition of another immunosuppressive drug to control the disease.6 More information on the use of additional immunosuppressive drugs is found in the section on treating IMHA. The immunosuppressive regime is continued until the platelet count has reached and remains above 75 to 100 × 109/L for at least 1 to 2 weeks. Attempts at reducing the dose should not be made unless the platelet count is acceptable and stable. The veterinarian should start by reducing the dose of any drug added to the glucocorticoid. There is no sense in reducing the dose if the patient is not in remission, as defined by a stable platelet count at a reasonable level and a cat that is not bleeding. It may not be possible, and indeed is unnecessary, to have the platelet count reach the reference range for the laboratory. Once the


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prednisolone dose reaches 0.5 mg/kg every 24 hours, alternate-day dosing may be attempted. If the platelet count starts to decrease at any point, the veterinarian should return to the last effective dose. Frequent monitoring is necessary because relapses are common.6 The etiology of hemostatic disorders is often difficult to identify, insofar as hemostasis is complex and difficult to fully understand. Lack of experience in dealing with these disorders contributes to the difficulty. Fortunately, hemostatic diseases in cats are rare, and significant spontaneous bleeding is even more uncommon.

DISORDERS OF THE SPLEEN The spleen has long been recognized as inessential for life. It is not, however, unimportant; its function in maintaining homeostasis is slowly being recognized. Understanding the microanatomy of the spleen is necessary to understand its function in health and disease. The functions of the spleen include storage of erythrocytes and platelets, extramedullary hematopoiesis, and blood filtration. It is also an important immune organ. Disorders of the feline spleen are uncommonly diagnosed.20

Microanatomy and Circulation The splenic parenchyma is made mostly of white and red pulp. White pulp is composed of lymphoid nodules and loose collections of lymphocytes surrounding small arterioles. Red pulp consists of venous spaces into which arteriolar blood empties along with the macrophagepopulated structural framework of the spleen. In addition to the macrophages, there are increased numbers of lymphocytes and megakaryocytes in the red pulp. Blood enters at the hilus and makes its way through small arterioles to capillaries terminating in the lymphoid nodules of the white pulp or to capillaries leading into the red pulp. Some of the arterioles entering the white pulp continue on to the venous side of the circulation. Venous blood exits the spleen at the hilus and enters the portal circulation. The path an erythrocyte takes between the arterioles and the venous circulation varies by species. In dogs the circulation is sinusoidal; to enter the red pulp, cells have to squeeze through splenic cords and vessel endothelial cells. Cats, however, have nonsinusoidal microcirculation.68 Most erythrocytes pass into the red pulp and flow directly into the venous circulation unimpeded by endothelial cells and unscrutinized by immune cells.44

Function The four major functions of the spleen are storing blood, filtering blood, serving as a site for hematopoiesis, and acting as an organ of immunity. The spleen can store

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between 10% and 20% of the circulation erythrocyte mass and up to 30% of the platelets.68,113 There are three patterns of blood flow through the spleen. Under normal conditions most (90%) of the blood enters the rapid pool and flows through the spleen in 30 seconds. The remainder flows through in approximately 8 minutes (the intermediate pool) or 60 minutes (the slow pool). Blood can be shunted in and out of these pools as needed during times of stress. Because of the nonsinusoidal nature of the feline spleen, splenic contraction does not result in the movement of as many erythrocytes into the circulation as it does in dogs.84 Most of the stored platelets are in the slow pool. Iron from recycled erythrocytes is stored in the spleen while awaiting transport to the bone marrow for use in the production of hemoglobin for incorporation into new erythrocytes. The spleen functions as an organ of filtration. As erythrocytes squeeze through the parenchyma, they come into contact with macrophages whose function is to remove rigid particulate matter from the cell. These particles include parasites, nuclear remnants (Howell– Jolly bodies), and denatured hemoglobin (Heinz bodies). The high metabolic activity in the spleen results in areas with a slightly anaerobic environment.113 The decreased oxygen content causes the cell membrane of old, badly damaged, or abnormal erythrocytes to stiffen. This renders them unable to undergo the deformation required to pass through the sinuses, and they are removed from circulation.113 These cells, and those coated in antibodies, are phagocytosed by nearby macrophages, which process the hemoglobin and recycle the iron. Owing to the nonsinusoidal nature of the feline spleen, the cat is less efficient at removing these cells than is the dog and is one reason that normal cats have higher numbers of Heinz bodies present in the circulation. In addition to obsolete erythrocytes, the spleen also removes bacteria from the blood.68 The fetal hematopoietic function of the spleen in cats ceases at birth.68 In situations of increased need overwhelming the bone marrow, the adult spleen can resume these functions. These conditions can include infiltrative bone marrow disease, immune-mediated hemolysis or thrombocytopenia, inflammatory or infectious diseases, and malignancy. Splenic extramedullary hematopoiesis results in either generalized or nodular splenomegaly and is less common than in dogs. The spleen serves as a major site for clearing microorganisms and is important in the immune response to circulating antigens.113 The spleen is the principle site of IgM production and is therefore important in the early immune response. The many macrophages act in the phagocytosis and processing of antigens. Various cytokines are produced in the spleen to both improve neutrophil function and activate complement. Soluble antigens are sent to the lymphoid centers of the white pulp, whereas particulate antigens lodge in the red pulp,

where they are phagocytosed and sent by macrophages to the lymphoid follicles in the white pulp for further processing.113 The spleen also removes antibody-coated erythrocytes (extravascular hemolysis) and platelets during immune-mediated events.

Clinical Signs and Physical Findings Historical findings in cats with splenic disorders are often vague and usually relate to an underlying disorder. Common complaints include anorexia, vomiting, diarrhea, weight loss, and an enlarged, sometimes painful abdomen. Most of these signs relate to a mass effect in the abdomen with organ displacement. Polyuria and polydipsia may occur; the pathogenesis is unclear, and it resolves after splenectomy.2 The most reliable physical finding in cats with splenic disease is splenomegaly. The enlargement may be generalized or focal. However, not all enlarged spleens are abnormal, nor are they always palpable. Gentle palpation is important because a diseased spleen is often friable and may rupture with rough handling. Other physical changes may be present depending on the primary disease. Peripheral or abdominal lymph node enlargement may be present. At times, it is difficult to differentiate splenomegaly from enlargement of the liver.

Diagnostic Plans When splenomegaly is identified in a patient, a search should begin for an underlying cause. Blood should be obtained for a CBC. Splenic disease is a possible cause for the presence of nucleated red blood cells in the face of a normal PCV. Hypercalcemia may be due to lymphosarcoma. If malignancy is suspected, radiographic views of the chest should be obtained to look for evidence of metastasis. Morphologically abnormal cells or a proliferation of normal cells in the circulation may suggest leukemia. A bone marrow biopsy may be required in this situation. All cats with splenic enlargement should also be checked for retroviral infection. Compiling a list of differentials may be facilitated by classifying the enlargement as generalized or focal. Generalized enlargement (or splenomegaly) can be caused by congestion or by infiltration with neoplastic or inflammatory cells and is the most common type found in cats.113 Focal enlargement can be caused by neoplastic or non-neoplastic lesions. The nonsinusoidal nature of the feline spleen decreases its susceptibility to the formation of nodular hyperplasia and hematomas.113 Visualizing the spleen is important in determining the type of enlargement. Abdominal radiography allows for easy visualization of the spleen, although the location varies owing to its mobility within the abdomen. The head of the spleen is located caudal to the stomach and cranial to the left kidney and appears triangular on a


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capsule and potentially catastrophic bleeding. If a mass is palpable in the spleen, fine-needle aspiration should be avoided until an ultrasound examination can verify that the lesion is not cavitated. Cavitated lesions, while uncommon in cats, are best dealt with by splenectomy. Aspiration biopsies may be unnecessary in cats with diffuse homogeneous splenomegaly without clinical signs.2 Normal cell types collected from a splenic biopsy include medium and large lymphocytes. Neutrophils are rare.

Generalized Splenomegaly

FIGURE 25-16 A transverse sonogram of the spleen of a cat with mast cell infiltration. Note the irregular hypoechoic (darker) area in the middle of the image.

ventrodorsal projection. The tail of the spleen is uncommonly seen in cats,2 so visualizing the tail on an abdominal radiograph is supportive of splenomegaly. Lesions rarely alter the radiodensity of the spleen. Ultrasonography allows assessment of the parenchymal architecture and the surface contour (Figure 25-16). Ultrasonography is sensitive in detecting splenic lesions, but a definitive diagnosis requires sampling the lesion.4 Focal changes in the parenchyma and irregularities in the surface are criteria for lesions in the spleen. Nodular changes within the parenchyma are easily identified as hypoechoic or hyperechoic to the rest of the parenchyma. Benign nodules are difficult to differentiate from malignant masses without using contrast ultrasonography or splenic biopsy techniques. Fine-needle aspiration biopsies can be guided by the ultrasound image. Unfortunately, there are no objective criteria for evaluating the size of the organ in cats. Sampling the splenic parenchyma is crucial in establishing an etiologic diagnosis. A fine-needle aspiration biopsy of a lesion may be sufficient because most diseases of the spleen exfoliate readily.2 In a study evaluating the correlation of the sonographic appearance of splenic lesions to cytologic and histologic diagnoses in 29 dogs and 3 cats, 19 of the aspirated samples matched the histologic diagnosis.4 Carefully performed fineneedle biopsies of the spleen are safe in cats with thrombocytopenia or coagulopathy.2 If ultrasound is unavailable for guidance, an enlarged spleen can be immobilized manually. A 22-gauge needle can be used to obtain cells by moving the needle in and out multiple times. Minimal blood contamination can be achieved by not applying suction with a syringe. The veterinarian must take care not to reposition the needle while it is in the spleen because this may result in laceration of the

Congestion of the spleen can occur after administration of a sedative or general anesthetic (Box 25-6). The capsule relaxes and allows for an increase in the storage capacity of the parenchyma. Portal venous or caudal vena caval obstruction or congestion from right-sided heart failure will infrequently cause splenic congestion. Infarcts may occur secondary to hepatic or renal disease and may obstruct the efferent blood supply. Infiltrative lesions of the spleen are the result of neoplasia, hyperplasia of normally occurring cell types, or inflammation. The most common splenic abnormalities in a report of 101 cats with splenic disease were lymphosarcoma (n = 30), mast cell tumor (n = 27), and extramedullary hematopoiesis and/or lymphoid hyperplasia (n = 27).45 Hyperplasia may occur in response to an increased workload. Massive hemolysis (whether immune mediated or caused by some other mechanism) or the presence of bloodborne antigens increases the number of mononuclear phagocytes and lymphocytes required to do the work. Extramedullary hematopoiesis requires an increase in blood-forming cells in the spleen. Eosinophilic infiltrates may be present in cats with hypereosinophilic syndrome. Different inflammatory cell types are associated with different types of infection. Infectious agents can cause splenomegaly by direct injury or by chronic antigenic stimulation. Potential infectious causes of splenomegaly in cats include retroviral infection, feline infectious peritonitis, hemotrophic Mycoplasma infections, ehrlichiosis, and cytauxzoonosis.2 Patients with peripheral neutrophilia or eosinophilia may have splenic aspirates with increases in those cell types because of the increased numbers in the circulation, not from neutrophilic or eosinophilic inflammatory disease.2

Localized Lesions Focal enlargements in the spleen of cats are less common than generalized splenomegaly.68 Non-neoplastic lesions are more common than neoplastic lesions, but these types are indistinguishable from each other at the time of surgery. Neoplastic lesions can be malignant, benign, or metastatic. Hematomas, nodular hyperplasia,

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BOX 25-6 Causes of Splenomegaly Focal Enlargement Infectious Inflammation Bacterial abscess

Neoplastic Lymphosarcoma Hemangiosarcoma Hemangioma Sarcomas arising from other splenic cell types Metastatic lesions

Non-neoplastic Extramedullary hematopoiesis Hematoma Myelolipoma Hyperplastic lymphoid nodules

Diffuse Enlargement Infectious Inflammation Bacterial: • Mycobacteriosis • Salmonellosis • Hemoplasmosis • Other various organisms Mycotic: • Sporotrichosis • Histoplasmosis Protozoal: • Toxoplasmosis Viral: • Feline leukemia virus • Feline immunodeficiency virus • Feline infectious peritonitis

Neoplastic Mast cell tumor Lymphosarcoma Multiple myeloma Myelolymphoproliferative disorder Malignant histiocytosis

Non-neoplastic Amyloidosis Extramedullary hematopoiesis Pyruvate kinase deficiency Excessive osmotic fragility Other noninflammatory hemolysis

Noninfectious Inflammation Plasmacytic–lymphocytic enteritis Hypereosinophilic syndrome Immune-mediated hemolytic anemia

Congestive Portal hypertension Drug induced (sedation, anesthesia) Right-sided heart failure

abscesses, and foreign bodies may present as focal lesions.

Therapy Treatment of generalized splenomegaly is focused on treating the underlying disorder. Splenectomy may be considered in cats with immune-mediated anemia or thrombocytopenia refractory to aggressive immunosuppressive therapy.2 Splenectomy should be performed in all cats with mass lesions of the spleen because it is difficult to tell neoplastic lesions from non-neoplastic ones. The outcome of this mode of therapy depends on the underlying disease and the patient’s preoperative condition. In a report of 19 cats undergoing splenectomy for various reasons, only weight loss had any prognostic significance.37 The median survival time following splenectomy for the three cats with weight loss was 3 days compared with 293 days for those without. The loss of the filtration function of the spleen can predispose the cat to infections.2 The loss of the filter may lead to increases in morphologically abnormal erythrocytes such as those with Heinz bodies.113 Because the spleen plays a major role in the removal of erythrocyte parasites, splenectomized cats may be more susceptible to infections with hemotrophic mycoplasma. Before performing splenectomy to treat cytopenias, it is important to be certain that the bone marrow is functioning properly. If splenic extramedullary hematopoiesis is the primary source of the missing blood cells, its removal could prove fatal.113

LYMPHADENOPATHY Definition Diseases of lymph nodes are almost always recognized by enlargement. The enlargement may be solitary, regional, or generalized. Solitary lymphadenopathy, as its name suggests, is enlargement of a single lymph node, whereas regional lymphadenopathy is enlargement of lymph nodes draining an anatomic area. Generalized lymphadenopathy refers to enlargement of lymph nodes draining multiple anatomic areas. The enlargement is due to infiltration of cells into the node; the cell types may be normal lymph node constituents, inflammatory cells, or neoplastic infiltrates.

Anatomy and Function Lymph nodes are kidney-shaped structures located throughout the body (Figure 25-17). Afferent and efferent blood vessels enter and exit at the hilus. Afferent lymphatic vessels enter at various points of the periphery. Lymph flows toward the hilus, percolating through cortical, paracortical, and medullary regions of the

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CHAPTER 25 Hematology and Immune-Related Disorders Cortex Outer cortex

Medulla

Inner cortex

Blood vessel

Paratrabecular sinus Medullary cord Lymphatic nodule

Medullary sinus

Subcapsular sinus

Afferent lymphatic vessel with valves

High endothelial venule

1 2

Vein

Paratrabecular sinus

Artery

Subcapsular sinus Capsule (dense connective tissue)

Hilum 3

4 Efferent lymphatic vessel

Lymphatic nodule with a germinal center in the outer cortex; lymphatic nodules contain mostly B lymphocytes

T lymphocytes in the deep or inner cortex The medulla contains medullary cords surrounding medullary sinuses; medullary cords contain mainly macrophages and plasma cells

Medullary sinus Lymph circulation through the lymph node 1 Afferent lymphatic vessels pierce the capsule and open into the subcapsular sinus. 2 Paratrabecular sinuses arise from the subcapsular sinus and penetrate the cortex. 3 Paratrabecular sinuses continue into the medulla as branching medullary sinuses surrounded by medullary cords. 4 The subcortical sinuses are confluent with the medullary sinuses at the hillum and penetrate the capsule to join the efferent lymphatic vessel.

FIGURE 25-17 Anatomic and histologic structure of a lymph node. (From Kierszenbaum AL: Histology and cell biology: an introduction to pathology, St. Louis, 2002, Mosby).

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BOX 25-7 Causes of Generalized Lymphadenopathy

BOX 25-8 Causes of Single or Regional Lymphadenopathy

Infectious

Infectious

Bacterial Viral: • Feline leukemia virus • Feline immunodeficiency virus • Feline infectious peritonitis • Postvaccinal

Bacterial: • Mycobacteriosis • Hemoplasmosis • Various other organisms Mycotic: • Histoplasmosis • Blastomycosis • Cryptococcosis • Sporotrichosis • Phycomycosis Viral: • Feline leukemia virus • Feline immunodeficiency virus • Feline infectious peritonitis

Noninfectious Immune mediated: • Chronic progressive polyarthritis Idiopathic: • Distinctive lymph node hyperplasia of young cats • Generalized lymphadenopathy resembling lymphosarcoma Neoplastic: • Lymphosarcoma • Myelolymphoproliferative disease • Myeloma • Mast cell tumor Non-neoplastic: • Hypereosinophilic syndrome

lymph node, and exits at the hilus through the efferent lymphatic vessel. Lymph then flows to other lymph nodes or into the venous circulation. The cortex of the lymph node is primarily composed of follicles of B cells surrounded by a rim of T cells. The medullary area is made of cords of macrophages, lymphocytes, and plasma cells. The endothelium in the medulla is discontinuous, allowing for exposure of fluid and particles to the immune cells. Between the cortex and medulla is the paracortical area containing small T cells and macrophages acting as antigen-presenting cells.46 The lymph node functions as a filter of interstitial fluid. It retains particles, cells, and antigens brought to it by the afferent lymphatics. The best known function of the lymph node is as an immune organ. All the cell types (B cells, T cells, macrophages, and plasma cells) required for an immune response are brought together in the lymph node.81 These functions form the basis for explaining why a lymph node enlarges. Proliferation of the normal population of immune cells in response to antigens presented to the lymph node will cause it to enlarge, as will neoplastic proliferation of the resident cells. Enlargement will also occur when there is infiltration by inflammatory or neoplastic cells from processes in the region drained by the lymph node. Etiologies causing lymphadenopathy can be found in Boxes 25-7 and 25-8. Neoplastic enlargement is discussed in Chapter 28.

Noninfectious Idiopathic: • Plexiform vascularization • Distinctive lymph node hyperplasia of young cats Local inflammation Neoplastic: • Hemolymphatic neoplasms • Metastatic neoplasia Non-neoplastic: • Eosinophilic granuloma complex

Clinical Signs and Physical Findings The discovery of an enlarged lymph node is often unexpected. The owner may be concerned about a lump found while petting the cat or enlarged lymph nodes may be discovered during a physical examination for a vague illness or during a wellness visit. Questions should be directed at identifying potential underlying illness, as well as the duration of the changes. It is also important to find out how fast the lump is growing. Normally palpable lymph nodes include the mandibular, superficial cervical (prescapular), and popliteal. The ileocecocolic lymph node is sometimes palpable in normal cats. All these nodes are more difficult to palpate in cats than in dogs.81 The fat surrounding a lymph node in an obese cat may give the impression of increased size; however, with more careful palpation the firmer node can be felt in the middle of the fat. If there is significant inflammation, the enlarged lymph node may be painful and the area warm to the touch. Clinical signs in other areas may be

present if the locally enlarged lymph node is acting as a space-occupying lesion: • Dysphagia may be present if a retropharyngeal node is enlarged. • Swelling of the head, neck, and cranial sternal areas (precaval syndrome) may be present if a mediastinal or cervical lymph node is enlarged. • Intrathoracic lymphadenopathy may cause pleural effusion and subsequent respiratory distress. • Horner’s syndrome may be present if there is mediastinal lymphadenopathy. • The cat may have tenesmus if the sublumbar lymph node is large.

Diagnostic Plans Numerous diagnostic procedures are available to evaluate a cat with lymphadenopathy. The easiest, fastest, and most noninvasive means of obtaining information about a palpably enlarged lymph node is a fine-needle biopsy. In some cases the results provide an etiologic diagnosis; in others the results lead to the selection of additional tests that may be helpful. Retroviral testing should be performed on all cats with generalized lymphadenopathy. Thoracic radiographs and thoracic and abdominal ultrasound examination may reveal an enlarged lymph node in these areas. An exploratory laparotomy should be considered if a lymph node presents as a large abdominal mass. The cytologic appearance of the normal lymph node is a heterogeneous population of small lymphocytes. Any enlarged lymph node with normal cytology should be considered reactive (hyperplastic) because normal nodes do not enlarge.46 Increased numbers of medium and large lymphocytes and plasma cells are also to be expected in a reactive lymph node. Lymphadenitis is either suppurative, pyogranulomatous, or eosinophilic. Suppurative lymph nodes should be cultured. If a fineneedle biopsy is inconclusive (as it often is in cats), an excisional biopsy should be performed. Other tests to contemplate depending on the results of the fine-needle biopsy include a CBC, serum biochemical profile, urinalysis, bone marrow biopsy, and infectious disease serology.81

Therapy Treatment of a cat with lymphadenopathy involves treating any identified underlying disease. If an underlying cause cannot be identified, the temptation to use glucocorticoids in an attempt to shrink the size of the lymph node should be resisted. Idiopathic lymphadenopathies have been reported in cats that either require only patience or can be treated surgically.


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Distinctive Lymph Node Hyperplasia of Young Cats There is a report of 14 cats with peripheral lymphadenopathy with microscopic architecture of the lymph nodes similar to cats with experimental feline leukemia viral infections.77 The 14 cats were young (5 months to 2 years of age) with no gender predilection. Eight of the 14 cats were healthy aside from the lymphadenopathy. The others had a combination of signs such as lethargy, anorexia, fever, or hepatosplenomegaly. Vaccines had not been administered for at least 4 months and were not considered responsible for the lymph node enlargement. Generalized peripheral lymphadenopathy was present in 13 of the 14 cats; the other had only an enlarged mandibular lymph node. The nodes were judged to be 2 to 3 times the normal size. Some of the cats had abnormalities such as anemia, neutrophilia, and lymphocytosis, and 6 of 9 cats tested were positive for FeLV antibodies. The outcome was known for 10 of the 14 cats. Two were euthanized because of the positive FeLV status; the other eight were followed for 5 years. One cat developed mediastinal lymphosarcoma, and six experienced complete resolution of the lymphadenopathy over a 2- to 28-week period. The remaining cat had episodic lymphadenopathy. The cause of the spontaneous lymph node hyperplasia in these young cats was not determined. The similarities of the lesions to those found in cats with experimental FeLV infections and the exposure to the feline leukemia virus in six of the cats suggest that the virus may be involved in the pathogenesis of the disease.

Generalized Lymphadenopathy Resembling Lymphosarcoma There is a report of six young cats with generalized lymphadenopathy with lesions similar to those of lymphosarcoma.76 The cats were 1 to 4 years of age and were either Maine Coons (three) or domestic shorthairs (three). Four of the cats were initially seen for urinary or upper respiratory disease. The other two were from FeLVpositive homes. The only significant physical finding was generalized lymphadenopathy. One cat was euthanized after an initial diagnosis of lymphosarcoma. Of the other five cats, four had a persistent leukocytosis with two of them having atypical lymphocytes or a lymphocytosis. FeLV antigen tests were negative in the five cats. Histopathologic evaluation of the lymph nodes revealed some features consistent with lymphosarcoma; however, some of the findings were not compatible with malignancy, such as a lack of high-grade anaplastic changes, no capsular invasion, a mix of infiltrating cell types, and the presence of normal follicles. None of the cats was treated because the clinical and histopathologic features of their disease were equivocal for neoplasia.

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Surprisingly, all went on to experience regression of the lymphadenopathy within 1 to 17 weeks. All the cats were still alive and doing well 1 to 7 years after the initial examination for lymphadenopathy, supporting the diagnosis of nonmalignant lymphadenopathy.

properties at high concentrations. Cytokine structure is not well preserved across mammalian species so that administration of a nonfeline cytokine to a cat often elicits an antibody response, resulting in loss of function.63

Plexiform Vascularization of Lymph Nodes

Physiology

An unusual cause of lymphadenopathy in cats has been reported,81 specifically in adult cats ranging in age from 3 to 14 years. All cats were clinically normal except for one or two enlarged lymph nodes. Two cats with inguinal lymphadenopathy were affected bilaterally. The disease was characterized by replacement of the follicles by a plexiform proliferation of small blood vessels. The cause of this change was unknown, but removal of the affected gland(s) was curative. Because lymphadenopathy has many potential causes, a cat presenting with generalized lymphadenopathy should not automatically be convicted of having malignant disease. Many cats may prove to have curable diseases when approached with a systematic, logical evaluation.

Currently, there is great interest in exploring the use of cytokines in feline medicine. Imbalances in cytokine profiles are associated with a wide range of diseases in cats. Potential uses include use as tools for investigating the underlying pathogenesis of disease and for the diagnosis, monitoring, and therapy of disease. Efforts are hampered by the lack of specifically cloned feline molecules, the complexity of the cytokine regulatory system, and the paucity of cats available for evaluation. Individual cytokines may have actions in cats that are not predicted by their effects in humans and mice.95

Production of cytokines is induced by alteration in gene expression and is usually transient. Cytokines act by binding to specific receptors on the surface of the target cell, with a subsequent modification of gene expression in that cell. This changes cell proliferation, differentiation, or function, often in concert with other mediators. Circulating non–cell-associated receptors for the cytokines may be present to prevent systemic actions if some should reach the circulation.23 Normal embryonic development may be affected by alterations in cytokine concentrations, leading to birth defects.23 Hematopoiesis is modified by the presence or absence of EPO, thrombopoietin (TPO), or colonystimulating factors (Figure 25-18). Cytokines are active in immunoregulation through a complex interaction among the various cytokines, which activate or suppress helper T cells (Th cells) (Figure 25-19). The outcome of these interactions is an alteration in the balance of cellmediated and humoral immunity. Activated macrophages elaborate various cytokines important in the acute inflammatory response by altering vascular permeability, increasing endothelial leukocyte adhesion and leukocyte chemotaxis (Box 25-9). The acute phase inflammatory response is, in part, mediated by cytokines secreted by these macrophages. Nonspecific effects of chronic inflammation such as cachexia and tissue destruction may be due to the presence of cytokines. Growth factors have a role in wound healing by stimulating the migration of fibroblasts into the wound and increasing angiogenesis.

Definition

Therapeutic Uses

Cytokines are small glycoproteins secreted by many different cells, including dendritic cells, lymphocytes, macrophages, monocytes, endothelial cells, and fibroblasts in response to specific stimuli. Interleukins, interferons, lymphokines, tumor necrosis factors, and hematopoietic growth factors such as EPO are examples of cytokines. They act locally in intercellular communication to regulate cell growth and maturation, regulate immune and inflammatory responses, and modify hematopoiesis. They affect multiple cell types and are important enough that the effects often overlap those of other cytokines, acting as a natural backup system. Some cytokines have different effects depending on the concentration; for example, interferon (INF)-alpha has immunostimulating properties at low concentrations but immunoinhibitory

Manipulation of cytokines for use in treating disease can involve administration of the cytokine itself in one form or another. Presently, cytokines are primarily used to treat hematocytopenias. The best-known example is the use of EPO to treat hypoproliferative anemia. Cytokines may also be used to treat tumors. Intralesional injections of IL-2 may be beneficial as an adjunctive therapy for fibrosarcoma.23 In the future it may be possible to use cytokines to augment the immune response to disease or alter tissue repair. Inhibiting cytokine activity may modulate the immune response and result in novel methods of treating immune-mediated and allergic disease. Glucocorticoids and cyclosporine are examples of drugs that inhibit production of proinflammatory cytokines such as IL-2. Glucocorticoids also stimulate

CYTOKINES


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FIGURE 25-18 Cytokines important in proliferation and differentiation of cell types during hematopoiesis. B, B-lymphocyte; BFU-E, burst-forming unit-erythrocyte; CFU-Ba, colony-forming unit-basophil; CFU-E, colony-forming unit-erythrocyte; CFU-Eo, colony-forming unit-eosinophil; CFU-G, colony-forming unit-granulocyte; CFU-Gemm, colony-forming unit-granulocyte-erythroid-monocyte-megakaryocyte; CFU-GM, colony-forming unit-granulocyte-monocyte; CFU-M, colony-forming unit-monocyte; CFU-Meg, colony-forming unit-megakaryocyte; EPO, erythropoietin; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-monocyte colony-stimulating factor; IL, interleukin; M-CSF, macrophage-monocyte colony-stimulating factor; MK, megakaryocyte; NK, natural killer cell; Pax-5, transcription factor produced by expression of PX-5 gene in B-lymphocyte development; T, T-lymphocyte; TPO, thrombopoietin.

BOX 25-9 Important Cytokines Released from Stimulated Macrophages Interleukin-8

Tumor Necrosis Factor

• Induces inflammation by stimulating leukocytes • Chemotactic for neutrophils • Serves as principle secondary mediator of inflammation

• Causes vascular endothelium to become adhesive for leukocytes • Activates inflammatory leukocytes • Stimulates nearby macrophages to produce interleukin-1, interleukin-6, and interleukin-8

Interleukin-6 • Stimulates hepatocytes to synthesize acute phase proteins • Serves as principle growth factor for B cells

Interleukin-1 • • • •

Enhances proliferation of helper T cells Enhances growth and differentiation of B cells Stimulates interleukin-2 production by Th1 cells Stimulates nearby macrophages to produce interleukin-6 and interleukin-8

Interferon-alpha • Inhibits viral replication in adjacent cells • Inhibits cell proliferation in adjacent cells • Increases class I major histocompatibility complex (MHC) expression in adjacent cells • Increases lytic potential of natural killer (NK) lymphocytes

Interleukin-12 • Enhances interferon-gamma production by Th1 cells and further activation of macrophages • Inhibits Th2 cell proliferation and activation

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FIGURE 25-19 Regulatory effects of interleukins secreted by macrophages and Th1 and Th2 lymphocytes on the cell-mediated and humoral immune response after antigen presentation by dendritic cells. Red, dashed lines represent inhibitory effects. Solid black lines represent stimulatory effects. IL, interleukin; INF, interferon.

the production of IL-10, an immunosuppressive cytokine. Antibodies against the cytokine or its receptor may help reduce its activity. Inactivation may also be accomplished by the use of direct cytokine antagonists or administration of their receptors in soluble form. IL-2 receptor antagonist protein (IRAP) has shown promise in reducing the severity of inflammatory bowel disease.23 Manipulation of a single cytokine may trigger mechanisms that control its activity and neutralize or enhance its effect.114 No treatment is without potential adverse effects, and cytokine therapy is no exception. Systemic use of cytokines has resulted in fever, anorexia, nausea, pain, anemia, shock, pulmonary edema, coma, or death.

Interleukins Interleukins are cytokines produced by antigenactivated dendritic cells, lymphocytes, and macrophages (see Figure 25-19). As with all cytokines, they act by binding to specific receptors on the effector cell. In health fewer than 15% of immune cells have

interleukin receptors on the surface. This guards against an overzealous immune response.48 Bacterial and viral infections stimulate Th1 cells to produce interleukins such as IL-2, interferon (INF)-gamma, and tumor necrosis factor-alpha that are responsible for enhancing cell-mediated immunity. These interleukins activate natural killer (NK) cells, cytotoxic lymphocytes, and macrophages. IL-12 is secreted by activated macrophages with subsequent activation and recruitment of new Th1 cells, thereby acting as a positive feedback loop to amplify the cell-mediated immune response. IL-12 is also a potent stimulator of NK cell and cytotoxic lymphocytes. Large, extracellular parasites activate Th2 cells to secrete interleukins that result in augmentation of the humoral arm of the immune system.48 Increases in B lymphocytes, eosinophils, and mast cells follow. Th2 cells also release the antiinflammatory interleukins, IL-4 and IL-10. These potent inhibitors of INF-gamma secretion by Th1 cells act to reduce cell-mediated immune activity. These two interleukins also stimulate activation of B lymphocytes and

mast cells.48 Of course, there is never stimulation or inhibition of only Th1 or Th2 cells; a balance must be maintained, or illness ensues. IL-2, part of cell-mediated immunity, may be useful in the treatment of malignancy. For example, IL-2 activates the tumoricidal effects of pulmonary alveolar cells.48 Animals with depressed cell-mediated immunity may have derangements in IL-2 production. Dogs with generalized demodicosis have decreased expression of IL-2 and decreased numbers of lymphocytes with IL-2 receptors. Production of IL-2 by feline lymphocytes infected with retroviruses is decreased. IL-8 is a potent neutrophil activator and may be useful in disorders characterized by neutrophil dysfunction. Antagonists of IL-8 may have a role in combating asthma. IL-12 is a potent inhibitor of tumor angiogenesis and has potent antitumor effects that may be used to treat neoplasia. IL-12 may also have a role in the development of autoimmune diseases.

Hematopoietic Growth Factors Differentiation, proliferation, and maturation of the different types of stem cells in the bone marrow are stimulated by various cytokines. EPO and TPO stimulate increases in production and release of erythrocytes and platelets, respectively. A number of cytokines mediate similar activities on leukocytes. Granulocyte colonystimulating factor (G-CSF) is produced by bone marrow stroma, neutrophils, and endothelial cells. The receptor for G-CSF is found on both immature and mature neutrophils and stimulates proliferation and maturation of neutrophils. G-CSF also enhances neutrophil chemotaxis and antibody-dependent cell-mediated cytotoxicity and increases the expression of Fc receptors on the neutrophil surface.63 A neutrophilia reliably occurs 24 hours after administration of recombinant human (rh)-G-CSF to healthy cats and is useful in preventing chemotherapeutic neutropenia. Using G-CSF to reverse an established neutropenia, such as seen in cats with FeLV infection, is unrewarding. The action of rh-G-CSF in cats ends when the patient starts making antibodies against the cytokine. The recombinant canine product, however, retains its efficacy, suggesting that antibodies are not produced.63 Granulocyte monocyte (GM)-CSF is made in fibroblasts, endothelial cells, T lymphocytes, and monocytes. The targeted cells are neutrophils, eosinophils, monocytes, and their respective progenitor cells. GM-CSF prolongs the survival of the target cells and enhances their function. GM-CSF–activated macrophages recognize and kill tumor cells and present their antigens to Th cells as a part of tumor immune surveillance.63 MacrophageCSF promotes the survival and functions of macrophages and may be useful in treating fungal infections.63 Stem cell factor is produced by bone marrow support cells and


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endothelial cells and may find uses in treating aplastic anemia, myelofibrosis, or bone marrow toxicity.

Investigational Use Cytokine profiles and individual cytokines are being used by researchers investigating many different disorders in cats. The cytokine profile information can elucidate the extent to which each arm of the immune system is involved in the pathogenesis of the disease. Are the increases or decreases in the various cytokines measured consistent with activation of Th1 or Th2 cells? Is the response stimulatory or inhibitory? Assessment of individual cytokines may present opportunities for intervention in the disease process. Many different body systems and individual infectious diseases have been examined with regard to cytokines. Tumor necrosis factor-alpha is produced by cardiac myocytes in response to ventricular pressure overload in cats with cardiomyopathy and has been implicated in the pathogenesis of cardiac cachexia, ventricular dysfunction, and the development of congestive heart failure.73 Evaluations of the cytokine profiles of the nasal and oral cavities in cats suggest that a Th1 profile of cytokines is present to protect against bacterial and viral infections of these tissues. An increase in Th1 cytokines is associated with progression of the signs and histologic changes of nasal cavity disease. Humans with allergic rhinitis have Th2 profiles.50 IL-4–producing lymphocytes have been found in lesional and nonlesional skin from cats with allergic dermatitis, but not from the skin of healthy control cats, which suggests a role for IL-4 in allergic skin disease in this species.96 IL-5, thought to be a major regulator for eosinophils, was not correlated with the number of eosinophils in cats with suspected allergic dermatitis, whereas IL-2 was.80 This is an example of an investigation with a conclusion that steers therapeutic intervention away from what theory suggests should be effective. Antibodies against IL-5 and IL-5 receptor blockers are under investigation for the treatment of hypereosinophilic syndrome.134 Inflammatory disease in other body systems would seem to be reasonable areas of investigation. Indeed, cytokine evaluation in cats with inflammatory bowel disease (IBD) is an ongoing area of interest. Nguyen Van and coworkers found a statistically significant increase in both proinflammatory and regulatory cytokine expression in cats with inflammatory lesions of the intestine compared with those without inflammation. They concluded that the pathogenesis of IBD involves aberrations in both regulatory and inflammatory aspects of the immune system.82 The ACVIM consensus statement on gastrointestinal inflammation suggests that a role for decreased immunoregulation is predicted in the pathogenesis of IBD in cats based on the cytokine profile from humans and rodents.123 The pathogenesis and response to treatment of allergic airway disease in cats involves

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alterations in cytokine profiles. An imbalance in cytokine production favoring Th2 cell products in response to environmental aeroallergens is thought to be a major part of the pathogenesis of this disease.101 These Th2derived cytokines lead to increased production of allergen-specific IgE. Investigators are evaluating different substances for their efficacy in altering or inhibiting the activity of these cytokines.101 Even behavior can be affected by cytokines. Increased IL-2 in certain areas of the brain has been found to potentiate defensive rage behavior in cats.5 Perhaps the most important area of study of cytokines is in the pathogenesis and treatment of infectious diseases. This area of study may be important in designing prevention and therapies for infections with FIV. Increased IL-10, an immunosuppressive Th2 cytokine, was found in the early stages of FIV infection corresponding to high viral replication. This was followed by an increase in IFN-gamma levels to bring the ratio back into balance. The increase in IFN-gamma was associated with a decreased tissue viral load.3 In a challenge study, cats infected with FIV and then challenged with Toxoplasma gondii infections produced significantly lower amounts of Th1 (proinflammatory) cytokines compared with challenged FIV-negative controls. The FIV-positive cats also maintained the elevated levels of IL-10 found before the challenge with T. gondii.61 Imbalances in Th1 versus Th2 cytokines were also suggested as a cause for the development of lesions in the neurologic form of FIP. It was also thought that a failure to increase IFN-gamma concentrations in the infected tissues might be an important reason these cats succumbed to the FIP infection.30 Another example of using a cytokine for the treatment of infectious disease is the use of rhIFN-alpha to treat cats with FeLV infections.23 Although the use of cytokines holds great promise for feline medicine, much research must still be performed to fully understand the complexity of the system and the implications of manipulating it and to develop new strategies for using cytokines to intervene in the management of sick cats.

SYSTEMIC LUPUS ERYTHEMATOSUS Definition Systemic lupus erythematosus (SLE) is a rare disease characterized by autoimmune damage to multiple tissues and organ systems. The most commonly affected tissues in cats include synovial joints, glomeruli, skin, blood cells, and the central nervous system (Box 25-10). The syndrome mimics many other disorders, and diagnosis can be difficult because diseases including infectious and neoplastic causes must first be eliminated.

BOX 25-10 Disorders Consistent with Systemic Lupus Erythematosus Major Signs Immune-mediated hematologic disease • Immune-mediated hemolytic anemia • Immune-mediated thrombocytopenia • Immune-mediated leukopenia Polymyositis Glomerulonephritis Non-erosive immune-mediated polyarthritis Vesicobullous dermatitis

Minor Signs Oral ulceration Fever of unknown origin Central nervous system disturbances • Seizures • Dementia • Coma Pleuritis Myocarditis Pericarditis Peripheral lymphadenopathy

Signalment Young to middle-aged cats are most commonly affected,65 and unlike in humans, there is no gender predilection.69 Purebred cats are more likely to be affected than domestic cats.106

Clinical Signs and Physical Findings Clinical signs depend on the body system affected. These can include fever; lameness; muscle pain; lymphadenopathy; ulcerative stomatitis; skin lesions such as crusts, erythema, and ulceration; depigmentation around the head and paws; pale mucous membranes; and central nervous system signs ranging from subtle behavioral changes to alterations in mentation and seizures. These signs may be exacerbated by ultraviolet radiation from the sun or concurrent infection.106

Pathophysiology The changes resulting from SLE are due to inflammation of the affected body part. Dysregulation of the immune system (possibly the result of abnormal function of T suppressor cells) leads to an attack against the body’s self-antigens and is responsible for the inflammation. Circulating antigen–autoantibody complexes deposit in the vessel walls of the synovium, glomerulus, or choroid plexus (type 3 hypersensitivity). Complement is


activated, and neutrophils and macrophages are recruited, resulting in vasculitis and damage to tissues. Less commonly, antibodies against nuclear, cytoplasmic, and membrane antigens (type 2 hypersensitivity) alter cell function. Direct T cell damage of tissues (type 4 hypersensitivity) is also possible.106

Diagnostic Plans Diagnosis of SLE requires an increased index of suspicion for a cat with apparent multisystemic disease. Various criteria have been proposed for the diagnosis of SLE in dogs and cats based on those used for the diagnosis in people. One such proposal requires evidence for autoimmune injury to at least two organ systems, along with a positive antinuclear antibody (ANA) test, or three affected organ systems with a negative ANA titer. A positive ANA titer is neither sufficient nor required for a diagnosis.106 Most commonly, a combination of the following occurs: • • • • • •

IMHA IMTP Immune-mediated skin disease Glomerulonephritis Central nervous system signs Non-erosive immune-mediated polyarthritis106

No single test is available to diagnose SLE. A CBC, serum biochemical profile, ANA test, and urinalysis should be performed along with thoracic radiographs to rule out potential bronchial infections. The ANA test is relatively sensitive in identifying anti-self antibodies. The results are reported as a titer along with an immunofluorescence pattern that is clinically insignificant.106 Many false-positive and false-negative tests occur. False-positive tests may occur in cats with infectious, neoplastic, or chronic inflammatory diseases. About 10% of healthy cats will have a low titer for ANA.106 Therefore a high ANA titer is more consistent with SLE than is a low titer. A lupus erythematosus (LE) cell preparation identifies neutrophils with phagocytosed nuclei in the cytoplasm. Interpretation depends on the experience of the technician, and many false-negatives occur.106 Because of the difficulty in performing the test and problems with sensitivity, it has largely been replaced with the ANA test. If there is evidence of a regenerative anemia, the veterinarian should perform a Coombs’ test and a PCR test for hemotrophic mycoplasmosis. The cat’s retroviral status should also be ascertained. If there is joint pain or effusion, synovial fluid should be obtained for cytology; the synovial neutrophils should be well preserved in a cat with SLE. If the neutrophils are lytic or if bacteria are present, a culture of the fluid should be performed.69 Cats with azotemia and proteinuria should have the urine protein to creatinine (UPC) ratio measured. A

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renal biopsy should be performed if the UPC ratio is high because the elevated protein may be due to glomerulonephritis. One cat was identified with coagulation defects because of the presence of a circulating lupus anticoagulant, an antibody against phospholipid that interferes with function of the common coagulation pathway and platelets (see the section on hemostasis). This cat had prolongation of both PT and aPTT. No overt bleeding was reported.65 Any skin lesions should be biopsied in an appropriate manner.69,106 To make a diagnosis of SLE, infectious and neoplastic causes must be eliminated as possible explanations for the cat’s clinical signs.

Therapeutic Plans Control of tissue inflammation and addressing organ failure are the goals of therapy for SLE. In situations where there is mild pain, NSAIDs may suffice.69,106 If not, or if the signs are more severe, immunosuppressive doses of corticosteroids should be started. Prednisolone at 2 to 4 mg/kg daily should be effective. If there is no improvement in 1 week, consideration should be given to a change in therapeutic plans such as the addition of cytotoxic immunosuppressants. Ultraviolet light can be a trigger for some cats with SLE, and they should be kept out of the sun. Additional immunosuppression can be achieved by adding cytotoxic drugs such as chlorambucil. Chlorambucil is well tolerated, with minimal side effects; however, the dose must be individualized to the particular patient. A good starting point is 0.25 to 0.5 mg/kg orally every 24 to 48 hours.69 Side effects include anorexia and myelosuppression. Constant communication between owner and veterinarian is essential. Once remission has been achieved, a reduction in drug dose can begin. Remission is defined as resolution of clinical signs and initial radiographic and laboratory changes.106 If combination therapy has been used, the chlorambucil should be reduced first. The dose is reduced by 50% for 4 weeks. As long as clinical remission continues, further reductions can take place every month. Usually a minimum of 6 months of therapy is required.106 If a relapse occurs, the veterinarian should return to the previous effective dosage until remission is accomplished. Further attempts at reducing drug dosages should be made more slowly. Some cats will require lifelong therapy.

Prognosis Because SLE in cats is rare, the natural course of the disease is unknown. Many cats will achieve remission, and drug doses can be tapered; however, relapses should be expected to occur. Frequent follow-up examinations and laboratory evaluations may be necessary.

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SYSTEMIC ANAPHYLAXIS Systemic anaphylaxis is a life-threatening allergic event resulting in massive, generalized mast cell degranulation. The inflammatory mediators released by mast cells result in grave consequences if not treated promptly. Because time is of the essence, recognizing the signs of anaphylactic shock is essential if the veterinarian is to institute appropriate therapy.

Pathophysiology An anaphylactic reaction is mediated by interactions among antigens, IgE antibodies, and mast cells. This type I hypersensitivity reaction requires previous exposure to an antigen and production of IgE against that antigen. Many different substances can play the role of antigen, including drugs such as NSAIDs and antibiotics, insect or reptile venom, food, vaccines, and inhaled allergens. Most animals produce IgA or IgG when exposed to an environmental allergen, whereas others have an exaggerated Th2 response and produce excessive amounts of IgE.116 Once the cat is re-exposed to the antigen, it can be bound to IgE molecules on the mast cell surface. Cross-linking occurs when the antigen is bound to two IgE molecules at the same time. Once the two antibodies are cross-linked, IgE receptors signal the mast cell to degranulate, produce increased quantities of phospholipase A2, and begin production of new inflammatory cytokines. Degranulation of mast cells results in the release of preformed mediators of inflammation. This occurs rapidly, with evidence of their effects appearing within seconds to minutes of exposure to the antigen. These mediators, which include but are not limited to histamine, heparin, kallikrein, and inflammatory cell chemotactic factors, result in physiologic changes responsible for many of the clinical signs recognized as anaphylactic shock. Histamine bound to H1 receptors causes smooth muscle contraction in the intestinal tract and in the airways and pulmonary vasculature. H1 activation also results in increased vascular permeability and neutrophil and eosinophil chemotaxis. Binding to the H2 receptor is followed by increased production of airway mucus and bronchodilation. The balance between H1 and H2 stimulation results in hypotension, bronchospasm, airway obstruction, hyperperistalsis, increased vascular permeability, and pruritus.15 Chemotactic factors amplify the inflammatory reaction by recruiting neutrophils and eosinophils. Consequences of the release of other mast cell mediators include complement activation, enhanced smooth muscle contraction, increased vascular permeability, and stimulation of pain sensors.121 Phospholipase A2 acts on the phospholipids in the cell membranes to form arachidonic acid. Although

not as immediate as degranulation, this process still occurs within minutes of exposure to the antigen. Production of secondary inflammatory mediators such as prostaglandins, leukotrienes, thromboxane, and plateletactivating factor augments inflammation, bronchoconstriction, and vascular permeability. A late-phase inflammatory reaction occurs after newly produced cytokines are released by the mast cell. This occurs between 2 and 24 hours after exposure to the antigen. Cytokines produced by mast cells include IL-4, IL-5, IL-6, IL-13, IL-16, tumor necrosis factor-alpha, and macrophage inflammatory protein 1-alpha. These are either proinflammatory or promote a Th2 response with increased IgE antibody production.116 They also augment vasodilation and stimulate the production of cell adhesion proteins on endothelial cell membranes, which increases the ability of circulating inflammatory cells to stick to and then move through the vessel wall into the tissues.15 An anaphylactoid reaction is the result of mast cell degranulation without an immune component.116 IgE is not involved, and previous exposure to the antigen is not required; mast cells are activated directly or, more commonly, indirectly by complement activation. Other than the initial stimulus, the two processes are virtually the same. Anaphylactoid reactions can be caused by drugs such as NSAIDs or opioids, iodinated radiographic contrast materials, or dextrans. Ingestion of certain types of spoiled fish can cause an anaphylactoid reaction. Bacterial contamination of tuna, mackerel, or mahi-mahi converts the abundant histidine in the fish to histamine.41 Anaphylactic and anaphylactoid reactions have the exact same clinical signs and treatment, so differentiating between the two is immaterial in the emergency situation.

Clinical Evaluation The major shock organ in the cat is the lung, with the intestinal tract involved to a lesser degree. The signs of anaphylaxis are the result of the actions of all the different inflammatory mediators released by the mast cells. Respiratory distress is the major sign of anaphylactic shock in cats. Increases in respiratory rate and effort are consequences of laryngeal edema, bronchoconstriction, and increased production of airway mucus; open-mouth breathing may be noticed. Pruritus about the face and head may be present, and increased salivation may be noted along with vomiting, pale mucous membranes, poor pulse quality, and a prolonged capillary refill time. Hypovolemia owing to increased vascular permeability and vasodilation leads to decreased tissue oxygenation. Progression to collapse, coma, and death may follow rapidly. Diagnosis of anaphylactic shock is based on recognizing the presenting signs and the acute nature of illness. A cursory initial examination of the cat is often


all that time will allow, insofar as many are lifethreateningly ill. A detailed history and physical examination of less severely affected cats may yield clues to the cause of the anaphylaxis. An insect stinger in the tongue of a cat with open-mouth breathing is suggestive of an allergic reaction to a bee sting.

Therapy Once anaphylaxis is recognized, rapid and aggressive treatment may be life saving. Following the precepts of basic emergency medicine gives the veterinarian the best chance at success. The veterinarian must first ensure that the airway is patent and be ready to intubate if laryngeal edema is causing an airway obstruction. Tracheotomy may be necessary if intubation is not possible. If the upper airway is not obstructed and the cat is having respiratory difficulties, administration of oxygen may be required. Cardiovascular and respiratory dysfunction can be addressed with intravenous fluids and drugs. Intravenous access should be established early on so that volume contraction can be corrected. Intravenous fluids at 50 to 60 mL/kg over the first hour should be administered to cats with severe anaphylaxis. After the first hour the cat should be reassessed and fluids continued. Fluid rates will likely need to be greater than maintenance rates but should be tailored to the individual patient. Monitoring the central venous pressure (CVP) is an excellent means of assessing fluid requirements. Fluids can be administered until the CVP reaches 3 to 5 cm of water. Otherwise, the pulse quality and rate, capillary refill time, and mucous membrane color are used as clinical guides to fluid therapy after the initial shock rates are completed. If DIC is present,

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blood products may be used to replace clotting factors consumed in the process. The addition of heparin alone to augment the effectiveness of the transfusion is controversial. In humans a combination of antithrombin and heparin has shown promise in reducing mortality, as has administration of activated protein C.99 Use of these modalities has not yet been reported in cats or dogs. Many of the pathophysiologic derangements that occur with anaphylactic shock can be ameliorated by the administration of epinephrine (Table 25-6). Stimulation of the alpha-adrenergic receptors results in vasoconstriction, thereby decreasing blood pooling in the splanchnic circulation, increasing venous return to the heart, and improving cardiac contractility. Beta-adrenergic receptor stimulation decreases bronchoconstriction and impedes further mast cell degranulation while also improving cardiac output through positive inotropic and chronotropic effects. Epinephrine is used as a 1 : 10,000 dilution and administered intravenously at 0.02 mg/kg, which is 0.2 mL/kg or 1 mL for a 5-kg cat. To create 10 mL of a 1 : 10,000 dilution of epinephrine, 1 mL of the 1 : 1,000 solution is mixed with 9 mL of sterile saline. If venous access cannot be established, the volume can be doubled and administered through a urinary catheter passed through an endotracheal tube and wedged in a small bronchus.131 Alternatively, epinephrine can be administered in the sublingual vein. If the patient’s condition is not serious, the epinephrine can be administered intramuscularly or subcutaneously. The cat’s heart rate and rhythm should be monitored because epinephrine can precipitate cardiac dysrhythmias. Epinephrine should be readministered in 15 to 20 minutes. A positive response to parenteral fluid and epinephrine administration should be noticed within minutes of

TABLE 25-6 Drugs Useful for the Treatment of Anaphylaxis Drug

Dose

Use

Epinephrine (intravenous)

0.2 mL/kg of a 1 : 10,000 dilution repeat in 15 minutes

Initial treatment along with intravenous fluids

Epinephrine (intratracheal or intrabronchial)

0.4 mL/kg of a 1 : 10,000 dilution repeat in 15 minutes

Initial treatment along with intravenous fluids; administer through a urinary catheter

Aminophylline

5 mg/kg IV slowly

Respiratory distress refractory to epinephrine

Atropine

0.02-0.04 mg/kg IV or IM

Bradycardia refractory to epinephrine

Dopamine

4-10 µg/kg/min constant-rate infusion

Refractory hypotension

Dexamethasone sodium phosphate

1-4 mg/kg IV

After correction of volume contraction

Prednisone sodium succinate (Solu-Delta-Cortef)

10-25 mg/kg IV slowly

After correction of volume contraction

Diphenhydramine (Benadryl)

0.5-1 mg/kg IV slowly

H1 receptor blockade After correction of volume contraction

Tripelennamine

1 mg/kg IV or IM

H1 receptor blockade After correction of volume contraction

IV, Intravenously; IM, intramuscularly.

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beginning therapy. If not, additional drugs should be considered. If respiratory distress is still present, aminophylline 5 mg/kg administered slowly and intravenously may help reduce bronchoconstriction and strengthen contraction of the respiratory muscles.121 If additional cardiovascular support is required, infusions of dopamine or dobutamine may be considered. Atropine at 0.02 to 0.04 mg/kg intravenously or intramuscularly may be used if bradycardia is refractory to epinephrine. Once the life-threatening crisis is dealt with, glucocorticoids and antihistamines can be administered. They are not useful for the acute treatment of anaphylaxis.121 Glucocorticoids cause vasodilation and decreased cardiac contractility and are detrimental if administered before correction of hypovolemia with intravenous fluids. Rapid-acting glucocorticoids such as dexamethasone sodium phosphate at 1 to 4 mg/kg intravenously may be beneficial by enhancing beta-receptor sensitivity and decreasing phospholipase A2 activity. H1-receptor– blocking antihistamines such as diphenhydramine (Benadryl, McNeil PPC) at 0.5 to 1 mg/kg administered slowly and intravenously or tripelennamine 1 mg/kg intravenously or intramuscularly may reduce the further effects of histamine on the target tissues. This may be of limited benefit insofar as histamine is only one of many mediators released by mast cells. H2-receptor–blocking antihistamines may be used if gastric ulceration is suspected. The cat experiencing anaphylactic shock should be monitored closely for the next 24 hours, the time period over which new cytokine synthesis and release occurs. Parameters to follow include respiratory rate and effort, heart rate and rhythm, pulse quality, capillary refill time, the patient’s attitude, urine output, systemic blood pressure, and oxygen saturation as measured by pulse oximetry. Bloody diarrhea may signal the presence of DIC. Preparations should be made to act on significant changes in any of these parameters.

Prognosis The effectiveness of therapeutic interventions in cats with anaphylactic shock depends on timely and aggressive action on the part of the veterinarian and support staff. The prognosis for these patients varies with the individual and the individual’s response to initial therapy. The sooner appropriate therapy can begin, the better chance the cat has of surviving. However, some patients will die despite the best efforts of the veterinarian.

Prevention Once the acute crisis is over, the owner can be questioned regarding recent vaccination and exposure to

insects, drugs, reptiles, and new foods. Any intravenous injections in the future should be administered slowly. Avoidance of any triggers is advisable. If this is not possible, as may be the case with vaccinations, pretreatment with antihistamines or glucocorticoids may help minimize the severity of any reaction. Any cat experiencing anaphylaxis after vaccination should remain at the hospital for 20 to 30 minutes after subsequent vaccinations to allow for immediate intervention should anaphylaxis recur. If a severe reaction has not begun within that time frame, it is unlikely to happen.17 Although they are uncommon, anaphylactic and anaphylactoid reactions can occur at any time. Anticipating the needs of a cat experiencing this frightening reaction is essential to a successful outcome.

Vaccine-Associated Adverse Events Vaccination represents a common scenario in which cats are exposed to foreign proteins. Fortunately, the chance of a vaccine-associated adverse event (VAAE) occurring, although slightly higher than in dogs, is quite low.78,117 Vaccine reactions are usually mild and transient.117 In a report of almost 500,000 vaccinated cats, VAAEs were reported in approximately 0.5% of these cats. The most common adverse event was lethargy followed by localized vaccine-site reactions, vomiting, facial edema, and generalized pruritus.78 Only four cats died within 48 hours of vaccine administration; two of them fit the description of anaphylaxis. The chances of developing a VAAE increased with the number of agents vaccinated against at one time.78 A reduction in the number of vaccinations administered at one time might reduce the chances of VAAE development. Localized swellings appear 24 hours after vaccination, may be painful and hot, and usually last about 1 week.117 These localized swellings occur two to five times more frequently in cats than in dogs.78 Although this has not been studied in cats, there is limited evidence supporting an association between vaccine administration and the development of immune-mediated disorders in dogs.117 Vaccination against calicivirus has been associated with polyarthritis and postvaccination lameness in cats.117 Injection-site sarcomas are covered in Chapter 28.

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CHAPTER 25 Hematology and Immune-Related Disorders 4. Ballegeer EA, Forrest LJ, Dickinson RM et al: Correlation of ultrasonographic appearance of lesions and cytologic and histologic diagnoses in splenic aspirates from dogs and cats: 32 cases (20022005), J Am Vet Med Assoc 230:690, 2007. 5. Bhatt S, Siegel A: Potentiating role of interleukin 2 (IL-2) receptors in the midbrain periaqueductal gray (PAG) upon defensive rage behavior in the cat: role of neurokinin NK(1) receptors, Behav Brain Res 167:251, 2006. 6. Bianco D, Armstrong PJ, Washabau RJ: Presumed primary immune-mediated thrombocytopenia in four cats, J Feline Med Surg 10:495, 2008. 7. Bighignoli B, Owens S, Froenicke L et al: Blood types of the domestic cat. In August J, editor: Consultations in feline internal medicine, ed 6, St Louis, 2010, Elsevier/Saunders, p 628. 8. Birkenheuer A, Cohn L, Levy M et al: Atovaquone and azithromycin for the treatment of Cytauxzoon felis, J Vet Intern Med 22:703, 2008. 9. Bondy P, Cohn L, Kerl M: Feline cytauxzoonosis, Compend Contin Educ Pract Vet 27, 2005. 10. Brockus C: Interpreting the leukogram. In August J, editor: Consultations in feline internal medicine, ed 5, St Louis, 2006, Elsevier/ Saunders, p 585. 11. Brockus C: Leukocyte disorders. In Ettinger S, Feldman E, editors: Textbook of veterinary internal medicine, ed 6, St Louis, 2006, Elsevier/Saunders, p 1937. 12. Brooks M, DeWilde L: Feline factor XII deficiency, Compend Contin Educ Pract Vet 28:148, 2006. 13. Brown R, Riogers K: Neutropenia in dogs and cats, Compend Contin Educ Pract Vet 23:534, 2001. 14. Christopher M: Disorders of feline red blood cells. In Bonagura J, editor: Kirk’s current veterinary therapy XIII small animal practice, Philadelphia, 2000, Saunders, p 421. 15. Cohen R: Systemic anaphylaxis. In Bonagura J, editors: Kirk’s current veterinary therapy XII small animal practice, Philadelphia, 1995, Saunders, p 150. 16. Cohn L: Glucocorticoid therapy. In Ettinger S, Feldman E, editors: Textbook of veterinary internal medicine, ed 6, St Louis, 2005, Elsevier/Saunder, p 503. 17. Cowell A, Cowell R: Management of bee and other hymenoptera stings. In Bonagura J, editor: Kirk’s current veterinary therapy XII small animal practice, Philadelphia, 1995, Saunders, p 226. 18. Cowell R, Tyler R, Meinkoth J: Diagnosis of anemia. In August J, editor: Consultations in feline internal medicine, ed 5, St Louis, 2006, Elsevier/Saunders, p 565. 19. Cowgill L: CVT update: use of recombinant human erythropoietin. In Bonagura J, editor: Kirk’s current veterinary therapy XII small animal practice, Philadelphia, 1995, Saunders, p 961. 20. Culp WT, Aronson LR: Splenic foreign body in a cat, J Feline Med Surg 10:380, 2008. 21. Dowers KL, Olver C, Radecki SV et al: Use of enrofloxacin for treatment of large-form Haemobartonella felis in experimentally infected cats, J Am Vet Med Assoc 221:250, 2002. 22. Dowers KL, Tasker S, Radecki SV et al: Use of pradofloxacin to treat experimentally induced Mycoplasma hemofelis infection in cats, Am J Vet Res 70:105, 2009. 23. Dunham SP: Cytokines and anti-cytokine therapy: clinical potential for treatment of feline disease, J Feline Med Surg 1:7, 1999. 24. Estrin MA, Wehausen CE, Jessen CR et al: Disseminated intravascular coagulation in cats, J Vet Intern Med 20:1334, 2006. 25. Feldman B: Blood transfusion guidelines. In Bonagura J, editor: Kirk’s current veterinary therapy XIII small animal practice, Philadelphia, 2000, Saunders, p 400. 26. Feldman B: Nonregenerative anemia. In Ettinger S, Feldman E, editors: Textbook of veterinary internal medicine, ed 6, St Louis, 2005, Elsevier/Saunders, p 1908.

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27. Feldman E, Nelson R: Glucocorticoid therapy: canine and feline endocrinology and reproduction, ed 3, St Louis, 2004, Saunders, p 464. 28. Felsburg P: Hereditary and acquired immunodeficiency diseases. In Bonagura J, editor: Kirk’s current veterinary therapy XIII small animal practice, Philadelphia, 2004, Saunders, p 516. 29. Foley J: Feline infectious peritonitis and feline enteric coronavirus. In Ettinger S, Feldman E, editors: Textbook of veterinary internal medicine, ed 6, St Louis, 2005, Elsevier/Saunders, p 663. 30. Foley JE, Rand C, Leutenegger C: Inflammation and changes in cytokine levels in neurological feline infectious peritonitis, J Feline Med Surg 5:313, 2003. 31. George JW, Rideout BA, Griffey SM et al: Effect of preexisting FeLV infection or FeLV and feline immunodeficiency virus coinfection on pathogenicity of the small variant of Haemobartonella felis in cats, Am J Vet Res 63:1172, 2002. 32. Gibson GR, Callan MB, Hoffman V et al: Use of a hemoglobinbased oxygen-carrying solution in cats: 72 cases (1998-2000), J Am Vet Med Assoc 221:96, 2002. 33. Giger U: Hereditary erythrocyte disorders. In August J, editor: Consultations in feline veterinary internal medicine, ed 4, Philadelphia, 2001, Saunders, p 484. 34. Giger U: Regenerative anemias caused by blood loss or hemolysis. In Ettinger S, Feldman E, editors: Textbook of veterinary internal medicine, ed 6, St Louis, 2005, Elsevier/Saunders, p 1886. 35. Giger U: Blood-typing and crossmatching. In Bonagura J, Twedt D, editors: Kirk’s current veterinary therapy XIV, St Louis, 2009, Saunders/Elsevier, p 260. 36. Giger U, Bucheler J: Transfusion of type-A and type-B blood to cats, J Am Vet Med Assoc 198:411, 1991. 37. Gordon SS, McClaran JK, Bergman PJ et al: Outcome following splenectomy in cats, J Feline Med Surg 12:256, 2010. 38. Goree M, Catalfamo JL, Aber S et al: Characterization of the mutations causing hemophilia B in 2 domestic cats, J Vet Intern Med 19:200, 2005. 39. Greene C, Meinkoth J, Kocan A: Cytauxzoonosis. In Greene C, editor: Infectious diseases of the dog and cat, ed 3, St Louis, 2006, Saunders, p 716. 40. Gregory C: Immunosuppressive agents. In Bonagura J, Twedt D, editors: Kirk’s current veterinary therapy XIV, St Louis, 2009, Saunders/Elsevier, p 254. 41. Guilford W: The gastrointestinal tract and adverse reactions to food. In August J, editor: Consultations in feline internal medicine, ed 4, Philadelphia, 2001, Saunders, p 113. 42. Haldane S, Roberts J, Marks S et al: Transfusion medicine, Compend Contin Educ Pract Vet 26, 2004. 43. Hall R: Interpreting the leukogram. In August J, editor: Consultations in feline internal medicine, ed 2, Philadelphia, 1994, Saunders, p 489. 44. Hammer A, Couto C: Disorders of the lymph nodes and spleen. In Sherding R, editor: The cat: diseases and clinical management, ed 2, Philadelphia, 1994, Saunders, p 671. 45. Hanson JA, Papageorges M, Girard E et al: Ultrasonographic appearance of splenic disease in 101 cats, Vet Radiol Ultrasound 42:441, 2001. 46. Hardie R, Petrus D: Lymphatics and lymph nodes. In Slatter D, editor: Textbook of small animal surgery, ed 3, Philadelphia, 2003, Saunders, p 1063. 47. Hasler A: Polycythemia. In Ettinger S, Feldman E, editors: Textbook of veterinary internal medicine, ed 6, St Louis, 2005, Elsevier/ Saunders, p 215. 48. Helfand S: Hematopoietic cytokines: the interleukin array. In Bonagura J, editor: Kirk’s current veterinary therapy XIII small animal practice, Philadelphia, 2000, Saunders, p 408. 49. Holan K: Feline hepatic lipidosis. In Bonagura J, Twedt D, editors: Kirk’s current veterinary therapy XIV, St Louis, 2009, Saunders/ Elsevier, p 570.

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50. Johnson LR, De Cock HE, Sykes JE et al: Cytokine gene transcription in feline nasal tissue with histologic evidence of inflammation, Am J Vet Res 66:996, 2005. 51. Jordan HL, Grindem CB, Breitschwerdt EB: Thrombocytopenia in cats: a retrospective study of 41 cases, J Vet Intern Med 7:261, 1993. 52. Kearns S, Ewing P: Causes of canine and feline pancytopenia, Compend Contin Educ Pract Vet 28, 2006. 53. Klaser DA, Reine NJ, Hohenhaus AE: Red blood cell transfusions in cats: 126 cases (1999), J Am Vet Med Assoc 226:920, 2005. 54. Knottenbelt S, Blackwood L: The blood. In Chandler E, Gaskell C, Gaskell R, editors: Feline medicine and therapeutics, ed 3, Oxford, 2004, Blackwell Publishing, p 235. 55. Kohn B, Fumi C: Clinical course of pyruvate kinase deficiency in Abyssinian and Somali cats, J Feline Med Surg 10:145, 2008. 56. Kohn B, Goldschmidt MH, Hohenhaus AE et al: Anemia, splenomegaly, and increased osmotic fragility of erythrocytes in Abyssinian and Somali cats, J Am Vet Med Assoc 217:1483, 2000. 57. Kohn B, Weingart C, Eckmann V et al: Primary immune-mediated hemolytic anemia in 19 cats: diagnosis, therapy, and outcome (1998-2004), J Vet Intern Med 20:159, 2006. 58. Langston C, Ludwig L: Renal transplantation. In Ettinger S, Feldman E, editors: Textbook of veterinary internal medicine, ed 6, St Louis, 2005, Elsevier/Saunders, p 1752. 59. Levy J, Crawford P: Feline leukemia virus. In Ettinger S, Feldman E, editors: Textbook of veterinary internal medicine, ed 6, St Louis, 2005, Elsevier/Saunders, p 653. 60. Levy JK, Crawford PC, Collante WR et al: Use of adult cat serum to correct failure of passive transfer in kittens, J Am Vet Med Assoc 219:1401, 2001. 61. Levy JK, Liang Y, Ritchey JW et al: Failure of FIV-infected cats to control Toxoplasma gondii correlates with reduced IL2, IL6, and IL12 and elevated IL10 expression by lymph node T cells, Vet Immunol Immunopathol 98:101, 2004. 62. Littlewood JD, Shaw SC, Coombes LM: Vitamin K-dependent coagulopathy in a British Devon rex cat, J Small Anim Pract 36:115, 1995. 63. London C: Hematopoietic cytokines: the myelopoietic factors. In Bonagura J, editor: Kirk’s current veterinary therapy XIII small animal practice, Philadelphia, 2000, Saunders, p 403. 64. Lucroy MD, Madewell BR: Clinical outcome and diseases associated with extreme neutrophilic leukocytosis in cats: 104 cases (1991-1999), J Am Vet Med Assoc 218:736, 2001. 65. Lusson D, Billiemaz B, Chabanne JL: Circulating lupus anticoagulant and probable systemic lupus erythematosus in a cat, J Feline Med Surg 1:193, 1999. 66. Mackin A: Platelet disorders. In August J, editor: Consultations in feline internal medicine, ed 5, St Louis, 2006, Elsevier/Saunders, p 575. 67. Maddison JE, Watson AD, Eade IG et al: Vitamin K-dependent multifactor coagulopathy in Devon Rex cats, J Am Vet Med Assoc 197:1495, 1990. 68. Marino D: Diseases of the spleen. In Bonagura J, editor: Kirk’s current veterinary therapy XIII small animal practice, Philadelphia, 2000, Saunders, p 520. 69. Marks S, Henry C: CVT update: diagnosis and treatment of systemic lupus erythematosus. In Bonagura J, editor: Kirk’s current veterinary therapy XIII small animal practice, Philadelphia, 2000, Saunders, p 514. 70. May S, Langston C: Managing chronic renal failure, Compend Contin Educ Pract Vet 28, 2006. 71. McSherry L: Techniques for bone marrow aspiration and biopsy. In Ettinger S, Feldman E, editors: Textbook of veterinary internal medicine, ed 6, St Louis, 2005, Elsevier/Saunders, p 285. 72. Meinkoth J, Kocan AA, Whitworth L et al: Cats surviving natural infection with Cytauxzoon felis: 18 cases (1997-1998), J Vet Intern Med 14:521, 2000.

73. Meurs KM, Fox PR, Miller MW et al: Plasma concentrations of tumor necrosis factor-alpha in cats with congestive heart failure, Am J Vet Res 63:640, 2002. 74. Miller C, Bartges J: Refeeding syndrome. In Bonagura J, editor: Kirk’s current veterinary therapy XIII small animal practice, Philadelphia, 2000, Saunders, p 87. 75. Miller E: Immune-mediated hemolytic anemia. In Bonagura J, Twedt D, editors: Kirk’s current veterinary therapy XIV, St Louis, 2009, Saunders/Elsevier, p 266. 76. Mooney SC, Patnaik AK, Hayes AA et al: Generalized lymphadenopathy resembling lymphoma in cats: six cases (1972-1976), J Am Vet Med Assoc 190:897, 1987. 77. Moore FM, Emerson WE, Cotter SM et al: Distinctive peripheral lymph node hyperplasia of young cats, Vet Pathol 23:386, 1986. 78. Moore GE, DeSantis-Kerr AC, Guptill LF et al: Adverse events after vaccine administration in cats: 2,560 cases (2002-2005), J Am Vet Med Assoc 231:94, 2007. 79. Museux K, Boretti FS, Willi B et al: In vivo transmission studies of ‘Candidatus Mycoplasma turicensis’ in the domestic cat, Vet Res 40:45, 2009. 80. Nakazato A, Momoi Y, Kadoya M et al: Measurement of feline serum interleukin-5 level, J Vet Med Sci 69:843, 2007. 81. Neer T: Splenomegaly and lymphadenopathy. In August J, editor: Consultations in feline internal medicine, ed 4, Philadelphia, 2001, Saunders, p 439. 82. Nguyen Van N, Taglinger K, Helps CR et al: Measurement of cytokine mRNA expression in intestinal biopsies of cats with inflammatory enteropathy using quantitative real-time RT-PCR, Vet Immunol Immunopathol 113:404, 2006. 83. Nibblett BM, Snead EC, Waldner C et al: Anemia in cats with hemotropic mycoplasma infection: retrospective evaluation of 23 cases (1996-2005), Can Vet J 50:1181, 2009. 84. Nitsche E: Erythrocytosis in dogs and cats: diagnosis and management, Compend Contin Educ Pract Vet 26, 2004. 85. Ogg A, Kruth S: Antimicrobial therapy for the neutropenic dog and cat. In Bonagura J, editor: Kirk’s current veterinary therapy XIII small animal practice, Philadelphia, 2000, Saunders, p 267. 86. Ottenjann M, Weingart C, Arndt G et al: Characterization of the anemia of inflammatory disease in cats with abscesses, pyothorax, or fat necrosis, J Vet Intern Med 20:1143, 2006. 87. Papich M: Drug therapy in cats: precautions and guidelines. In August J, editor: Consultations in feline internal medicine, ed 5, St Louis, 2006, Elsevier/Saunders, p 279. 88. Paterson S: Diagnosis and management of pemphigus foliaceus. In August J, editor: Consultations in feline internal medicine, ed 5, St Louis, 2006, Elsevier/Saunders, p 261. 89. Peterson JL, Couto CG, Wellman ML: Hemostatic disorders in cats: a retrospective study and review of the literature, J Vet Intern Med 9:298, 1995. 90. Platt S, Abramson C, Garosi L: Administering corticosteroids in neurological disease, Compend Contin Educ Pract Vet 27, 2005. 91. Plotnick A: Feline chronic renal failure: long-term medical management, Compend Contin Educ Pract Vet 29, 2007. 92. Plumb D: Leflunomide. In Plumb’s veterinary drug handbook, ed 6, Stockholm, WI, 2008, PharmaVet Inc. 93. Polzin D, Osborne C, Ross S: Chronic kidney disease. In Ettinger S, Feldman E, editors: Textbook of veterinary internal medicine, ed 6, St Louis, 2005, Elsevier/Saunders, p 1756. 94. Randolph JE, Scarlett JM, Stokol T et al: Expression, bioactivity, and clinical assessment of recombinant feline erythropoietin, Am J Vet Res 65:1355, 2004. 95. Rojko J, Hardy W: Feline leukemia virus and other retroviruses. In Sherding R, editor: The cat: diseases and clinical management, ed 2, Philadelphia, 1994, Saunders, p 263. 96. Roosje PJ, Dean GA, Willemse T et al: Interleukin 4-producing CD4+ T cells in the skin of cats with allergic dermatitis, Vet Pathol 39:228, 2002.

97. Roudebush P, Polzin DJ, Ross SJ et al: Therapies for feline chronic kidney disease. What is the evidence? J Feline Med Surg 11:195, 2009. 98. Roux FA, Deschamps JY, Blais MC et al: Multiple red cell transfusions in 27 cats (2003-2006): indications, complications and outcomes, J Feline Med Surg 10:213, 2008. 99. Rudloff E, Kirby R: Disseminated intravascular coagulation: diagnosis and management. In Bonagura J, Twedt D, editors: Kirk’s current veterinary therapy XIV, St Louis, 2009, Saunders/ Elsevier, p 287. 100. Sartor L, Trepanier L: Rational pharmacological therapy of hepatobiliary disease in dogs and cats, Compend Contin Educ Pract Vet 25, 2003. 101. Schooley EK, McGee Turner JB, Jiji RD et al: Effects of cyproheptadine and cetirizine on eosinophilic airway inflammation in cats with experimentally induced asthma, Am J Vet Res 68:1265, 2007. 102. Segev G, Klement E, Aroch I: Toxic neutrophils in cats: clinical and clinicopathologic features, and disease prevalence and outcome—a retrospective case control study, J Vet Intern Med 20:20, 2006. 103. Smith J, Day T, Mackin A: Diagnosing bleeding disorders, Compend Contin Educ Pract Vet 27, 2005. 104. Stieger K, Palos H, Giger U: Comparison of various blood-typing methods for the feline AB blood group system, Am J Vet Res 66:1393, 2005. 105. Stokol T, Brooks M: Diagnosis of DIC in cats: is it time to go back to the basics? J Vet Intern Med 20:1289, 2006. 106. Stone M: Systemic lupus erythematosus. In Ettinger S, Feldman E, editors: Textbook of veterinary internal medicine, ed 6, St Louis, 2005, Elsewhere/ Saunders, p 1952. 107. Stutzer B, Muller F, Majzoub M et al: Role of latent feline leukemia virus infection in nonregenerative cytopenias of cats, J Vet Intern Med 24:192, 2010. 108. Sykes JE, Drazenovich NL, Ball LM et al: Use of conventional and real-time polymerase chain reaction to determine the epidemiology of hemoplasma infections in anemic and nonanemic cats, J Vet Intern Med 21:685, 2007. 109. Sykes JE, Terry JC, Lindsay LL et al: Prevalences of various hemoplasma species among cats in the United States with possible hemoplasmosis, J Am Vet Med Assoc 232:372, 2008. 110. Tasker S, Caney SM, Day MJ et al: Effect of chronic FIV infection, and efficacy of marbofloxacin treatment, on Mycoplasma haemofelis infection, Vet Microbiol 117:169, 2006. 111. Tasker S, Lappin M: Update on hemoplasmosis. In August J, editor: Consultations in feline internal medicine, ed 5, St Louis, 2006, Elsevier/Saunders, p 605. 112. Tholen I, Weingart C, Kohn B: Concentration of D-dimers in healthy cats and sick cats with and without disseminated intravascular coagulation (DIC), J Feline Med Surg 11:842, 2009. 113. Tillson D: Spleen. In Slatter D, editor: Textbook of small animal surgery, ed 3, Philadelphia, 2003, Saunders, p 1046. 114. Tizard I: Drugs and other agents that affect the immune system. In Tizard I, editor: Veterinary immunology: an introduction, ed 8, St Louis, 2009, Saunders/Elsevier, p 480. 115. Tizard I: Primary immunodeficiencies. In Tizard I, editor: Veterinary immunology: an introduction, ed 8, St Louis, 2009, Saunders/ Elsevier, p 448.


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116. Tizard I: Type I hypersensitivity. In Tizard I, editor: Veterinary immunology: an introduction, ed 8, St Louis, 2009, Saunders/ Elsevier, p 329. 117. Tizard I: The use of vaccines. In Tizard I, editor: Veterinary immunology: an introduction, ed 8, St Louis, 2009, Saunders/Elsevier, p 270. 118. Tocci LJ, Ewing PJ: Increasing patient safety in veterinary transfusion medicine: an overview of pretransfusion testing, J Vet Emerg Crit Care (San Antonio) 19:66, 2009. 119. Trepanier L: Idiopathic inflammatory bowel disease in cats. Rational treatment selection, J Feline Med Surg 11:32, 2009. 120. Vail D, Thamm D: Hematopoietic tumors. In Ettinger S, Feldman E, editor: Textbook of veterinary internal medicine, ed 6, St Louis, 2005, Elsevier/Saunders, p 732. 121. Waddell L: Systemic anaphylaxis. In Ettinger S, Feldman E, editor: Textbook of veterinary internal medicine, ed 6, St Louis, 2005, Elsevier/Saunders, p 458. 122. Wardrop KJ, Reine N, Birkenheuer A et al: Canine and feline blood donor screening for infectious disease, J Vet Intern Med 19:135, 2005. 123. Washabau RJ, Day MJ, Willard MD et al: Endoscopic, biopsy, and histopathologic guidelines for the evaluation of gastrointestinal inflammation in companion animals, J Vet Intern Med 24:10, 2010. 124. Weinstein NM, Blais MC, Harris K et al: A newly recognized blood group in domestic shorthair cats: the MiK red cell antigen, J Vet Intern Med 21:287, 2007. 125. Weiss D: Nonregenerative anemias. In Bonagura J, Twedt D, editors: Kirk’s current veterinary therapy XIV, St Louis, 2009, Sanders/Elsevier, p 272. 126. Weiss D, Tvedten H: Erythrocyte disorders. In Willard M, Tvedten H, editors: Small animal clinical diagnosis by laboratory methods, ed 4, St Louis, 2004, Saunders, p 38. 127. Weiss DJ: Aplastic anemia in cats—clinicopathological features and associated disease conditions 1996-2004, J Feline Med Surg 8:203, 2006. 128. White C, Reine N: Feline nonregenerative anemia: diagnosis and treatment, Compend Contin Educ Pract Vet 31, 2009. 129. White C, Reine N: Feline nonregenerative anemia: pathophysiology and etiologies, Compend Contin Educ Pract Vet 31, 2009. 130. Williams CR, Sykes JE, Mehl M et al: In vitro effects of the active metabolite of leflunomide, A77 1726, on feline herpesvirus-1, Am J Vet Res 68:1010, 2007. 131. Wohl J, Murtaugh R: Use of catecholamines in critical care patients. In Bonagura J, editor: Kirk’s current veterinary therapy XII small animal practice, Philadelphia, 1995, Saunders, p 188. 132. Wondratschek C, Weingart C, Kohn B: Primary immunemediated thrombocytopenia in cats, J Am Anim Hosp Assoc 46:12, 2010. 133. Woods JE, Wisnewski N, Lappin MR: Attempted transmission of Candidatus Mycoplasma haemominutum and Mycoplasma haemofelis by feeding cats infected Ctenocephalides felis, Am J Vet Res 67:494, 2006. 134. Young K, Moriello K: Eosinophils and eosinophilic diseases. In August J, editor: Consultations in feline internal medicine, ed 5, St Louis, 2006, Elsevier/Saunders, p 239.

C H A P T E R

26

Musculoskeletal Diseases Greg L.G. Harasen and Susan E. Little O U T L I N E Fractures, 704 Arthridities, 709 Conditions of the Front Limb, 717 Conditions of the Hind Limb, 718 Neoplasia, 724

Osteomyelitis, 725 Dysostoses, 725 Miscellaneous Musculoskeletal Conditions, 726 Myopathies, 728

Conditions of the musculoskeletal system in the cat have received comparatively little attention in the literature. Much of what has been published assumes similarities with dogs and humans that may not be accurate. Developmental diseases, especially genetically determined conditions, are much less common in the cat than in the dog. Even those that are seen, including patellar luxation and hip dysplasia, are relatively uncommon. Trauma is the major source of musculoskeletal abnormality in the cat, and thus the entire patient must be evaluated. The feline patient also presents challenges in examination and observation of abnormal gaits because many cats are uncooperative at best and fractious at worst when exposed to the clinic environment. To appreciate subtle gait disturbances, the clinician must frequently rely on patience when examining the cat, as well as on owner observations or videotapes taken in the home environment. The cat has a number of anatomic and physiologic differences compared with the dog. Some are mere curiosities, whereas others can be extremely significant from a diagnostic perspective.96 The presence of a free-floating clavicle in the cranial shoulder region falls into the category of curiosity, but it is sometimes mistaken for a fracture or foreign body (Figure 26-1). The median nerve and brachial artery pass through the supracondylar foramen on the medial side of the distal humerus in the cat, whereas the same structures lie medial to the humerus in the dog (Figure 26-2). The presence of these vital structures within the humeral metaphysis of the cat restricts the placement of orthopedic hardware in this region. In the condylar region of the distal humerus,


there is no supratrochlear foramen in the cat as there is in the dog. This is one of the main reasons that humeral condylar fractures are relatively less common in cats.65 Approximately 40% of cats have a sesamoid bone in the tendon of origin of the supinator muscle on the dorsal surface of the proximal radius (Figure 26-3). This structure may be visible on lateral radiographic projections of the elbow and should not be mistaken for a chip fracture. The round ligament of the femoral head provides significant vascular supply to the femoral head in the cat, which is not the case in the dog. This may be one reason that aseptic necrosis of the femoral head is not described in the cat. The cranial cruciate ligament is larger and thicker than the caudal cruciate ligament in cats, which is the reverse of what is found in the dog. This may be an important factor explaining why rupture of the cruciate ligament is much less common in the cat. The range of motion in the feline shoulder and hip is greater than in the dog, but in the feline carpus and stifle range of motion is less than in the dog. However, supination of the carpus and paw is much greater in the cat and is important in grooming behavior.13,65,96,103

FRACTURES Fractures make up a large percentage of musculoskeletal problems in the cat, with the distribution of fractures being somewhat unique to this species. Although both dogs and cats suffer a majority of their fractures in the hind limb or pelvis, this percentage exceeds 70% of all fractures seen in the cat.48 When the 11% to 23% of feline

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FIGURE 26-3 Approximately 40% of cats have a sesamoid bone located in the origin of the supinator muscle. It can be seen on a lateral radiographic projection of the elbow.

FIGURE 26-1 The clavicle is located cranial to the proximal humerus.

trauma, which may affect not only the treatment plan but also the patient’s very survival.13 Much commonality exists between dogs and cats in the fractures that are seen and the repair techniques that can be used successfully. Certain fractures with unique considerations in the cat bear special consideration.

Mandibular and Maxillary Fractures

FIGURE 26-2 The supracondylar foramen is a unique anatomic feature of the medial aspect of the distal humerus in the cat through which pass the brachial artery and median nerve.

fractures that involve the maxillae, mandible, or facial bones are included, these two regions account for the overwhelming majority of fractures in the cat. Because most fractures are associated with significant trauma, a thorough evaluation of the entire cat beyond the fracture is essential. Published estimates suggest that as many as 40% of fracture patients also have thoracic

Fractures involving the mandible or maxillae of cats are unique if for no other reason than that they are at least tenfold more common in the cat than in the dog.86 Vehicular trauma and high-rise syndrome are the most common causes of these fractures, which occur when the cat absorbs a face-first impact. Not surprisingly, such trauma is frequently associated with additional injuries, including broken teeth, thoracic injury, head trauma, and forelimb fractures. Fracture of the mandibular symphysis accounts for nearly three quarters of mandibular and maxillary injuries.47,86 Circumferential wiring of the symphysis combined with 3 to 4 weeks of a soft diet followed by wire removal is usually successful (Figure 26-4). At the time of wire removal, some residual mobility may still be present at the symphysis, but this is due in part to the fact that the joint is cartilaginous and is not rigid, even in the normal state. Most patients do well clinically, regardless of the mobility. Midsagittal splits of the hard palate are another common consequence of frontal facial impact trauma in the cat. Minor splits of 1 to 2 mm usually require no specific repair; however, wider splits should be compressed. This can be accomplished by running surgical wire in a figure-of-eight pattern across the split along the oral surface of the hard palate and around the base of a tooth on each side of the maxillae. Alternatively, a Kirschner wire can be driven across the maxillae between teeth so that the ends of the wire are exposed through the gingiva on either side of the maxillae, just dorsal to

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SECTION IV Feline Internal Medicine 2

1

A

of the muzzle wrap on the each side of the muzzle. Another wrap of tape is placed around the muzzle to hold the second length of tape in place. A final length of tape is placed from the head strap on both sides and beneath the cat’s throat to prevent the head strap from pulling up over the ears.47,96 In cases in which fracture comminution precludes surgical reconstruction and stabilization, when financial constraints eliminate a surgical option, or in young kittens whose soft bone and erupting teeth make the use of surgical hardware difficult, a tape muzzle permits the maintenance of normal dental occlusion and often produces surprisingly good results.47,86,96

Patellar Fractures

B FIGURE 26-4 Mandibular symphyseal fractures can be stabilized with a loop of surgical wire passed around the cranial mandible, caudal to the canine teeth. (Reprinted with permission from Piermattei D, Flo G, DeCamp C: Brinker, Piermattei, and Flo’s handbook of small animal orthopedics and fracture repair, ed 4, St Louis, 2006, Saunders Elsevier.)

the level of the hard palate. A figure-of-eight tension band wire is then placed around each end of the wire and tightened to achieve compression of the palatine split. The Kirschner wire ends can be bent over to prevent trauma to the lips. The hardware is removed after 4 weeks.47 Treatment of more complex mandibular or maxillary fractures can involve many of the same techniques used in dogs, including interdental wiring, intraoral splints, bone plates, and external skeletal fixators. Regardless of the technique, the primary goal is to restore perfect dental occlusion. It bears remembering that the most beautiful surgical repair is of little consequence if the teeth do not fit. An adhesive tape muzzle can be used effectively in the cat despite its short, conical muzzle. A length of tape is wrapped around the muzzle with the adhesive side facing out, caudal to the level of the canine teeth. Care is taken to ensure that the canine teeth interdigitate properly but that there is enough space between the incisor teeth to allow the cat to lap liquid diets and water. Performing the procedure under general anesthesia with an endotracheal tube in place usually provides the proper amount of space. A length of tape is then passed behind the ears and stuck to the adhesive surface

Traumatic fractures of the patella can occur in cats. If fracture fragments are sufficiently large, they can be stabilized with a pin and tension band wire. Small fragments may be removed. In either case the integrity of the quadriceps muscle and patellar tendon mechanism must be maintained.63 Some cats may be born with bipartite patellas. The radiographic appearance reveals smooth edges to the patellar fragments and frequently a similar appearance bilaterally. The condition is usually an incidental finding but can cause diagnostic confusion in a lame cat. An additional subset of young adult cats develops fractures of one or both patellae with no history or evidence of trauma. Lameness is acute but usually mild to moderate. Although the etiology is unclear, these have been characterized as stress fractures.62 Evidence for this pathogenesis includes the lack of known trauma in most cases and the presence of radiographic sclerosis of the fracture fragments and often the contralateral patella if it is intact. The fractures are simple transverse, involve the proximal one third of the patella, and are bilateral about half the time. In one survey about half of the contralateral patellae subsequently fractured at a mean time of 3 months.62 Attempts at surgical repair by pin and tension band wire have met with almost universal failure, characterized by iatrogenic fracture of the remaining fragments; hardware failure; or, most often, nonunion. However, most cats regained reasonable function of the limb, with stiffness or intermittent lameness in about half the cases.62 Some of the cats were found to have retained deciduous teeth or delayed dental eruption (Figure 26-5, A). In humans there is a connection between dentinogenesis imperfecta, which involves a number of dental abnormalities, and osteogenesis imperfecta, a condition involving brittle, easily fractured bones that is also seen in cats (discussed later). Of 34 cats with apparently atraumatic patellar fractures, 10 also had a history of previous, concurrent, or subsequent fracture of other bones (see Figure 26-5, B).62 It may be that some of these cats with patellar fractures


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A

FIGURE 26-6 Unilateral slipped capital femoral epiphysis.

B FIGURE 26-5 A, Persistent deciduous teeth are evidence of dentinogenesis imperfecta in this cat with a patellar fracture. B, A patellar fracture in a cat without history of trauma. (A courtesy Dr. Steven Bailey.)

have a form of osteogenesis imperfecta. Conservative treatment of these patellar fractures would appear to be the most prudent course, especially if distraction of fracture fragments is mild to moderate. If fragments are significantly distracted, then a circumferential wire may be preferred over an attempt to pass a pin through sclerotic bone. Alternatively, partial patellectomy may be performed. Complete patellectomy does not usually produce satisfactory function.62

Radial and Ulnar Fractures Fractures of the radius and ulna are relatively uncommon in cats, composing between 5% and 13.8% of feline fractures.84 Further, surgical repair of these fractures, especially when comminuted or open, is associated with a high complication rate.103 This would appear to be primarily due to the cat’s ability to pronate the front limb and paw to a much greater degree than the dog. This increased mobility between the bones means that the standard surgical approach in the dog of stabilizing only the radius, when both bones are fractured, may not

confer enough stability to produce consistently good results in the cat. Adding an intramedullary pin to the ulna in addition to the radial repair has been associated with more reliable surgical outcomes in this species.103 In addition, the ulna, especially its proximal portion, has been identified as a common site of nonunion in the cat, which may also be a significant contributory factor to surgical complication statistics for these fractures.84

Capital Femoral Physeal Fractures Capital femoral physeal fracture is a common traumatic injury in cats, but it appears as though just as many cases arise without a traumatic episode (Figure 26-6). Affected cats usually present with acute hind limb lameness, although the lameness may be mild and chronic in some instances. Most of these cases are seen in overweight, neutered males between 4 and 24 months of age.11,19,45,79 One report found a preponderance of domestic shorthairs,79 whereas another found a large number of Siamese cats.19 The first report of this problem described it as metaphyseal osteopathy of the femoral neck, which was thought to result from an aseptic necrosis, not unlike Legg-CalvePerthes disease in the dog.88 However, further examination of serial radiography and histopathologic specimens suggests that the changes in the femoral neck are more likely to be resorptive and remodeling changes secondary to the Salter–Harris I physeal fracture rather than a vascular impairment as is seen in Legg-Calve-Perthes disease in the dog (Figure 26-7).19,45,79 The etiopathogenesis of this condition seems to revolve around abnormalities of the physis. Radiographically and histologically, these cats have abnormally wide physes that remain open long after they would be expected to have closed.

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FIGURE 26-7 An acute slipped capital femoral epiphysis on the right side of the figure and a chronic example of the same injury on the left side. Note the resorption of the femoral neck and extensive remodeling.

FIGURE 26-8 A kitten with multiple pelvic fractures. Note the significant decrease in pelvic canal diameter.

Pelvic Fractures Histologically, these physes are characterized by an irregular arrangement of chondrocytes rather than the normal columnar appearance, which has resulted in the use of the term physeal dysplasia to describe the process. Although genetic factors may certainly be involved in the development of the physeal dysplasia, endocrine factors may also play a role. Neutering at an early age has been shown to delay physeal closure times in the cat,53 and it has been suggested that neutering before 6 months of age may be the endocrine factor contributing to the physeal dysplasia and slipped femoral capital physis.79 A similar syndrome occurs in young, overweight adolescent humans, especially those that are hypothyroid, are receiving growth hormone supplementation, or have hypogonadism.72 It may be that early neutering is one factor in the development of a physeal dysplasia, a wide physis, and a physis that remains open longer than normal, particularly in individuals that may be predisposed. If the cat becomes overweight, the stresses on the abnormal capital femoral physis may cause it to “slip,” producing the characteristic Salter– Harris I fracture. Published reports suggest that between 24% and 38% of affected cats will develop bilateral fractures.19,45,79,88 The condition is best treated with femoral head and neck excision (FHNE), which will produce a return to normal function in the majority of cases.45,79 Primary repair with Kirschner wires has been described20,29 but has much greater potential for comp lications than FHNE, with few, if any, demonstrated advantages.

Pelvic fractures are extremely common in the cat, especially after vehicular trauma, and make up at least 22% of all fractures seen (Figure 26-8).64 Most pelvic fractures are multiple, unstable, and displaced, at least to some degree. Regardless, most will heal with conservative therapy. However, the issue is not whether they will heal but rather the severity and consequences of the malunion that almost invariably results. Although surgery can be considered to hasten pain relief and return to function, in most practical applications there are two primary indications for surgery: Displaced acetabular fractures: Approximately 17.5% of feline pelvic fractures involve the acetabulum. Any degree of fracture malunion in the coxofemoral joint will lead to degenerative joint disease (DJD) and pain. Such a fracture can be addressed near the time of the initial trauma by primary fixation methods that include plates, screws, and tension band wires.64 Traditionally, caudal acetabular fractures have often been treated conservatively because this area of the acetabulum was not considered to be weight bearing. However, recent research has suggested that the central and caudal portions of the acetabulum are actually the major weight-bearing regions within the coxofemoral joint of the cat.4 Alternatively, femoral head and neck ostectomy can be performed several days or weeks later, once the patient’s condition has stabilized, and where there is evidence of ongoing disability. Pelvic canal narrowing: Ilial and acetabular fractures commonly displace axially, producing a narrowing of the pelvic canal. This can have immediate traumatic


effects on bladder and bowels, but the greater concern is the prospect of producing obstipation and megacolon in the longer term. These problems are extremely frustrating to treat and are much better prevented. Thus pelvic fractures that produce more than 25% to 30% narrowing of the pelvic canal are best treated surgically. This can be efficiently done, in most cases utilizing bone plates, within 5 days of the initial trauma. After that time it becomes more difficult to break down fibrous tissue and surgically reduce these fractures. Pelvic canal–widening procedures such as pelvic symphyseal osteotomy can be performed if constipation has been present for less than 6 months. If constipation has been present for more than 6 months, the colon is often beyond reclamation and subtotal colectomy should be performed.17

Nonunion Fractures Cats may be characterized as the “perfect orthopedic patient” in many ways because their straight bones, lightweight frames, and legendary healing abilities have resulted in many amazing outcomes in fracture cases. However, the old adage that fractured feline bones will heal if placed in the same room is not always true. Feline fracture nonunions do occur, at a rate of 4.3% according to one report.84 The tibia and proximal ulna were identified as the most common sites for nonunions. Increasing age and body weight, as well as open and comminuted fractures, were identified as risk factors.84

ARTHRIDITIES Degenerative Joint Disease The slowly progressive degeneration of articular cartilage with osteophyte production, usually associated with acute or chronic joint trauma, is the most common form of joint disease seen in the cat and is variously described as DJD, osteoarthritis, or osteoarthrosis. It is only relatively recently that the common occurrence of DJD has been recognized in the cat. Knowledge about DJD in cats—prevalence, impact on lifestyle, efficacy of therapy—is less well developed than for the dog. Because cats have a small body size and are light and agile, they compensate for orthopedic diseases better than dogs. Cats are also notorious for hiding signs of illness, especially if onset is insidious, and it is more difficult to interpret signs of pain or discomfort in this species.100 Twenty-two percent of cats in a general population older than 1 year of age37 and 90% of cats older 12 years of age51 were found to have radiographic evidence of DJD. The elbow was the most frequently affected joint in the older population. The coxofemoral joint may also be affected, and most cats have bilateral involvement.15 Relatively few of these cats had clinical signs associated

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BOX 26-1 Clinical Signs Associated with Degenerative Joint Disease in the Cat3,15,37,50 1. 2. 3. 4. 5. 6. 7. 8.

Pain Reduced activity, difficulty with jumping or stairs Anorexia, weight loss Irritability, aggression Inappropriate urination, constipation Decreased grooming Lameness or stiff gait Alopecia over affected joints

BOX 26-2 Physical Examination Findings Associated with Degenerative Joint Disease in Cats3 1. 2. 3. 4. 5. 6. 7. 8.

Pain on joint manipulation Soft tissue swelling Periarticular thickening Joint effusion Restricted range of movement Muscle atrophy Crepitus Heat

with the radiographic findings, or, perhaps more accurately, clinical signs were infrequently recognized by owners and veterinarians.16 This may be because the most common clinical sign associated with DJD in the dog is lameness. Owing to the cat’s lightweight frame and behavioral differences, it appears as though there may be other, more significant clinical signs of DJD that need to be recognized (Box 26-1). Physical examination findings for DJD in cats are also different than those for dogs (Box 26-2). It is assumed that the etiopathogenesis of DJD is the same for cats and dogs, although little evidence currently exists to support this assumption. Suspected causes include primary degeneration (wear and tear), joint dysplasia, joint injury, fractures, luxations and dislocations, congenital malformations, cranial cruciate ligament rupture, infection, and neoplasia. The clinical presentation of DJD in cats is different from dogs, and the radiographic signs differ slightly. Joint injuries are less common in cats than dogs, but hip dysplasia is probably underestimated in cats. The hallmark of DJD is the progressive and permanent damage of articular cartilage.82 Injury of the chondrocytes leads to the production of inflammatory mediators such as cytokines (especially interleukin-1 [IL-1]) and tumor necrosis factor-alpha. IL-1 stimulates

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production of degradative enzymes, inhibits production of proteoglycans, and stimulates fibroplasia of the joint capsule. The thickened joint capsule contributes to stiffness and decreased range of movement. The degradative enzymes set in motion a process that damages collagen and causes it to swell. The abnormal cartilage cannot bear loads normally, causing increased load on certain areas of the joint and leading to further cartilage damage. The underlying subchondral bone is stressed, and pain receptors are stimulated. Osteophytes are bony proliferations formed at the conjunction of the synovium, perichondrium, and periosteum. They are believed to be caused by mechanical instability of the joint and joint inflammation. They may contribute to joint pain. Even though the clinical signs of DJD may wax and wane, the changes to the joint are permanent, with limited ability to repair the articular surface or joint capsule. The vicious cycle of inflammation, degeneration, and mechanical dysfunction leads to progressive disease. The diagnostic approach to joint disease in cats is similar to that in dogs. A medical history, physical examination, and radiographs are most commonly employed. Further diagnostic steps might include joint fluid analysis and culture, arthroscopy, myelography, or advanced imaging such as magnetic resonance imaging (MRI) or computed tomography (CT). When taking a medical history, especially for senior cats, the veterinarian should focus the questions on changes in activity and behavior rather than solely on lameness. Many signs of chronic pain are not obvious to owners or may be misinterpreted as due to aging.100 The degree of impairment caused by chronic pain may not be apparent to some owners until improvements occur after treatment. Unfortunately, gait analysis is rarely helpful in cats, and orthopedic examinations are limited by the lack of data on normal ranges of motion for feline joints and the difficulty of detecting small changes associated with joint disease. In the examination room it may be possible to evaluate gait by allowing the cat to walk around the room. In addition, the cat can be encouraged to jump off a chair or jump up to get into its carrier. Cats with lumbosacral joint disease may be reluctant to jump and may exhibits signs of being in pain when the lower back is petted or examined. Cats with hip dysplasia may have no clinical signs at all, although cats with more advanced disease may have lameness and pain. Radiographic signs of DJD in cats are variable.1,16,36 Radiographs are best at demonstrating bony changes, and changes in the cartilage and synovium are not well demonstrated on plain radiographs. Joint effusions and joint capsule thickening are rarely evident. Typical bony changes include osteophyte development, subchondral sclerosis, perichondral bone erosion, and change in

congruity of articular surfaces. Soft tissue swelling around the joint may be present. Lumbosacral DJD may be indicated by collapse of the L7-S1 disk space, sclerosis of the L7-S1 endplates, and spondylosis deformans.

Infectious Arthridities Bacterial Septic bacterial arthritis is most commonly associated with bite wounds sustained in cat fights. Hematogenous spread of bacteria from other sites in the body appears to be relatively rare in the cat, although it may occasionally be seen in kittens. Septic arthritis may develop secondary to orthopedic surgical procedures. Clinical signs include pain and swelling of the affected joint. Pyrexia and leukocytosis are usual but not invariable.56 Radiographic signs in the early stages will be confined to joint effusion and soft tissue swelling. As the condition progresses, and depending on the infective organism, there may be evidence of a periosteal reaction, bony sclerosis, and varying degrees of bone lysis at the periosteum and in the subchondral bone. Diagnosis is based on clinical signs and the results of arthrocentesis. Cytology, as well as aerobic and anaerobic culture combined with bacterial sensitivity testing, is essential, although a negative culture result is not uncommon. Therapy with bactericidal antibiotics (based on sensitivity testing) is indicated for 4 to 6 weeks. In the absence of a positive culture, while awaiting results, or where empirical treatment is desired, cephalosporin or amoxicillin–clavulanate antibiotics are reasonable choices, with metronidazole a useful addition in confirmed or suspected anaerobic infections.56 All of these antibiotic choices, and others besides, commonly cause vomiting or inappetence in cats, which may necessitate changes in therapy. Surgical drainage or flushing of infected joints is rarely necessary except in the most severe cases. Analgesics and other supportive care may be indicated. Although up to 15% of cats have been found to be seropositive for Borrelia burgdorferi, they seem to be resistant to clinical disease, and no reports of arthritis associated with Lyme disease have been documented in this species.56 Mycoplasma Rare cases of polyarthritis and tenosynovitis associated with Mycoplasma gateae and Mycoplasma felis have been reported in the literature.56,107 Hematogenous spread from areas of active or latent infection in respiratory mucous membranes or the urogenital tract, most often in otherwise debilitated or immunocompromised individuals, appears to be the pathogenesis of the arthritis. There is potential for diagnostic confusion with immunemediated arthridities because Mycoplasma arthritis may appear similar. Radiographically, there is the potential for erosive lesions. Synovial fluid analysis and a

negative aerobic culture may suggest immune-mediated arthritis. The organisms may be detected on a synovial fluid smear stained with Wright, Leishman, or Giemsa stains, or it may be grown on anaerobic culture from synovial fluid or synovium.56,107 The clinician should have an index of suspicion for Mycoplasma arthritis when dealing with debilitated individuals that appear to have immune-mediated arthritis. Tylosin, erythromycin, and gentamicin have traditionally been the most recommended therapies. However, fluoroquinolones represent a more recent, readily available alternative that is effective, convenient, and safe in cats.107 Viral A short-term, self-limiting polyarthritis associated with calicivirus has been described in kittens younger than 6 months of age.7,21 The arthritis may be caused by infective intraarticular live virus or by the deposition of immune complexes within the synovium. The condition may be seen in association with the typical respiratory infection, or it may be seen 5 to 7 days after vaccination with modified-live calicivirus vaccine. Vaccine-associated arthritis is now uncommon because vaccine manufacturers have for the most part discontinued the use of virus strains associated with the problem. Diagnosis is made largely on the basis of history and clinical signs, and therapy is supportive, including analgesia, because the condition is self-limiting.7,21

Autoimmune Arthridities Autoimmune arthridities are characterized in the first instance by inflammation of the synovium. They may be subdivided as “erosive” when there are deforming, lytic lesions to cartilage and subchondral bone, and “nonerosive” when no such lesions are found and inflammation is confined to the synovium. Arthrocentesis produces similar results in most cases. Increased amounts of a watery, turbid joint fluid with a poor mucin clot are commonly encountered. White cell counts in the joint fluid are increased, and the majority of cells are nondegenerate polymorphonuclear cells. Bacteria are not seen, and culture is negative. All types are similar clinically, presenting with stiffness and swollen, painful joints and typically resulting in an irritable cat. Some cases may have fever and inappetence or anorexia. Erosive PERIOSTEAL PROLIFERATIVE POLYARTHRITIS

Periosteal proliferative polyarthritis (PPP) is the most common erosive form of arthritis seen in the cat. It most often affects the hocks and carpi of young adult male cats. Clinical signs begin acutely with fever, depression, stiffness, joint effusion, and pain. Over the course of a few weeks, the disease enters a chronic phase in which extensive periosteal new bone forms around the hocks


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BOX 26-3 Criteria Proposed for the Diagnosis of Periosteal Proliferative Polyarthritis7 1. 2. 3. 4. 5.

Erosive polyarthritis Periosteal new bone formation at affected joints Negative for rheumatoid factor in the blood Enthesopathies Primarily the hocks and carpi are involved

NOTE: The first three criteria must be met to make the diagnosis; however, the last two are variable.

and carpi and at the attachments of ligaments and tendons. New bone production may be extensive enough to produce ankylosis of joints. Erosive lesions may also be seen in subchondral bone and at tendinous attachments.21,56 Erosive lesions or periosteal new bone formation at attachment points of ligaments, tendons, or fascia are referred to as enthesopathies.7 The criteria proposed by Bennett and Nash for diagnosing PPP are found in Box 26-3.7 An etiologic link has been proposed between feline syncytium-forming virus (FeSFV) and PPP insofar as all cats with PPP appear to have FeSFV. However, attempts to experimentally induce PPP by inoculating cats with the virus have failed, and FeSFV has been found as a normal inhabitant in the joints of many asymptomatic cats.21 A role for feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) has also been proposed in producing immunosuppression that allows proliferation of FeSFV; however, FeLV and FIV are frequently not found in cats with PPP.5,21 Occasionally symptoms of immune-mediated arthritis may be found in cats immunocompromised for other reasons, including chemotherapy and hyperadrenocorticism. PPP bears some similarities to Reiter’s disease, which is seen most commonly in men. Urethritis and diarrhea can be seen, in addition to the arthritic lesions in humans, and there is at least one report of hematuria associated with polyarthritis in a cat.5 Conjunctivitis and lesions of skin and mucous membranes, which are common in humans, have been found in some cats. In light of these types of lesions, a link between Reiter’s disease and Chlamydia infection has been explored, and the organism has been implicated in humans.7 The prognosis for cats with PPP is guarded to poor. Few will experience anything more than marginal improvement on therapy, and many will end up being euthanized. However, decisions of that sort should be based on assessments of the patient’s function and comfort level. RHEUMATOID ARTHRITIS

By all accounts, rheumatoid arthritis (RA) is much less common in the cat than in the dog. RA is a synovitis

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BOX 26-4 Diagnostic Criteria for Establishing a Diagnosis of Rheumatoid Arthritis in the Cat7 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

Stiffness after rest Pain on manipulation of at least one joint Swelling of at least one joint Swelling of at least one other joint within a 2-month period Symmetric joint swelling Subcutaneous nodules Erosive radiographic changes Positive rheumatoid factor blood test Abnormal synovial fluid (poor mucin clot, predominance of polymorphonuclear cells) Characteristic histologic changes in the synovium (villous hypertrophy) Characteristic histologic changes in the subcutaneous nodules

NOTE: Criteria 1 to 5 must be present for at least 6 weeks, and at least two of criteria 7, 8, and 10 must be present to establish the diagnosis.

caused by the production of autoantibodies against immunoglobulin G (rheumatoid factor). The deposition of immune complexes within the synovium leads to an erosive, deforming arthritis. As with other immunemediated arthridities, RA causes generalized stiffness, pain, and swelling of joints. In contrast to PPP and idiopathic immune-mediated arthridities, there is seldom malaise or inappetence, and the course tends to be more gradual in onset. Joint deformity to the point of subluxation and luxation is often a prominent feature. Bennett7,21 has described 11 diagnostic criteria, patterned after those used in man and the dog, for establishing a diagnosis of RA in the cat (Box 26-4). The criteria recognize the fact that a positive blood test for rheumatoid factor is not always present, and a positive test is not necessarily specific for the disease. The presence of subcutaneous nodules is common in humans but has not been described in the cat.7 One report of 12 cases of RA in the cat described an average age of 5.9 years, with Siamese cats overrepresented.44 With aggressive forms of antirheumatic therapy, discussed at the end of this section, the prognosis for RA seems to be much better than PPP, with 58% showing a marked improvement.44 Non-Erosive SYSTEMIC LUPUS ERYTHEMATOSUS

Systemic lupus erythematosus (SLE) is an uncommon cause of arthritis in cats. It is characterized by multisystemic involvement with polyarthritis and usually one of the following: autoimmune hematologic disease (thrombocytopenia, hemolytic anemia, and leukopenia),

BOX 26-5 Idiopathic Polyarthritis Subgroups7 Type I: idiopathic Type II: idiopathic associated with other infections. These may be found in the respiratory or urogenital tracts, skin, or oral cavity. Type III: idiopathic associated with gastrointestinal disease Type IV: idiopathic associated with neoplasia. In the cat this is most often myeloproliferative neoplasia, which may be FeLV or FIV.

dermatitis, glomerulonephritis, or meningitis.7 There are no destructive or deforming lesions on radiography or gross examination. The disease results from an autoimmune reaction to nucleic acid, which manifests as the hemolytic anemia, leukopenia, or thrombocytopenia. Deposition of the resulting immune complexes produces synovitis, glomerulonephritis, meningitis, dermatitis, or occasionally polymyositis. Onset of symptoms is usually acute and includes pain, especially on handling, and joint swelling. Clinical pathology is essential to diagnose SLE. Antinuclear antibody (ANA) blood tests are invariably positive at a level of 1 : 40 or greater in the cat.7 Although a diagnosis of SLE cannot be established without such a positive ANA value, the test is not specific and may be elevated in the acute phase of other disease conditions, including FeLV, FIV, and feline infectious peritonitis (FIP). Moreover, lower titers of ANA can be found in otherwise healthy cats.7 Hematologic abnormalities (anemia, thrombocytopenia, and leukopenia) are common, as is proteinuria.7 The diagnostic criteria to establish SLE are as follows: 1. Multisystem involvement, which most often includes polyarthritis and one other body system 2. ANA titre of 1 : 40 or greater 3. Presence of antibodies to blood cells or immune complexes in histopathology of affected tissues Criteria 1 and 2 are essential for the diagnosis, which cannot be made solely on the basis of an elevated ANA titer.7 Reports of treatment for SLE in cats are rare in the literature, but the prognosis appears to be guarded. IDIOPATHIC POLYARTHRITIS

Polyarthridities that do not fit into any of the other classifications end up in the idiopathic category. There are four subgroups of idiopathic polyarthritis (Box 26-5).7 Idiopathic arthritis may present at any age, but most affected cats are young adults that develop symptoms acutely or subacutely. The pathogenesis is undoubtedly a synovitis arising from the deposition of immune


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complexes. Clinical signs are acute in all but type IV cases, which have a more chronic course. Most cases of all types exhibit signs of stiffness and pain, with occasional lameness. Joint and soft tissue swelling is usually present. These changes, along with the clinical signs, tend to be bilaterally symmetric. Pyrexia and inappetence are common. Type II idiopathic polyarthritis in the cat is most often associated with respiratory symptoms, including increased lung sounds, congestion, and conjunctivitis. Cats with type III frequently have diarrhea and dysentery, with occasional vomiting.7 Toxoplasmosis has been identified as one possible cause.7 Radiography is normal, except for joint effusion in some cases. The prognosis with treatment is generally good, especially in type I cases or in type II and III cases in which the underlying systemic illness can be identified and treated. Relapses, especially in types I and IV, are common.

Scottish Fold Arthropathy Scottish Fold cats have an autosomal dominant trait that impairs enchondral ossification and produces abnormal cartilage maturation called Scottish Fold arthropathy (also known as osteochondrodysplasia and osteodystrophy). Heterozygotes for this trait have the characteristic “folded ear” appearance for the breed and may have mild signs of arthropathy. Homozygotes develop a progressive ankylosing arthropathy with radiographic lesions evident as early as 7 weeks of age. The condition is characterized by the production of new bone that bridges joints throughout the body but most prominently in the paws, spine, tail, and distal hind limbs (Figure 26-9). Affected individuals have a short, squat appearance that has been described as a form of dwarfism14 and experience decreased range of motion in affected joints. Clinical signs include stiffness, lameness, and inability to jump. The condition is progressive and can produce dramatic periarticular new bone, most prominently on the plantar aspect of the calcaneal–tarsal–metatarsal articulation. Exostoses in this area can produce ulceration of overlying skin. Surgical excision of the exostoses or radiation therapy have been used as successful palliative therapies for extended periods.14,54,78 Nonsteroidal antiinflammatory drugs (NSAIDs), pentosan polysulfate, and oral glycosaminoglycans have been reported to provide symptomatic relief.14,74 One report has described the use of pantarsal arthrodesis to improve function.78

Arthritis Therapy It has been argued that no pharmaceutical therapy has a greater impact on the arthritic patient than weight control in the obese patient. The owner may also be able to make adjustments in the cat’s environment, such as placing litter boxes within easy access of the arthritic cat

FIGURE 26-9 Scottish Fold arthropathy. Note the ankylosing arthropathy characterized by new bone production in the hock, stifle, and vertebral (especially coccygeal) joints.

or making it easier for the cat to attain its customary perch in several small steps instead of one big jump. Therapy for Degenerative Joint Disease The goals of treatment for cats with DJD include reduction of pain and inflammation, improvement in joint function, and slowing the disease process, if possible. Treatments fall into four broad categories: 1. Weight loss 2. Drug therapy 3. Chondroprotectants 4. Nutraceuticals Weight loss is indicated if the patient is overweight or obese and will reduce forces on the joint surfaces. Weight loss may also lead to decreased dose or frequency of drug administration. Drug therapy is indicated to control inflammation, provide pain relief, and improve function. The development of several NSAIDs specifically for the small animal veterinary market is arguably one of the most significant therapeutic advances in veterinary medicine during the last 50 years. Despite this, relatively little information exists regarding the safety and efficacy of these drugs in the cat, and virtually nothing is known about the longterm use of these drugs in this species for chronic pain and inflammation, such as is seen in DJD. What is known is that the cat has a significantly decreased ability to metabolize most of these drugs through hepatic glucuronidation. The result is a much longer half-life for most NSAIDs in the cat and thus a greater potential for

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accumulation and toxicity. Whereas gastrointestinal upset characterized by vomiting, inappetence, and diarrhea is the most common toxic effect, renal insufficiency is the most serious potential adverse reaction. Both of these adverse reactions arise from the antiprostaglandin effect of NSAIDs, specifically on the cyclooxygenase 1 (COX-1) isomer in the inflammatory pathway. Prostaglandins have a protective effect on gastric mucosa, presumably through increased secretion of mucus in the gastrointestinal tract. Inhibition of this secretion, combined with the acidic nature of most NSAIDs, produces gastric inflammation and ulceration. In the kidney, prostaglandins play a role in maintaining renal blood flow, particularly in the face of dehydration or hypotension. Inhibition of this effect has been associated with catastrophic renal failure in some cats.13,67,91 The potential for these adverse reactions undoubtedly explains some of the reluctance on the part of pharmaceutical manufacturers to pursue the use of NSAIDs in this species. Nevertheless, limited research has resulted in label recommendations in some parts of the world for feline use of carprofen, ketoprofen, tolfenamic acid, and meloxicam.13,43,67,80,91 Only meloxicam has a label for extended duration of administration in some countries, but cautious off-label use of various NSAIDs has been successful for much longer periods.43,91,99a Carprofen is labeled for use in the cat in the United Kingdom, Europe, Australia, and New Zealand; however, the indication is for one-time postsurgical subcutaneous administration at a dose of 4 mg/kg.67,80,91 No information exists on long-term use other than an individual report of toxicity after oral administration.67 The drug has an extremely variable half-life (9 to 49 hours) in the cat, which increases the likelihood for toxicity with repeated use in some cats. Consequently, carprofen cannot be recommended as a safe option for management of DJD. Ketoprofen is approved for use in the cat in Europe, Australia, and Canada at a dose of 1 mg/kg orally, once daily for up to 5 days, and 2 mg/kg subcutaneously, once daily for up to 3 days. Although the drug is eliminated by hepatic glucuronidation in the dog, the halflives in both dogs and cats are similar. This, combined with other evidence, suggests the possibility of another excretory pathway for ketoprofen in the cat, which may imply a higher degree of safety; however, no long-term data corroborate this.67 The drug is known to have a relatively greater activity against COX-1, which increases its inhibitory effect on platelet aggregation and may be significant in terms of renal or gastrointestinal side effects with long-term use.67 Tolfenamic acid is licensed for use in cats in Canada, Australia, New Zealand, and most of Europe. The recommended dose is 4 mg/kg orally or subcutaneously, once daily for 3 to 5 days. The product is labeled for the treatment of fever and upper respiratory disease,

although its use as an analgesic and antiinflammatory is established in the literature.67 Information provided by the manufacturer claimed no significant toxic effects when up to twice the recommended dose of the oral tablet or the injectable solution were given for up to 10 days to two groups of 12 cats. Increases characterized as “mild” were noted in the alanine transaminase (ALT) and aspartate aminotransferase (AST) of treated cats, and a positive test for fecal occult blood was noted in two cats from each group. There are anecdotal reports of DJD treatment in cats with tolfenamic acid for 3 to 5 consecutive days each week for extended periods, but little information in the literature supports this recommendation. Most of what little information exists regarding the chronic use of NSAIDs for DJD in the cat concerns meloxicam. In contrast to the metabolism of most other NSAIDs in the cat, meloxicam is excreted by oxidative enzymes and thus has a similar half-life in both the cat and dog.67 One recent study showed a COX-1–sparing effect for meloxicam in cats.38 Consequently, the drug lends itself more readily to longer-term use in this species. In North America meloxicam is supplied in a 1.5 mg/mL honey-flavored oral formulation that is well tolerated by cats. In many countries it is supplied in a cat-specific formulation of 0.5 mg/mL. The same strength is available in the United States as a small dog formulation. It is labeled for feline use in the United States, Europe, Australia and New Zealand at a dose of 0.3 mg/kg for one-time subcutaneous use. Further, chronic use of the oral solution at 0.05 mg/kg per day is described on the package insert in many countries.91 Several other recommendations for oral dosing appear in the literature (Box 26-6). Administration of 1 drop of the 1.5 mg/mL oral liquid preparation on the cat’s daily food was tolerated without significant adverse effects compared with controls in 46 cats with a mean age of 12.9 years that were given the drug for a mean duration of 5.8 months.43 Good to excellent results were reported by at least 80% of the owners and veterinarians surveyed.43 Palatability was not reported to be a problem with meloxicam. The most commonly encountered side effect appears to be gastrointestinal upset.91 The currently available information, although far from overwhelming, would suggest that meloxicam is a viable option for long-term treatment of DJD in cats. Before starting NSAID therapy, a complete blood cell count, serum chemistries, and a urinalysis should be performed. Ideally, NSAIDs should be prescribed only to normotensive, normovolemic adult cats with no history of renal, hepatic, or gastrointestinal disease. However, for some cats the benefits of NSAID therapy outweigh the risks, insofar as the quality of life may be more important than the length of life. NSAIDs are not recommended in patients taking certain medications,


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BOX 26-6 Published Doses for Meloxicam in the Cat Source Label: US, Australia, New Zealand, EU Label: Australia, New Zealand, EU Wallace 2003,103a Carroll & Simonson 200512a Lascelles 200767 Robertson 200891 Gunew 200843

Dose 0.3 mg/kg subcutaneously, once 0.1 mg/kg on day one, followed by 0.05 mg/kg per day, orally 0.2 mg/kg on day 1, followed by 0.1 mg/kg/day for 2 days, then 0.025 mg/kg/day or 0.1 mg/cat 2-3 times/week 0.1 mg/kg on day 1, followed by 0.05 mg/kg for 1 to 4 days, then reduction to the lowest effective dose (0.025 mg/kg every 24-48 hours) 0.05 mg/kg given once, followed by 0.025 mg/kg or less once daily 0.1 mg/kg for four days, followed by 0.1 mg/cat once daily

such as diuretics and corticosteroids. Blood tests should be monitored periodically for cats on long-term therapy, and owners should be cautioned to monitor for vomiting, diarrhea, anorexia, increased thirst, increased urination, and lethargy. One author suggests re-evaluation every 8 to 12 weeks.90 Renal values and urine protein levels should be monitored; hepatic sensitivity to NSAIDs seems to be primarily a canine problem.13,67,91 It may be helpful to recommend that cats taking NSAIDs be fed only or primarily canned foods because this increases water consumption by up to 50% and may help prevent subclinical dehydration in predisposed patients. Glucocorticoids are controversial drugs for treatment of DJD. These drugs can reduce inflammation through various mechanisms, but chronic use has been found to delay healing and even damage cartilage.3 Furthermore, the potential adverse effects of glucocorticoids in cats are well known. Use of these drugs should be limited to cases in which all other therapies have failed and for short periods only. Analgesics can be very useful in the treatment of feline DJD and may be added to other therapies. Commonly used analgesics include buprenorphine (0.01 to 0.03 mg/kg every 8 to 12 hours, by way of buccal mucosa), gabapentin (3 to 5 mg/kg orally, every 8 to 12 hours), and tramadol (2 mg/kg orally, every 12 hours). Although the use of oral and injectable chondroprotectives is reported for arthritic conditions of various kinds in the cat,14,74 little objective evidence exists as to their effectiveness. Oral preparations include several combinations in which chondroitin sulfate and either hydrochloride or sulfate salts of glucosamine predominate. Little is known about the differences, if any, among various formulations; what dose rates and durations of therapy are best; and which patients, if any, will benefit. Virtually all of the currently available research has been done in the dog. Injectable chondroprotectants include polysulfated glycosaminoglycan (Adequan, Novartis)

and pentosan polysulfate (Cartrophen, Biopharm, Australia or Pentosan, Naturevet, Australia), which are labeled for use in the dog but have been used with apparent benefit and without adverse effect in the cat.14,78 Pentosan polysulfate is given at a dose of 3 mg/kg subcutaneously, once weekly for four consecutive treatments. Polysulfated glycosaminoglycan is given at a dose of 4 mg/kg intramuscularly, twice weekly for 4 weeks. Both chondroprotectants are given as needed after the first course of therapy. Oral or parenteral chondroprotectants have their beneficial effect in three primary ways: 1. By stimulating and enhancing the metabolism of chondrocytes and synoviocytes, including the provision of substrate for the production of cartilage matrix and synovial fluid 2. By inhibiting degradative enzymes and other entities, including prostaglandins, complement, and free radicals that play a role in the osteoarthritic destruction of the joint 3. By inhibiting the production of thrombi in the microvasculature of the synovium and subchondral bone, which have been shown to play a role in osteoarthritis46 Omega-3 fatty acids have been shown to have an inhibitory effect on arachidonic acid, which is a key player in the inflammatory pathway in arthritic joints. Supplements of omega-3 fatty acids or diets containing these compounds have been used with apparent success in dogs. Diets for joint health are relatively new for cats. The first products on the market (Medi-Cal Royal Canin Mobility Support, Hill’s Prescription Diet Feline j/d) contain omega-3 fatty acids as well as glucosamine and chondroitin sulfate. Therapy for Immune-Mediated Arthritis Prednisolone at immunosuppressive doses is the firstline treatment for immune-mediated arthritis in the cat.

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Prednisone and prednisolone are interchangeable in the dog, but many cats are unable to adequately absorb prednisone and convert it to the active metabolite, prednisolone, within the liver.40 The cat with immunemediated arthritis should be started on a total daily dose of 2 to 4 mg/kg in two divided doses. This dose is continued for 2 weeks and then gradually tapered over a further 6 to 8 weeks.7,28,56,80 The short- and long-term side effects of corticosteroid therapy are well known, but most cats seem to be relatively more resistant to these effects compared with dogs or humans. The determination of when to begin tapering the dose and how quickly that should be done is based on improvement of clinical signs and the results of follow-up joint taps starting at 2 weeks after the initiation of therapy. Most immune-mediated arthridities have synovial fluid profiles with high numbers of nondegenerate polymorphonuclear cells. Follow-up samples should show significant declines in absolute white cell counts (preferably below 4000/µL), but equally important is a shift to a predominantly mononuclear cell population. Results satisfying those criteria would suggest a favorable prognosis and would also be an indication to begin tapering the corticosteroid.7,56 If, however, follow-up joint taps do not show favorable changes in cell numbers and populations, then the addition of a cytotoxic drug, most often cyclophosphamide in the cat, should be considered. Similarly, if clinical signs cannot be kept in remission or doses of prednisolone become high and side effects are problematic, cyclophosphamide should be added. Some have advised that both prednisolone and cyclophosphamide should be used together from the outset of therapy, especially in the erosive arthridities, for which the prognosis is much less favorable.7 Cyclophosphamide is given at a dose of 2.5 mg/kg orally, once daily for 4 consecutive days a week in combination with prednisolone at an antiinflammatory dose of 1 mg/kg orally, divided twice daily. This regimen should be continued for 4 weeks after remission of clinical signs.7 The introduction of cytotoxic drugs mandates a higher level of monitoring because of their potential for adverse effects. Hematuria is one such side effect and should be monitored with urinalysis every 2 weeks during therapy. Every 1 to 2 weeks, complete blood counts (CBCs) should also be done to detect any significant decrease in white cell or platelet counts. Neutrophil counts below 1000/µL or platelet counts below 50,000/µL should result in a decrease in cyclophosphamide dose by 25%. If neutropenia (16 months versus 9 months) than those whose excisions were incomplete.6,16

CHAPTER 28 Oncology

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Although surgical excision is the primary treatment modality for most cats with injection-site sarcomas, a multimodality treatment approach may provide better outcomes for cats with incomplete surgical excisions (whether or not the surgical margins are assessed to be “clean”). Radiation therapy can be incorporated into the treatment plan either preoperatively or postoperatively. There is no clear evidence as to whether preoperative or postoperative irradiation is better for injection-site sarcoma. In one study evaluating the effectiveness of preoperative radiation and surgery in 33 cats, the median disease-free interval was 398 days and the median overall survival time was 600 days.5 Local recurrence of the tumor was noted in 45%. In another study 76 cats received postoperative radiation. The median diseasefree interval was 405 days, and the median overall survival time was 469 days. The local recurrence rate was 41%.3 Because these are different studies, with different confounding factors, results are not directly comparable. No clinical study has ever directly compared the two treatment approaches. When used, radiation treatment is typically performed in conjunction with surgery, except in the palliative setting. The role of chemotherapy in the treatment of injectionsite sarcoma is poorly defined. There are no studies that support its use as the primary, or sole, form of treatment in the gross disease setting and little evidence for its use in the adjuvant (after surgery or radiation) setting either. Nonetheless, chemotherapy is commonly used in an attempt to palliate nonresectable tumors; in the neoadjuvant setting to cytoreduce large tumors before surgery; and in the adjuvant setting, especially for histologically high-grade tumors. It has also been used as a radiation sensitizer. Chemotherapy drugs that have been used clinically include doxorubicin, cyclophosphamide, carboplatin, mitoxantrone, and vincristine.24 In general, use of these drugs has resulted in some partial responses and infrequent complete responses. Usually, responses are not durable. Of these drugs doxorubicin has received the most attention, both as a single agent and in combination with cyclophosphamide. In one study evaluating the use of combined doxorubicin and cyclophosphamide in cats with nonresectable tumors, the overall response rate was 50%, with 17% having resolution of all clinically detectable tumor.1 Unfortunately, the responses were not durable, with a median response duration of 125 days. In another study 69 cats were treated with four cycles of doxorubicin combined with surgical excision 10 days after the second chemotherapy cycle. No differences in the rates of recurrence or overall survival were found between the groups.23 Several studies have investigated multimodality treatment, combining preoperative or postoperative radiation, surgery, and/or chemotherapy. One study compared surgery and radiation therapy with or without doxorubicin, and the other compared surgery and radiation therapy with or without doxorubicin and

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cyclophosphamide.2,3 No significant differences between the group receiving adjuvant chemotherapy and the group that did not were found in either study for overall survival or median time to recurrence. In conclusion, aggressive wide surgical excision performed by an experienced specialist surgeon that includes advanced imaging in the treatment planning is recommended for most cats with injection-site sarcomas. There is evidence that some cats may benefit from preoperative or postoperative radiation therapy. The role for chemotherapy in a multimodality approach for this disease remains to be defined; however, its continued empiric use is reasonable in light of the lack of definitive studies addressing its efficacy and the potential benefits some drugs might provide. Based on what is known and suspected regarding the pathogenesis of injection-site sarcomas in cats, prevention strategies are likely to have the greatest impact in decreasing the morbidity and mortality rates associated with injection-site sarcoma in the pet cat population. The VAFSTF and others have suggested strategies and guidelines that may help decrease the incidence of injectionsite sarcoma and decrease morbidity and mortality rates. In addition to the 3-2-1 recommendations for management of vaccine reactions, it is recommended that rabies vaccines be administered as far distally as possible in the right rear limb; FeLV vaccines (unless containing rabies antigen as well) be given as distally as possible in the left rear limb; and vaccines containing any other antigens except rabies or FeLV be given on the right shoulder, with care taken to avoid the midline or interscapular space.32 The location of the injection should be in an area that is amenable for possible surgical removal. The vaccination site, dose, manufacturer, and lot number should be accurately recorded.33 The recommended vaccination protocols for cats are critically important, with the understanding that these protocols should be tailored to the individual needs of the patient.26 Additionally, discussion with cat owners regarding vaccination practices and sarcoma risk should be part of routine client education by veterinarians.

References 1. Barber LG, Sorenmo KU, Cronin KL et al: Combined doxorubicin and cyclophosphamide chemotherapyfor nonresectable feline fibrosarcoma, J Am Anim Hosp Assoc 36:416, 2000. 2. Bregazzi VS, LaRue SM, McNiel E et al: Treatment with combination of doxorubicin, surgery, and radiation versus surgery and radiation alone for cats with vaccine-associated sarcomas: 25 cases (1995-2000), J Am Vet Med Assoc 218:547, 2001. 3. Cohen M, Wright JC, Brawner WR et al: Use of surgery and electron beam irradiation, with or without chemotherapy, for treatment of vaccine-associated sarcomas in cats: 78 cases (1996-2000), J Am Vet Med Assoc 219:1582, 2001. 4. Coyne MJ, Reeves NC, Rosen DK: Estimated prevalence of injection-site sarcomas in cats during 1992, J Am Vet Med Assoc 210:249, 1997.

5. Cronin K, Page RL, Sponick G et al: Radiation therapy and surgery for fibrosarcoma in 33 cats, Vet Radiol Ultrasound 39:51, 1998. 6. Davidson EB, Gregory CR, Kass PH: Surgical excision of soft tissue sarcomas in cats, Vet Surg 26:265, 1997. 7. Dubielzig RR, Everitt J, Shadduck JA, et al: Clinical and morphologic features of post-traumatic ocular sarcomas in cats, Vet Pathol 27:62, 1990. 8. Ellis JA, Jackson ML, Barfsch RC et al: Use of immunohistochemistry and polymerase chain reaction for detection of oncornaviruses in formalin-fixed, paraffin-embedded fibrosarcomas from cats, J Am Vet Med Assoc 209:767, 1996. 9. Esplin DG, Campbell R: Widespread metastasis of a fibrosarcoma associated with vaccination site in a cat, Feline Pract 23:13, 1995. 10. Esplin DG, Jaffe MH, McGill LD: Metastasizing liposarcoma associated with a vaccination site in a cat, Feline Pract 24:20, 1996. 11. Giudice C, Stefanello D, Sala M et al: Feline injection-site sarcoma: recurrence, tumour grading and surgical margin status evaluated using the three-dimensional histological technique, Vet J 186:84, 2010. 12. Gobar GM, Kass PH: World Wide Web–based survey of vaccination practices, postvaccinal reactions, and vaccine site-associated sarcomas in cats, J Am Vet Med Assoc 220:1477, 2002. 13. Hendrick MJ, Goldschmidt MH, Shofer FS et al: Postvaccinal sarcomas in the cat: epidemiology and electron probe microanalytical identification of aluminum, Cancer Res 52:5391, 1992. 14. Hendrick MJ, Shofer FS, Goldschmidt MH et al: Comparison of fibrosarcomas that developed at vaccination sites and at nonvaccination sites in cats: 239 cases (1991-1992), J Am Vet Med Assoc 205:7425, 1994. 15. Hendrick MJ, Brooks JJ: Postvaccinal sarcomas in the cat: histology and immunohistochemistry, Vet Pathol 31:126, 1994. 16. Hershey AE, Sorenmo KU, Hendrick MJ et al: Prognosis for presumed feline vaccine-associated sarcoma after excision: 61 cases (1986-1996), J Am Vet Med Assoc 216:58, 2000. 17. Kass PH, Barnes WG, Spangler WL et al: Epidemiologic evidence for a causal relation between vaccination and fibrosarcoma tumorigenesis in cats, J Am Vet Med Assoc 203:396, 1993. 18. Kass PH, Spangler WL, Hendrick MJ et al: Multicenter casecontrol study of risk factors associated with development of vaccine-associated sarcomas in cats, J Am Vet Med Assoc 223:1283, 2003. 19. Kidney BA, Ellis JA, Haines DM et al: Evaluation of formalin-fixed paraffin-embedded tissues obtained from vaccine site-associated sarcomas of cats for DNA of feline immunodeficiency virus, Am J Vet Res 61:1037, 2000. 20. Kidney BA, Haines DM, Ellis JA et al: Evaluation of formalin-fixed paraffin-embedded tissues from vaccine site-associated sarcomas of cats for polyomavirus DNA and antigen, Am J Vet Res 62:828, 2001. 21. Kidney BA, Haines DM, Ellis JA et al: Evaluation of formalin-fixed paraffin-embedded tissues from vaccine site-associated sarcomas of cats for papillomavirus DNA and antigen, Am J Vet Res 62:833, 2001. 22. Lidbetter DA, Williams FA, Krahwinkel DJ et al: Radical lateral body wall resection with reconstruction using polypropylene mesh and a caudal superficial epigastric axial pattern flap: a retrospective clinical study of the technique and results in 6 cats, Vet Surg 31:57, 2002. 23. Martano M, Morello E, Ughetto M et al: Surgery alone versus surgery and doxorubicin for the treatment of feline injection site sarcomas: a report on 69 cases, Vet J 170:84, 2005. 24. McEntee MC, Page RL: Feline vaccine-associated sarcomas, J Vet Intern Med 15:176, 2001. 25. Nieto A, Sanchez MA, Martinez E et al: Immunohistochemical expression of p53, fibroblast growth factor-b, and transforming growth factor-alpha in feline vaccine-associated sarcomas, Vet Pathol 40:651, 2003.

CHAPTER 28 Oncology

26. O’Rourke K: Controversy, confusion continue to surround vaccine guidelines, J Am Vet Med Assoc 225:814, 2004. 27. Petterino C, Martano M, Cascio P et al: Immunohistochemical study of STAT3 expression in feline injection-site fibrosarcomas, J Comp Path 134:91, 2006. 28. Rudmann DG, Van Alstine WG, Doddy F et al: Pulmonary metastasis of a feline vaccine-site fibrosarcoma, J Vet Diagn Invest 10:79, 1998. 29. Shaw SC, Kent MS, Gordon IK et al: Temporal changes in characteristics of injection-site sarcomas in cats: 392 cases (1990-2006), J Am Vet Med Assoc 234:376, 2009. 30. Smith AJ, Njaa BL, Lamm CG: Immunohistochemical expression of c-KIT protein in feline soft tissue fibrosarcomas, Vet Pathol 46:934, 2009. 31. Thomas R, Valli VE, Ellis P et al: Microarray-based cytogenetic profiling reveals recurrent and subtype-associated genomic copy number aberrations in feline sarcomas, Chromosome Research 17:987, 2009. 32. Vaccine-Associated Feline Sarcoma Task Force: Diagnosis and treatment of suspected sarcomas, J Am Vet Med Assoc 214:1745, 1999. 33. Vaccine-Associated Feline Sarcoma Task Force: The current understanding and management of vaccine-associated sarcomas in cats, J Am Vet Med Assoc 226:1821, 2005.

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FIGURE 28-4 Gross appearance of a solitary ulcerated mammary tumor in an adult cat diagnosed by histopathology as an adenocarcinoma.

CLINICAL FEATURES

MAMMARY TUMORS

Mammary tumors are the third most common feline tumor, accounting for up to 17% of all neoplasms in female cats.6,10,19,24 Male cats can also be affected by mammary tumors, although much less often, with reported incidence of up to 5% compared with females.9,31 Domestic short hair and Siamese breeds appear to have an elevated risk for mammary tumors.9,24 Mammary neoplasia is generally seen in older cats with a median age of 10.8 years (mean 10 to 12 years), although cats as young as 9 months have been reported to be affected.* The precise etiology of feline mammary tumors is uncertain, but hormones, particularly estrogen and proge sterone, are thought to play a significant role in tumorigenesis.22 In a case control study, cats that underwent ovariohysterectomy before 6 months and 1 year of age had a 91% and 86% reduction in risk, respectively, of developing mammary carcinoma compared with intact cats.22 Parity was not found to significantly affect risk for tumor development.22 Both female and male cats regularly exposed to exogenous progestins or estrogen– progestin combinations such as medroxyprogesterone acetate have been identified to be at increased risk of developing mammary carcinoma.15,17,22,28

In contrast to canine mammary tumors, the vast majority (80% to 96%) of feline mammary masses are malignant, with most diagnosed as adenocarcinomas (tubular, papillary, and solid types). Less common malignant lesions include SCCs, soft tissue sarcomas, mucinous carcinomas, complex and mixed carcinomas, and inflammatory mammary carcinomas.* Cats are typically presented for palpable nodules of single or multiple mammary glands detected by the owner or found incidentally during routine physical examination. More than half of affected cats have multiple gland involvement.34 Mammary tumors in cats may remain undetected until they become large, fixed, and ulcerated and involve multiple mammary glands or local lymph nodes (Figure 28-4).11,12 Thus mammary carcinomas are often in an advanced state at the time of examination. If pulmonary metastatic disease is present, cats may present with acute dyspnea as a result of malignant pleural effusion, often containing exfoliating malignant cells.27,34 Feline fibroepithelial hyperplasia, a benign hypertrophy of the mammary glands, should not be confused with malignant mammary neoplasms. Other terms for this condition include mammary fibroadenomatosis, pericanalicular fibroadenoma, benign mammary hypertrophy, and mammary adenomatosis. Unlikely mammary carcinomas, which are less common in males, fibroepithelial hyperplasia is seen in both sexes. The condition is seen most typically in young cats shortly after a silent estrus or after chronic exogenous progestins. One or more glands may be enlarged, with occasional severe bilateral

*References 9, 10, 18, 23, 24, 27, 31.

*References 1-3, 10-12, 21, 24, 27, 29, 34.

Kevin Choy

INCIDENCE, ETIOLOGY, AND PATHOGENESIS

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TABLE 28-3 Modified World Health Organization (WHO) Staging System for Classification of Feline Mammary Tumors T = PRIMARY TUMOR SIZE T1

3 cm maximum diameter

N = REGIONAL LYMPH NODE INVOLVEMENT N0

No histologic/cytologic evidence of metastasis

N1

Histologic / cytologic evidence of metastasis

M = DISTAL METASTASIS

FIGURE 28-5 Left lateral thoracic radiograph from a 12-year-old domestic shorthair with metastatic mammary carcinoma. Note the diffuse interstitial to nodular metastatic pattern (small arrows) along with malignant pleural effusion (large arrow).

enlargement noted. The affected glands are often traumatized, leading to secondary ulceration, necrosis, and discomfort. Benign feline fibroepithelial hyperplasia is treated by removing hormonal exposures of exogenous progestin therapy or performing ovariohysterectomy. It may take several months for mammary lesions to resolve.1,12,27,34 More information on treatment of this condition is found in Chapter 40.

DIAGNOSIS AND STAGING Because feline mammary tumors are often malignant, thorough evaluation of cats with mammary tumors is prudent to confirm diagnosis and, if malignancy is confirmed, to establish clinical stage for prognostication. Evaluation should include CBC, serum biochemistry profile and urinalysis, and evaluation of the primary tumor, regional lymph nodes, and distant metastatic sites (particularly the thoracic cavity). The primary tumor(s) should be assessed for number, site, size, consistency, ulceration, fixation to skin or abdominal wall, and nipple discharge if present. Local lymph nodes should be carefully palpated with any identified nodes aspirated or biopsied. Three-view thoracic radiographs (right lateral, left lateral, and ventrodorsal views) are vital to assess for pulmonary, lymph node, and pleural metastatic disease. Mammary tumor pulmonary metastases appear as interstitial densities ranging from small and indistinct to large and discrete nodules and may be accompanied by miliary pleural lesions with or without pleural effusion (Figure 28-5).

M0

No evidence of metastasis

M1

Evidence of metastasis

STAGES I

T1

N0

M0

II

T2

N0

M0

III

T1-2 T3

N1 N0-1

M0 M0

IV

Any T

Any N

M1

Reported metastatic rates for feline mammary carcinomas range from 25% to 100%, with the most common sites being lungs and draining lymph nodes (axillary, inguinal, sternal).11,12,33 Metastasis to other organs or body tissues is less common, with involvement of the liver, spleen, kidney, adrenal gland, peritoneal surface, heart, and bone reported.3,27 A literature review of 799 cats with malignant mammary tumors found extraskeletal metastases in 338 cases. Skeletal metastasis was rare in cats compared with breast cancer in humans and mammary carcinoma in dogs.33 Biopsy of the mammary lesion is required for histopathologic confirmation of malignancy. Samples may be obtained before surgery by incisional biopsy or at the time of definitive surgery by excisional biopsy. Cytologic examination using fine-needle aspiration of mammary lesions in cats may confirm an epithelial neoplasm but will not distinguish reliably between benign and malignant tumors. Cytology may be helpful in ruling out nonmammary cutaneous or subcutaneous neoplasms such as mast cell tumors. Cytology is also indicated to assess suspected lymph node metastasis or malignant pleural effusions.11,12 Staging of feline mammary tumors is based on the modified WHO scheme first established in 1980 that assesses primary tumor size, lymph node involvement, and evidence of distant metastasis (Table 28-3).12,34

CHAPTER 28 Oncology

TREATMENT Surgery Surgery remains the most widely accepted primary treatment modality for feline mammary carcinomas; however, it is usually not curative. Surgery can be considered alone or, more commonly, in combination with adjuvant chemotherapy. Unilateral or bilateral (staged 2 weeks apart) radical chain mastectomies are generally recommended. Complete mastectomies are associated with decreased rate of local recurrence but do not have a significant effect on overall survival rates. The cat, unlike the dog, has four pairs of mammary glands: two cranial (thoracic) and two caudal (abdominal). The cranial glands drain to axillary and sternal lymph nodes, whereas the caudal glands drain to the inguinal nodes. The inguinal node should always be removed if the caudal mammary gland is affected. Excision of the axillary lymph node should be attempted only if enlarged and tumor involvement is confirmed on cytology because prophylactic removal of axillary lymph nodes can create significant subcutaneous dead space and is unlikely to have a therapeutic benefit.7,11,12,25,34 Malignant mammary tumors in the cat often have lymphatic or vascular invasion, and therefore principles of surgical oncology must be observed, including early vessel ligation, gentle tumor tissue handling, en bloc resection of tumor, and copious flushing of the resulting surgical bed to help remove neoplastic cells.7 The entire mammary chain should be submitted for histologic examination for tissue grading and assessment of margins. The role of ovariohysterectomy in the management of malignant mammary tumors is controversial. No impact of concurrent ovariohysterectomy with mastectomy has been demonstrated on survival rates, but some authors continue to recommend the practice to remove hormonal stimulation of the tumor.3,9,30

Chemotherapy Chemotherapy is generally recommended as adjuvant therapy; however, there are no well-controlled largescale studies documenting its role in the management of feline mammary gland tumors. Doxorubicin-based protocols are the most frequently reported, but protocols and efficacy vary among studies. Doxorubicin and cyclophosphamide combination therapy has been described, with short-term measurable responses observed in approximately half of cats with metastatic or nonresectable local disease (stage III or IV).16,20 Retrospective analysis of single-agent doxorubicin in 67 cats (1 mg/kg intravenously every 21 days for five planned treatments) given postoperatively starting at the time of suture removal resulted in a MST of 448 days, with 1-, 2-, and 5-year survival rates at 58.9%, 37.2%, and 16.7%,

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respectively.26 Doxorubicin should be used with care in cats because of the risk of nephrotoxicity. Mitoxantrone may be a suitable alternative for cats with compromised renal function. In an unpublished randomized prospective trial comparing mitoxantrone (6 mg/m2 intravenously every 21 days for four doses) to doxorubicin (20 mg/m2 intravenously every 21 days for four doses) for adjuvant therapy of feline mammary tumors after unilateral or bilateral radical mastectomy, no significant difference in MST or metastasis-free interval was observed between the two groups (Carolyn Henry, personal communication). MST was 747 days for mitoxantrone-treated cats and 484 days for doxorubicintreated cats.11-13

Radiation The role of radiation therapy is not well established for feline mammary tumors and is not used routinely as primary therapy. There is no evidence in current published literature supporting its efficacy or influence on survival for cats with mammary tumors. Anecdotally, according to the author’s experience, hypofractionated radiation therapy in conjunction with concurrent chemotherapy may play a palliative role in inoperable local disease, with clinical responses observed.

PROGNOSIS Average survival time between detection of primary tumor and death in untreated cats is 10 to 12 months.8 Prognosis for malignant mammary tumors in male cats is comparable to that for female cats.1 Tumor size is the single most important and reliable prognostic factor in feline mammary cancer. In one study of 39 cats with mammary adenocarcinoma, a MST of 12 months for tumors larger than 3 cm was reported, compared with a MST of 21 months for tumors smaller than 3 cm after surgical excision only.32 Prognosis for cats treated with combination surgery and adjuvant chemotherapy was discussed earlier. Other negative prognostic factors include increased WHO stage (lymph node or distant metastasis), lymphatic invasion, or immunohistochemical markers such as high AgNOR count or Ki-67 index greater than 25.2.* Histologic diagnosis is also prognostic; cats with complex carcinomas have a more favorable prognosis, with a reported MST of 32.6 months compared with 15.5 months for other mammary carcinomas. Inflammatory mammary carcinomas in cats, as in dogs, carry a poor prognosis, with rapid onset of clinical signs and euthanasia between 10 and 45 days after diagnosis.29

*References 4, 5, 13, 14, 27, 32.

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References 1. Argyle DJ, Brearly MJ, Turek MM: Decision making in small animal oncology—feline mammary tumors, Ames, Iowa, 2008, WileyBlackwell, pp 332-335. 2. Bostock DE: Canine and feline mammary neoplasms, Br Vet J 142:506-515, 1986. 3. Carpenter JL, Andrews LK, Holzworth J et al: Tumors and tumorlike lesions. In Holzworth J, editor: Diseases of the cat: medicine and surgery, Philadelphia, 1987, Saunders. 4. Castagnaro M, Casalone C, Ru G et al: Argyrophilic nucleolar organizer regions (AgNORs) coindicator of post-surgical prognosis in feline mammary carcinomas, Res Vet Sci 64:97, 1998. 5. Castagnaro M, de Maria R, Bozetta E et al: Ki-67 index as indicator of the post-surgical prognosis in feline mammary carcinomas, Res Vet Sci 65:223, 1998. 6. Dorn CR, Taylor DON, Schneider R et al: Survey of animal neoplasms in Alameda and Contra Costa Counties, California. II. Cancer morbidity in dogs and cats from Alameda County, J Natl Cancer Inst 40:307, 1968. 7. Gimenez F, Hecht S, Craig LE et al: Early detection, aggressive therapy: optimizing the management of feline mammary masses, J Feline Med Surg 12(3):214, 2010. 8. Hahn KA, Adams WH: Feline mammary neoplasia: biological behavior, diagnosis and treatment alternatives, J Feline Pract, 25:5, 1997. 9. Hayes HM Jr, Milne KL, Mandell CP: Epidemiological features of feline mammary carcinomas, Vet Rec 108:476, 1981. 10. Hays AA, Mooney S: Feline mammary tumors, Vet Clin North Am 15:513-520, 1985. 11. Henry CJ: Feline mammary cancer. In Bonagura JR, Twedt DC, editors: Kirk’s current veterinary therapy XIV, St Louis, 2009, Saunders, pp 366-368. 12. Henry CJ, Higginbotham ML: Cancer management in small animal practice—feline mammary cancer, St Louis, 2010, Saunders Elsevier, pp 280-282. 13. Henry CJ, Higginbotham ML, Rodriguez C et al: Prospective evaluation of doxorubicin versus mitoxantrone for adjuvant therapy of feline mammary carcinoma, Proceedings of the 2006 Veterinary Cancer Society, Callaway Gardens, Oct 19-22, 2006, p 54. 14. Ito T, Kadosawa T, Mochizuki M et al: Prognosis of malignant mammary tumors in 53 cats, J Vet Med Sci 58(8):723, 1996. 15. Jacobs TM, Hoppe BR et al: Mammary adenocarcinomas in three male cats exposed to medroxyprogesterone acetate (1990-2006), J Feline Med Surg 12:169, 2010. 16. Jeglum KA, DeGuzman E, Young K: Chemotherapy of advanced mammary adenocarcinoma in 14 cats, J Am Vet Med Assoc 187: 157, 1985. 17. Keskin A, Yilmazbas G et al: Pathological abnormlaities after longterm administration of medroxyprogesterone acetate in a queen, J Feline Med Surg 11:518, 2009. 18. Kessler M, Vonbomhard D: Mammary tumors in cats: epidemiologic and histologic features in 2,386 cases (1990-1995), Kleinterpraxis 42:459, 1997. 19. MacEwen EG, Hayes AA, Harvey JK et al: prognostic factors for feline mammary tumors, J Am Vet Med Assoc 185:201, 1984. 20. Mauldin GN, Matus RE, Patnaik AK et al: Efficacy and toxicity of doxorubicin and cyclophosphamide used in the treatment of selected malignant tumors in 23 cats, J Vet Intern Med 23:60, 1988. 21. Meuten DJ: Tumors in domestic animals, ed 4, Ames, Iowa, 2010, Blackwell, pp 575-606. 22. Misdorp W: Progestagens and mammary tumors in dogs and cats, Acta Endocrinol (Cophnh)125 Suppl 1:27-31, 1991. 23. Morrison WB: Cancer in dogs and cats, ed 2, Jackson Hole, Wyo, 2002, Teton NewMedia, pp 570-571. 24. Moulton JE: Tumors in domestic animals, ed 2, Berkeley, 1978, University of California Press, pp 367.

25. Novosad CA: Principles of treatment for mammary gland tumors, Clin Tech Small Anim SA Pract 18(2): 107-109, 2003. 26. Novosad CA, Bergman PJ, O’Brien MG et al: Retrospective evaluation of adjunctive doxorubicin for the treatment of feline mammary gland adenocarcinoma: 67 cases, J Am Anim Hosp Assoc 42:110, 2006. 27. Ogilvie GK, Moore AS. Feline oncology—mammary tumors, Trenton, NJ, 2001, Veterinary Learning Systems, pp 355-365. 28. Overley B, Shofer FS, Goldschmidt MH: Association between ovariohysterectomy and feline mammary carcinoma, J Vet Intern Med 19:560, 2005 29. Perez-Alenza MD, Jimenez A, Nieto AL: First description of feline inflammatory mammary carcinoma: clinicopathological and immunohistochemical characteristics of three cases, Breast Cancer Res 6(4):R300, 2004. 30. Rutteman GR, Misdorp W: Hormonal background of canine and feline mammary tumors, J Reprod Fertil Suppl 47:483-487, 1993. 31. Skorupski KA, Overly B, Shoter FS et al: Clinical characteristics of mammary carcinoma in male cats, J Vet Intern Med 19:52, 2005. 32. Viste JR, Myers SL, Singh B et al: Feline mammary adenocarcinoma: tumor size as a prognostic indicator, Can Vet J 43:33, 2002 33. Waters DJ, Honeckman A, Cooley DM et al: Skeletal metastasis in feline mammary carcinoma: case report and literature review, J Am Anim Hosp Assoc 34:103, 1998. 34. Withrow SJ, Vail DM: Withrow and MacEwen’s small animal clinical oncology, St Louis, 2007, Saunders, pp 628-633.

PARANEOPLASTIC SYNDROMES Chamisa Herrera A paraneoplastic syndrome (PNS) is a phenomenon by which cancer cells cause a disease that is not due to the physical presence of the tumor or its metastasis. This is most often by secretion of cytokines or hormones that have some effect on body systems distant to the tumor. In cats there are a unique set of PNSs of which the veterinary clinician should be aware, including the dermatologic syndromes associated with pancreatic and thymic tumors. There are also PNSs shared among species, such as hypercalcemia and anemia. Early detection of a PNS can alert the clinician to the need for a cancer workup, including a CBC, biochemical profile, urinalysis, FeLV and FIV serology, thoracic radiographs, and abdominal imaging. It is important to recognize that PNSs may occur before any other signs of cancer, and they may also serve as a sentinel for return of cancer in patients believed to be in remission. For this reason, if a PNS is suspected, the cat should be thoroughly screened for cancer and should be closely monitored for return of the syndrome once the cancer is in remission. Some PNSs are related to only one or a few types of neoplasia, and their presence can help narrow the differential list. PNSs can also serve as the main source of morbidity in the feline patient. When responsible for decreasing quality of life, a PNS may necessitate prioritizing symptomatic treatment before the cancer itself can be addressed. Documented feline PNSs, their differentials, and their treatments are discussed in the subsequent sections. The

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reader is directed to a veterinary oncology textbook for documented canine PNSs. There is crossover in the syndromes associated with cancer in both dogs and cats. As yet undocumented PNSs in cats could recapitulate those syndromes documented in dogs.

DERMATOLOGIC MANIFESTATIONS Feline Paraneoplastic Alopecia Feline paraneoplastic alopecia (FPA) is a syndrome that is unique to the cat and has been associated with pancreatic, bile duct, and hepatocellular carcinomas.32,55,69 Cats with FPA present with a nonpruritic bilaterally symmetric progressive alopecia of the ventral thorax and abdomen, limbs, and perineum.92 The foot pads can also be involved and appear dry and crusted.98 FPA is unique in that the skin appears thin and glistening, devoid of elasticity, and the hairs are easily epilated (Figure 28-6).69 On histopathologic examination, findings consistent with FPA include a nonscarring alopecia with follicular telogenization, miniaturization, and atrophy.97 The exact mechanism of alopecia is unknown, although it has been proposed that hypoproteinemia or deficiencies in biotin, zinc, or fatty acids may be responsible for the skin lesions.32 Resolution of the alopecia has been reported with surgical removal of the tumor,92 but FPA usually appears late in the course of malignancy. If surgical resection of the primary tumor is not possible, the prognosis is usually poor. Noncancerous differentials for alopecia include dermatophytosis, ectoparasites, demodecosis, hyperthyroidism, and hyperadrenocorticism. It is important to note that in the workup of a cat with alopecia, the finding of pruritus or Malassezia infection does not rule out FPA alopecia. In fact, a retrospective

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study of feline skin biopsies with Malassezia-associated dermatitis found that 7 out of 15 cases had dermatopathologic findings consistent with FPA.58

Thymoma-Associated Exfoliative Dermatitis Thymoma-associated exfoliative dermatitis is a rare PNS that has been described in cats diagnosed with mediastinal thymoma. The disease is characterized by a mild erythema of the head and pinnae that progresses to a nonpruritic generalized exfoliative dermatitis.97 Most cats demonstrate generalized desquamation, alopecia on the body, and multifocal crusts, particularly on the head.77 Differentials for this form of dermatitis include systemic lupus erythematosus, drug eruptions, epi theliotropic T-cell lymphoma, erythema multiforme, cheyletiellosis, demodecosis, Malassezia dermatitis, dermatophytosis, FeLV/FIV dermatitis, parapsoriasis, and sebaceous adenitis.77 Histopathology of full-thickness skin lesions is helpful for diagnosis and shows perkeratotic hyperkeratosis with lymphocytic interface dermatitis.86,88 The pathophysiology of thymoma-associated exfoliative dermatitis has not been completely elucidated; however, one theory is that an immune-mediated process directed against the tumor is occurring. This hypothesis is supported by the fact that the interface dermatitis is composed predominately of CD3+ lymphocytes.77 The prognosis for feline thymoma and associated dermatitis is good with excision of the primary tumor, with a 1-year survival rate approaching 90%.109 Another PNS that has been documented in cats with thymoma is myasthenia gravis, which in a recent report occurred along with thymoma-associated dermatitis in a single cat.86

Cutaneous Necrosis of the Hindfeet Symmetric cutaneous necrosis of the hindfeet has been described in a single cat with multicentric lymphoma as a presumed PNS. In this case the cat had necrosis of the hindfeet, but there were no neoplastic cells present on histopathology of this lesion, which is suggestive of a PNS.1 Paraneoplastic digital necrosis has been described in humans with multiple malignancies, and there may be crossover between species. One hypothesis for the pathogenesis of this lesion is local or systemic vasculitis secondary to circulating tumor antigens.11,39,72

HEMATOLOGIC ALTERATIONS FIGURE 28-6 Abdomen of a cat with feline paraneoplastic alope-

Hyperglobulinemia

cia. The entire abdomen is alopecic and the underlying skin is thin and glistening, which is typical of this syndrome. (From Hnilica KA, editor: Small animal dermatology, a color atlas and therapeutic guide, ed 3, St Louis, 2011, Saunders.)

A hyperglobulinemia is an increase in serum proteins other than albumin. In cats PNSs resulting in hyperglobulinemia are rare and include multiple myeloma,

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plasmacytoma, and lymphoma.6,23,93 The primary mechanism of paraneoplastic hyperglobulinemia is production of excess gammaglobulin(s) by the tumor. Serum protein electrophoresis can be used to differentiate polyclonal from monoclonal gammopathies.93 Monoclonal gammopathies are rare and, when observed in cats, are most often associated with neoplasia.50,93 Other differentials for hyperglobulinemia include chronic infectious diseases such as feline infectious peritonitis, FeLV, FIV, inflammatory bowel disease, fungal disease, tick-borne disease, and immune-mediated disease (e.g., rhinitis and immune-mediated hemolytic anemia).93 Cats with hyperglobulinemia can develop a host of secondary complications, including infection, bleeding, and end-organ damage. Infections are common because of the decreased production of normal immunoglobulins, and antimicrobial treatment should be considered even when signs of infection are absent.34,104 As hyperglobulinemia worsens, serum viscosity increases and leads to hyperviscosity syndrome. In humans hypergammaglobulinemia is the most common cause of hyperviscosity syndrome.62 Increased blood viscosity results in decreased perfusion, ultimately leading to multiorgan damage. Patients with hyperviscosity syndrome present with or develop renal, retinal, or cardiac disease or neurologic abnormalities.6,27,34 They may also have spontaneous hemorrhage with a normal platelet count, although the mechanism for this is unknown.34 The treatment of choice for hyperglobulinemia is control of the underlying neoplasm. When immediate relief from hyperviscosity syndrome is needed, plasmapheresis can be used, including for immediate relief from congestive heart failure secondary to hyperviscosity syndrome.9,27 Prognosis is poor if end-organ damage has occurred or the underlying neoplasm cannot be controlled.

Anemia The causes of anemia in the feline cancer patient are numerous, including hemorrhage, immune-mediated destruction of red blood cells, and decreased red blood cell production. If a minimum database including a CBC with a manual differential, a biochemical profile, and FeLV/FIV serology do not reveal the etiology of the anemia, cancer should be considered on the differential list. The first step in differentiating causes of anemia is to determine if the anemia is regenerative (corrected reticulocyte count >60,000) or nonregenerative. A regenerative anemia is likely due to hemorrhage or hemolysis, although a hemorrhage identified early will not always be accompanied by regeneration. A common cause of a nonregenerative anemia is inflammatory disease, but such an anemia can also be attributed to decreased erythropoietin (EPO) production or bone marrow pathology. Immune-mediated destruction of red blood cells

can result in either a regenerative or nonregenerative anemia.105 In cats retroviral infection commonly causes cytopenias of various cell lines, including red blood cells, neutrophils, and platelets. A negative FeLV antigen test is a reliable means for ruling out FeLV infection as a cause of cytopenias, with only approximately 5% of cats harboring latent infections testing negative on antigen tests and positive on bone marrow polymerase chain reaction.91 Anemia associated with cancer can be secondary to most of the aforementioned mechanisms, making anemia difficult to definitively pinpoint as a PNS. For example, hemorrhage can occur secondary to a bleeding tumor in the gastrointestinal tract, the nasal cavity, or the thoracic or abdominal cavities. Although hemoperitoneum in cats is rare, almost half of cats with that diagnosis in one study had intraabdominal neoplasia, most often hemangiosarcoma.19 Hemolysis of red blood cells with cancer is secondary to production of anti-erythrocyte antibodies. This has been documented in lymphoma in the cat.44,52 Renal failure, and therefore decreased EPO production, can be secondary to a primary renal tumor or a tumor that is metastatic to the renal parenchyma or caused by renal hypoxia secondary to a neoplastic embolism. Cancer itself can serve as a chronic source of inflammation and lead to anemia of inflammatory disease (AID). The mechanisms of AID are multifactorial and include decreased red blood cell survival, iron sequestration, and insufficient EPO production or bone marrow response (or both).68 One of the main mediators of AID is believed to be hepcidin, which is a hormone responsible for iron homeostasis that is upregulated in inflammatory conditions in response to interleukin-6. This upregulation of hepcidin is thought to deprive infectious agents of iron but also reduces iron stores necessary for erythropoiesis.17,61,87,106 A unique mechanism that can contribute to anemia in cancer is erythrophagocytosis of red blood cells by the tumor. This has been documented in an extranodal T-cell lymphoma, histiocytic sarcoma, mast cell tumors, and multiple myeloma in the cat.13,40,54,103 The prognosis for anemia associated with cancer depends on the underlying mechanism, the degree of anemia, and the animal’s response to symptomatic treatment of the anemia or treatment of the underlying neoplasia.

Polycythemia Polycythemia is another neoplastic syndrome that is more commonly described in cats than dogs, but it is rare in veterinary medicine. Diagnosis of polycythemia is uncomplicated and easily diagnosed by performing packed cell volume and total protein measurements. It is important to rule out non-neoplastic causes of polycythemia. A relative polycythemia results from

dehydration or hypovolemia, is often accompanied by high serum total protein, and will resolve with fluid therapy. An absolute polycythemia can be primary, as in polycythemia vera, or secondary to conditions such as chronic hypoxia, excessive EPO production, and cancer. Serum EPO concentrations have been used for differentiating polycythemia vera from secondary polycythemia; however, there is overlap between the two groups, and testing is not readily available.35 Secondary polycythemia in feline cancer patients has been documented in primary renal tumors.37,43 Similar to hyperglobulinemia, polycythemia can result in hyperviscosity syndrome. The most common clinical signs are neurologic and include seizures and ataxia.43,75 Paraneoplastic polycythemia is thought to arise from renal hypoxia, production of EPO by the tumor, or both.22 In patients with an absolute secondary polycythemia and a hematocrit greater than 65%, symptomatic treatment is achieved by therapeutic phlebotomy.28 Leeching as an initial treatment for feline patients for whom phlebotomy proves impossible has also been documented.66 Prognosis is variable. Resolution of polycythemia has been achieved with nephrectomy of the affected kidney, although this requires unilateral disease and adequate function of the contralateral kidney.43

Thrombocytopenia and Disseminated Intravascular Coagulation Thrombocytopenia is conservatively defined as a platelet count of less than 200,000/µL and frequently occurs in various disease states. One of the most common reasons for this finding is laboratory error because of the tendency of feline platelets to aggregate and be misread by automated systems.67 The first step when thrombocytopenia is suspected in a cat is to have a manual platelet count performed to rule out platelet aggregation as a cause. Differentials for a true thrombocytopenia include infectious disease (e.g., FeLV, FIV, feline infectious peritonitis, other infectious and inflammatory causes), neoplasia (e.g., leukemia, lymphoma, hemangiosarcoma), cardiac disease, and primary immune-mediated disease, with infectious disease and neoplasia within the bone marrow being the most common causes.41 The pathophysiologic mechanisms of thrombocytopenia include destruction, decreased production, consumption, and sequestration within the spleen. Many of these mechanisms may also play a role in thrombocytopenia associated with cancer. For example, platelet-bound antibodies have been demonstrated in cats with immune-mediated thrombocytopenia secondary to lymphoma.44 Cancer can also cause thrombocytopenia as a result of decreased production secondary to bone marrow invasion, sequestration of platelets within the spleen, and consumption resulting from disseminated intravascular coagulation

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(DIC). When DIC occurs in cats, neoplasia is often an underlying etiology and survival rates are poor.25 Thrombocytopenia can result in spontaneous hemorrhage when platelet numbers fall below 30,000/µL. Prognosis for thrombocytopenia secondary to a malignancy is variable and depends on the underlying mechanism leading to thrombocytopenia, the degree of thrombocytopenia, and the responsiveness of the tumor to antineoplastic therapies.

Eosinophilia Dramatic increases in peripheral eosinophil counts can occur for a variety of reasons in the cat, including parasitism, allergic diseases, hypereosinophilic syndrome, and eosinophilic leukemia.16,18,108 Eosinophilia can also occur as a PNS and in cats has been documented in lymphoma, mast cell tumors, and transitional cell carcinoma.4,71,82 Lymphoma and various other sarcomas and carcinomas have also been documented as causes of paraneoplastic eosinophilia in dogs and humans.26,49,89,99,100 The mechanism of eosinophilia is believed to be production of cytokines important in eosinophil proliferation, particularly interleukin-3, interleukin-5, granulocyte macrophage colony-stimulating factor, and potentially some other eosinophilotactic factors produced by the tumor.3,82,94,102 Diagnosis of paraneoplastic eosinophilia relies on ruling out other causes of eosinophilia, including hypereosinophilic syndrome and eosinophilic leukemia, or seeing resolution of the eosinophilia with treatment of the underlying neoplasia. Prognosis for paraneoplastic eosinophilia in cats is not well studied. In humans peripheral eosinophilia in association with a tumor usually carries a poor prognosis—not because of the eosinophils themselves but because this is associated with widespread metastasis of the underlying malignancy.53

ENDOCRINOLOGIC MANIFESTATIONS Hypercalcemia of Malignancy Hypercalcemia of malignancy (HM) is one of the most recognized paraneoplastic syndromes in veterinary medicine; however, it is less commonly reported in the cat than in the dog.24 In cats the most common tumors resulting in HM are lymphoma and SCC.78 Other tumors reported to cause HM in cats include leukemia, fibrosarcoma, osteosarcoma, multiple myeloma, and various carcinomas, particularly bronchogenic adenocarcinoma.8,15,70,78,80 The distribution of clinical signs in the cat is unique, with the most common being anorexia and lethargy followed by gastrointestinal signs, polyuria and polydipsia, urinary signs, and neurologic signs.78 Hypercalcemia commonly causes significant morbidity

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when elevations are profound, including renal failure, arrhythmias, seizures, and coma. The most common mechanism of HM is thought to be production of parathyroid hormone–related peptide (PTH-rp) by the tumor; however, other mechanisms of HM include skeletal metastasis and diffuse osteolysis caused by production of humoral products produced by the tumor.78 The most common non-neoplastic cause of hypercalcemia is renal failure.78 Other causes include idiopathic hypercalcemia, vitamin D toxicosis, and granulomatous disease.38,60,63,73 Primary hyperparathyroidism has been reported in cats and, although extremely rare, also results in hypercalcemia.20 In general, hypercalcemia is more profound when related to a malignant process than hypercalcemia associated with non-neoplastic diseases, and may be indicative of, although not definitive for, the underlying process.78 Diagnosis relies on ruling out other causes of hypercalcemia. In the past a PTH-rp assay could be performed to look for production of parathyroid hormone– related peptide production by the tumor,8 but this diagnostic tool recently became unavailable. The best treatment option for HM is to treat the underlying neoplasia. When this is not possible or when the hypercalcemia itself is causing significant morbidity (e.g., renal failure, arrhythmias, seizures), symptomatic treatment should be aggressive and immediate. Initial treatment is fluid diuresis with a calcium-poor solution (0.9% NaCl).79 Furosemide, prednisone, salmon calcitonin, and bisphosphonates can also be used to decrease serum calcium.64,79,107 Use of furosemide should be limited to patients that are well hydrated. In the patient with hypercalcemia of unknown origin, treatment with prednisone can make diagnosis of lymphoma difficult by inducing remission and can also cause chemotherapeutic resistance. For this reason steroid treatment of hypercalcemia should not be instituted until lymphoma has been ruled out. In cases of severe hypercalcemia that require management without a cancer diagnosis, administration of bisphosphonates is preferred. Prognosis for patients with HM is considered poor, regardless of the underlying neoplasia.

Hypoglycemia Hypoglycemia, defined as a blood glucose below 70 mg/ dL, has been documented to occur as a PNS in both cats and dogs suffering from cancer. The mechanisms of paraneoplastic hypoglycemia are variable, but production of insulin by an insulinoma is probably the most common.46 Other mechanisms of cancer-associated hypoglycemia include liver failure secondary to metastasis and production of insulin-like growth factor II by the tumor.76 In the cat tumor types that have been shown to cause hypoglycemia include insulinoma, lymphoma, and hepatoma.30,36,45,95 In dogs tumors associated with

hypoglycemia include hepatocellular carcinoma, leiomyosarcoma, hemangiosarcoma, melanoma, and various carcinomas5,51,76 and could theoretically also cause hypoglycemia in a similarly affected cat. Clinical signs associated with hypoglycemia include weakness, lethargy, muscle twitching, and seizures. Neurologic complications might become irreversible with chronic hypoglycemia secondary to insulinoma, even after treatment and normalization of glucose levels.45 A diagnosis of paraneoplastic hypoglycemia should be considered when an adult cat presents with a persistent hypoglycemia and other causes have been ruled out. Non-neoplastic differentials include sepsis, hepatic disease, hypoadrenocorticism, portosystemic shunt, and insulin overdose. Diagnosis of an insulinoma can be made when a persistent hypoglycemia with concurrent normal to increased serum insulin concentrations are present. Diagnosis of other causes of paraneoplastic hypoglycemia is likely to be presumptive or require biopsy and immunohistochemical staining to demonstrate the underlying mechanism. Alternatively, documenting glycemic control with treatment of the tumor supports the diagnosis of this PNS. Prognosis for an insulinoma in cats is guarded because of the metastatic nature of the disease; however, prolonged survival times have been documented with surgical excision when no metastases were present.33 Prognosis with other causes of paraneoplastic hypoglycemia varies depending on the tumor type and mechanism by which the tumor induces glucose dysregulation.

NEUROMUSCULAR MANIFESTATIONS Peripheral Neuropathy The characteristic physical examination findings associated with a peripheral neuropathy include hyporeflexia, motor or sensory involvement (or both), and occasionally autonomic dysfunction. There are numerous etiologies of peripheral neuropathies in cats, including inherited disorders, endocrine diseases (e.g., diabetes mellitus, hyperthyroidism), infectious disease (FeLV, FIV), nutritional disorders (e.g., phenylalanine deficiency, tyrosine deficiency), toxins (e.g., organophosphates, carbamates, heavy metals), drugs (e.g., aminoglycosides, vincristine), neoplastic invasion of a tumor into a nerve, and paraneoplastic peripheral neuropathies (PPNs).14 In cats a single case report of PPN has been described in a cat with renal lymphoma.14 Muscle and nerve sections from the cat showed demyelination, axonal degeneration, and muscle denervation.14 No neoplastic cells were observed in the affected muscle or nerve biopsies, which is consistent with a PPN.14 Although this is the first described case in a cat, several tumors have been implicated in PPN in dogs,

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including insulinoma, lymphoma, primary lung tumors, multiple myeloma, mammary adenocarcinoma, and melanoma.10,56,74,101 Polyneuropathy has been reported in various neoplasms in human-medicine literature as well.31 The underlying cause is thought to be autoimmunity through the production of onconeural antibodies by the tumor.59,90 These antibodies can be directed at any part of the peripheral nerve, including the cell body, axon, myelin sheath, and presynaptic region. Treatment of PPN is removal or treatment of the underlying neoplasm and supportive care; however, given the presumed immune-mediated component, immunosuppressive medications may be another treatment modality to consider.

Myasthenia Gravis Acquired myasthenia gravis is an immune-mediated neuromuscular disorder by which antibodies alter, block, or destroy acetylcholine receptors (AChRs), resulting in muscle weakness and fatigue. In cats myasthenia gravis usually results in generalized weakness, although focal signs such as dysphagia and megaesophagus can also be seen.84 Other clinical signs may include gait abnormalities, voice change, neck ventroflexion, and regurgitation.42 Approximately 25% of cats in a study of risk factors for myasthenia gravis had a cranial mediastinal mass, most of which were thymomas.84 This is very different from myasthenia in dogs, in which only about 3% of cases have a mediastinal mass.85 Production of onconeural antibodies by the tumor is the likely mechanism of AChR blockade and is by definition a type of PNS. Definitive diagnosis of myasthenia gravis can be achieved by demonstrating AChR antibodies by immunoprecipitation radioimmunoassay. A feline-specific immunoprecipitation radioimmunoassay should be used, although there is some cross-reactivity between species.83 Treatment for paraneoplastic myasthenia gravis in cats is not well described, although removal of the tumor has been shown to cause complete resolution of focal myasthenia gravis in a dog.48 Acetylcholine esterase inhibitors and antiinflammatory doses of corticosteroids may also be useful in the absence of aspiration pneumonia.81

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or without anorexia, although weight loss is often seen despite normal caloric intake.7 The mechanisms of this disease are multifactorial and poorly understood but result in weight loss through the depletion of lean muscle mass and adipose tissue, which differentiates it from malnutrition.65 The true prevalence of cachexia in human cancer patients is unknown, and the literature reveals huge variability, ranging from less than 3% to 87% of cancer patients, depending on the definition, type of cancer, and stage of disease used in each study.21,29 One well-recognized phenomenon in human oncology patients is that cancer cachexia is associated with a higher incidence of treatment failure and reduced survival.21,57 Production of cytokines and hormones by the tumor or host immune system are thought to contribute to cachexia and anorexia by altering appetite, increasing resting energy expenditure, increasing lipolysis, altering fat metabolism, increasing protein catabolism, and depressing protein synthesis.96 Excessive glucose use by tumor cells may also play a role in weight loss.12 A single study investigating the prevalence and prognostic significance of weight loss and body condition score (BCS) has been reported in cats. This study evaluated cats with various tumor types and found that 60% had reduced fat mass and 91% had reduced muscle mass. They also found that patients with a BCS below 5 (on a 9-point scale) had an MST of 3.3 months compared with 16.7 months for cats with a BCS of 5 or above.2 Based on this information, physical examination monitoring (including estimates of muscle and fat mass), as well as recording of BCS and trends in weight, should occur in all cats with cancer. This information may provide prognostic data and serve as a guide for attempted intervention. Because cancer cachexia is not solely caused by inadequate caloric intake, treatment aimed at increasing caloric intake may not be effective. Studies in humans have investigated various drugs for treatment of cancer cachexia and anorexia, including appetite stimulants, 5-HT3 antagonists, and cyclooxygenase-2 inhibitors, none of which have proved successful.47 With continued research and understanding of the mechanisms involved in cancer cachexia and anorexia, new pharmacologic interventions may become available.

References CANCER CACHEXIA AND ANOREXIA Some cancer patients experience anorexia or weight loss secondary to treatment or because of the location of the tumor (gastrointestinal), which is beyond the scope of this discussion and occurs by a mechanism likely to be different from that of cancer cachexia. Those patients who involuntarily lose weight before diagnosis or independent of treatment of their disease have the PNS termed cancer cachexia. Cancer cachexia can occur with

1. Ashley PF, Bowman LA: Symmetric cutaneous necrosis of the hind feet and multicentric follicular lymphoma in a cat, J Am Vet Med Assoc 214(2):211, 1999. 2. Baez JL, Michel KE, Sorenmo K et al: A prospective investigation of the prevalence and prognostic significance of weight loss and changes in body condition in feline cancer patients, J Feline Med Surg 9(5):411, 2007. 3. Bain BJ: Review: eosinophils and eosinophilic leukemia, Clin Adv Hematol Oncol 8(12):901, 2010. 4. Barrs VR, Beatty JA, McCandlish IA et al: Hypereosinophilic paraneoplastic syndrome in a cat with intestinal T cell lymphosarcoma, J Small Anim Pract 43(9):401, 2002.

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5. Battaglia L, Petterino C, Zappulli V et al: Hypoglycaemia as a paraneoplastic syndrome associated with renal adenocarcinoma in a dog, Vet Res Commun 29(8):671, 2005. 6. Bienzle D, Silverstein DC, Chaffin K: Multiple myeloma in cats: variable presentation with different immunoglobulin isotypes in two cats, Vet Pathol Online 37(4):364, 2000. 7. Blum D, Omlin A, Baracos VE et al: Cancer cachexia: a systematic literature review of items and domains associated with involuntary weight loss in cancer, Crit Rev Oncol Hematol, 2011. Accessed March 26, 2011 at http://www.ncbi.nlm.nih.gov/pubmed/ 21216616. 8. Bolliger AP, Graham PA, Richard V et al: Detection of parathyroid hormone-related protein in cats with humoral hypercalcemia of malignancy, Vet Clin Pathol 31(1):3, 2002. 9. Boyle TE, Holowaychuk MK, Adams AK et al: Treatment of three cats with hyperviscosity syndrome and congestive heart failure using plasmapheresis, J Am Anim Hosp Assoc 47(1):50, 2011. 10. Braund KG, McGuire JA, Amling KA et al: Peripheral neuropathy associated with malignant neoplasms in dogs, Vet Pathol 24(1):16, 1987. 11. Burnouf M, Mahé E, Verpillat P et al: [Cutaneous necrosis is predictive of cancer in adult dermatomyositis], Ann Dermatol Venereol 130(3):313, 2003. 12. Burt BM, Humm JL, Kooby DA et al: Using positron emission tomography with [(18)F]FDG to predict tumor behavior in experimental colorectal cancer, Neoplasia 3(3):189, 2001. 13. Carter JE, Tarigo JL, Vernau W et al: Erythrophagocytic lowgrade extranodal T-cell lymphoma in a cat, Vet Clin Pathol 37(4):416, 2008. 14. Cavana P, Sammartano F, Capucchio MT et al: Peripheral neuropathy in a cat with renal lymphoma, J Feline Med Surg 11(10):869, 2009. 15. Cavana P, Vittone V, Capucchio MT et al: Parathyroid adenocarcinoma in a nephropathic persian cat, J Feline Med Surg 8(5):340, 2006. 16. Center SA, Randolph JF, Erb HN et al: Eosinophilia in the cat: a retrospective study of 312 cases (1975 to 1986), J Am Anim Hosp Assoc 26(4):349, 1990. 17. Cheng P, Jiao X, Wang X et al: Hepcidin expression in anemia of chronic disease and concomitant iron-deficiency anemia, Clin Exp Med 11(1):33, 2011. 18. Craig LE, Hardam EE, Hertzke DM et al: Feline gastrointestinal eosinophilic sclerosing fibroplasia, Vet Pathol 46(1):63, 2009. 19. Culp WTN, Weisse C, Kellogg ME et al: Spontaneous hemoperitoneum in cats: 65 cases (1994-2006), J Am Vet Med Assoc 236(9):978, 2010. 20. den Hertog E, Goossens MM, van der Linde-Sipman JS et al: Primary hyperparathyroidism in two cats, Vet Q 19(2):81, 1997. 21. Dewys WD, Begg C, Lavin PT et al: Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group, Am J Med 69(4):491, 1980. 22. Durno AS, Webb JA, Gauthier MJ et al: Polycythemia and inappropriate erythropoietin concentrations in two dogs with renal T-cell lymphoma, J Am Anim Hosp Assoc 47(2):122, 2011. 23. Dust A, Norris AM, Valli VE: Cutaneous lymphosarcoma with IgG monoclonal gammopathy, serum hyperviscosity and hypercalcemia in a cat, Can Vet J 23(8):235, 1982. 24. Engelman RW, Tyler RD, Good RA et al: Hypercalcemia in cats with feline-leukemia-virus-associated leukemia-lymphoma, Cancer 56(4):777, 1985. 25. Estrin MA, Wehausen CE, Jessen CR et al: Disseminated intravascular coagulation in cats, J Vet Intern Med 20(6):1334, 2006. 26. Fews D, Scase TJ, Battersby IA: Leiomyosarcoma of the pericardium, with epicardial metastases and peripheral eosinophilia in a dog, J Comp Pathol 138(4):224, 2008.

27. Forrester SD, Greco DS, Relford RL: Serum hyperviscosity syndrome associated with multiple myeloma in two cats, J Am Vet Med Assoc 200(1):79, 1992. 28. Foster ES, Lothrop CD: Polycythemia vera in a cat with cardiac hypertrophy, J Am Vet Med Assoc 192(12):1736, 1988. 29. Fox KM, Brooks JM, Gandra SR et al: Estimation of cachexia among cancer patients based on four definitions, J Oncol 2009:1, 2009. 30. Gabor LJ, Canfield PJ, Malik R: Haematological and biochemical findings in cats in Australia with lymphosarcoma, Aust Vet J 78(7):456, 2000. 31. Giglio P, Gilbert MR: Neurologic complications of cancer and its treatment, Curr Oncol Rep 12(1):50, 2010. 32. Godfrey DR: A case of feline paraneoplastic alopecia with secondary Malassezia-associated dermatitis, J Small Anim Pract 39(8): 394, 1998. 33. Greene SN, Bright RM: Insulinoma in a cat, J Small Anim Pract 49(1):38, 2008. 34. Hanna F: Multiple myelomas in cats, J Feline Med Surg 7(5):275, 2005. 35. Hasler AH, Giger U: Serum erythropoietin values in polycythemic cats, J Am Anim Hosp Assoc 32(4):294, 1996. 36. Hawks D, Peterson ME, Hawkins KL et al: Insulin-secreting pancreatic (islet cell) carcinoma in a cat, J Vet Intern Med 6(3):193, 1992. 37. Henry CJ, Turnquist SE, Smith A et al: Primary renal tumours in cats: 19 cases (1992-1998), J Feline Med Surg 1(3):165, 1999. 38. Hodges RD, Legendre AM, Adams LG et al: Itraconazole for the treatment of histoplasmosis in cats, J Vet Intern Med 8(6):409, 1994. 39. Iamandi C, Dietemann A, Grosshans E et al: Unusual presentations of lung cancer: case 3. Paraneoplastic digital necrosis in a patient with small-cell lung cancer, J Clin Oncol 20(23):4600, 2002. 40. Ide K, Setoguchi-Mukai A, Nakagawa T et al: Disseminated histiocytic sarcoma with excessive hemophagocytosis in a cat, J Vet Med Sci 71(6):817, 2009. 41. Jordan HL, Grindem CB, Breitschwerdt EB: Thrombocytopenia in cats: a retrospective study of 41 cases, J Vet Intern Med 7(5):261, 1993. 42. Joseph RJ, Carrillo JM, Lennon VA: Myasthenia gravis in the cat, J Vet Intern Med 2(2):75, 1988. 43. Klainbart S, Segev G, Loeb E et al: Resolution of renal adenocarcinoma-induced secondary inappropriate polycythaemia after nephrectomy in two cats, J Feline Med Surg 10(3):264, 2008. 44. Kohn B, Weingart C, Eckmann V et al: Primary immune-mediated hemolytic anemia in 19 cats: diagnosis, therapy, and outcome (1998-2004), J Vet Intern Med 20(1):159, 2006. 45. Kraje AC: Hypoglycemia and irreversible neurologic complications in a cat with insulinoma, J Am Vet Med Assoc 223(6):812-814, 2003. 46. Kruth SA, Carter RF: Laboratory abnormalities in patients with cancer, Vet Clin North Am Small Anim Pract 20(4):897, 1990. 47. Kumar NB, Kazi A, Smith T et al: Cancer cachexia: traditional therapies and novel molecular mechanism-based approaches to treatment, Curr Treat Options Oncol 11(3-4):107, 2010. 48. Lainesse M, Taylor S, Myers S et al: Focal myasthenia gravis as a paraneoplastic syndrome of canine thymoma: improvement following thymectomy, J Am Anim Hosp Assoc 32(2):111, 1996. 49. Laingo Andrianarison JF, Ranoharison D, Rakotoarivelo RA et al: [A misleading case of hypereosinophilia revealing colonic adenocarcinoma in a patient from a tropical area], Med Trop (Mars) 69(5):517, 2009. 50. Larsen AE, Carpenter JL: Hepatic plasmacytoma and biclonal gammopathy in a cat, J Am Vet Med Assoc 205(5):708, 1994. 51. Leifer CE, Peterson ME, Matus RE et al: Hypoglycemia associated with nonislet cell tumor in 13 dogs, J Am Vet Med Assoc 186(1):53, 1985.

CHAPTER 28 Oncology 52. Lenard ZM, Foster SF, Tebb AJ et al: Lymphangiosarcoma in two cats, J Feline Med Surg 9(2):161, 2007. 53. Lowe D, Jorizzo J, Hutt MS: Tumour-associated eosinophilia: a review, J Clin Pathol 34(12):1343, 1981. 54. Madewell BR, Gunn C, Gribble DH: Mast cell phagocytosis of red blood cells in a cat, Vet Pathol 20(5):638, 1983. 55. Marconato L, Albanese F, Viacava P et al: Paraneoplastic alopecia associated with hepatocellular carcinoma in a cat, Vet Dermatol 18(4):267, 2007. 56. Mariani CL, Shelton SB, Alsup JC: Paraneoplastic polyneuropathy and subsequent recovery following tumor removal in a dog, J Am Anim Hosp Assoc 35(4):302, 1999. 57. Mariani L, Lo Vullo S, Bozzetti F: Weight loss in cancer patients: a plea for a better awareness of the issue (on behalf of the SCRINIO Working Group), Support Care Cancer 2011. Accessed March 25, 2011 at http://www.springerlink.com/content/ 7n59570606038676/. 58. Mauldin EA, Morris DO, Goldschmidt MH: Retrospective study: the presence of Malassezia in feline skin biopsies. A clinicopathological study, Vet Dermatol 13(1):7, 2002. 59. Maverakis E, Goodarzi H, Wehrli LN et al: The etiology of paraneoplastic autoimmunity, Clinic Rev Allerg Immunol 2011. Accessed March 18, 2011, at http://www.springerlink.com/ content/k9540n712385517v/. 60. Mealey KL, Willard MD, Nagode LA et al: Hypercalcemia associated with granulomatous disease in a cat, J Am Vet Med Assoc 215(7):959, 1999. 61. Means RT: Hepcidin and anaemia, Blood Rev 18(4):219, 2004. 62. Mehta J, Singhal S: Hyperviscosity syndrome in plasma cell dyscrasias, Semin Thromb Hemost 29(5):467, 2003. 63. Midkiff AM, Chew DJ, Randolph JF et al: Idiopathic hypercalcemia in cats, J Vet Intern Med 14(6):619, 2000. 64. Milner RJ, Farese J, Henry CJ et al: Bisphosphonates and cancer, J Vet Intern Med 18(5):597, 2004. 65. Moley JF, Aamodt R, Rumble W et al: Body cell mass in cancerbearing and anorexic patients, JPEN J Parenter Enteral Nutr, 11(3):219, 1987. 66. Nett CS, Arnold P, Glaus TM: Leeching as initial treatment in a cat with polycythaemia vera, J Small Anim Pract 42(11):554, 2001. 67. Norman EJ, Barron RCJ, Nash AS et al: Prevalence of low automated platelet counts in cats: comparison with prevalence of thrombocytopenia based on blood smear estimation, Vet Clin Pathol 30(3):137, 2001 68. Ottenjann M, Weingart C, Arndt G et al: Characterization of the anemia of inflammatory disease in cats with abscesses, pyothorax, or fat necrosis, J Vet Intern Med 20(5):1143, 2006. 69. Pascal-Tenorio A, Olivry T, Gross TL et al: Paraneoplastic alopecia associated with internal malignancies in the cat, Vet Dermatol 8(1):47, 1997 70. Patel RT, Caceres A, French AF et al: Multiple myeloma in 16 cats: a retrospective study, Vet Clin Pathol 34(4):341, 2005. 71. Peaston AE, Griffey SM: Visceral mast cell tumour with eosinophilia and eosinophilic peritoneal and pleural effusions in a cat, Aust Vet J 71(7):215, 1994. 72. Peschken CA, Walker SL, El-Gabalawy HS et al: Digital necrosis as a paraneoplastic syndrome, J Clin Rheumatol 3(6):339, 1997. 73. Peterson EN, Kirby R, Sommer M et al: Cholecalciferol rodenticide intoxication in a cat, J Am Vet Med Assoc 199(7):904, 1991. 74. Presthus J, Teige J: Peripheral neuropathy associated with lymphosarcoma in a dog, J Small Animal Practice 27(7):463, 1986. 75. Quesnel AD, Parent JM, McDonell W et al: Diagnostic evaluation of cats with seizure disorders: 30 cases (1991-1993), J Am Vet Med Assoc 210(1):65, 1997. 76. Rossi G, Errico G, Perez P et al: Paraneoplastic hypoglycemia in a diabetic dog with an insulin growth factor-2-producing mammary carcinoma, Vet Clin Pathol 39(4):480, 2010.

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77. Rottenberg S, von Tscharner C, Roosje PJ: Thymomaassociated exfoliative dermatitis in cats, Vet Pathol 41(4):429, 2004. 78. Savary KC, Price GS, Vaden SL: Hypercalcemia in cats: a retrospective study of 71 cases (1991-1997), J Vet Intern Med 14(2):184, 2000. 79. Schaer M: Therapeutic approach to electrolyte emergencies, Vet Clin North Am Small Anim Pract 38(3):513, 2008. 80. Schoen K, Block G, Newell SM et al: Hypercalcemia of malignancy in a cat with bronchogenic adenocarcinoma, J Am Anim Hosp Assoc 46(4):265, 2010. 81. Scott-Moncrieff JC, Cook JR, Lantz GC: Acquired myasthenia gravis in a cat with thymoma, J Am Vet Med Assoc 196(8):1291, 1990. 82. Sellon RK, Rottman JB, Jordan HL et al: Hypereosinophilia associated with transitional cell carcinoma in a cat, J Am Vet Med Assoc 201(4):591, 1992. 83. Shelton GD: Routine and specialized laboratory testing for the diagnosis of neuromuscular diseases in dogs and cats, Vet Clin Pathol 39(3):278, 2010. 84. Shelton GD, Ho M, Kass PH: Risk factors for acquired myasthenia gravis in cats: 105 cases (1986-1998), J Am Vet Med Assoc 216(1):55, 2000. 85. Shelton GD, Schule A, Kass PH: Risk factors for acquired myasthenia gravis in dogs: 1,154 cases (1991-1995), J Am Vet Med Assoc 211(11):1428, 1997. 86. Singh A, Boston SE, Poma R: Thymoma-associated exfoliative dermatitis with post-thymectomy myasthenia gravis in a cat, Can Vet J 51(7):757, 2010. 87. Smirnov OA: [Anemia during inflammatory processes: pathogenesis and clinical and morphological manifestations], Arkh Patol 72(2):56, 2010. 88. Smits B, Reid MM: Feline paraneoplastic syndrome associated with thymoma, N Z Vet J 51(5):244, 2003. 89. Snyder MC, Lauter CB: Eosinophilic and neutrophilic leukemoid reaction in a woman with spindle cell sarcoma: a case report, J Med Case Reports 4:335, 2010. 90. Storstein A, Monstad SE, Haugen M et al: Onconeural antibodies: improved detection and clinical correlations, J Neuroimmunol 232(1-2):166, 2011. 91. Stützer B, Müller F, Majzoub M et al: Role of latent feline leukemia virus infection in nonregenerative cytopenias of cats, J Vet Intern Med 24(1):192, 2010. 92. Tasker S, Griffon DJ, Nuttall TJ et al: Resolution of paraneoplastic alopecia following surgical removal of a pancreatic carcinoma in a cat, J Small Anim Pract 40(1):16, 1999. 93. Taylor SS, Tappin SW, Dodkin SJ et al: Serum protein electrophoresis in 155 cats, J Feline Med Surg 12(8):643, 2010. 94. Tefferi A, Patnaik MM, Pardanani A: Eosinophilia: secondary, clonal and idiopathic, Br J Haematol 133(5):468, 2006. 95. Thompson JC, Hickson PC, Johnstone AC et al: Observations on hypoglycaemia associated with a hepatoma in a cat, N Z Vet J 43(5):186, 1995. 96. Tisdale MJ: Mechanisms of cancer cachexia, Physiol Rev 89(2):381, 2009. 97. Turek MM: Cutaneous paraneoplastic syndromes in dogs and cats: a review of the literature, Vet Dermatol 14(6):279, 2003. 98. van der Luer R, van den Ingh T, van Hoe N: [Feline paraneoplastic alopecia], Tijdschr Diergeneeskd 133(5):182, 2008. 99. Van Mens SP, Buist MR, Walter AW et al: [Eosinophilia and a solid tumour: ovarian sarcoma], Ned Tijdschr Geneeskd 154(8):A1031, 2010. 100. Vassilatou E, Fisfis M, Morphopoulos G et al: Papillary thyroid carcinoma producing granulocyte-macrophage colonystimulating factor is associated with neutrophilia and eosinophilia, Hormones (Athens) 5(4):303, 2006.

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101. Villiers E, Dobson J: Multiple myeloma with associated polyneuropathy in a German shepherd dog, J Small Anim Pract 39(5):249, 1998. 102. Wasserman SI, Goetzl EJ, Ellman L et al: Tumor-associated eosinophilotactic factor, N Engl J Med 290(8):420, 1974. 103. Webb J, Chary P, Northrup N et al: Erythrophagocytic multiple myeloma in a cat, Vet Clin Pathol 37(3):302, 2008. 104. Weber NA, Tebeau CS: An unusual presentation of multiple myeloma in two cats, J Am Anim Hosp Assoc 34(6):477, 1998. 105. Weiss DJ: Bone marrow pathology in dogs and cats with nonregenerative immune-mediated haemolytic anaemia and pure red cell aplasia, J Comp Pathol 138(1):46, 2008. 106. White C, Reine N: Feline nonregenerative anemia, Compend Contin Educ Vet 31(7):E1-E19, 2009. 107. Whitney JL, Barrs VRD, Wilkinson MR et al: Use of bisphosphonates to treat severe idiopathic hypercalcaemia in a young Ragdoll cat, J Feline Med Surg 13(2):129, 2011. 108. Wilson SC, Thomson-Kerr K, Houston DM: Hypereosinophilic syndrome in a cat, Can Vet J 37(11):679, 1996. 109. Zitz JC, Birchard SJ, Couto GC et al: Results of excision of thymoma in cats and dogs: 20 cases (1984-2005), J Am Vet Med Assoc 232(8):1186, 2008.

PALLIATIVE CARE Jackie M. Wypij The term palliative care refers to medical therapy primarily administered to treat the symptoms of cancer, as opposed to directly treating the cancer itself. The ultimate goal is to maintain or improve quality of life. Palliative care is commonly used for advanced stage and terminal cancer alone or in combination with standard cancer therapies. Palliative care is not synonymous with giving up. Unfortunately, in very advanced-stage disease traditional cancer therapy may in fact worsen the pet’s quality of life and offer little chance of providing significant benefit to the patient. Conversely, palliative care still improves patient comfort levels, even when prolongation of life is not possible. Compassionate and humane palliative treatment for the pet also contributes to client satisfaction. The primary clinical signs associated with advanced feline cancer include physical and mechanical dysfunction (e.g., dysphagia, cramping, obstipation, dyspnea) and concerns secondary to metabolic or paraneoplastic processes (e.g., anorexia, nausea, fever, anemia, cachexia, and electrolyte imbalances). These problems may be exhibited as overt pain, discomfort, lack of social interaction, or anxiety, in addition to physical dysfunction.

QUALITY OF LIFE SCORE SYSTEMS Although many feline cancers are not curable, palliation of clinical signs will improve the quality of life in most cats with cancer. This is a major concern for pet owners; quality of life is often more important than the length of

TABLE 28-4 The HHHHHMM Quality of Life Scale* Score

Criterion

Hurt: 0-10

Is pain successfully managed?

Hunger: 0-10

Is the cat eating enough? Is a feeding tube required?

Hydration: 0-10

Is the cat dehydrated? Is subcutaneous fluid therapy necessary?

Hygiene: 0-10

The cat should be groomed and cleaned regularly; avoid pressure sores and keep all wounds clean.

Happiness: 0-10

Does the cat express interest in its environment? Is it responsive to family, toys, other pets, and so forth?

Mobility: 0-10

Can the cat move without assistance? Are neurologic signs or pain impairing mobility?

More good days than bad: 0-10

When bad days outnumber good days, quality of life may be compromised. When a healthy human-animal bond is no longer possible, the owner should be aware that the end is near. Euthanasia may be necessary to prevent further pain and suffering.

Total =

A total of 35 points or more is acceptable for good quality of life.

*Score patients on a scale of 1 (poor) to 10 (best). Adapted from Myers F: Palliative care: end of life “pawspice” care. In Villalobos A, Kaplan L, editors: Canine and feline geriatric oncology: honoring the human-animal bond, Ames, Iowa, 2007, Wiley-Blackwell.

life. Assessing quality of life in feline patients can be very difficult and depends on the individual cat’s behavior as well as owners’ perceptions. Several quality of life score systems have been proposed for cats.3,4 Dr. Villalobos’s quality of life scoring system, “HHHHHMM,” incorporates measures of “hurt, hunger, hygiene, hydration, happiness, mobility, and more good days than bad” and attempts to provide a more objective means for the caregiving team (client and veterinary staff) to determine appropriate intervention or euthanasia (Table 28-4).3 The key is open communication between veterinarian and pet owner about factors that contribute to decreased quality of life, as well as monitoring relatively feline-specific behaviors such as hiding, lack of grooming, and lack of social interaction.

ANALGESIA Pain control is an important aspect of cancer care in feline patients. Pain may be visceral (e.g., gastrointestinal lymphoma), somatic (e.g., jaw pain with oral tumor), or neuropathic (e.g., extension of a soft tissue sarcoma along nerve fibers). If pain is suspected despite a lack of apparent clinical signs, analgesic intervention may function as a diagnostic test for pain as well as a directed

therapy. To address cancer-related pain in cats, the veterinarian should consider several strategies,2 including the following: 1. Direct treatment of painful site: Bulky tumors or those involving bone may be amenable to direct therapy such as cytoreductive surgery or palliative (coarse fraction) radiation therapy. Intravenous aminobisphosphonates (e.g., pamidronate, zoledronate) may also be useful for malignant bone lysis, such as a primary bone tumor (e.g., osteosarcoma), metastatic bone tumor (e.g., digital metastasis of primary lung tumor), and local tissue invasion (e.g., oral SCC, injection-site sarcoma). These drugs are potentially nephrotoxic and should be used with caution, especially in conjunction with other analgesics and chemotherapeutics. In some cases systemic chemotherapy may also be effective to palliate clinical signs. The treatment goals may focus on reduction of inflammation or pain, reduction in tumor volume, or slowing of growth to improve clinical signs rather than cure of the disease. 2. Remove or reduce contributing environmental factors: Care should be taken to modify the cat’s home environment for maximal comfort. Cats with intranasal tumors may benefit from a room humidifier. To help cats with limited mobility, items such as litter boxes, food, and water bowls should be easily accessible (e.g., at floor level). The owner should minimize the necessity of high jumps and stairs and provide safe, comfortable, and accessible private resting areas away from other household pets that might contribute to patient stress. For cats with oral tumors, moistened or canned food and soft toys should be used. 3. Local analgesic techniques: Although rarely practical for long-term use, local analgesic options (e.g., nerve blocks, topical analgesics, local analgesic patches) may be considered in certain cases. 4. Systemic analgesia: This is the most common form of clinical pain management in cats and often includes nonsteroidal antiinflammatory drugs and opioids. Patients with cancer may be at increased risk of organ toxicity as a sequela of the tumor, primary treatment, or supportive medications. Cats are more sensitive than dogs to the toxic side effects of many analgesics, and most feline cancer patients are also geriatric. Contraindications and interactions with other medications should be taken into consideration, particularly with drugs that are potentially nephrotoxic or hepatotoxic. Some chemotherapy agents may potentiate organ toxicity. For example, doxorubicin and carboplatin are commonly used chemotherapy agents that are potentially nephrotoxic. Sedation and anesthesia

CHAPTER 28 Oncology

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should be minimized but may be necessary for procedures such as radiation therapy or feeding tube placement; this may place additional stress on kidneys and other organs. 5. Complementary therapies: Physical therapy and rehabilitation techniques such as physical manipulation are poorly tolerated by most cats but could be considered in certain cases. Options include range-of-motion exercises, massage therapy, acupuncture, acupressure, and chiropractic care. Client instruction for home care may be more feasible than in-hospital physical therapy. For more complete information on feline analgesia, please refer to Chapter 6.

NUTRITIONAL CARE Nutritional care of feline cancer patients should address route of administration, optimal nutritional content, palatability, appetite stimulation, nutritional supplementation, supportive care of gastrointestinal upset, and recognition of the effects of cancer cachexia. Cancerbearing cats are often underweight, with most exhibiting reduced fat stores and muscle mass. BCS is prognostic in cats, with average or obese cats living significantly longer than thin cats.1 Cancer cachexia is a poorly understood paraneoplastic process in veterinary patients. In human oncology cancer cachexia is recognized as a complex metabolic syndrome that manifests as severe weight loss, muscle wasting, and inappetence. Contributing factors include maldigestion and malabsorption as well as functional abnormalities leading to decreased nutritional intake. Examples include painful oral tumors, obstructive or malabsorptive gastrointestinal tumors, and systemic cancers that induce nausea, vomiting, and diarrhea. Metabolic and physiologic alterations are more subtle contributing factors to cachexia and may include altered nutrient metabolism (carbohydrates, protein, and fats), altered insulin response, and cytokine abnormalities. These derangements can result in severe weight loss even in the face of normal or apparent increased food intake. Enteral feeding is always preferred because it maintains gastrointestinal epithelial health and offers safety and convenience. For short-term care of hospitalized patients, a nasogastric tube is easily managed. Esophagostomy tubes (E-tubes) are ideal for both short- and longer-term home care for patients with oral tumors or nonspecific inappetence that are not actively vomiting. E-tubes are easily placed during a short anesthesia procedure and are extremely well-tolerated by cats (see Chapter 18). Newer feline-specific E-tubes are commercially available and are appropriately sized, flexible, and

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radio-opaque to optimize placement. Cats are able to eat on their own with E-tubes in place, and this provides a low-stress option for owners to administer both nutrition and medication. Another less commonly used longterm home option is a gastrostomy tube. In select cases partial parenteral or total parenteral nutrition is used in the intensive care unit for short-term support of hospitalized patients, such as after an invasive surgical procedure. Hand feeding may also encourage food intake, although assisted feeding in the form of force feeding or syringe feeding is often poorly tolerated and may lead to food aversion and bite injuries to pet owners. The ideal diet for the feline cancer patient has yet to be determined. Given the metabolic alterations of cancer cachexia, a diet low in simple carbohydrates with moderate lipids and easily digestible protein sources is ideal. Many adult commercial cat foods meet these criteria. Because many cats may be geriatric or have chronic renal insufficiency, these medical concerns should also be taken into consideration when selecting an appropriate diet. In addition to adequate nutritional composition, palatability is a major concern. The best answer to the question, “What should I feed my cat with cancer?” is usually, “Whatever he or she will eat.” Standard methods to improve palatability include trying different brands of cat food, canned cat food, or human food, such as tuna, deli meats, and cheese. Warming up the food or adding cooking liquids or milk may also improve palatability for some cats. The role of specific nutritional supplements is poorly understood in clinical feline patients. However, supplementation should be instituted as clinically indicated (e.g., vitamin B12 supplementation in cats with intestinal lymphoma). Specific recommendations for nutritional care of feline cancer patients can be found in Chapter 18. Appetite stimulants are most effective in mildly affected cats or in temporary situations such as when the cat is recovering from anesthesia or surgery. Appetite stimulants may not adequately improve food intake and may have inconsistent results. Mirtazapine is a newer appetite stimulant with good efficacy in cats. Cyproheptadine may also be effective, although cyproheptadine and mirtazapine should not be used concurrently because their actions are antagonistic. In a hospital or short-term situation, oral diazepam could be administered if other oral medications are ineffective. Side effects and toxicity may occur with all these medications, and they should be prescribed with appropriate monitoring. For example, mirtazapine dose should be reduced in the presence of renal insufficiency. Other supportive gastrointestinal medications include histamine receptor (H2) antagonists (e.g., famotidine), coating agents such as sucralfate, and proton pump inhibitors (e.g., omeprazole) (Table 28-5). Fiber supplementation or lactulose may alleviate constipation in predisposed cats or in cases complicated by abdominal,

pelvic, or intestinal discomfort. Antiemetics may be effective for nonobstructive gastrointestinal cancer or nonspecific/systemic cancers that contribute to nausea or vomiting. Some options include metoclopramide (a prokinetic and centrally acting antiemetic); 5-HT3 receptor antagonists (ondansetron, dolasetron); and, more recently, the neurokinin-1 receptor antagonist maropitant citrate (Cerenia). Although routinely used in small animal patients, metoclopramide is less effective in cats than in dogs because of differences in CNS neurotransmitter receptors at the chemoreceptor trigger zone. Options for management of acute and chronic diarrhea in feline cancer patients include dietary modification, addition of dietary prebiotics and feline-specific probiotics, and direct medical therapy. Metronidazole is most commonly used and should be prescribed at the lowest effective dose. Outpatient or at-home subcutaneous fluid therapy should be instituted for cats with inadequate fluid intake and those with increased risk of renal toxicity. Cats with preexisting renal insufficiency or those receiving nephrotoxic medications (e.g., nonsteroidal antiinflammatory drugs, chemotherapy agents such as doxorubicin and carboplatin) and geriatric animals undergoing procedures requiring sedation should be supported with appropriate fluid therapy. For further information on drug therapy and fluid therapy, please refer to Chapters 4 and 5.

MISCELLANEOUS CARE Sick cats and those with oral tumors often stop grooming, necessitating additional home care by the pet owner. Oral health concerns such as bacterial infections and malocclusion should be assessed and treated as needed. Cats undergoing systemic chemotherapy may be at increased risk of myelosuppression and susceptibility to secondary bacterial infections. Common routes of entry include the oral cavity, colon and intestinal tract, lower urinary tract, skin, and ears. Pleural effusion secondary to mediastinal lymphoma, primary or metastatic lung tumors, or carcinomatosis (microscopic tumor seeding of pleura) may decrease the cat’s quality of life, and thoracocentesis can be performed as an acute palliative measure, although effusion often progresses quickly. Abdominal effusion is less likely to reduce the patient’s quality of life, and therapeutic abdominocentesis should be performed only if clinically necessary to reduce losses of protein and electrolytes and minimize patient stress. In summary, a variety of supportive and medical therapies can be instituted for feline cancer patients. The goal of palliative care is to maintain and maximize the pet’s quality of life and should incorporate a wholehealth approach.

Gastric acid reduction

Gastric acid reduction Prokinetic

Gastric acid reduction

Antiemetic

Antiemetic

Antiemetic

Appetite stimulant

Anticolitis Antidiarrheal

Famotidine (Pepcid AC)

Ranitidine (Zantac)

Omeprazole (Prilosec)

Maropitant (Cerenia)

Metoclopramide (Reglan)

Ondanestron (Zofran)

Mirtazapine

Metronidazole (Flagyl)

PO, Orally; SC, subcutaneously; IV, intravenously.

Action

Drug

Antibiotic Other

Noradrenergic agonist Serotonin agonist

5-HT3 serotonin antagonist

Dopaminergic antagonist Suspected acetylcholine sensitization?

NK-1 antagonist

Proton pump inhibitor

Peripheral

Central

Central Peripheral

Peripheral Central

Central Peripheral

Peripheral

Peripheral

Peripheral

Histamine H2-receptor antagonist Histamine H2-receptor antagonist

Site of Action

Mechanism

TABLE 28-5 Selected Supportive Gastrointestinal Medications in Feline Cancer Patients

10-15 mg/kg PO every 12 hours, short-term (3-5 days)

3.75 mg PO/cat every 72 hours or 1 mg/cat per day, compounded

Empirical 0.1-0.5 mg/kg every 12 hours

Empirical 0.2-0.4 mg/kg PO, SC every 6-8 hours

Empirical 0.5-1 mg/kg short-term

0.5-1 mg/kg PO every 24 hours

1-2 mg/kg PO, SC, IV every 12 hours

0.5-1 mg/kg PO, SC, IV every 12 to 24 hours

Feline Dose

CHAPTER 28 Oncology

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References 1. Baez JL, Michel KE, Sorenmo K et al: A prospective investigation of the prevalence and prognostic significance of weight loss and changes in body condition in feline cancer patients, J Feline Med Surg 9:411, 2007. 2. Looney A: Oncology pain in veterinary patients, Top Companion Anim Med 25:32, 2010.

3. Myers F: Palliative care: end of life “pawspice” care. In Villalobos A, Kaplan L, editors: Canine and feline geriatric oncology: honoring the human-animal bond, Ames, Iowa, 2007, Wiley-Blackwell. 4. Tzannes S, Hammond MF, Murphy S et al: Owners perception of their cats’ quality of life during COP chemotherapy for lymphoma, J Fel Med Surg 10:73, 2008.

C H A P T E R

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Ophthalmology Christine C. Lim and David J. Maggs O U T L I N E Ophthalmic Examination and Diagnostic Techniques, 807 Orbital Disease, 812 Eyelid and Adnexal Disease, 813 Corneal and Conjunctival Disease, 817

Diseases of the Uveal Tract, 827 Diseases of the Lens, 834 Glaucoma, 836 Chorioretinal Disease, 837

Feline ophthalmology is a vast and important field in which feline practitioners need to be reasonably adept, given the frequency with which clients note ocular disease in their cats and the importance they place on good vision from a pain-free globe. In this chapter we have attempted to highlight conditions that are unique to cats and emphasize feline-specific considerations for more common ocular diseases. Less attention has been paid to those conditions for which management strategies differ little from those employed in dogs, insofar as these topics have been amply covered in standard veterinary ophthalmology texts.

OPHTHALMIC EXAMINATION AND DIAGNOSTIC TECHNIQUES History A great deal of information can be gleaned from a complete history and thorough ophthalmic examination. A detailed history does much to narrow the list of differential considerations. Important background information includes the chief complaint, duration of clinical signs, concurrent ocular or systemic medical conditions, previous therapies, and current ophthalmic or systemically administered medications.

Examination Techniques and Order Basic necessities for a complete ophthalmic examination include a consistent, systematic approach to the


examination; a bright, focal light source; magnification; and a darkened room. Diagnostic tests such as the Schirmer tear test (STT), tonometry (assessment of intraocular pressure), fluorescein staining, and funduscopic examination are important components of the examination and need to be done at prescribed times. The following is a recommended order for the ophthalmic examination. Whereas assessment of dogs begins by observing while the patient navigates into the examination room, most cats are carried in and refuse to participate in any obstacle courses set up by the examiner. Cats also seem to mask vision loss much more effectively than dogs; therefore clinical assessment of vision tends to be much more difficult in the cat than in the dog. For this the examiner may need to rely more heavily on historical information and other examination findings. The examiner should begin at eye level with the cat. The cat’s head should first be observed from a distance, avoiding excessive manipulation of the face by the restrainer. This allows for detection of nonocular abnormalities that may be related to the ocular disease, such as facial asymmetry, oral or nasal discharge, and the presence of a head tilt. The examiner should then perform the neuro-ophthalmic examination (Table 29-1). The neuro-ophthalmic assessment for cats can yield very different results than that for the dog. For example, the menace response (Figure 29-1) tends to be inconsistently elicited in cats, with many normal cats failing to blink in response to a menacing gesture. Likewise, stressed cats with higher sympathetic tone often have resting mydriasis and diminished pupillary light reflexes (PLRs).

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FIGURE 29-1 Proper technique for eliciting the menace response. The contralateral eye must be covered with one hand to prevent it from viewing the menacing gesture. Care should be taken to keep from generating wind currents or directly touching the highly sensitive vibrissae when performing the menacing gesture.

FIGURE 29-2 The Schirmer tear test in a cat. The test strip should be folded at the notch and placed in the ventrolateral conjunctival fornix and left in place for 60 seconds. Care should be taken not to touch the lower part of the strip with the hands because oil on the skin can affect the capillary action of the strip and test result. (From Maggs D: Slatter’s fundamentals of veterinary ophthalmology, ed 4, St Louis, 2007, Saunders.)

TABLE 29-1 Components of the Neuro-Ophthalmic Examination Test

Tested Structures

Menace response

CN II and VII, visual cortex, and cerebellum

Palpebral reflex

CN V and VII

Oculocephalic reflex

CN III, IV, and VI

Direct and consensual pupillary light reflexes

CN II and III and central visual pathways excluding the visual cortex

Dazzle reflex

CN II and VII and subcortical visual pathways

If a STT is to be performed, it must be done before any eye drops are applied to the eye. It is performed in the same manner as in the dog (Figure 29-2); however, normal STT measurements vary widely in cats.194 For example, the authors have recorded STT values less than 5 mm/min in cats without detectable ocular disease. Conversely, cats with significant keratoconjunctival disease may have STT results within the normal reference range.106 Such discrepancies emphasize the importance of interpreting the STT in context with the overall clinical examination and comparing them between the affected and unaffected eyes in cats with unilateral or asymmetric ocular disease. After the STT, intraocular pressure (IOP) should be assessed. Although there is some variability, normal feline IOP tends to be between 10 and 25 mm Hg.140 Both the Schiotz and TonoPen tonometers require application of a topical anesthetic agent before obtaining an IOP measurement, whereas the TonoVet does not (Figure 29-3). Although

retropulsion can be useful in detecting space-occupying lesions of the orbit, it is not considered an acceptable technique for measurement of IOP. If the IOP is within normal limits, a single drop of 0.5% or 1% tropicamide should then be applied to each eye to achieve pupillary dilation, which is essential for examination of the lens, vitreous, and ocular fundus. In cats tropicamide induces mydriasis within 15 minutes, for 8 to 9 hours.87 Pharmacologic mydriasis is not recommended if the IOP is elevated because dilation may further increase the IOP. The remainder of the ophthalmic examination may be performed during and after pupillary dilation, and the techniques used in cats differ little from those used in other species. Sequential examination of all structures moving from peripheral to axial and from superficial to deep ensures a complete and orderly examination. The examiner should begin with retroillumination of the tapetal reflection from arm’s length (Figure 29-4) to identify opacities in the visual axis. Magnification, in the form of head loupes (Figure 29-5), should then be employed throughout the entire ophthalmic examination, except for the fundic examination. The examiner should employ focal illumination and transillumination (Figure 29-6) from various angles when assessing the ocular surface. Depth and spatial relationships are best assessed using the slit beam of the direct ophthalmoscope. The detection of aqueous flare (plasma protein in the anterior chamber) is a pathognomonic change in anterior uveitis, and therefore its detection forms a critical part of the ophthalmic examination in all cats. Aqueous flare is best detected when the room has been darkened completely and the smallest, most focal white light beam on the direct ophthalmoscope head is used

CHAPTER 29 Ophthalmology

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A

FIGURE 29-5 Magnification is an essential component of the entire ophthalmic examination, with the exception of the fundic examination. It is especially important for assessment of aqueous flare and after application of fluorescein stain. The Optivisor is inexpensive and extremely useful for the ophthalmic examination, as well as surgery and suture removal in general practice.

B FIGURE 29-3 The TonoVet (A) and TonoPen (B) being used to measure intraocular pressure in cats. The tips of both instruments should be directed toward the central cornea according to the manufacturer’s directions. The operator should take care to ensure that excessive pressure is not placed directly on the globe when holding the eyelids open or on the jugular veins as the animal is restrained because both can elevate intraocular pressure readings.

FIGURE 29-6 Technique for transillumination. The light source and examiner should move around the animal such that multiple highly variable combinations of viewing and illumination angles are achieved throughout the ophthalmic examination. This will greatly increase the chance that lesions will be found. In particular, this technique improves or facilitates depth perception within the eye, assessment of topography, and evaluation of reflections from transparent surfaces. (From Maggs D: Slatter’s fundamentals of veterinary ophthalmology, ed 4, St Louis, 2007, Saunders.)

FIGURE 29-4 Correct technique for performing retroillumination. The light source is held next to the examiner’s eye and the patient examined at arm’s length in a darkened room. The examiner should alter his or her viewing angle until the fundic reflection is elicited. This can be used to assess pupil symmetry and any opacities within the tear film, cornea, anterior chamber, lens, and vitreous.

very close to the cat’s eye to examine the clarity of the anterior chamber. Any “smokiness” detected as the beam traverses the anterior chamber between the cornea and the lens should prompt consideration of and further investigation for anterior uveitis. The iris face is a frequent site of pathology in cats and must be evaluated before dilation. By contrast, thorough assessment of the lens, vitreous, and fundus can be performed only after full dilation has been achieved. Also, aqueous flare may be more easily detected after full mydriasis has been

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A FIGURE 29-8 The binocular headset improves depth perception and frees one hand for manipulation of the patient’s eyelids and head.

B FIGURE 29-7 Two variations of the normal feline fundus. A, A subalbinotic fundus is a normal variation typically seen in pigmentdilute individuals. The relative lack of melanin in the retina and choroid allows visualization of the choroidal vessels in the nontapetal fundus. In some subalbinotic fundi, the tapetum is absent. B, Normal feline fundus. Melanin in the retina and choroid prevents visualization of the choroidal vessels seen in image A. The optic disc appears circular and gray because of the lack of myelin and is located immediately dorsal to the tapetal–nontapetal junction. Three or four larger retinal venules extend from the edges of the optic disc to the periphery of the retina. The tapetum is usually green or yellow.

achieved, insofar as the black background of the pupil provides contrast with which to view the gray beam of light traversing the anterior chamber. Direct and indirect ophthalmoscopy are the two traditional methods for examining the fundus (Figure 29-7). Direct ophthalmoscopy is relatively easy to learn and provides the examiner with an upright image of the retina but is not a good method for examination of the fundus. The main disadvantage of direct ophthalmoscopy is the limited field of view, a result of extreme magnification. This makes complete retinal examination difficult, and peripheral regions and smaller lesions are often missed. Indirect ophthalmoscopy is considered to be the best method for viewing the fundus, despite the steeper learning curve. The image produced is an inverted representation of the

FIGURE 29-9 Technique for fundic examination using the Panoptic. After the instrument is focused for the examiner’s eye, the fundic reflection is identified while looking through the Panoptic from approximately 10 to 15 centimeters away from the patient. The examiner then moves toward the patient until the eyecup of the ophthalmoscope contacts the patient’s face. If this causes eyelid closure, the eyecup can be removed.

fundus. When the binocular headset (Figure 29-8) is used, indirect ophthalmoscopy provides superior depth perception. The larger field of view obtained by indirect ophthalmoscopy makes complete fundic examination easier and allows the practitioner to view a larger portion of the fundus in less time, which is extremely valuable for uncooperative patients. The direct ophthalmoscope can then be used for more detailed examination of any focal lesions identified. A newer ophthalmoscope, the Panoptic offers a field of view and level of magnification intermediate to the traditional ophthalmoscopes (Figure 29-9). Although it is unable to provide much depth perception, its ease of use and moderate field of view make the Panoptic a reasonable compromise between direct and indirect ophthalmoscopy.


811

FIGURE 29-10 The Jones test. Appearance of fluorescein dye at the

FIGURE 29-11 Technique for collection of corneal or conjunctival

nares or in the mouth within a few minutes after application to the ocular surface indicates patency of the nasolacrimal ducts, or a positive Jones test. In many cats, especially those with brachycephalic conformation, the nasolacrimal duct opens sufficiently caudally within the nose that fluorescein is noted on the tongue rather than at the naris. This highlights the importance of testing the side of interest first, because laterality cannot be determined when fluorescein is detected in the mouth. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

samples for diagnostic testing. After application of topical anesthetic, the blunt end of a scalpel blade is used to carefully scrape surface cells from the cornea or conjunctiva. These can then be gently blotted onto a microscope slides for cytologic or immunologic assessment or can be inoculated onto a swab or directly into agar plates for microbiologic assessment.

Application of fluorescein dye may be used to detect corneal ulceration and corneal perforation and may be used to assess tear film stability and patency of the nasolacrimal drainage system. It should be performed only after all other parts of the examination are complete because it will affect results of microbial testing, the STT, and the appearance of many ocular structures. The Jones test is an assessment of nasolacrimal duct patency (Figure 29-10). A minimum of 2 minutes after placing fluorescein dye into the conjunctival sacs, the nares and mouth are examined for evidence of fluorescein. Presence of fluorescein (positive Jones test) confirms patency of the nasolacrimal duct, whereas absence of fluorescein (negative Jones test) is suggestive of obstruction and should be followed with nasolacrimal flushing. The tear film break-up time (TFBUT) evaluates stability of the precorneal tear film. It is the time between eyelid opening and the first spot of evaporation within the precorneal tear film. The examiner first places fluorescein dye into the conjunctival sac, then closes the eyelids. Timing begins when the eyelids are opened. Using magnification, the examiner observes one area of the cornea, usually the dorsolateral aspect. Timing ends when the first black spot, signifying evaporation, appears within the green tear film. The normal TFBUT in a cat is 16.7+/−4.5 seconds,36 whereas more rapid TFBUTs suggest tear film instability.

Ancillary Tests Techniques for ancillary diagnostic tests such as corneal scrapings (Figure 29-11), conjunctival swabs, and

FIGURE 29-12 A biopsy of the conjunctiva can be easily obtained in almost all cats without sedation or general anesthesia. After application of topical anesthetic, forceps are used to tent the conjunctiva, which is then incised with small scissors. The conjunctival defect will heal by second intention. (From Maggs D: Slatter’s fundamentals of veterinary ophthalmology, ed 4, St Louis, 2007, Saunders.)

conjunctival biopsies (Figure 29-12) are identical to those for the dog. However, the effect of topical anesthetics required to obtain these samples is shorter in cats than it is in dogs. Whereas a single drop of 0.5% proparacaine provides up to 45 minutes of corneal anesthesia in the dog, the same dose achieves only 25 minutes of corneal anesthesia for the cat, with maximal effect 5 minutes after application.16,88 This time difference should be taken into account if the practitioner is unable to obtain samples shortly after administering topical anesthesia. Cannulation of the nasolacrimal puncta is more challenging in cats than dogs because of the tight fit of the eyelids to the globe. Also, in cats more often than in dogs, the nasal opening of the nasolacrimal duct is located more

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FIGURE 29-13 Ultrasonographic appearance of the normal feline globe. This technique is particularly useful for assessing intraocular structures, especially retinal detachment, in globes with anterior segment pathology that prevent direct visualization. Normal features include the highly echoic convex anterior lens capsule and concave posterior lens capsule; the anechoic anterior chamber, lens, and vitreous cavity; and the echoic concave monolayer of the posterior globe representing sclera, choroid, and retina in close apposition with one another. Orbital structures such as the optic nerve and extraocular muscle cone are sometimes seen. Because of the close proximity of the ultrasound probe to the anterior structures, the anteriormost ocular structures are less well defined than those posterior to them. In the example shown, the anterior chamber and anterior lens appear artifactually hyperechoic. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

caudally, such that fluid will be flushed into the oral cavity rather than out the nares (as with fluorescein in Figure 29-10). Advanced imaging is required when opaque ocular media prevent complete examination of the globe or when orbital or neurologic disease is suspected. Ocular ultrasound is very useful for characterizing lesions within the globe but may not allow full evaluation of orbital lesions156 (Figure 29-13). Skull radiography and computed tomography (CT) also may not clearly show borders of a lesion, but they will detect bony changes.156 Magnetic resonance imaging (MRI) is of limited value for bony lesions but offers excellent resolution of soft tissues, including the globe, orbit, and optic nerves.73

FIGURE 29-14 Left-sided orbital disease in a cat. Comparison of the palpebral fissures shows distortion of the left palpebral fissure, as well as dorsal and lateral displacement of the left globe and elevation of the left nictitans, all of which are highly supportive of orbital, rather than ocular, disease. (Image courtesy WCVM Veterinary Ophthalmology Service.)

A

ORBITAL DISEASE In cats the most common clinical sign accompanying orbital disease is exophthalmos.66 Epiphora, enophthalmos, strabismus, elevation of the third eyelid, and decreased retropulsion are other possible examination findings (Figure 29-14). If eyelid movement has been compromised, exposure keratitis or corneal ulceration may also be found (Figure 29-15). Inflammatory and neoplastic conditions make up the bulk of feline orbital disease; orbital vascular anomalies and cystic lesions

B FIGURE 29-15 Right-sided orbital disease caused by squamous cell carcinoma. The globe is enophthalmic. In this patient tumorinduced facial nerve paralysis resulted in exposure keratitis and ulceration of the central cornea. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

have not been reported in cats. Identification of the underlying disease process is important because of significant differences in treatment and prognosis. At minimum, a complete blood count (CBC), serum biochemical profile, urinalysis, and fine-needle aspirate or biopsy of the orbital lesion are recommended. Based on the results of these tests, CT or MRI may be warranted to determine the extent of the lesion.

Infectious and Neoplastic Orbital Disease Orbital cellulitis and abscess formation in the cat are diagnosed and treated in a similar manner as in dogs. As in dogs, orbital extension of dental disease is responsible for many of these cases, but foreign body migration, fungal infections, and iatrogenic trauma (mainly during dental procedures) are also documented causes.110,157 However, these conditions occur much less frequently in cats than in dogs, and neoplasia should always be considered when a cat presents with orbital disease.157 In cats the majority of orbital neoplasia is secondary, with direct extension from adjacent structures accounting for 71% of cases.66 Squamous cell carcinoma (SCC) is the most common orbital neoplastic process in cats,66 but many other neoplasms may occur.* Regardless of type, 90% of orbital neoplasms are malignant, with mean postdiagnosis survival times less than 2 months.8,66

Ocular Proptosis Ocular proptosis is seen less commonly in cats than in dogs, likely because of cats’ deep orbits and relatively tightly fitting adnexa. For this reason the amount of force required to displace the globe from the feline orbit is large, and cats with ocular proptosis usually present with severe intraocular trauma, as well as concurrent cranial or systemic injuries that require more immediate attention. Ocular proptosis in cats often occurs in conjunction with skull fractures and trauma to the globe.65 As with dogs, enucleation or emergency replacement of the globe followed by temporary tarsorrhaphy is required. However, the prognosis after traumatic ocular proptosis in cats is worse than in dogs. In one retrospective review, all proptosed feline eyes were permanently blind, and 12 of 18 required enucleation.65

Feline Orbital Pseudotumor Feline orbital pseudotumor (FOP) is currently described as a progressive inflammatory disease with similarities to idiopathic orbital inflammation in humans. However, only eight feline cases have been described, and the definition is still evolving.15,127 All affected cats were middleaged to older.15,127 The majority of cats presented with *References 8, 44, 66, 73, 94, 161, 197, 206.


813

unilateral disease that later became bilateral. In all cases onset of clinical signs was insidious, ultimately characterized by exophthalmos, lagophthalmos, exposure keratitis, and restriction of ocular movements.15,127 Resistance to retropulsion was also found in the majority of cases.15,127 No specific changes are seen on blood work, and fineneedle aspirates tend to be nondiagnostic. Orbital ultrasound may show increased echogenicity of orbital tissues.15 CT appears to be the most useful imaging modality, often revealing physical compression of the globe. Biopsy of orbital tissues (often obtained during enucleation or exenteration) is essential, with histopathology being characterized by proliferating fibrous tissue with lymphocytic–plasmacytic inflammation.15 As for its human counterpart,20 prognosis for FOP is poor and specific therapeutic guidelines do not exist. Immunosuppressive doses of systemic corticosteroids, oral antibiotics, and radiation therapy have all been attempted with little success.15,127,192 One author reports having managed FOP for a period of 1.5 years with immunosuppressive corticosteroid therapy before clinical disease returned.192 This author also reports clinical improvement in one cat after radiation therapy, but this case has not been described nor followed up in the literature.192 Enucleation or exenteration followed medical therapy in all published cases,15,127 and in one case series, all seven cats were eventually euthanized because of either recurrence of disease or appearance of the disease in the contralateral orbit.15 A viral etiology has been suggested for FOP, perhaps in part because of the suggestion that herpes simplex virus (HSV-1) is a proposed cause of human idiopathic orbital inflammation.189 In the case series of seven cats, three exhibited signs suggestive of feline herpesvirus (FHV-1) infection, including upper respiratory disease before or after development of clinical signs of orbital disease, followed by development of gingival hyperplasia.15 However, the authors were unable to establish FHV-1 infection in these cats. More recently, FOP has been suggested to be a neoplastic disease, with spindle cell sarcoma identified in the orbital tissue of one cat and the suggestion that FOP be renamed feline restrictive orbital sarcoma.48

EYELID AND ADNEXAL DISEASE Eyelid Agenesis Eyelid agenesis, or eyelid coloboma, is the most common congenital eyelid disease of cats.133 It has been documented to occur in the Persian, Burmese, and domestic shorthair, as well as snow leopards and a Texas cougar.11,40,100,124,205 Affected cats have bilateral, incomplete development of the upper lateral eyelids (Figures

814


FIGURE 29-16 Right eye of a cat with agenesis of approximately 30% of the upper lateral eyelid margin. The result is trichiasis, incomplete eyelid closure (lagophthalmos), and exposure keratitis. (Image courtesy WCVM Ophthalmology Service.)

FIGURE 29-17 Agenesis of almost 50% of the left upper eyelid. Although the eyelid defect in this patient is larger than the defect in Figure 29-16, the degree of keratitis is less. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

29-16 and 29-17). The extent of the defect ranges widely, from a barely perceptible absence of the eyelid margin at the lateral extent of the eyelid to complete absence of the upper eyelid margin. The cause is unknown; viral etiologies, intrauterine events, and genetic mutations are proposed mechanisms, although there is no clear evidence supporting any of these theories.124 Most owners do not notice abnormalities until kittens are a few months of age, probably because of the small eye size of young kittens. On occasion, eyelid agenesis has been mistaken for upper eyelid entropion; however, close inspection reveals absence of the eyelid margin rather than an inward roll. Varying degrees of chronic keratitis resulting from trichiasis and lagophthalmos almost always accompany the eyelid defect (see Figure

FIGURE 29-18 Patient in Figure 29-17 after completion of a rotating skin flap and subsequent cryoepilation of resulting trichiasis. Although the eyelids are not completely normal, there is improved coverage of the globe during normal blinking and the trichiasis is decreased from before surgery. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

29-16). The conjunctival fornix at the site of the malformed eyelid also tends to be shallow or replaced by a thin band of conjunctiva directly connecting the globe to the eyelid. Other ocular abnormalities may accompany eyelid agenesis—most commonly, persistent pupillary membranes, which are remnants of dysplastic uveal tissue visible as thin sheets of pigmented tissue usually extending from the iris to the cornea. Colobomas of the iris, choroid, or optic nerve; retinal dysplasia; and keratoconjunctivitis sicca may also accompany eyelid agenesis.71,124 Like the eyelid defect itself, the associated developmental abnormalities range in severity, sometimes even among kittens from the same litter.124 Treatment varies with the extent of the eyelid malformation. Very small defects may require cryoepilation or primary closure for resolution of trichiasis; however, most defects of clinical significance require more extensive blepharoplasty. Surgical reconstruction usually involves two separate surgeries, the first to correct the defect and the second to correct residual trichiasis. The most common procedure is rotation of a flap of skin from the lower eyelid with a functional outcome (Figure 29-18). Subsequent cryoepilation or a Holtz–Celsus procedure can be employed to address trichiasis from the skin flap.

Entropion In the authors’ experience, feline breed-related entropion differs greatly from the same condition in dogs. In cats the majority of breed-related entropion is mild and located at the medial aspect of the lower eyelid in brachycephalic cats (Figure 29-19). The clinical significance is often minimal but may be associated with


815

FIGURE 29-20 Herpetic dermatitis causing a chronic ulcerative FIGURE 29-19 Ventromedial entropion is present in all brachycephalic cats and usually does not require treatment. Surgical correction is required when entropion causes excessive frictional irritation with corneal ulcer or sequestrum formation or epiphora with moist dermatitis and tear staining. (Image courtesy Dr. Kathleen Doyle.)

epiphora and tear staining caused by wicking of the tears by trichiasis, kinking of the nasolacrimal canaliculi, and frictional irritation of the cornea. However, these cats frequently have other abnormalities, such as exophthalmos, poor corneal sensitivity, unstable tear film, low blink rates, and lagophthalmos, that predispose them to chronic keratitis, including sequestrum formation. In these patients medial canthoplasty may be necessary to correct the entropion, lagophthalmos, and macropalpebral fissure. Breed-related entropion is believed to be more clinically significant in intact male Maine Coon cats, where it may be related to excessive skin around the face.202 Unlike breed-related entropion, acquired entropion in cats is often associated with clinically significant keratitis. Acquired entropion occurs in response to a primary pathologic process, typically as a result of blepharospasm or symblepharon formation caused by keratoconjunctivitis, or because of changes in globe position or size owing to enophthalmos or phthisis–microphthalmos, respectively. Enophthalmos may be seen in older cats or cachexic cats because of the loss of orbital fat. Surgical correction of feline entropion uses similar techniques as for the dog, which are published elsewhere. However, treatment (and preferably resolution) of any underlying cause before surgery is essential, and some authors have suggested that although the surgical technique is the same, cats require excision of a larger amount of tissue than do dogs.202

Herpetic Dermatitis Periodically, FHV-1 has been identified as a cause of dermatologic lesions, particularly those surrounding the

dermatitis of the periocular skin, nasal planum, and muzzle. Histology revealed extensive eosinophilic infiltration and viral inclusion bodies and polymerase chain reaction confirmed presence of feline herpesvirus-1 DNA. This patient responded very well to famciclovir administration. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

FIGURE 29-21 In contrast to Figure 29-20, in this cat the herpetic dermatitis manifests as dry, proliferative crusts over the nasal planum. (Image courtesy UC Davis Veterinary Dermatology Service.)

eyes and involving nasal skin of domestic and wild felidae* (Figures 29-20 and 29-21). This is not surprising given the marked epithelial tropism of this virus and the reliability with which HSV-1 causes dermal lesions.115 Herpetic dermatitis typically presents with raised, thickened plaques and chronic, nonhealing cutaneous ulcers. Most commonly, the periocular skin, nasal planum, and the skin around the muzzle are affected; however, lesions may also occur on forelimbs and other sites in contact with oral and ocular secretions.80,97 Oral ulcers and rhinitis may accompany dermal lesions.80,132,184 Most published cases had concurrent immune compromise, in the form of recent glucocorticoid administration or systemic *References 79, 80, 93, 97, 132, 184.

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FIGURE 29-22 An alopecic, hyperemic ulcerative lesion is charac-

FIGURE 29-23 Immediate postoperative photograph of the cat in

teristic of eyelid squamous cell carcinoma in cats. Usually, the adjacent skin and conjunctiva are inflamed to some degree. Cats with lightly pigmented skin are more often affected. These tumors tend to be locally invasive and can require extensive blepharoplasty procedures. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

Figure 29-22. An advancement flap was performed to close the large defect created by excision of the eyelid tumor with adequate surgical margins. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

disease.80,184 Histologic changes are often diagnostic; however, because of the eosinophilic infiltration, misinterpretation of lesions as eosinophilic granuloma may occur.80 Unlike herpetic corneal or conjunctival disease, which is not reliably diagnosed using the polymerase chain reaction (PCR), this assay seems diagnostically useful for herpetic dermatitis. When results of histologic examination were used as the gold standard in one study of cats with dermatitis, sensitivity and specificity of the PCR assay were 100% and 95%, respectively.93 Although prospective controlled studies are lacking, this disease seems responsive to systemic administration of famciclovir (see the section on corneoconjunctival disease later in this chapter).

Regardless, presurgical diagnosis through incisional biopsy or aspirate, diagnostic assessment for systemic metastases, and tumor resection with wide surgical margins are recommended for all eyelid tumors of cats. Given the essential role that eyelids play in ocular, especially corneoconjunctival, health, extensive blepharoplasty procedures are often required to guarantee postoperative eyelid function when surgical margins result in loss of more than 25% of the eyelid length (Figure 29-23). In some cases sufficiently wide margins cannot be achieved without enucleation or exenteration of a normal globe, and even then these procedures are often accompanied by extensive axial pattern flaps to cover the defect created (Figure 29-24). Apocrine hidrocystoma is an unusual and relatively uncommon neoplasm affecting feline eyelids and, as one of the few benign neoplasms affecting the eyelid of cats, warrants separate discussion. It represents a proliferative lesion of the apocrine glands within the eyelid. Although histologic confirmation is necessary for definitive diagnosis, the typical appearance of the lesion is a smooth-surfaced, hairless, often pigmented, slightly translucent eyelid mass (Figure 29-25). Apocrine hidrocystomas may occur singly, or there may be multiple lesions on the same eyelid.69 Persian cats are predisposed.25,69,208 Isolated masses may be removed with simple excision, although recurrence is common and cryosurgery is recommended as an adjunctive therapy.25,28 There is one report of ablation using trichloroacetic acid (TCA).208 In this case the hidrocystomas were eliminated without adverse effects, and no recurrence was noted 1 year after treatment.208 This treatment should be used with caution because TCA has the ability to cause painful blisters and burns to normal skin.208

Eyelid Neoplasia In contrast to dogs, most feline eyelid neoplasms are malignant, and many tumors are locally invasive.125,138,204 SCC is the most common feline eyelid tumor, although a variety of neoplasms have been reported (Figure 29-22).* Eyelid neoplasia tends to occur in cats older than 10 years of age.125,138 However, one study found SCC affected slightly older cats (12.4 years), whereas mast cell tumors were more common in younger cats (6.5 years).138 This same study also underscored the systemic significance of eyelid tumors. Cats with eyelid or third eyelid lymphoma, adenocarcinoma, SCC, and peripheral nerve sheath tumors frequently experienced tumor recurrence or died as a result of tumor-related causes.138 Conversely, the literature suggests that recurrence is unlikely after excision of hemangiosarcoma or mast cell tumor.83,138,149 *References 83, 92, 125, 138, 204, 206.

FIGURE 29-24 Immediate postoperative photograph after exenteration of the globe and orbital contents for removal of a large, infiltrative eyelid squamous cell carcinoma. Previous surgeries in this patient failed to completely remove the eyelid tumor, and exenteration was necessary to obtain adequate surgical margins. An advancement flap was required to close the surgical defect. (Image courtesy UC Davis Veterinary Ophthalmology Service.)


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FIGURE 29-26 Haw’s syndrome is characterized by bilateral elevation of the nictitans. This condition is idiopathic and self-limiting, usually within days. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

investigations are similar to those used for dogs. Cats also occasionally have bilateral elevation of the third eyelids without other ocular abnormalities (Haw’s syndrome) (Figure 29-26). Infectious etiologies have been proposed for this syndrome when it occurs in conjunction with diarrhea,123,131 but the condition is thought to be self-limiting when no other abnormalities are found.

Nasolacrimal System Disease

FIGURE 29-25 The typical appearance of an apocrine hidrocystoma is a smooth, hairless, darkly pigmented round mass on the eyelid of a cat. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

Third Eyelid Disease Disease affecting only the third eyelid in cats appears to be uncommon; however, the third eyelid is occasionally the site of primary neoplasia.138,149 Prolapse of the gland of the third eyelid (“cherry eye”) has been reported in the cat, and it has been suggested that the Burmese may be predisposed.100 As in the dog, surgical replacement of the gland is required, with specific techniques being published elsewhere.7 Elevation of the third eyelid, without gland prolapse, may be a sign of Horner’s syndrome if accompanied by signs such as miosis and ptosis. Pharmacologic testing and other diagnostic

Primary disease of the nasolacrimal duct occurs infrequently in the cat. However, its physical characteristics make it prone to involvement when adjacent structures are diseased. For example, the lack of osseous protection of the distal lacrimal sac leaves it susceptible to inflammation from adjacent respiratory mucosa.139 In addition, a portion of the nasolacrimal duct lies in very close proximity to the root of the canine tooth, which is a common site of dental disease in cats.122,139 Because of ventromedial entropion, the puncta are often in poor apposition with the globes of brachycephalic cats. This, combined with the fact that the nasolacrimal ducts of brachycephalic cats undergo sharper turns, increases the chances of impaired tear drainage and epiphora21 (Figure 29-27).

CORNEAL AND CONJUNCTIVAL DISEASE Surface ocular disease is common in cats and, in contrast to dogs, is almost always infectious in origin. The most commonly implicated agents are FHV-1—a primary conjunctival and, to a lesser extent, corneal pathogen—and Chlamydophila felis (previously Chlamydia psittaci)—a pathogen of the conjunctiva but not the cornea.

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FIGURE 29-27 Brachycephalic cats often exhibit chronic epiphora

FIGURE 29-28 Primary infection with feline herpesvirus-1 is char-

as a result of ventromedial entropion and sharper turns in the course of the path of the nasolacrimal ducts. (Image courtesy Dr. Kathleen Doyle.)

acterized by upper respiratory disease in addition to bilateral ocular disease. The mucopurulent and serosanguineous ocular and nasal discharge seen in this photo is typical. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

Mycoplasma species and Bordetella bronchiseptica are also conjunctival, but not corneal, pathogens. Although feline calicivirus is often included in lists of differential considerations for feline conjunctivitis, patients infected with calicivirus are presented to veterinarians with severe upper respiratory disease and glossitis, although close examination can sometimes reveal mild conjunctivitis. This knowledge leads to a basic philosophical approach to feline surface ocular disease that can be helpful: Corneal disease should be presumed infectious and likely caused by FHV-1, and conjunctivitis should be assumed to be caused by C. felis or FHV-1 until proven otherwise. Because therapy for these two organisms differs so markedly, the obvious question is how to make a definitive etiologic diagnosis. Because both FHV-1 and C. felis can be detected in normal cats, diagnostic tests are unable to differentiate vaccine from wild-type organism, and false-positive and false-negative test results are common, laboratory testing is usually unhelpful. For these reasons the mainstay of diagnosis in cats with surface ocular disease is critical observation of clinical signs and judgment of response to therapy. This requires understanding of the biologic behavior of both organisms and the mode of action and expected effect of common antichlamydial and antiviral therapies. This will be the major focus of the subsequent sections.

pathology. Although the virus typically persists for life in the ganglia of latently infected cats, it is extremely labile in the environment and is susceptible to most disinfectants and to desiccation. For example, FHV-1 is relatively rapidly killed in fluorescein stain and proparacaine; however, it can survive in eyewash for 5 days.181 Assuming that adequate hygiene is practiced in veterinary clinics, this short environmental survival time means that cats, rather than fomites, are the major source of viral persistence. Infection results from direct mucosal (oral, nasal, conjunctival) transfer of viral-laden macrodroplets, generated during sneezing but not normal respiratory movements. Up to 97% of cats are seropositive, and the virus is considered to be responsible for 45% of all upper respiratory infections.58,118,182 All studies to date suggest little variation in pathogenicity between viral strains, found worldwide.95,111-112,166 After initial infection of a naïve cat, the incubation period is 2 to 10 days; however, this and disease severity are likely dose dependent. Viral shedding in ocular, oropharyngeal, and nasal secretions begins as early as 24 hours after inoculation and can persist for 1 to 3 weeks. Subsequent intermittent shedding is characteristic of the lifelong carrier state. The virus causes disease through a number of theorized mechanisms, each of which requires a different therapeutic approach. The initial period of rapid intraepithelial replication and associated cytolysis manifests clinically as erosion and ulceration of the ocular, oropharyngeal, and nasal mucosa, often with a serosanguineous discharge (Figure 29-28). The pathognomonic dendritic ulcerative pattern is sometimes seen in the cornea (Figure 29-29); however, their absence should not be used to rule out FHV-1 as a causative agent. Primary disease is usually self-limiting within 10 to 20 days. Viremia occurs during this phase of infection,

Feline Herpesvirus As a typical alphaherpesvirus, FHV-1 is highly hostspecific; replicates rapidly in epithelial cells, where it causes cytolysis; establishes lifelong latency within ganglia; periodically reactivates from latency, especially during periods of stress; and during reactivation can either cause cell lysis again or activate immune-mediated


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FIGURE 29-30 Stromal keratitis is characterized by vascularizaFIGURE 29-29 Dendritic corneal ulcers are considered pathognomonic for disease resulting from feline herpesvirus-1 infection. These can be very small and reinforce the need for examination with a cobalt blue light and a source of magnification after application of fluorescein dye. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

but because systemic FHV-1-related syndromes are poorly defined, its significance is unknown. Also during this period, viral latency is established in the majority of cats, often as early as 4 days after infection, presumably by way of the ascent of the sensory axons of the trigeminal nerve. Latency is a period of viral quiescence during which there is no clinical evidence of disease, no histologically detectable inflammation within nerves or ganglia, no detectable virus using standard culture techniques, and limited viral transcriptional activity. In some animals intermittent episodes of viral reactivation from the latent state may be followed by centrifugal spread of virus along the sensory axons to peripheral epithelia. Viral recrudescence occurs when this results in clinically evident disease at peripheral epithelial sites. Recrudescent disease may be of the same ulcerative character as primary disease or may cause disease through recruitment of host immunologic mechanisms. It is often unilateral and typically not associated with generalized malaise or severe respiratory signs. The severity and extent of recrudescent disease range widely among individuals and even between episodes, making diagnosis more challenging. However, as a rule, conjunctivitis is milder and less ulcerative than seen in the primary infection, sometimes instead with substantial conjunctival thickening and hyperemia secondary to inflammatory cell infiltration. Corneal recrudescence may involve only the epithelial tissues, in which case dendritic and later geographic corneal ulceration may be seen; however, stromal keratitis is also common. This is characterized by vascularization, fibrosis, edema, and white blood cell infiltration of a nonulcerated cornea (Figure 29-30) and is believed to be due to FHV-1 antigen persistence within these tissues. Predicting which animals within a

tion, fibrosis, edema, and white blood cell infiltration of a nonulcerated cornea. It is believed to be due to persistence of feline herpesvirus-1 antigen within the corneal stroma. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

population are going to suffer recrudescent disease is currently not possible. The important concept is that although the majority of cats appear to become latently infected, only a minor percentage of them experience chronic or recurrent herpetic disease (Box 29-1). The pathogenesis of FHV-1 is summarized in Figure 29-31.

Chlamydophila felis Although C. felis has some unique biological features, it shares a number of them with FHV-1: It is an obligate intracellular organism spread by macrodroplets and direct contact, it replicates within epithelial cells, it persists within the host but poorly in the environment, and it is highly host adapted. The recent reclassification of the feline chlamydial organism from Chlamydia psittaci var. felis to its own distinct species reflects this host specificity and low zoonotic potential.108 Although there is little evidence of zoonotic transmission,84 owners, especially the immunosuppressed, should be advised to practice adequate hygiene when handling cats with suspect chlamydial conjunctivitis. Like FHV-1, C. felis prefers to replicate in epithelial cells; however, it appears to do so in a more diverse range of tissues than does FHV-1, including rectal and vaginal epithelia, as well as lung, spleen, liver, peritoneum, and kidneys.185 This knowledge helps explain why systemic therapy is now recommended for cats with chlamydial conjunctivitis, even if no extraocular signs are noted. After an incubation period of approximately 3 to 5 days, cats develop conjunctivitis, mild fever, and sometimes submandibular lymphadenopathy. In contrast to FHV-1, respiratory signs are mild to absent, and the clinical disease course tends to be more insidious and persistent but not lifelong. The typical clinical

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BOX 29-1 Important Virologic Considerations for Cats Infected with Feline Herpesvirus-1 1. Feline populations themselves, not the environment, act as the major reservoir of feline herpesvirus-1 (FHV-1). 2. FHV-1 infection (but not necessarily disease) is common in individual cats. 3. FHV-1 establishes lifelong latency within neural tissues in approximately 80% of infected individuals. 4. FHV-1 reactivates from latency commonly with or without obvious cause and with or without clinical evidence of reactivation. 5. FHV-1 reactivation is associated with recrudescent disease in only a small percentage of cats. 6. FHV-1 induces disease by way of (at least) two distinct mechanisms, with important therapeutic implications: • Cytolysis (cell-rupturing) due to viral replication. An antiviral agent may be needed; immunomodulation is contraindicated. • Immunopathology (immune-mediated injury); however, the antigen is not proven, and the immune-mediated disease may involve no or low-grade viral replication. Antiviral agents may not be effective as sole therapeutic agents. In these cases, antiinflammatory therapy may be indicated, usually in addition to antiviral agents.

Diseased cats

Normal cats

Primary infection (Cytolytic disease)

Virus cleared

Latent virus

Recrudescent disease (Cytolytic or immunologic disease)

Subclinical shedding

FIGURE 29-31 Summary of the pathogenesis of feline herpesvirus-1. Although most cats are exposed to the virus, become infected, and may even shed virus later in life, only a minority of these cats are expected to experience recrudescent disease. This figure also highlights why diagnostic tests can produce false-positive results.

presentation is periods of chronic mild conjunctivitis alternating with quiescent phases. Many cats shed chlamydial organisms for at least 60 days. Although the organisms may be spontaneously cleared, many cats require appropriate therapy for complete elimination. This helps explain why treatment of in-contact cats is often recommended for individual cats with chlamydial conjunctivitis. Co-infection with FHV-1 and C. felis appears to be very uncommon.24,109,155,195,196

TABLE 29-2 Comparison of the Biological Behavior of Chlamydophila felis and Feline Herpesvirus-1 Feline herpesvirus-1

Chlamydophila felis

Organism

Obligate intracellular alphaherpesvirus

Obligate intracellular gram-negative bacterium

Strains

Few; biologically similar

Multiple; variable virulence

Environmental stability

12-18 hours

A few days

Preferred replication site

Conjunctival epithelium

Conjunctival epithelium

Infection

Macrodroplets

Macrodroplets

Carrier state

Lifelong latency within trigeminal ganglia

Persistent (6-9 months) ocular and nonocular infections

Reinfection

Unlikely

Common

Subclinical shedding

More likely

Less likely

Diagnosis A major paradox exists with respect to the diagnosis of FHV-1.118 Cats experiencing primary FHV-1 infection shed virus in sufficient quantities that viral detection is relatively easy. However, clinical signs during this phase of infection tend to be characteristic and self-limiting, making definitive diagnosis less necessary. By contrast, the diversity and ambiguity of clinical signs in more chronic FHV-1–associated syndromes makes viral identification more desirable, but the elusive nature of the virus in these syndromes makes this difficult. Indeed, the diagnosis of FHV-1 in individual cats represents one of the greatest challenges in the management of chronic FHV-1–related diseases. The situation is equally challenging for C. felis. Culture is the gold-standard method of diagnosis; however, this requires special transport media and conditions and rigorous culture techniques and is expensive. The increased sensitivity and ease of organism detection using PCR have made it a preferred technique; however, it appears that many chlamydial organisms may not be detected by standard PCR assay.196 For these reasons clinical judgment using assessment of a number of helpful, but not pathognomonic, characteristics (Table 29-2) followed by response to appropriate therapeutic trials may be preferred. Antiviral Treatment Several antiviral drugs have been studied for their efficacy against FHV-1 and their safety in cats. However, it is critical to realize that because they were developed for use against human herpesviruses, they are not approved for use in cats, many are toxic to cats, some have


BOX 29-2 General Principles Regarding Antiviral Drugs Virostatic • Apply frequently • Do not taper Not antibacterial or antifungal • Use an adjunctive antimicrobial when indicated Generally more toxic than antibacterial drugs • Use only when necessary Monitor for systemic or topical toxicity

dramatically reduced efficacy against FHV-1, and the pharmacokinetics and metabolism are often notably different in cats compared with humans. Provided that these limitations are understood and antiviral drugs are chosen in an evidence-based manner, response to therapy is an excellent way to support or refute the clinical diagnosis of FHV-1. Naturally, this must be tempered by an appreciation that both chlamydial and herpetic disease can wax and wane without therapy. The more commonly used and available antiviral drugs will be individually discussed in subsequent sections; however, some general comments regarding antiherpetic drugs are possible (Box 29-2). First and perhaps most important is the fact that all antiviral drugs are virostatic and therefore merely reduce viral replication, permitting host immune response to overcome the virus. An appreciation that inappropriate immune response is likely what allows viral reactivation and disease recrudescence helps moderate clinical expectations for antiviral drugs in FHV-1–infected cats. It also reinforces the critical importance of administering these drugs at an appropriately high frequency. Next, the fact that no antiviral drugs have antibacterial or antifungal properties necessitates that the clinician consider adjunctive antimicrobial therapy for primary or secondary nonviral organisms. This is most relevant when treating a herpetic corneal ulcer, when a topical antibiotic is also required. Finally, these drugs typically target enzymes or replicative mechanisms that are shared between viruses and their eukaryotic hosts, creating a much narrower margin of safety than for most antibacterial agents. This is most important when antiviral agents are administered systemically but may also be evident after topical use, especially if therapy is protracted. Signs of topical toxicity include conjunctivitis and punctate corneal erosions, which closely mimic the signs of viral infection; it is therefore particularly important that the clinician remain alert to this potential and discontinue or change topical antiviral agents if there is worsening of disease during therapy or after prolonged therapy. One reasonable approach is to discontinue topical antiviral therapy after 4 to 6 weeks of therapy, even if clinical signs have

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not resolved, and to wait 1 to 2 weeks before restarting or changing the topical antiviral. Corneal toxicity can also be avoided through use of systemic, rather than topical, antiviral medication. In vitro efficacy data permit us to concentrate in vivo attention on the more efficacious agents and to ignore, for example, foscarnet. Clinical application requires at a minimum that consideration be given to cost, frequency of application, adverse effects, toxicity, pharmacokinetics, and route of therapy. This often means that some of the more potent drugs are not widely used clinically. Idoxuridine is a nonspecific inhibitor of DNA synthesis. Therefore host cells are affected, systemic therapy is not possible, and corneal toxicity can occur. It was commercially available in Canada and the United States as a 0.1% ophthalmic solution or 0.5% ointment but now must be compounded. It should be applied to the affected eye a minimum of 5 to 6 times daily. This drug is reasonably tolerated by most cats and seems efficacious in many. Vidarabine is believed to reduce viral DNA synthesis by interfering with DNA polymerase. Like idoxuridine, vidarabine is well tolerated when applied topically but because it is nonselective in its effect, it is associated with notable host toxicity if administered systemically. Vidarabine may be effective in patients whose disease seems resistant to idoxuridine because it affects a viral replication step different from that targeted by idoxuridine. Vidarabine is also commercially unavailable in Canada and the United States but can be compounded as a 3% ophthalmic ointment, which should be applied at least 5 to 6 times daily. Trifluridine is a nucleoside analog of thymidine that is too toxic to be administered systemically and often produces unacceptable signs of toxicity (keratoconjunctivitis and apparent stinging on application), even when applied topically. This is unfortunate because it is the most potent drug against FHV-1 in vitro and it has excellent corneal epithelial penetration. It is commercially available in both Canada and the United States as a 1% ophthalmic solution that should be applied to the affected eye at least 5 to 6 times daily. Acyclovir has relatively low potency, poor bioavailability, and potential bone marrow toxicity when systemically administered to cats.142 In the authors’ opinion, the availability of safer and more effective drugs makes systemic administration of acyclovir difficult to justify. However, in countries where acyclovir is available as an ophthalmic ointment and can be applied very frequently, this may be effective and should circumvent systemic toxicity.203 In vitro data suggest that interferon exerts a synergistic effect with acyclovir that could permit an approximately eightfold reduction in acyclovir dose,198 but in vivo validation of these data is needed. Valacyclovir is a prodrug of acyclovir that is more efficiently absorbed from the feline gastrointestinal tract and is converted to acyclovir within the liver. Unfortunately,

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valacyclovir administration is associated with plasma acyclovir concentrations that are elevated to a point of causing fatal myelosuppression and renal and hepatic necrosis,135 and valacyclovir should never be used in cats. Penciclovir has a similar mechanism of action as acyclovir but with much more potent antiviral activity against FHV-1. Like acyclovir, its relatively poor bioavailability can probably be overcome by oral administration of the prodrug famciclovir. Pharmacokinetic, safety, and efficacy studies in cats reveal that famciclovir is remarkably effective and apparently safe in cats when administered at 90 mg/kg orally, thrice daily.121,187,188 Although clinical efficacy at lower doses has been reported,121 because of the nonlinear pharmacokinetics of famciclovir in the cat, further research is needed to establish the appropriate dose. Cidofovir is a relatively new antiviral with good efficacy against FHV-1. When compounded with methylcarboxycellulose into a 0.5% ophthalmic solution and administered twice daily to experimentally infected cats, cidofovir was associated with reduced viral shedding and clinical disease.62 Although twice-daily dosing offers a clear advantage over all other topical antiherpetic drugs, cidofovir is not yet commercially available in Canada or the United States, and there are reports of its topical use in humans being associated with stenosis or cicatrization of the nasolacrimal drainage system components. As cidofovir becomes used more widely in cats, this potential side-effect should be monitored. Lysine is an adjunctive therapy for FHV-1, but there are contradictory research data regarding its efficacy. In vitro data suggest that lysine exerts its antiviral effect by antagonism of arginine.116 In vivo studies demonstrated that administration of 500 mg lysine orally, twice daily, was associated with less severe conjunctivitis during primary infection179 and that 400 mg lysine orally, once daily, reduced viral shedding during latent infections.119 However, other clinical studies failed to show a positive effect or even demonstrated worsening of disease and increased viral shedding47,120,158 in two studies in which lysine was administered as a dietary supplement rather than in bolus form.47,120 For that reason cat owners should be advised to administer lysine as a twice-daily 500-mg bolus rather than by sprinkling it on food. Because lysine appears to be most effective when initiated before clinical disease, it may be most useful when administered indefinitely to cats experiencing repeated recrudescent disease,179 rather than being administered only during periods of active disease. The interferons are a group of cytokines that have diverse immunologic and antiviral functions largely through limiting cell-to-cell viral spread. Although interferons may play important physiologic roles in the control of viral infections, data regarding potential therapeutic applications are conflicting. In vitro, interferon significantly reduced FHV-1 titer or cytopathic effect (or

both) without detectable cytotoxic changes in the host cell lines162,170 and was associated with a nearly eightfold reduction in the required dose of acyclovir, especially when introduced to the viral culture before infection.198 However, there are relatively few peer-reviewed, placebo-controlled, prospective clinical trials of interferon administration in cats. Those that exist show minimal or no beneficial effects.76 Further research is necessary to determine dosage, timing, and efficacy (if any) of this group of compounds, especially in the more chronic or recrudescent infections. Antichlamydial Treatment Traditionally, feline chlamydial conjunctivitis has been treated with topical tetracycline ointment. However, because cats harbor and shed C. felis from nonocular sites and apparently normal cats can shed organisms, systemic drugs should also be used and consideration should be given to treating all cats in contact with the affected cat.141,172,185 The preferred systemic drug is doxycycline at 5 to 10 mg/kg orally once to twice daily for at least 3 to 4 weeks. Azithromycin has good efficacy against chlamydial (and mycoplasmal) organisms and shows reasonably rapid absorption, adequate bioavailability, and useful concentrations in ocular tissues for at least 3 days after a single oral dose of 5 mg/kg. However, doxycycline has superior capacity to reduce organism shedding. A topical tetracycline or erythromycin ointment should be considered in addition to systemic doxycycline if conjunctivitis is severe so as to guarantee high drug concentrations at the ocular surface and provide some surface ocular lubrication. Contraindicated Therapies Because triple antibiotic is ineffective against C. felis and FHV-1, it should not be used to treat primary conjunctivitis in cats. It is useful for prevention of infection of a superficial corneal ulcer. Topically or systemically administered corticosteroids may sometimes produce symptomatic improvement in infectious corneoconjunctival disease but do not reduce, and may actually increase, organism load. This is presumably why they are often associated with rebound worsening of disease once they are discontinued. Ironically, this can falsely lead the clinician to reinstitute the steroid therapy, further exacerbating the underlying disease. Topically administered corticosteroids induce deeper and more persistent corneal disease and protracted viral shedding.137 Systemic administration of corticosteroids is contraindicated and is a well-established, reliable means of inducing viral reactivation.91 Although steroids may be used in select cases that are suspected to be due to immunopathologic mechanisms, the potential for dramatic clinical decompensation warrants extreme caution, close monitoring, and concurrent use of antiviral medication. The potential complications from using

corticosteroids have prompted interest in the use of nonsteroidal antiinflammatory drugs (NSAIDs) for managing the inflammatory effects of ocular FHV-1 infection. Although there are no studies of their effects in cats infected with FHV-1, they have similar negative effects to corticosteroids in humans infected with HSV-1. Use of cyclosporine in chronic feline herpetic disease has been inadequately studied. Cyclosporine is capable of suppressing inflammatory events operative in viral stromal and eosinophilic keratitis but also impairs viral clearance from the eye and suppresses some beneficial immune responses. The authors are unaware of any studies examining the effects of tacrolimus on ocular herpetic infections in any species. This suggests that use of these agents should, as a minimum, be restricted by the same principles that govern the use of corticosteroids in humans with HSV-1.

Conjunctivitis Conjunctivitis is an extremely common finding in the cat. However, when reaching this clinical diagnosis, clinicians must always first determine if the cat is affected by conjunctivitis only and then must determine the cause of the conjunctivitis. The first consideration is crucial because many diseases, including blepharitis, keratitis, uveitis, glaucoma, orbital disease, and scleritis all produce conjunctival hyperemia (Figure 29-32). However, these diverse diseases often have completely different causes, require completely different diagnostic investigations, have different ramifications for vision or even patient survival, and necessitate completely


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different treatments. This emphasizes why a complete ophthalmic examination should always be performed, even if the clinical presentation looks like simple conjunctivitis. If ocular examination fails to reveal further pathology, then it is justifiable to diagnose conjunctivitis and begin searching for the cause. Fortunately, in contrast to dogs, there are few likely causes of feline conjunctivitis. As discussed previously, FHV-1 and C. felis are the top two etiologic diagnoses with Mycoplasma spp., Bordetella, and possibly Bartonella lower on the list. Once clinical judgment has identified the most likely cause (see Table 29-2), specific and evidence-based treatment should be initiated because response to therapy is the next “diagnostic test.” These therapies are described earlier in this chapter and should include systemic doxycycline with or without topical tetracycline or erythromycin ointment if C. felis is suspected, or a topical or systemic antiviral with or without lysine if FHV-1 is suspected. Antichlamydial treatment is required for 3 to 4 weeks, whereas antiviral drugs should be continued for approximately 1 week after clinical resolution is noted. Mucinomimetic therapy is a safe and important component of the treatment of conjunctivitis. Chronic conjunctivitis is associated with conjunctival goblet cell atrophy and an associated mucin-deficient qualitative tear film abnormality characterized by premature evaporation of the tear film and corneal drying. This, in turn, worsens conjunctivitis, leading to a perpetually exacerbating cycle unless remedied with topical mucin replacement.38 Although this is likely true for many causes of conjunctivitis, FHV-1 has specifically been proved to induce a drastic decline of conjunctival goblet cell density to normalize for at least 1 month after FHV-1 infection.106 Mucinomimetic tear replacement agents break this cycle by increasing stability of the precorneal tear film. Numerous formulations exist; however, sodium hyaluronate demonstrates superior corneal retention time compared with other tear substitutes.171 Unlike most medications, artificial tear substitutes have the added advantage of being available in single-dose packaging, bypassing corneal cytotoxicity that is a feature of preservatives in ophthalmic medications23,30 (Figure 29-33).

Symblepharon

FIGURE 29-32 Conjunctival and episcleral vascular congestion and mild corneal edema in a cat with uveitis. Although the conjunctival hyperemia suggests “simple” conjunctivitis, the larger episcleral vascular engorgement along with the corneal edema make this diagnosis untenable and instead make glaucoma or uveitis most likely. This underscores the importance of always performing a complete ophthalmic examination, including assessment of aqueous flare and intraocular pressure. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

Symblepharon is a term that describes adhesions between conjunctiva and adjacent conjunctiva or cornea, and is expected after marked or chronic ulceration and exposure of subepithelial connective tissue. Its clinical appearance is characteristic, but significance varies greatly depending on the extent and location of adhesions (Figure 29-34). Corneal involvement is associated with reduced vision, and conjunctival adhesions may obstruct lacrimal drainage, prohibit normal globe or

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FIGURE 29-35 Symblepharon involving the bulbar and palpebral FIGURE 29-33 Artificial tear formulations are often available in single-dose containers. Single-dose medications are advantageous because they are free of preservatives, which are toxic to the corneal epithelium. This is especially important when medications are administered 4 or more times daily, multiple medications are being administered, or there is known hypersensitivity.

conjunctiva, nictitans, and cornea. The adhesions in this cat prevent normal movement of the third eyelid. Epiphora is caused by adhesions over the nasolacrimal puncta. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

accompanied by a staged approach, have been used. Referral for these procedures is recommended.

Corneal Ulceration As in dogs, there are three main principles for treating corneal ulceration in cats: 1. Find and treat the primary cause. 2. Prevent secondary infection. 3. Provide specific supportive care if stromal involvement or chronicity are present.

FIGURE 29-34 Symblepharon between the conjunctiva and the cornea following primary infection with feline herpesvirus-1. Because of the central location of the adhesions in this cat, reduced vision is probable. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

eyelid movements and position, or cause nictitans protrusion (Figure 29-35). Feline herpesvirus is most frequently blamed, presumably because it is so common in cats. Because medications cannot break down adhesions, surgical resection is the only possible therapy. However, recurrence is common because surgery involves a combination of conjunctivectomy and superficial lamellar keratectomy, which re-expose subepithelial connective tissue. Minor adhesions are therefore best left untreated. When surgical management is elected, preoperative and postoperative control of active herpetic recrudescence is essential. In addition, various mechanical devices to separate the exposed surfaces during healing, often

The major difference between feline and canine ulcers is that infectious causes of ulcers are rare in dogs, whereas feline ulcers are considered to be due to FHV-1 until proved otherwise. If thorough clinical examination fails to reveal evidence of a foreign body, ectropion, entropion, distichia, ectopic cilia, trichiasis, lagophthalmos, blepharitis with an abrasive eyelid margin (all of which are very uncommon in cats), or periocular or intraocular trauma, then the ulcer should be assumed to be herpetic in origin. Herpetic ulcers have either a pathognomonic dendritic pattern or a highly suggestive appearance—superficial, epithelial loss, sometimes with a nonadherent lip. Herpetic ulcers do not involve stromal loss unless there is secondary bacterial infection. If FHV-1 is believed to be the originating cause, then a decision must be made regarding antiviral therapy. If the ulcer is acute, unilateral, and in an otherwise healthy cat without previous recrudescent herpetic disease, then allowing the patient’s own immunity the chance to overcome the herpetic reactivation is justifiable. Otherwise, the clinician must initiate topical or systemic antiviral medication. Antiviral therapy should be continued until ulcer resolution and should not be tapered.


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FIGURE 29-37 Corneal sequestrum with chronic, superficial keraFIGURE 29-36 Deep corneal ulcer secondary to feline herpesvirus-1. Note the loss of corneal stroma; the thickened, hyperemic conjunctiva; mild corneal edema; and deep corneal vessels. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

All ulcers require topical antibiotics because the epithelial barrier is lost and because secondary infection is one of the more devastating complications that can occur. This is true even if an antiviral drug is instituted, because antivirals do not have antibacterial properties. A broad-spectrum bactericidal antibiotic such as triple antibiotic is an excellent choice. In ulcers that are not bacterially infected, twice- or thrice-daily application until the cornea no longer retains fluorescein stain is adequate. Additional supportive treatment is required for any ulcer with stromal involvement (stromal loss, malacia, or white blood cell infiltration) (Figure 29-36). These changes typically indicate secondary bacterial infection, and as in other species, cytology and culture and sensitivity are recommended. Unlike in dogs, Mycoplasma spp. can cause rapidly progressive stromal ulcers in cats; this should be considered when requesting culture at the laboratory. A broad-spectrum bactericidal ophthalmic antibiotic solution such as fluoroquinolone should be administered as often as 6 times daily until culture results are available. If Mycoplasma is suspected, then tetracycline ointment should be considered. In all deep ulcers, adjunctive therapy with serum should be considered to provide anticollagenases, which reduce stromal melting, and growth factors, which speed healing. Typically, serum is administered at the same frequency as the topical antibiotic. If there is danger of rupture or healing is delayed, referral for placement of a conjunctival graft is recommended. Third eyelid flaps are not recommended because they prohibit the two things the ulcer needs most: medication and observation. Ulcers are also classified as complicated when they persist beyond 7 days, even if they remain superficial. A particular type of chronic nonhealing superficial ulcer occurs in cats and shares some features with the

titis. Superficial corneal vessels span the entire visible cornea, and a lip of granulation tissue is seen at the ventral edge of the sequestrum. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

indolent ulcer of dogs; it involves epithelium only (no stromal loss) and has a lip of nonadherent epithelium that is easily débrided with a cotton-tipped applicator. However, indolent ulcers of dogs are caused by an anatomical defect preventing adhesion between the corneal epithelium and stroma and are treated by grid keratotomy. No such syndrome has been proved to occur in cats. In fact, if nonhealing ulcers in cats are treated by grid keratotomy, they are particularly likely to form corneal sequestra (discussed later in this chapter). These chronic, superficial ulcers, which débride easily in cats, may be due to FHV-1. One treatment protocol involves use of a topical antiviral and antibacterial agent following corneal débridement. If this is unsuccessful, referral is wise.

Corneal Sequestration Corneal sequestration is an entity unique to the cat. It is an area of ulcerated, necrotic cornea characterized clinically by gradual progression of a dark (amber, brown, or black) discoloration usually involving the central cornea (Figure 29-37). Prior, and usually chronic, corneal ulceration is common but not always reported. Blood vessels often extend to the lesion and are deep or superficial, depending on depth of the sequestrum. The necrotic corneal stroma may be surrounded by zones of variably intense corneal stromal edema, inflammatory cell infiltration, or both. Sequestra are usually unilateral but may occur bilaterally. Frequently, the eye appears to be causing the cat pain, but some cats display only minor signs of discomfort. Histologically, the plaque consists of a sequestered, desiccated region of necrotic corneal stroma surrounded by a variable “foreign body– type” inflammatory cell response with extensive granulation tissue development. The characteristic

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FIGURE 29-38 Postoperative photo after excision of a corneal sequestrum. In this case excision of the sequestrum resulted in a deep corneal defect that required grafting. A corneoconjunctival transposition was performed to maintain a relatively clear visual axis in the central cornea. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

clinical appearance is considered diagnostic; however, differential diagnoses should include corneal foreign body; dermoid, anterior synechia–staphyloma; or limbal melanoma. Feline herpesvirus may be involved in approximately 50% of cases.136 Other causes of chronic corneal irritation such as entropion, distichiasis, tear film deficiencies, and lagophthalmos appear also to predispose to sequestrum formation. This may explain the predilection for Persian, Himalayan, and Siamese cats to develop corneal sequestra. Identification and correction of any underlying causes are important whenever possible. Lamellar keratectomy with a sliding corneal or conjunctival graft is the treatment of choice, especially if the cat appears to be in pain or the lesion is deep or chronic (Figure 29-38). Unfortunately, approximately 33% of cases experience recurrence. Medical management is generally not recommended because of the potential for corneal perforation and the degree of discomfort usually present. However, if the cat appears comfortable, it may be attempted because sequestra can spontaneously slough over a period of weeks to months. Medical management includes prophylactic topical antibiotics, as for corneal ulceration and treatment of reflex uveitis, if evident. Many recommend using antiviral medications and mucinomimetic tear-replacement formulations because altered tear film quality or evaporation or both have been blamed for these lesions. Surgical procedures to reduce corneal exposure and irritation such as temporary or permanent partial tarsorrhaphy and correction of entropion should be considered to reduce recurrences.

Eosinophilic Keratoconjunctivitis Feline eosinophilic keratitis (FEK) is an enigmatic disease of cats. Clinically, FEK appears as a focal, raised, yellow

FIGURE 29-39 The characteristic appearance of feline eosinophilic keratitis includes thickened and hyperemic conjunctiva, corneal vascularization, and white corneal plaques. Cytologic assessment of the corneal plaques revealed eosinophils and mast cells. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

to pink corneal plaque resembling granulation tissue (Figure 29-39). Typically, only the lateral cornea is affected initially, but in advanced cases the entire cornea may be involved. Adjacent areas of corneal ulceration are often present. Eyelid or conjunctival involvement (including third eyelids) is seen relatively commonly with keratitis but occasionally occurs alone. Cytologic evaluation of scrapings from affected cornea or con junctiva reveals neutrophils, eosinophils, and mast cells, along with hyperplastic or dysplastic epithelial cells. Histology may reveal lymphocytes and plasma cells. Diagnosis is suggested by clinical appearance and confirmed using cytology. The cause is undetermined; however, the condition appears to be due to an aberrant immune response. In many cases the antigenic stimulus is unrecognized; however, FHV-1 DNA can be detected in corneal samples from approximately 75% of cats with FEK.136 Given the inability to identify the inciting antigen, this disease has traditionally been treated with topical corticosteroids. Potential involvement of FHV-1 presents clinicians with a dilemma, because use of immunomodulatory drugs, especially topical corticosteroids, for treatment of an eye that is potentially infected with FHV-1 warrants caution. Given the likely involvement of FHV-1, it is prudent to simultaneously administer an antiviral agent and recheck frequently. If there is improvement and the owners are compliant, continuation of this regimen may be all that is necessary. The use of 1.5% cyclosporine has recently been described, with promising results.173 Antiviral treatment should be continued for as long as there is evidence of active viral replication and certainly while ulceration is present, and corticosteroids are tapered judiciously as clinical signs improve. Early diagnosis and treatment of recurrences will limit the need for protracted therapy.


S

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CB I Co

R ON Ch

FIGURE 29-41 Basic anatomy of the globe. The anterior uvea is FIGURE 29-40 Acute bullous keratopathy is characterized by rapid onset of massive corneal edema, with bulla formation and keratoconus. Superficial corneal vessels are also visible in this cat, suggesting a previous keratitis. This is not a necessary feature. Urgent surgical intervention is required to stabilize the cornea. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

Acute Bullous Keratopathy Although acute bullous keratopathy (ABK) is a rare condition, feline clinicians should be aware of it because it is seen only in cats, has a characteristic clinical appearance, and requires emergency management to avoid globe rupture. As its name suggests, ABK involves the cornea only and is extremely rapid in onset, occurring within minutes to hours. Profound edema and bullae formation within the corneal stroma are the predominant features72 (Figure 29-40). There is usually marked epiphora and blepharospasm, as well as some conjunctival hyperemia and chemosis, as is expected with all cases of keratitis. With this clinical appearance, the major differential considerations are a peracute progressive stromal ulcer or a corneal laceration; however, the bullous nature of the corneal distention and the typical lack of stromal inflammatory cells are characteristic of ABK. The condition can present in one or both eyes. Cats of any age may be affected, but the few cases reported in the literature suggest that the syndrome is more common in younger cats. To date, no predisposing cause or history is recognized, although an association with systemic antiinflammatory and immunosuppressive medication has been suggested.147a Unlike other causes of corneal edema, which result from defects in the corneal epithelium or endothelium, the defect in ABK is proposed to involve the corneal stroma itself. Bacterial, viral, protozoal, and fungal organisms have not been detected when tested for by cytology, culture, or serology. Some cases have been reported to improve without treatment; however, most require referral for emergency conjunctival grafting and sometimes

composed of the iris and ciliary body, and the posterior uvea is composed of the choroid. Co, Cornea; I, iris; CB, ciliary body; R, retina; Ch, choroid; S, sclera; ON, optic nerve. (From Maggs D: Slatter’s fundamentals of veterinary ophthalmology, ed 4, St Louis, 2007, Saunders.)

thermokeratoplasty. In the latter technique, the cornea is treated with multiple, very carefully applied, highly focal applications of heat. A scar forms in the treated area, and associated tissue contraction expels fluid from the corneal stroma, limiting further corneal distention. Application of a bandage in the form of a temporary tarsorrhaphy has also been reported to reduce edema. Although third-eyelid flaps may provide some support to the cornea, they are not recommended because they prevent medication and observation of the cornea, which are critical to proper management. If aggressive treatment is initiated promptly, the prognosis for vision and for the globe is good; however, extensive bullous keratopathy, especially with globe perforation, carries a poorer prognosis.

DISEASES OF THE UVEAL TRACT Uveitis The uvea or vascular layer of the eye is composed of the iris and ciliary body (anterior uvea), and choroid (posterior uvea) (Figure 29-41). Uveal inflammation may involve the iris and ciliary body alone (anterior uveitis), the choroid and adjacent retina (posterior uveitis or chorioretinitis), or the entire uveal tract (panuveitis). Recognition of this common, painful condition is vital, as the consequences of untreated uveitis can be blinding and underlying causes of uveitis can be fatal. Unlike dogs, cats with uveitis less commonly present with sudden, overt clinical signs. Instead, feline uveitis is insidious, with subtle changes that may easily be dismissed, often as “conjunctivitis,” unless a thorough ophthalmic examination is performed. Therefore all reddened eyes in cats should be assessed for signs considered pathognomonic or at least highly suggestive of

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FIGURE 29-42 Examination findings typical of uveitis include

FIGURE 29-43 Multiple focal bullous retinal detachments around

corneal edema, rubeosis iridis, a thickened or “muddy” iris, and keratic precipitates on the ventral corneal endothelium. (Image courtesy of the WCVM Ophthalmology Service.)

the optic nerve of a cat that also demonstrated neurologic abnormalities. A diagnostic workup failed to reveal an underlying cause; however, the owner reported that the cat regained normal mentation, neurologic status, and vision. This case reinforces the importance of a fundic examination in patients demonstrating neurologic signs. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

anterior uveitis (or at the very least incompatible with a diagnosis of conjunctivitis), such as aqueous flare; hypopyon; hyphema; anterior chamber fibrin; keratic precipitates; episcleral congestion; corneal edema; rubeosis iridis; a thickened, swollen, or “muddy”-looking iris; miosis (or a delayed response to mydriatic agents); anterior or posterior synechiae; and altered IOP (Figure 29-42). The IOP in eyes with anterior uveitis is generally low; however, with secondary glaucoma, it may also be normal or elevated. Posterior uveitis is not always accompanied by outward clinical signs or anterior segment changes, which emphasizes the importance of performing a fundic examination with each ophthalmic examination. Clinical findings indicative of posterior uveitis include vitreous debris, hyporeflective areas within the tapetum, chorioretinal infiltration with white blood cells, retinal vascular tortuosity, retinal or vitreous hemorrhage (or both), or retinal detachment (Figure 29-43). Once uveitis has been diagnosed, the next important step is to search for an underlying cause, even if this is expected to be unrewarding (Table 29-3). Causes of uveitis are generally referred to as exogenous or endogenous. Exogenous causes are usually easily diagnosed by clinical examination, tend to result from trauma or surgery, and include corneal ulceration and blunt or penetrating ocular trauma. Endogenous causes require further testing to achieve a diagnosis, and include infectious, neoplastic, and immune-mediated factors. Although examination findings are nonspecific with regard to etiology, some clinical findings are more suggestive of certain etiologies. For example, large, cellular keratic precipitates (often described as resembling mutton fat) usually reflect diseases causing granulomatous inflammation, such as systemic mycoses or feline

FIGURE 29-44 Mild corneal edema and granulomatous keratic precipitates in a cat with uveitis caused by feline infectious peritonitis. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

infectious peritonitis (FIP) (Figure 29-44). Presence of a mature or hypermature cataract may be suggestive of lens-induced uveitis; however, unlike dogs, cats tend to develop cataracts secondary to uveitis, and the cataract should not be assumed to be the original cause of intraocular inflammation. Idiopathic uveitis occurs more often in male cats older than 9 years and is more likely to be unilateral, whereas uveitis secondary to systemic disease is more often bilateral.43 Because many systemic diseases have been implicated as being able to cause uveitis in cats, the list of differential considerations is long (Box 29-3). Feline immunodeficiency virus (FIV) and FIP directly cause


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TABLE 29-3 Suggestive Clinical Examination Findings for Several Common Causes of Uveitis in the Cat Cause

Clinical Course

Typical Location

Suggestive Signs*

Trauma

Acute

Anterior uveitis

Hyphema; AC fibrin; miosis; aqueous flare; hypotony

Reflex uveitis (due to ulcerative keratitis)

Acute

Anterior uveitis

Miosis; aqueous flare; hypopyon (if ulcer is infected); hypotony

FIP

Subacute

Panuveitis (anterior uveitis may dominate)

KPs; aqueous flare; AC fibrin; hypopyon; retinal vascular engorgement and increased tortuosity; perivascular chorioretinal granulomas; retinal detachment

Lymphoma

Subacute

Anterior uveitis

Hypopyon; hyphema; AC fibrin; aqueous flare; iridal thickening; iridal nodules; rubeosis iridis; iris bombé; secondary glaucoma

Systemic mycoses

Subacute

Panuveitis (posterior uveitis dominates)

Hypopyon; hyphema; AC fibrin; aqueous flare; iridal thickening; rubeosis iridis; iris bombé; vitreal debris/ infiltrates; secondary glaucoma; chorioretinal granulomas; retinal detachment

Lens-induced uveitis

Phacoclastic (acute)

Anterior uveitis

Hypopyon; hyphema; AC fibrin; aqueous flare; iridal thickening; posterior synechiae; ocular hypertension; miosis Aqueous flare; iridal thinning/atrophy; rubeosis iridis; posterior synechiae; mature/hypermature cataract; secondary glaucoma

Phacolytic (chronic)

Idiopathic

Chronic or recurrent

Anterior or intermediate uveitis

Iridal thinning/atrophy; iridal nodules; rubeosis iridis; aqueous flare; KPs; snow banking; vitreous debris/ infiltrates; posterior synechiae; cortical cataract; secondary glaucoma

Primary uveal neoplasia

Chronic

Anterior uveitis or chorioretinitis depending on site of tumor

Anteriorly located Hypopyon; hyphema; AC fibrin; aqueous flare; anterior iridal displacement; rubeosis iridis; vitreous debris/ infiltrates; secondary glaucoma Posteriorly located Retinal detachment; subretinal neoplasm; vitreous debris/ infiltrates

FIV

Chronic

Intermediate uveitis

Vitreous debris/infiltrates; snow banking; iridal thinning/ atrophy; rubeosis iridis; aqueous flare; posterior synechiae; cortical cataract; secondary glaucoma

AC, Anterior chamber; FIP, feline infectious peritonitis; KPs, keratic precipitates; FIV, feline immunodeficiency virus. *Note the considerable overlap of signs. No sign is pathognomonic for a given cause, and absence of one or more of the signs listed does not allow a cause to be eliminated. Rather, these features can be used to rank the likelihood of potential causes for further diagnostic testing. From Maggs DJ: Feline uveitis: an “intraocular lymphadenopathy,” J Feline Med Surg 11:167-182, 2009.

BOX 29-3 Infectious Causes of Uveitis in Cats Viral FIP FeLV* FIV* FHV

Bacterial Bartonella species Mycobacterium species Ehrlichia species‡ Borrelia burgdorferi‡

Fungal/algal Cryptococcus neoformans† Histoplasma capsulatum† Blastomyces dermatitidis† Candida albicans Coccidioides immitis† Aspergillus species

Parasitic Cuterebra

FIP, Feline infectious peritonitis; FeLV, feline leukemia virus; FIV, feline immunodeficiency virus; FHV, feline herpesvirus. *Via immunosuppression or oncogenesis. † Chorioretinitis predominates. ‡ Seroprevalence data only (no clinical evidence). From Maggs DJ: Feline uveitis: an “intraocular lymphadenopathy,” J Feline Med Surg 11:167-182, 2009.

Protozoal Toxoplasma gondii Leishmania species

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FIGURE 29-45 Multiple focal bullous retinal detachments and chorioretinal hemorrhage in a cat with systemic cryptococcosis. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

uveitis in cats.59,114 Lymphoma or superinfection resulting from immunosuppression and anemia induced by feline leukemia virus (FeLV) also cause uveitis; however, FeLV itself does not seem to directly result in ocular disease.22 There is also evidence suggesting that intraocular presence of FHV-1 may be associated with feline uveitis.117 Bacteremia or septicemia may also manifest as uveitis. Although Bartonella species have been implicated by some authors,103 other controlled studies have revealed that many normal animals are seropositive61 and can even have organism DNA demonstrated in their aqueous humor.103 These facts confound diagnosis of these and many other organisms. By contrast, Toxoplasma gondii and Leishmania species are well established as a cause of feline uveitis.* Intraocular migration of nematodes such as Cuterebra species may cause uveitis.82,177,207 Dematiaceous fungi, as well as systemic infections of Cryptococcus species, Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides immitis, may also cause uveitis in cats† (Figure 29-45). Primary and metastatic neoplasia also causes uveitis. In cats, iris melanoma is the most common primary ocular tumor, whereas lymphoma is the most common metastatic tumor associated with feline uveitis.43,147 Although a large number of systemic diseases are capable of causing uveitis, uveitis remains idiopathic in approximately 70% of cats undergoing a thorough diagnostic investigation.43,147 Regardless, thorough diagnostic investigation is indicated because many causes are treatable, have human health implications, or affect management of cats. In particular, failure to identify a *References 42, 89, 90, 105, 151, 152. †

References 6, 13, 19, 67, 75, 144, 147.

cause means that corticosteroids may be used at sufficiently high doses to be effective without concern regarding their safety in systemically infected animals or animals with neoplasia in which a more complete chemotherapeutic protocol might be chosen. Therefore a diagnosis of uveitis without obvious exogenous cause should always be followed by a complete physical examination, CBC, serum biochemical profile, urinalysis, and testing for FIV and FeLV. Further diagnostics, such as chest or abdominal radiography and ultrasonography or fine-needle aspirates of lymph nodes, may be indicated depending on clinical suspicion. Serology for infectious disease is variably useful for obtaining a diagnosis. Serology is unable to differentiate between vaccine-associated virus and wild-type virus, and titers against some infectious diseases may remain elevated long after infection has occurred. For example, immunoglobulin G titers to T. gondii remain elevated for years after initial exposure in healthy cats.104 With Bartonella there appears to be no correlation between titers and uveitis.61 It may be of more value to use negative titers to rule out disease than to use positive titers to rule in infectious disease; however, care must be taken not to falsely interpret negative titers in acutely affected animals. Aqueous humor may also be submitted for infectious disease titers. However, similar pitfalls exist for interpretation of aqueous titers as for serum titers. In addition, intraocular antibody production can persist or recur in response to nonspecific antigenic stimuli and may occur in the absence of uveitis. Cytology of aqueous humor also tends to be of lowyield except for lymphoma. Culture is of benefit only with endophthalmitis, typically after a penetrating injury. However, evaluation of aqueous may be of some value when uveitis is unresponsive to treatment and other diagnostics have been unrewarding. When an eye has become blind and painful despite treatment, enucleation is indicated and histopathologic evaluation of the globe is essential. Treatment for uveitis should be aggressive and prompt given the high potential for blinding sequelae. The main goals of treatment are to address any underlying etiology, control intraocular inflammation, provide analgesia, and minimize secondary complications. Anterior uveitis may be treated with topical medications alone; however, the presence of posterior uveitis requires systemic administration of medications because of the inability of eye drops to achieve therapeutic drug concentrations posterior to the lens. Treatment of an identified underlying etiology is essential. Failure to address an underlying cause will almost certainly lead to failure to control uveitis. In addition, specific treatment often does more to reduce inflammation than nonspecific antiinflammatory medications and can result in lower doses of and shorter treatment periods with antiinflammatory medications.

Corticosteroids or NSAIDs are used to control intraocular inflammation. In the absence of corneal ulceration, topical 1% prednisolone or 0.1% dexamethasone ophthalmic suspensions may be used up to 4 times daily to treat anterior uveitis. Hydrocortisone, found in combination antibiotic–corticosteroid preparations, is a weak steroid that does not penetrate an intact corneal epithelium and should not be used to treat uveitis. Because systemic absorption from topically applied medications is generally minimal, especially acutely, and because control of inflammation is essential (irrespective of cause), topical steroids are usually safe for use when infectious systemic disease is present. However, when treating posterior uveitis, the clinician should refrain from using systemic steroids until infectious etiologies have been ruled out or when results of diagnostic tests may be affected by the use of corticosteroids. Topical 0.1% diclofenac, 0.03% flurbiprofen, and 0.1% nepafenac are NSAIDs that may all be used up to 4 times daily to control uveitis. Because they tend to be more expensive and less potent than steroids, they are usually reserved for situations in which when corticosteroids are contraindicated. Because of the potential for platelet inhibition, these medications should be avoided if hyphema is present. Likewise, systemic NSAID therapy is used when systemic corticosteroids are contraindicated or while awaiting results of diagnostic testing but should be avoided if a bleeding disorder is suspected. The pain associated with anterior uveitis results from spasm of the ciliary body muscle. Although this cannot be assessed directly, it can be assumed to be present if the pupil is miotic. Administration of cycloplegic medication such as 1% atropine will provide analgesia by preventing ciliary muscle spasm. Clinicians should use the presence of a dilated pupil to infer that paralysis of the ciliary muscle has also occurred. Initially, atropine may be required up to 3 times daily to achieve mydriasis. After the pupil has dilated, atropine is administered only as often as is required to maintain dilation, which may be as infrequently as every other day or every few days. The bitter taste of atropine may result in profuse salivation after administration in cats; use of the ointment form rather than the solution may minimize this side effect. In addition to its analgesic effects, atropine also stabilizes the blood–ocular barrier, and the resulting mydriasis decreases the chance of posterior synechia formation. The IOP should be checked frequently in patients receiving atropine treatment because the dilated pupil may potentiate peripheral anterior synechia, which obstruct the iridocorneal angle, and cycloplegia can also reduce aqueous outflow, thereby increasing IOP. Initial uveitis treatment should be aggressive, with judicious tapering of antiinflammatory and cycloplegic


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FIGURE 29-46 Bilateral uveitis in a cat. Rubeosis iridis and keratic precipitates are visible in the right eye. Mydriasis and buphthalmos of the left eye are due to glaucoma, which has developed secondary to uveitis. There is also a cataract in the left eye, likely caused by the uveitis. This case reinforces the need for early and aggressive therapy of uveitis in cats, with slow tapering of therapy based only on reduction of clinical evidence of uveitis. Unrecognized or inadequately treated uveitis is associated with severe and blinding sequelae. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

agents based on clinical improvement. Recheck examinations should be frequent and at increasing intervals as signs abate. Initial rechecks may need to be as frequent as twice weekly to manage complications should they arise. Patients should also be rechecked beyond the time that all medications are completely discontinued on account of the potential for recurrence. Owners should also be warned that patients who have experienced past bouts of uveitis are at risk of future episodes. Some patients, particularly those diagnosed with idiopathic uveitis, may require lifelong low-doseantiinflammatory medications to control clinical signs, reduce complications, and minimize recurrence of disease. In some cases uveitis may prove intractable. Secondary complications in these patients are common. The most important sequelae of chronic uveitis in cats are glaucoma, lens luxation, cataract, and retinal detachment43,147 (Figure 29-46). Should glaucoma arise, treatment with the carbonic anhydrase inhibitor dorzolamide, twice or thrice daily, should be instituted. Unfortunately, glaucoma can be challenging to treat and may ultimately necessitate enucleation of the affected eye. Cataract formation and lens luxation are other common complications of uveitis that may be difficult to treat. An advanced cataract may exacerbate ocular disease by inciting phacolytic uveitis; however, most cats are not candidates for phacoemulsification because of the severity of ocular pathology. Similarly, surgical removal of a luxated lens carries a poor prognosis if uveitis is ongoing. In many patients with these sequelae to uveitis, a blind and painful globe eventuates, and enucleation is necessary

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FIGURE 29-48 Multiple, diffuse to coalescing areas of iridal hyperFIGURE 29-47 Note the anisocoria in this patient. Pupillary light reflexes were also abnormal, and the degree of anisocoria changed over time. These features are suggestive of feline spastic pupil syndrome, which is thought to be due to neuritis of cranial nerve 3, induced by feline leukemia virus. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

pigmentation, highly suggestive of diffuse iris melanoma. At this stage, where the only ocular change is iridal hyperpigmentation, determining if these lesions are due to benign melanosis or malignant melanoma is highly challenging. Referral is recommended. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

to reduce pain, permit cessation of medical therapy and frequent recheck examinations, minimize risk of intraocular sarcoma development (discussed later in this chapter), and allow a histologic diagnosis that may permit more appropriate treatment of the opposite eye.

Spastic Pupil Syndrome Spastic pupil syndrome (SPS) is a condition unique to cats in which clients report anisocoria, which may sometimes be transient and independent of ambient light levels (Figure 29-47). Clinically, cats with SPS appear to be healthy, are visual, and have no ocular abnormalities besides unusual behavior of the pupils. Clinical examination reveals anisocoria, failure to achieve complete mydriasis in dark conditions, and sluggish PLRs; however, examination findings can be normal because signs may be transient. It is claimed that all cats with SPS test positive for FeLV, although this is not always the case at the initial examination. The lesion is proposed to result from virally induced neuritis involving cranial nerve 3. No treatment is possible, and the prognosis for long-term survival is poor.174

Uveal Neoplasia Few primary intraocular tumors have been documented in cats. These include iridociliary epithelial tumors,145 melanoma,143 feline ocular sarcoma (FOS),49 and perhaps extramedullary plasmacytoma.126 Ultimately, an eye with a suspected primary neoplastic process should be removed after a thorough physical examination and diagnostic workup are performed to rule out obvious systemic metastasis. However, both diffuse iris

FIGURE 29-49 Diffuse iris melanoma. Although histology is ultimately required to confirm a diagnosis, the raised nature of the melanotic lesions and the dyscoria are highly suggestive of a malignant process. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

melanoma (DIM) and FOS have special considerations that warrant specific discussion. They are considered to be the two most common and most significant primary intraocular tumors in cats. FOS is discussed in the upcoming section on diseases of the lens.

Iris Melanoma DIM is the most common primary intraocular tumor in cats.130 Unlike dogs with intraocular melanoma, which typically develop a discrete raised mass on their anterior iris face, cats most commonly demonstrate diffuse and insidious iridal melanosis with little or no projection above the iris surface (Figures 29-48 and 29-49). Clinical recognition in the early stages of disease can be difficult

because of the similar appearance of benign iris melanosis, a common aging change in cats.50 Definitive diagnosis is further complicated by the difficulty of obtaining an iris biopsy, as well as the potential for benign areas of melanosis to later undergo transformation into malignant melanoma.56,130 Until better methods to differentiate these syndromes are discovered, practitioners and owners must sometimes elect to remove an eye that potentially has only benign melanosis or risk metastatic disease by delaying removal of an eye containing neoplastic cells. No breed or gender predilection exists, but the average affected cat is middle-aged to older, presenting at an average age of 11 years.12,143 DIM usually first appears as a focal area of brown iridal hyperpigmentation.1,50,53,130 In the early stages distinguishing between DIM and benign iris melanosis is sometimes impossible.50 The appearance of early DIM may remain static for months or years, but it is ultimately progressive, resulting in visible enlargement of iridal discoloration.1,56 Although DIM has no pathognomonic clinical features, thickening of the iris, hyperpigmentation extending beyond the anterior iris surface, and alterations of pupillary function increase the suspicion for melanoma.12,130 Without treatment, there is progressive infiltration of the anterior uvea and ocular drainage pathways, eventually resulting in uveitis and secondary glaucoma.53,130,200 Diode laser photocoagulation, as reported for the treatment of focal areas of iridal hyperpigmentation in dogs,33 has not been recommended for cats because of incomplete destruction and potentially dispersal of neoplastic cells and tissue. One reasonable management approach is to monitor areas of iris color change over time. Photographic documentation of such lesions is extremely helpful. However, because of the risk of metastatic disease, enucleation is ultimately the recommended treatment for enlarging iridal hyperpigmentation.53,56,98,130 Latency times of up to a few years have been reported for metastatic disease, with documented metastatic rates as high as 62.5%.143 The liver is the most common site for metastatic disease; however, lungs, regional lymph nodes, and other sites may also be affected.14,56,130,143 A thorough diagnostic workup is therefore recommended before surgery. Enucleation should be performed early in the disease course.98 Although this may risk removal of eyes with subsequent histologically diagnosed benign iridal melanosis, this risk should be weighed against treatment delay, given the fact that survival time decreases with progressive tumor infiltration into the uvea.98 Compared with a control group, equivalent survival times were achieved when enucleation was performed while the melanoma was confined to the iris stroma.56,98 In contrast, tumor infiltration into the ciliary body or drainage pathways, especially with development of glaucoma, strongly correlates with markedly


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decreased survival time.56,98 Although increased metastatic rate is associated with high mitotic index and evidence of scleral invasion,56,98 cellular characteristics such as cell shape, nucleus to cytoplasm ratio, number of nucleoli, and melanin content do not appear to be of value for determining prognosis.56 Amelanotic DIM has been described and presents similarly to the classical DIM except that the discoloration appears gray rather than brown.17 Clinical progression and potential for metastasis should be considered to be the same as for classical DIM. A second variant, atypical ocular melanoma, has also been reported. Unlike DIM, atypical ocular melanoma originates from multiple areas within the uveal tract and may have a more aggressive clinical course.81 Cats with atypical ocular melanoma had neoplastic infiltration of the entire uveal tract and sclera at the time of initial presentation,81 whereas in DIM neoplastic cells remain in the anterior uvea. At this time it is not clear if the advanced nature of disease at presentation was due to more aggressive behavior at the cellular level or a result of tumor arising from the posterior, rather than anterior, uvea. Iris melanoma can be experimentally induced after anterior chamber inoculation with FeLV and feline sarcoma virus (FeSV), leading to speculation that these viruses may play a role in the development of DIM.4,5 An association has been documented between naturally arising DIM and FeLV/FeSV; however, this was seen in a minority of cases of one study only.175 At this time there is no evidence that FeLV or FeSV is involved in the pathogenesis of DIM.37

Secondary Intraocular Neoplasia Any systemic neoplastic process has the potential to metastasize to the eye. Intraocular metastases secondary to SCC, pulmonary adenocarcinoma, hemangiosarcoma, and lymphosarcoma have been documented.32,34,68,99 Of these, lymphosarcoma is by far the most common204 (Figure 29-50). Because hematogenous spread appears to be the main route into the eye, metastatic intraocular neoplasia first affects the uvea.27,54,68 In cats choroidal metastases may occur more often than metastases to the anterior uvea.54 A discrete uveal mass is possible; however, more diffuse metastases with signs of uveitis are more common.34,54 In fact, uveitis may be the first clinical sign of underlying systemic neoplasia.34 For this reason systemic neoplasia should always be considered when evaluating a patient presenting with uveitis. Thorough physical examination and diagnostic investigation are essential, as for all other cases of uveitis. Ocular ultrasound is useful when intraocular structures are not easily seen on clinical examination. Although rare, intraocular metastasis of pulmonary adenocarcinoma warrants special mention because of its unique presentation in cats. In addition to the nonspecific signs of uveitis,

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FIGURE 29-50 Dyscoria due to an iridal mass in the right eye of a cat. The histopathologic diagnosis was lymphosarcoma. (Image courtesy WCVM Ophthalmology service.)

FIGURE 29-51 Incomplete cataract involving the lens nucleus. (Image courtesy UC Davis Veterinary Ophthalmology Service).

this tumor causes characteristic wedge-shaped areas of fundic discoloration resulting from ischemic chorioretinopathy.27 Treatment for metastatic intraocular neoplasia should include both nonspecific treatment for uveitis as well as treatment of the underlying neoplastic process. With tumors that are responsive to chemotherapy (in particular, lymphosarcoma), the reduction in uveitis tends to correlate well with response of the tumor at extraocular sites and is often dramatic. By contrast, ocular tissues do not tolerate irradiation, and so radiation-responsive intraocular tumors often necessitate enucleation as a palliative measure.

DISEASES OF THE LENS Cataract and Lens Luxation The most common diseases of the feline lens are cataract and lens luxation, both of which occur as primary syndromes much less frequently in cats than in dogs70 (Figure 29-51). Rather, in cats both diseases tend to occur as a result of chronic uveitis; therefore patients should be thoroughly examined for signs of uveitis and its causes. Diabetic cats rarely develop cataracts, presumably because of decreased aldose reductase centrations in the feline lens compared with the canine lens.159 Congenital cataracts have been reported in conjunction with such ocular abnormalities as eyelid agenesis, microphakia, and Chédiak–Higashi syndrome but are also considered to be uncommon.2,31,128 Primary lens luxation is believed to occur in cats, but peer-reviewed descriptions do not exist and a breed predilection has not been reported. Instead, lens dislocations in the cat occur secondary to other ocular disease, such as uveitis, glaucoma, and senile zonular degeneration165 (Figure 29-52). Treatments for cataracts and lens luxation are similar to

FIGURE 29-52 Complete cataract and anterior lens luxation in the left eye of a cat. The lens is seen anterior to the iris. Note the superficial corneal vessels, which are commonly seen with lens luxation. Serology indicated that this cat was positive for feline immunodeficiency virus. Lens luxation in cats is associated with uveitis, cataract, and glaucoma and should initiate referral. If the eye is irreversibly blind, enucleation with histopathology should be performed. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

those for dogs and require referral to a veterinary ophthalmologist.

Feline Ocular Sarcoma FOS is an aggressive ocular tumor resulting in tumorrelated death of the majority of affected cats. Because of this, many ophthalmologists strongly recommend enucleation of blind and painful feline globes, regardless of cause, to prevent subsequent malignant transformation to FOS. For these reasons, this tumor warrants special mention here. Most cats diagnosed with primary ocular sarcoma have a known history of trauma to the affected eye


FIGURE 29-53 An intraocular mass has caused glaucoma, buphthalmos, and rupture of the right eye of this cat. Histopathology identified this tumor to be feline ocular sarcoma that had migrated into the orbit. The orbit was exenterated as a palliative measure, but the owner was warned to expect tumor recurrence and death as a result of local invasion and recurrence. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

several years prior.* For this reason FOS is sometimes referred to as posttraumatic intraocular sarcoma. Chronic uveitis and intraocular injections have also been reported as precursors to the development of FOS.180 Quite often, the affected eye has been blind for several years, and the reason for presentation is a change in the appearance of the eye.52,77 Cats rarely show overt signs of discomfort at the time of presentation.49,51 Clinical examination often shows an opaque cornea.49,52,77 An anterior chamber mass can sometimes be appreciated, but intraocular structures are often difficult to discern52,77,180 (Figure 29-53). Ultrasound may be useful for confirmation of an intraocular mass when clinical examination is limited. The affected globe may also have an abnormal shape; quite frequently, the globe is phthisical or buphthalmic.9,52 Histologically, there is obliteration of normal architecture of globes from cats with FOS.† Neoplastic cells tend invade the sclera, preferentially exiting the globe at the posterior pole/optic nerve and the limbus.49,52,146 Severe pathology of the lens, particularly lens rupture, has been found in almost all cases.49,52,146 Although the origin of FOS was unknown for years, it is now accepted that the tumor arises from lens epithelial cells.26,55,209 It is believed that the anterior epithelium of the lens undergoes a malignant transformation in response to trauma in a manner similar to the development of fibrosarcoma at sites of vaccination.209 FeLV and FeSV are not believed to play a role in the pathogenesis of FOS.37 Given the relationship between FOS and lens rupture, cats with perforating lens injury should be referred for *References 9, 49, 52, 55, 77, 146. †

References 9, 52, 53, 77, 146, 180.

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FIGURE 29-54 Clinical signs of globe perforation. Note the anterior synechiae at the 9 o’clock position, indicating corneal perforation. Dyscoria is a result of posterior synechiae along the lateral pupillary margin, consistent with uveitis. The presence of melanin on the anterior lens capsule and within the lens as well as early cataract are highly suggestive of lens capsule perforation. This cat is at risk of developing of developing feline ocular sarcoma. (Image courtesy WCVM Ophthalmology Service.)

treatment immediately and followed up rigorously for life. Treatment options include medical management, phacoemulsification, or enucleation. A small lens capsule perforation may self-seal and respond to medical management for the associated uveitis; however, the liberation of lens material into the eye necessitates long-term follow-up for these patients. Larger lens capsule ruptures require either phacoemulsification to remove free lens material from the eye or enucleation (Figure 29-54). Development of FOS has been reported in cats that previously underwent surgical lens extraction.55 Although development of FOS has not been reported after phacoemulsification specifically, its development is theoretically possible, thus necessitating long-term follow-up. Likewise, cats with a known history of ocular trauma should also be monitored closely because of the potential for FOS. Clinical suspicion of an intraocular mass or observation of a phthisical globe in a cat, especially one known to have undergone ocular trauma, should prompt the clinician to recommend enucleation after diagnostic investigation for metastatic disease. Although it is not known if early enucleation decreases the mortality rate, treatment should not be delayed because of the aggressive nature of the disease. In the vast majority of reported cases, patients died from tumor-related disease within months of enucleation as a result of local invasion of the orbit, extension along the optic nerve into the central nervous system, or metastatic disease.9,49,52,77,146 At this time, there are no reports of adjunctive treatments, such as radiation or chemotherapy, for the management of FOS.

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GLAUCOMA It is essential to measure IOP during every ophthalmic examination to avoid overlooking a diagnosis of glaucoma, especially because glaucoma can be a very subtle and insidious disease in cats. In contrast to dogs, glaucoma occurs infrequently in the cat, and secondary glaucoma is far more common than primary glaucoma.18,160,200 In addition, the rare aqueous humor misdirection syndrome (AHMS) arises naturally in cats but has not yet been reported in dogs. Although any animal can be affected, the typical feline patient with glaucoma is middle-aged or older.18,41,78,160,190 Because clinical signs of feline glaucoma tend to develop gradually rather than acutely, irreversible blindness is frequently present by the time of presentation for ophthalmic evaluation.18,160 Cats often do not develop obvious corneal edema or overtly red eyes in the same manner that dogs do. Instead, the most common findings on initial presentation include absent menace response, absent PLR, and buphthalmos.18 A diagnosis of glaucoma is made on the basis of IOP measurements greater than 25 to 30 mm Hg combined with evidence of ocular abnormalities (Figure 29-55). A single elevated IOP reading, in the absence of clinical signs, should not be used to make a diagnosis of glaucoma. Tonometry technique, excessive neck pressure, diurnal variation, and fractious patients can all contribute to elevated readings.45,102 Eyes should be re-evaluated if IOP is greater than 25 mm Hg or there is a greater than 12 mm Hg difference between eyes.102 As mentioned previously in this chapter, the neuro-ophthalmic examination will be abnormal. Retinal degeneration may be present if disease is advanced. Optic disc cupping, a feature of canine glaucoma, is often difficult to appreciate in the cat because of the unmyelinated nature of the feline optic disc. Because the vast majority of feline glaucoma is secondary to anterior uveitis and intraocular neoplasia,18,200 abnormalities such as aqueous flare, cataract, intraocular mass, or iris discoloration are often also present. Primary glaucoma is possible if such clinical findings are absent, although this condition is rare.18,96,200 Referral for gonioscopy is necessary to make the diagnosis of primary glaucoma. AHMS is a rare condition arising from misdirection of aqueous humor into the vitreous cavity instead of into the posterior then anterior chambers and out through the iridocorneal angle. The pathogenesis for this condition is not well understood. It is hypothesized that a defect of the anterior hyaloid membrane acts as a one-way valve, allowing aqueous humor to enter, but not exit, the vitreous cavity. As pressure builds up within the vitreous, the lens and anterior uvea are anteriorly displaced. As a consequence of this shift, there is increased iris–lens contact, producing mydriasis and

A

B FIGURE 29-55 A, Uveitis and marked secondary glaucoma in the right eye of a cat. Despite the intraocular pressure in the right eye being 73 mm Hg, the signs of discomfort, mydriasis, and visible ophthalmic abnormalities are minimal. Signs to look for in this cat are mydriasis, subtle corneal edema, and episcleral injection, none of which can be associated with conjunctivitis alone. Note too that buphthalmos is evident only when the entire head is viewed and symmetry of the globes is assessed. B, Finally, note the difference in tapetal reflection between the eyes. This subtle change is sometimes the most obvious sign of ophthalmic disease, usually indicates serious intraocular disease, and should therefore never be ignored. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

reduced flow of aqueous humor to the anterior chamber as a result of “pupillary block,” which further exacerbates ocular hypertension. Patients with AHMS present with similar neuro-ophthalmic examination abnormalities as cats with other forms of glaucoma.41 Ophthalmic findings required for diagnosis of AHMS include intact lens zonules, juxtaposition of the ciliary body, consolidated anterior vitreous face, narrow approach to the iridocorneal angle, and a uniformly shallow anterior chamber.41 Compared with the other examination findings, a uniformly narrow anterior chamber is more easily recognized in a general practice setting and is the characteristic sign of AHMS41 (Figure 29-56). The uniform narrowing helps differentiate between AHMS and glaucoma due to other causes. In other forms of glaucoma,

FIGURE 29-56 A narrow anterior chamber is characteristic of aqueous humor misdirection syndrome. The slit beam of the direct ophthalmoscope helps identify the narrowed distance between the bright reflections off the cornea and the anterior lens capsule. In this cat the presence of an anterior cortical cataract also helps demonstrate forward displacement of the lens. This cat’s intraocular pressure was 40 mm Hg but responded well to phacoemulsification and anterior vitrectomy. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

buphthalmos causes deepening of the anterior chamber. With iris bombé, the peripheral anterior chamber narrows but the central anterior chamber remains deep. The IOP in patients with AHMS is elevated, sometimes markedly so. However, unlike most other forms of glaucoma wherein pharmacologic mydriasis causes a further elevation in IOP, the IOP of some patients with AHMS may be reduced by pupil dilation because of a reduction in pupillary block. AHMS may occur unilaterally at first but often becomes bilateral. Regardless of cause, treatment of glaucoma should always address the underlying disease if identified. Because many of these primary conditions are intractable, feline glaucoma is usually advanced at presentation, and few antiglaucoma medications are effective in the cat, feline glaucoma is particularly challenging to treat. Medical control of IOP is achieved in 21% to 58% of treated eyes.18,160 The carbonic anhydrase inhibitor dorzolamide appears to be one of the most useful antiglaucoma drugs for cats. Topical carbonic anhydrase inhibitor therapy is preferred over systemic therapy because of the susceptibility of cats to adverse systemic effects. Dorzolamide is effective for lowering IOP when applied twice daily; however, 4 or 5 days of therapy are needed to reach a reliable decrease.154 Dorzolamide may also be administered in combination with timolol twice daily, although the additional benefit of timolol appears to be marginal.46 The carbonic anhydrase inhibitor brinzolamide is ineffective in cats,74 as are the prostaglandin analogs bimatoprost, unoprostone, and latanoprost, which are quite successful in dogs.10,183 The hypotensive effect of travoprost in cats is not known. Although prostaglandin analogs do not effectively decrease IOP, they


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do induce miosis in cats as they do in dogs. Pilocarpine also has hypotensive effects in cats201; however, on account of its propensity to induce uveitis,101 as well as systemic side effects, its use is generally discouraged.41 Mydriatics are generally contraindicated in glaucoma. Although atropine therapy is a vital component of the treatment of aqueous misdirection in humans, beneficial effects of mydriatic therapy for AHMS have not been demonstrated. In one study application of tropicamide was followed by an increase in IOP.41 Use of miotics such as pilocarpine and timolol may worsen glaucoma associated with AHMS and should therefore be avoided. Unfortunately, cyclodestructive procedures appear to provide limited benefit in cats, perhaps because they exacerbate or fail to address the underlying inflam mation present in most cases.78,160 A combination of lensectomy by phacoemulsification in association with posterior capsulotomy and anterior vitrectomy appears to permit redirection of aqueous from the vitreous and correct pupillary block and narrowing of the anterior chamber and holds promise for the control of IOP in AHMS.41 When medical and surgical interventions fail to control IOP, enucleation should be performed for all blind globes that appear to be causing pain.

CHORIORETINAL DISEASE Hypertensive Chorioretinopathy Because it is an end organ, the eye is susceptible to damage resulting from systemic hypertension. Specifically, persistently elevated blood pressure causes pathology to the retina, choroid, and optic nerve. Hypertensive retinopathy is a blanket term used to describe all the ocular lesions arising from damage to these structures. Incidence of ophthalmic lesions in hypertensive cats has been estimated to be as high as 60% to 77%.57,176 A short review of anatomy may assist in understanding pathogenesis (Figure 29-57). Briefly, vessels are located in only the innermost layers of the feline retina. The outermost retina is highly metabolically active but avascular. The choriocapillaris is a network of capillaries supplying choroidal blood to the outer retina. Although the choroidal vasculature is permeable to most substances, the blood–ocular barrier prevents entry of solutes and fluid into the retina from the choroid and systemic circulation. Exclusion of substances from the retina assists in maintaining retinal attachment. Hypertensive ocular lesions ultimately arise from ischemic injury to vessel walls. In the face of chronically elevated blood pressure, autoregulatory mechanisms within the retina become deranged and there is leakage of angiotensin II into both the extracellular choroidal space and optic nerve. Consequently, there is vasoconstriction of the retinal vessels, choriocapillaris, and

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SECTION IV Feline Internal Medicine N/S retina Tapetum Sclera RPE Choroid

FIGURE 29-57 Normal anatomy of the feline fundus, including the sclera, choroid proper, tapetum (which is actually part of the choroid), retinal pigment epithelium, and neurosensory retina. The blood–retinal barrier normally prevents solutes and fluid from entering the potential space between the retinal pigmented epithelium and the neurosensory retina. Leakage of substances from the choroidal vasculature into this potential space results in retinal detachment.

FIGURE 29-58 Evidence of retinal detachment can often be seen during retroillumination, before performing the fundic examination. In this patient complete, bilateral retinal detachment has resulted in mydriasis, and the retinal vessels can be seen in focus immediately posterior to the lens. (Image courtesy WCVM Ophthalmology Service.)

vessels supplying the optic nerve. The ischemic damage resulting from prolonged vasoconstriction causes vessel wall necrosis and leakage of fluid from these vessels. Clinically, these changes are manifested as retinal edema, retinal hemorrhage, and serous retinal detachment (Figures 29-58 and 29-59). Papilledema, seen in other species, has not been reported in cats.35 The magnitude and duration of blood pressure elevation required to induce ocular lesions is not known. In one study hypertensive ocular lesions were associated with systolic blood pressure measurements above 168 mm Hg164; however, the majority of studies show the systolic blood pressure in most cats with hypertensioninduced ocular lesions to be above 200 mm Hg.107,129,163,191

FIGURE 29-59 Complete retinal detachment and multiple retinal hemorrhages are characteristic findings in cats with systemic hypertension, with vision loss being the most frequent reason for presentation to a veterinarian. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

Ocular lesions may be more likely to develop after pronounced hypertension of prolonged duration, and hypertensive cats with ocular lesions have significantly higher blood pressure than hypertensive cats without ocular lesions.29,129 For cats with ocular lesions, no significant difference was found between systolic blood pressure of cats presenting with retinal detachment (and acute blindness) compared with that of cats that did not present with acute blindness.57 Hypertensive cats with ocular lesions are likely to have more severe cardiac pathology than hypertensive cats without ocular lesions.29 The typical cat with systemic hypertension is older than 10 years of age.107,129,164,176 Gender predilections have been suggested but not confirmed.107,164 The most common reason for presentation is acute blindness.57,107,163 In fact, in many patients ocular disease is the first indicator of systemic disease.186 Serous retinal detachment, usually accompanied by retinal hemorrhage, is the most common examination finding, supporting the notion that choroidal pathology accounts for the majority of ocular lesions in cats.113 Other common examination findings include resting mydriasis, slow to absent PLRs, hyphema, iris hemorrhage, retinal edema, and retinal vessel tortuosity (see Figure 29-59). Systemic hypertension should be considered in all cats presenting with intraocular hemorrhage or retinal detachment. A thorough diagnostic work up is essential. Diagnosis of hypertensive retinopathy is confirmed when systolic blood pressure measurements exceed 160 to 170 mm Hg and potential causes of posterior uveitis have been excluded. Chronic renal failure is the most common underlying disease associated with systemic hypertension.107,113,129,176 Primary hypertension and

hypertension associated with hyperthyroidism, diabetes mellitus, and hyperaldosteronism should also be considered, but these occur less frequently.113,176,193 Antiinflammatory treatment should be considered in cats with anterior segment disease. Corticosteroids are preferred over NSAIDs, which can exacerbate bleeding. To prevent potential systemic effects of corticosteroid therapy, these should be administered topically.150 Ultimately, the most important components of treating hypertensive retinopathy are control of blood pressure and treatment of any underlying disease. Medical control of blood pressure will allow for improvement of hypertensive ocular lesions in the majority of patients.57,107,113,129,191 In recent years the calcium channel blocker amlodipine besylate has emerged as a successful treatment for systemic hypertension and related ocular lesions. At doses ranging from 0.625 to 1.25 mg orally, every 12 to 24 hours, amlodipine may be more effective than other classes of drugs for reduction of intraocular hemorrhage and retinal edema and reattachment of serous retinal detachments.113 For further discussion about the treatment of systemic hypertension, please see Chapter 20. Prognosis for return to vision depends on both duration and severity of ocular lesions. Mild retinal edema and hemorrhage, without retinal detachment, may completely resolve with successful control of blood pressure.113 Prognosis becomes guarded if retinal detachment is present. Histologically, retinal degeneration is visible within 1 hour of detachment, and extensive photoreceptor damage occurs within 2 weeks.60 Therefore, although retinal reattachment is possible with medical management, many cats remain blind or visually impaired due to the retina becoming irreversibly degenerated while detached.113,129 Prognosis is also guarded in cats with intraocular hemorrhage, particularly hyphema, because of the increased potential of secondary glaucoma.163

Enrofloxacin Toxicity Accounts of blindness in association with enrofloxacin administration in cats were rare until almost a decade after Baytril was first approved by the Food and Drug Administration for use in dogs and cats; these reports appeared to coincide with a labeling change that allowed higher doses to be given to cats. Subsequent toxicologic studies have confirmed that retinal degeneration is dose related rather than idiosyncratic and led to a maximum recommended oral dose of 5 mg/kg per day for cats. Blindness of rapid onset, sometimes as soon as 4 days into treatment, and mydriasis are the typical signs noted by owners. Clinical findings included absent menace responses, sluggish to absent PLRs, variable degrees of tapetal hyperreflectivity, and retinal vascular attenuation64 (Figure 29-60). Electroretinography has confirmed reduction in retinal function as early as 24 hours after initiation of therapy at 50 mg/kg per day.63 No common


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FIGURE 29-60 Tapetal hyperreflectivity and marked retinal vascular attenuation are indicators of advanced retinal degeneration in this cat. Although these signs are pathognomonic for retinal degeneration, they do not permit definitive diagnosis of a cause, which may include taurine deficiency, progressive retinal atrophy, enrofloxacin toxicity, glaucoma, and severe and prolonged previous retinal detachment from any cause. Reaching an etiologic diagnosis requires a complete history and ophthalmic and general physical examination. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

signalment, duration of therapy, or underlying medical condition for which enrofloxacin was prescribed has been noted.64 In one study oral enrofloxacin doses ranged from 4.6 mg/kg once daily to 27 mg/kg twice daily.64 After cessation of treatment, a limited amount of vision was preserved or regained in four cats. At higher doses (50 mg/kg daily), some cats also demonstrate neurologic signs.63 Although the exact mechanism by which enrofloxacin exerts its effects is not known, hypertensive retinopathy does not appear to be a contributing cause.63 Although a dose of 5 mg/kg daily is in accordance with the manufacturer’s recommendations, retinal degeneration may still be possible at this dose.64 Several factors, such as large drug doses or plasma drug concentrations, rapid intravenous infusion, prolonged treatment, and advanced patient age, may increase the risk of toxicity.199 In particular, cats older than 12 years are more likely to experience adverse effects than are cats younger than 9 years, perhaps because of a higher incidence of hepatic or renal disease causing impaired drug clearance.199 Exposure to ultraviolet A light during treatment, drug interactions, and drug accumulation (secondary to impaired metabolism or clearance) may also increase the likelihood of retinal degeneration.199 A study conducted in 2- to 8-week-old kittens found that oral administration of enrofloxacin at a dose of 5 mg/kg daily failed to achieve therapeutic plasma concentrations but that parenteral administration was successful in achieving target plasma concentrations.169 This study also suggested that doses higher than 5 mg/kg per day were necessary. This was attributed to the

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differences in volume of distribution and drug clearance in kittens compared with adult cats. No ocular lesions were found in this study. It is worth noting, however, that at this time the manufacturer’s label indicates that enrofloxacin should not be used in kittens younger than 12 weeks of age and that parenteral administration is not licensed in cats. Because there is no treatment for enrofloxacin toxicity and the vast majority of cats remain permanently blind, practitioners must exercise caution when dispensing fluoroquinolones to cats. Selection of a fluoroquinolone should be made only after culture and sensitivity testing confirms that alternative antibiotics are not suitable. A complete ophthalmic examination, including a fundic examination, should be performed before and after treatment. Owners should be warned of the potential for adverse effects. Should signs of mydriasis, altered PLRs, or visual impairment be noted, treatment should be stopped immediately and the cat brought in for evaluation. Enrofloxacin oral doses in cats should never exceed a maximum of 5 mg/kg per day, and duration should not exceed the manufacturer’s recommendation of 2 to 3 days beyond cessation of clinical signs. Caution is especially warranted in patients of advanced age or those with concurrent medical conditions that may impair drug metabolism or elimination. Enrofloxacin is not approved for parenteral use in cats; therefore offlabel use of injectable enrofloxacin should be avoided.

FIGURE 29-61 A focal, elliptical area of tapetal hyperreflectivity dorsolateral to the optic disc is one of the early signs of taurinedeficient retinopathy. This would be considered stage 2 degeneration in a 5-stage scaling system. (Image courtesy UC Davis Veterinary Ophthalmology Service.)

Taurine-Deficient Retinopathy In the 1970s several authors demonstrated that cats fed taurine-deficient diets showed funduscopic evidence of retinal degeneration and decreased retinal function. In the following years, naturally arising cases of taurinedeficient retinopathy were documented. In particular, this syndrome was recognized in cats fed dog food, which tends to have minimal taurine concentrations.3 Since then, the practice of feeding dog food to cats has largely stopped, and because most cat foods contain adequate levels of taurine,178 retinopathy secondary to dietary taurine deficiency is relatively rare. However, with the increased interest in homemade pet diets, the potential for resurgence of this condition remains. Recognition of this condition is important not only for prevention of blindness but also for prevention of dilated cardiomyopathy; another disease associated with taurine deficiency.148 Because the half-life of retinal taurine is protracted, it may take several months of dietary deficiency for retinal degeneration to occur.167,168 Early signs of taurinedeficient retinopathy are similar to those of early progressive retinal atrophy. The first abnormality is a granular appearance to the area centralis, followed by the development of hyperreflectivity167 (Figures 29-61 and 29-62). If taurine deficiency is corrected, this is the

FIGURE 29-62 Prolonged taurine deficiency has led to stage 3 retinal degeneration with hyperreflective regions dorsolateral and dorsomedial to the optic disc. Continued dietary deficiency will lead to complete retinal degeneration (stage 5). (Image courtesy UC Davis Veterinary Ophthalmology Service.)

limit of the fundic changes; however, with continued dietary deficiency, extension of degeneration to the midperipheral retina is possible. Should the clinician suspect dietary taurine deficiency in a cat with retinal degeneration, confirmation of low plasma taurine is warranted. If plasma taurine is demonstrated to be low, dietary supplementation is required. With supplementation partial reversal of retinal degeneration is possible in cats with mild to moderate stages of disease, but prevention of further progression is the major therapeutic goal.85,86


Progressive Retinal Atrophy Inherited retinal degeneration or dysplasia (often grouped together as progressive retinal atrophy) occurs in cats, particularly the Abyssinian and Persian breeds.39,134,153 An autosomal recessive, early onset retinal photoreceptor dysplasia is seen in Persian cats and as an autosomal dominant condition in Abyssinian cats as early as 2 to 3 weeks of age.39,153 In the Persian the earliest ocular abnormalities are subtly diminished PLRs at 2 weeks of age, progressing to minimal PLRs and resting mydriasis by 17 weeks of age. Funduscopic signs of retinal degeneration, such as retinal vascular attenuation, tapetal hyperreflectivity, and optic nerve head darkening, are minimal at 4 to 5 weeks but marked by 17 weeks of age. In the Abyssinian early onset retinal degeneration is a result of an autosomal dominant photoreceptor dysplasia.39 As with the Persian, abnormal PLRs are first noted at approximately 2 to 3 weeks of age, but the terminal stage of disease is not reached until approximately 1 year of age.39 Nystagmus accompanies this form of retinal degeneration.39 A later onset autosomal recessive retinal degeneration also occurs in the Abyssinian. Early ophthalmoscopic evidence of retinal degeneration is visible at approximately 1.5 to 2 years of age, in the form of a gray discoloration of the peripapillary fundus and the area centralis in particular.134 Disease progression is much slower than for early onset disease, with terminal stages being reached at approximately 3.5 to 4 years of age.134 No treatment is possible for any of these conditions. Affected animals should not be bred.

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194. Veith LA, Cure TH, Gelatt KN: The Schirmer tear test—in cats, Mod Vet Pract 51:48, 1970. 195. Volopich S, Benetka V, Schwendenwein I et al: Cytologic findings, and feline herpesvirus DNA and Chlamydophila felis antigen detection rates in normal cats and cats with conjunctival and corneal lesions, Vet Ophthalmol 8:25, 2005. 196. von Bomhard W, Polkinghorne A, Lu ZH et al: Detection of novel chlamydiae in cats with ocular disease, Am J Vet Res 64:1421, 2003. 197. Ward D, McEntee M, Weddle D: Orbital plasmocytoma in a cat, J Small Anim Pract 38:576, 1997. 198. Weiss R: Synergistic antiviral activities of acyclovir and recombinant human leukocyte (alpha) interferon on feline herpesvirus replication, Am J Vet Res 50:1672, 1989. 199. Wiebe V, Hamilton P: Fluoroquinolone-induced retinal degeneration in cats, J Am Vet Med Assoc 221:1568, 2002. 200. Wilcock B, Peiffer R, Davidson M: The causes of glaucoma in cats, Vet Pathol 27:35, 1990. 201. Wilkie D, Latimer C: Effects of topical administration of 2.0% pilocarpine on intraocular pressure and pupil size in cats, Am J Vet Res 52:441, 1991. 202. Williams D, Kim J: Feline entropion: a case series of 50 affected animals (2003-2008), Vet Ophthalmol 12:221, 2009. 203. Williams D, Robinson J, Lay E et al: Efficacy of topical aciclovir for the treatment of feline herpetic keratitis: results of a prospective clinical trial and data from in vitro investigations, Vet Rec 157:254, 2005. 204. Williams LW, Gelatt KN, Gwin RM: Ophthalmic neoplasms in the cat, J Am Anim Hosp Assoc 17:999, 1981. 205. Wolfer J: Correction of eyelid coloboma in four cats using subdermal collagen and a modified Stades technique, Vet Ophthalmol 5:269, 2002. 206. Wray JD, Doust RT, McConnell F et al: Retrobulbar teratoma causing exophthalmos in a cat, J Feline Med Surg 10:175, 2008. 207. Wyman M, Starkey R, Weisbrode S et al: Ophthalmomyiasis (interna posterior) of the posterior segment and central nervous system myiasis: Cuterebra spp. in a cat, Vet Ophthalmol 8:77, 2005. 208. Yang S-H, Liu C-H, Hsu C-D et al: Use of chemical ablation with trichloroacetic acid to treat eyelid apocrine hidrocystomas in a cat, J Am Vet Med Assoc 230:1170, 2007. 209. Zeiss C, Johnson E, Dubielzig R: Feline intraocular tumors may arise from transformation of lens epithelium, Vet Pathol 40:355, 2003.

C H A P T E R

30

Respiratory and Thoracic Medicine O U T L I N E Neoplasia, 877 Lower Respiratory Tract Infections, 877 The Thoracic Cavity, 892 General Considerations, 892 Clinical Signs, 892 Physical Examination, 892 Pleural Effusion, 892 Causes of Pleural Effusion, 895 Pneumothorax, 906 Diaphragmatic Hernia, 907 Chest Wall Pathology, 909

The Upper Respiratory Tract, 846 Clinical Signs, 846 General Diagnostics, 847 Disease-Specific Recommendations: The Nasal Cavity, 851 Disease-Specific Recommendations: The Larynx, 858 Lower Respiratory Tract Diseases, 861 Clinical Signs, 862 Diagnostics, 862 Lower Respiratory Tract Diseases, 866 Asthma and Chronic Bronchitis, 866 Other Noninfectious Lower Respiratory Tract Disease, 875

CLINICAL SIGNS

THE UPPER RESPIRATORY TRACT Nasal Disease

Jessica Quimby and Michael R. Lappin Clinical signs of upper respiratory tract disease, including sneezing and nasal discharge, are common in cats (Box 30-1). Some diseases are associated with sneezing, and others are more commonly associated with stertorous breathing, with or without gagging. Coughing can sometimes be present, as well as epiphora, halitosis, dysphagia, and nonspecific signs such as lethargy, inappetence, and weight loss.1,12,33 Laryngeal disease is rare in the cat but may present as acute or chronic dyspnea, stridor, dysphagia, and signs of upper airway obstruction.84 Common causes of upper respiratory disorders in cats include trauma, foreign bodies, infectious agents, brachycephalic syndrome, inflammatory polyps, tooth root infections or other oral disease, nasopharyngeal stenosis, chronic rhinosinusitis, and neoplasia.1,12,33 The most common causes of laryngeal disease in the cat are laryngeal paralysis and laryngeal neoplasia.92 A complete diagnostic workup is important to determine the etiology so that the treatment regimen can be appropriately directed and maximal response to therapy is obtained.76,77


Nasal discharge is the most common clinical sign associated with nasal disease and can be serous, mucopurulent, or hemorrhagic1,12,33 (see Box 30-1). Serous nasal discharge is characteristic of most acute diseases of the nasal cavity and may precede mucopurulent nasal discharge. If the serous nasal discharge is chronic, viral and allergic etiologies are most common. Mucopurulent nasal discharge implies inflammation and occurs in association with fungal disease, primary bacterial disease, or overgrowth of normal bacterial flora secondary to any chronic nasal disease, including neoplasia, chronic rhinosinusitis, oronasal fistula, foreign body, inflammatory polyp, fungal disease, and viral disease. In addition, cats with vomiting or regurgitation can develop sneezing or nasal discharge by aspirating gastrointestinal content into the nose through the nasopharynx. Epistaxis alone is most common with trauma, acute foreign body, hypertension, and coagulopathy. Epistaxis that develops in conjunction with or after mucopurulent discharge is most common with fungal disease,

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CHAPTER 30 Respiratory and Thoracic Medicine

BOX 30-1 Differential Diagnoses for Nasal Discharge in Cats Serous Viral infection Precursor to disease with mucopurulent discharge Normal

Mucopurulent Associated with oral disease • Tooth root abscess • Oronasal fistula Nasopharyngeal polyp Foreign body Bacterial infection • Primary or secondary Viral infection • Feline herpesvirus-1 • Feline calicivirus Fungal infection • Cryptococcus spp. • Aspergillus spp. Chronic rhinosinusitis Neoplasia • Lymphoma • Squamous cell carcinoma • Adenocarcinoma

Hemorrhagic Nasal disease • Trauma • Foreign body • Chronic rhinosinusitis • Neoplasia • Fungal disease Systemic disease • Hypertension • Polycythemia • Coagulopathy • Hyperviscosity syndrome

neoplasia, oronasal fistula, and occasionally chronic foreign bodies. Vasculitis occurs in dogs with diseases such as ehrlichiosis and bartonellosis but is rare in cats. Unilateral nasal discharge is more likely with foreign bodies, oronasal fistula, and neoplasia, although the latter can become bilateral as it progresses. Bilateral discharge is nonspecific and can be found with almost any etiology.33 Sneezing is a superficial reflex that originates in the mucous membranes lining the nasal cavity and is easily induced by chemical or mechanical stimuli. The sneeze results in forceful expulsion of air that passes through

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the airways with great velocity to clear the respiratory passageways. Sneezing is a common manifestation of nasal disease but is relatively nonspecific. Stertor is a harsh, audible snoring sound associated with inspiratory breathing. Cats that experience stertor while awake are also likely to snore when sleeping. Stertor indicates airway obstruction and is most common with such conditions as nasopharyngeal polyps, nasopharyngeal stenosis, and neoplastic masses that occlude the airway. It may also occur as a result of airway occlusion caused by turbinate inflammation. Facial deformity is relatively uncommon but is usually associated with neoplastic processes and fungal infections, particularly Cryptococcus spp.1

Laryngeal Disease Laryngeal disease is rare in the cat but may present as acute or chronic dyspnea, signs of upper airway obstruction, stridor (a harsh, high-pitched sound heard on inspiration), and dysphagia. Coughing or gagging may also be appreciated, and aphonia (loss of voice) or a change in voice has been reported.84

GENERAL DIAGNOSTICS Signalment and lifestyle will often help refine the differential list and direct a diagnostic workup. Brachycephalic breeds may be predisposed to nasal disorders because of their physical conformation.85,112 Neoplasia is more likely in older cats,33 and nasopharyngeal polyps are more common in younger cats.40 Cats with outdoor access are more likely to develop foreign bodies, trauma, or infectious etiologies.33 Cats in crowded housing conditions such as catteries, shelters, and multicat households are more likely to develop acute or chronic viral or bacterial rhinitis.32 Obtaining a complete history is important for determining the duration of the clinical signs. Acute onset of clinical signs is common with viral agents, foreign bodies, and trauma. The diagnostic workup of sneezing and nasal discharge is commonly completed in three phases (Box 30-2).

Phase 1: Noninvasive Tests Most cats with acute disease are generally evaluated with noninvasive tests and therapeutic trials. A complete physical examination with careful attention to the head and neck should be performed, including ocular retropulsion. Firm resistance to retropulsion of the orbit or a painful reaction could be indicative of a retrobulbar lesion. Otic examination should be completed to evaluate for bulging or discoloration of the tympanum; these changes commonly occur with nasopharyngeal polyps. Deformation of the nose or face, exophthalmia, or pain

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BOX 30-2 Staged Workup of Upper Respiratory Disease Phase 1 (Noninvasive) History Physical exam CBC, chemistry, urinalysis Thoracic +/− cervical radiographs Cytology of nasal discharge Cryptococcus antigen titer Feline leukemia/feline immunodeficiency virus serology

Phase 2 (Sedation or Anesthesia Required) Oral, pharyngeal, and laryngeal exam Computed tomography Nasal radiography Nasal biopsy and histopathology Tissue fungal and bacterial culture

Phase 3 Exploratory rhinotomy Repetition of earlier phases

on palpation of the nasal or facial bones is most consistent with fungal disease or neoplasia.1 Oral examination should be performed to assess for dental disease that could be causing an oronasal fistula, gingivostomatitis that could be consistent with feline herpesvirus (FHV-1) or feline calicivirus (FCV) infections, and defects in the hard or soft palate. External ocular examination may reveal conjunctivitis that could indicate FHV-1, FCV, Mycoplasma spp., or Chlamydophila felis infections. Fundic examination is performed to evaluate for lesions consistent with lymphoma or Cryptococcus neoformans infection. A cold microscope slide can be placed in front of the nose to assess airflow and may aid in determining if disease is unilateral or bilateral, although this should not limit diagnostic investigation to the obstructive side of the nose because bilateral disease may be present. Although fungal organisms are uncommonly identified, cytology of nasal discharge should be performed on all cats with mucoid to mucopurulent nasal discharge to evaluate for the presence of C. neoformans, Sporothrix schenckii, or hyphae consistent with Aspergillus spp. or Penicillium spp. Neutrophils and bacteria are commonly detected if mucopurulent disease is present but do not prove primary bacterial disease. Hyphae also do not confirm primary fungal disease; they may represent contamination or infection secondary to another underlying cause. Secondary infections result in the same discharge as primary infections. If lymph nodes draining the head are enlarged, they should be aspirated to evaluate for the presence of

lymphoma, metastatic neoplasia, and fungal agents. Bacterial culture and antimicrobial susceptibility testing on nasal discharges are generally not recommended because results are difficult to interpret in that they typically yield normal intranasal bacterial flora.43 However, in respiratory outbreaks in catteries, pet stores, shelters, and multicat households, culture may be indicated to determine whether a pathogenic Bordetella bronchiseptica isolate is present. Molecular diagnostic assays are now available for many respiratory agents, including FHV-1, FCV, C. felis, Mycoplasma spp., and B. bronchiseptica. However, cats can be asymptomatic carriers of these agents, and the FHV-1, FCV, B. bronchiseptica, and C. felis assays also amplify vaccine strains of the organisms, which means that positive results do not prove a disease association. This is especially true for FHV-1 and FCV, which may have a relatively high prevalence in the healthy cat population.52,78,98 Recently, a study failed to link Bartonella spp. infection to rhinitis in cats; therefore at this time recommendations to perform Bartonella spp. serology, culture, or polymerase chain reaction (PCR) assays in cats with upper respiratory tract signs are controversial.6 If a clinician chooses to test for evidence of Bartonella spp. infection, the cat should be evaluated by serology and PCR or culture because serology alone has been shown to yield false-negative results in up to 15% of infected cats.8 In addition, because only approximately 40% of seropositive cats are currently infected, a positive serologic test result does not prove bartonellosis.8 See Chapter 33 and the subsequent sections in this chapter about individual agents for a further discussion of molecular assays. A complete blood cell count (CBC), serum biochemical panel, and urinalysis is recommended to rule out other systemic disease processes in cats with chronic disease. In general, results of the CBC are of low yield but may reveal eosinophilia in some cats with fungal or allergic disease, thrombocytopenia in some cats with epistaxis, or other cytopenias that might accompany feline leukemia (FeLV) or feline immunodeficiency virus (FIV) infections. FeLV and FIV do not cause sneezing and nasal discharge primarily, but they have been associated with lymphoma and may induce immunodeficiency that predisposes to other infections; therefore testing for these agents is indicated. A Cryptococcus antigen test is also recommended as a preliminary test for any cat with chronic nasal discharge, but particularly for those with nasal deformation, lymphadenopathy, or retinal lesions.59 Although thoracic radiographs are generally normal, they are still indicated to rule out pulmonary involvement of fungal disease and metastatic neoplasia. In cats with epistaxis, blood pressure measurement, coagulation profile, and buccal mucosal bleeding test are recommended, and thromboelastography may also be useful.


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During phase 1, therapeutic trials are commonly attempted in cats with mild disease and usually consist of antibiotics, antiviral drugs, immunomodulators, or antihistamines (see the discussions of specific diseases that follow).

Phase 2: Imaging, Biopsy, Deep Cultures If the physical examination indicates further diagnostic workup, a definitive diagnosis is not made during phase 1, or routine therapeutic trials fail, more aggressive diagnostic testing is indicated (typically requiring general anesthesia). Phase 2 diagnostics usually consist of pharyngeal and laryngeal examination, computed tomography (CT) scan or skull and dental radiographs, rhinoscopy, bacterial and fungal cultures, and biopsy to obtain samples for histology. In preparation for biopsies, a platelet estimate and an activated clotting time or other coagulation function test should be performed before anesthesia. General anesthesia is induced by administering approximately one third of an induction dose of propofol (4 to 6 mg/kg intravenously), a short-acting thiobarbiturate, or ketamine combined with diazepam (ketamine 5 mg/kg intravenously and valium 0.3 mg/kg intravenously). The arytenoids are examined before intubation to make sure both are abducting normally on inspiration. Dopram can be used to stimulate respiration and increase intrinsic laryngeal motion at a dose of 2.2 mg/ kg, administered intravenously. Oropharyngeal examination is performed to evaluate thoroughly for masses, foreign bodies, or palate defects. A spay hook and dental mirror can be used to help manipulate the soft palate to a position allowing visualization of the nasopharynx so that polyps, other masses, foreign material, or nasopharyngeal stenosis can be checked (Figure 30-1). A thorough dental examination should be performed and all teeth probed for evidence of oronasal fistula. If a definitive diagnosis is not made, a CT scan or nasal, sinus, and dental radiographs are performed. If radiographs are performed, anesthesia is required for accurate positioning and should include a lateral view, ventrodorsal view, and intraoral and open-mouth bullae views. Nasal imaging can reveal increased density in the nasal cavity or bony lysis that could be consistent with a mass, turbinate destruction consistent with chronic rhinosinusitis or fungal disease, as well as radio-opaque foreign objects or tooth root abscessation.44,69 Although more expensive and not widely available, a CT scan has the added advantage of better visualization of the sinuses and tympanic bullae and better assessment of bony lysis; it also allows assessment of the cribriform plate and brain so that the extent of a lesion can be evaluated86 (Figure 30-2). It is also faster to perform than a full series of skull radiographs and allows for radiotherapy treatment planning if indicated. It is the preferred imaging

FIGURE 30-1 A spay hook and mirror can be used to assess the nasopharyngeal area.

A

B FIGURE 30-2 CT appearance of chronic rhinitis (A) versus nasal tumor (B). A mass effect and bony lysis is noted in the nasal cavity.

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A

FIGURE 30-4 Nasal flush can be performed for diagnostic and therapeutic purposes.

B FIGURE 30-3 A, Rhinoscopy allows visualization of the nasal mucosa as well as sample collection. B, Erythematous and irregular nasal mucosa.

modality, especially if a mass is suspected. Imaging should be performed before rhinoscopy and biopsy to prevent hemorrhage from obscuring details in the nasal passages. Depending on imaging findings, the nasopharynx is examined with a flexible rhinoscope, and rigid rhinoscopy of the anterior nasal cavity is then performed (Figure 30-3). Rhinoscopy allows direct visualization of the nasal cavity, detection and removal of foreign objects, detection and débridement of fungal plaques, as well as assessment for inflammation, turbinate destruction, and masses. However, should a mass be present, rhinoscopy does not allow assessment of the extent of bony lysis (hence the importance of additional imaging). In addition, because gross appearance of the nasal mucosa on rhinoscopy does not always correlate with histopathologic diagnosis, biopsies should always be performed.37 If no foreign material is visualized on rhinoscopy, the nasal cavity is flushed with sterile saline to evaluate for the presence of hidden material. The cuff of the endotracheal tube should be checked for full inflation before performing nasal lavage with saline administered under

pressure. In cats lavaging should be performed from the anterior nares caudally. Gauze should be placed in the oropharyngeal area and then a 20-, 35-, or 60-mL syringe can be used to forcefully flush saline through the nose while the nares are being pinched off to create pressure (Figure 30-4). Material flushed from the nose (or oropharynx) should be caught on the gauze and examined for foreign objects. If no foreign material is located, biopsies are then made using a bone curette or the largest biopsy instrument that can be passed through the nares. Most rigid endoscopes are too large for the biopsy sleeve to be used in many cats; a gastroscopic biopsy instrument can often be passed next to the camera of a rigid scope to perform directed biopsies. Alternatively, the biopsy site can be directed by the results of diagnostic imaging or by rhinoscopy. If indicated, bacterial and fungal cultures are made using material from flush or biopsied tissues.39

Phase 3: Exploratory Rhinotomy Exploratory rhinotomy allows for direct visualization of the nasal cavity to identify foreign objects, masses, or fungal plaques and is occasionally performed to aid in the diagnostic workup and the treatment of some diseases. However, in cats it is rarely performed, except for cases requiring removal of chronically embedded foreign bodies or cases of Aspergillus spp. or other infections in the sinus in which endoscopic débridement was not sufficient or the condition was refractory to treatment. Surgical debulking is rarely required for cats with nasal cryptococcosis. In general, there is also no added benefit to debulking nasal tumors before chemotherapy (e.g., lymphoma) or radiation therapy. Although turbinate tissue can be removed to increase airflow through the


nasal cavities, bacterial osteomyelitis is often present as well as nasal discharge, so this procedure is generally not recommended for cats with chronic inflammatory rhinitis.

DISEASE-SPECIFIC RECOMMENDATIONS: THE NASAL CAVITY Anatomic and Functional Disorders Nasopharyngeal Polyps Nasopharyngeal polyps are non-neoplastic, inflammatory nodules that occur most commonly in young cats. They originate in the middle ear or auditory canal and can grow out through the nasopharynx or, alternatively, the tympanum.34,40 Why the growths occur is unknown, but because they tend to occur when the cat is young, a congenital etiology has been postulated.2 The possible association of polyps with infectious agents has also been explored, including FHV-1, FCV, C. felis, Mycoplasma spp., and Bartonella spp.,41,108 but to date no organism has definitely been proven to be a cause. Large polyps can be detected by palpation through the soft palate, and otic examination may reveal discoloration or bulging of the tympanum. When extending into the nasopharynx, polyps disrupt the normal flow of secretions, resulting in secondary bacterial infections, mucopurulent nasal discharge, stertorous breathing, and gagging. Signs of middle ear involvement, such as Horner’s syndrome and head tilt, can also be seen. Diagnosis can be confirmed with examination of the nasopharynx under sedation with a dental mirror and spay hook or rhinoscope, as previously described. A bulla radiography series or CT scan should be performed to determine whether there is bulla involvement. However, if there is

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no evidence of middle ear–associated clinical disease and the polyp can be removed by way of the mouth, many clinicians will perform removal using traction and wait for a recurrence before performing a bulla osteotomy on account of the high incidence of morbidity associated with bulla osteotomy40,108 (Figure 30-5). Complications of this procedure include Horner’s syndrome, facial nerve paralysis, and discomfort, and the recovery period is similar to that for a relatively invasive surgery. Without bulla osteotomy approximately 30% will be recurrent.108 However, combining removal by traction with a tapering course of glucocorticoids (1 to 2 mg/kg per day, by mouth, for 14 days followed by a taper dosage over the next 2 weeks) may improve the success rate.64 Bulla osteotomy is an effective surgical treatment, and when it is performed at initial presentation or at recurrence, most cases generally experience complete resolution.40,103,108 Brachycephalic Syndrome Cats with brachycephalic conformation may experience difficulty with airflow due to the severe malformation of their nasal passages and nares, and potentially could be predisposed to nasal disease. A recent CT study of brachycephalic cats documented some of the abnormalities associated with this condition. It was found that the greater the degree of brachycephalia, measured by the amount of dorsal rotation of the maxillary canine tooth, the narrower the nasal cavity, nasal passages and nares.85 Stenotic nares also serve to limit inspired airflow. This condition may be improved by alar fold excision, performed with a laser or scalpel technique or alternatively a punch resection alaplasty.104 Nasopharyngeal turbinates have also been documented in brachycephalic cats and may serve to further reduce airflow through the nasopharyngeal area.25 Little information is available regarding surgical options for nasopharyngeal turbinates.

FIGURE 30-5 Manual removal of nasopharyngeal polyp.

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Nasopharyngeal Stenosis Nasopharyngeal stenosis is a rare condition that involves narrowing of the choanae to the extent that little air is able to pass. This can occur as a result of chronic infections, aspiration rhinitis, or congenital defect.33,96 Clinical signs typically include stertorous, labored breathing and, less typically, nasal discharge. Diagnosis is determined by retroflex rhinoscopic assessment of the nasopharynx. In the past manual dilation and advanced surgical procedures combined with steroid therapy were the only therapeutic options, and recurrence was common.33 More recently, stenting of the nasopharynx has been described as a successful palliative measure.5

Infectious Disorders Bacterial Agents DIAGNOSIS

Almost all cats with mucopurulent or purulent nasal discharge have a bacterial component to their disease. The bacterial agents that have been described as primary respiratory pathogens in cats include B. bronchiseptica, C. felis, Streptococcus canis, and Mycoplasma spp. However, Corynebacterium spp., Escherichia coli, Pasteurella multocida, Pseudomonas aeruginosa, Streptococcus viridans, and Staphylococcus intermedius are also commonly detected but generally thought to be secondary invaders.* Culture of either nasal flush samples or tissue biopsy samples yields similar species results, but aerobic and anaerobic cultures of nasal flushes were positive significantly more often in one study.39 Culture of nasal biopsies may be more representative for deep mucosal infections,38 but this has not been definitively shown. In another study different organisms were isolated from each collection technique, so it may be most complete to culture both nasal flush and biopsy samples.38 However, it should be remembered that positive culture results may not correlate with the cause of the disease on account of the presence of normal flora and other superficial bacteria. Although B. bronchiseptica is a well-defined primary pathogen in dogs, the organism can be isolated from many clinically normal cats.32 Thus the positive predictive value (PPV) of serologic test results, culture, and PCR assay is low in cats. Many cats have antibodies against B. bronchiseptica, the organism is commonly cultured from cats in crowded environments, and there are sporadic reports of severe lower respiratory disease caused by bordetellosis in kittens and cats in crowded environments or other stressful situations.7,110 The organism was cultured on necropsy from the lower airways of several cats from shelters in Colorado, and in one shelter the organism was cultured from 19 of 40 cats (47.5%) with upper respiratory disease.91 However, the significance of infection in otherwise healthy pet cats appears *References 7, 9, 16, 31, 83, 88, 91, 109, 110.

to be minimal. For example, in client-owned cats in north central Colorado, the organism was rarely cultured from cats with rhinitis or lower respiratory disease (approximately 3%).109 B. bronchiseptica is easily grown, and culture is superior to PCR for this agent because antimicrobial susceptibility testing can be performed on isolates. Because the organism is not usually eliminated by treatment, follow-up culture or PCR assay after treatment has minimal benefit.9 C. felis is a common differential diagnosis for cats with clinical evidence of conjunctivitis and rhinitis; it is not a common cause of lower airway disease. The organism is difficult to culture, so PCR detection of microbial DNA from conjunctival swabs can be useful clinically. Because of the intracellular nature of the organism, adequate cellular material must be obtained from the conjunctival swab for analysis.28 PCR assay results can be used to prove a cattery has been cleared of the infection after treatment.95 Most, but not all, PCR-positive cats are clinically ill (e.g., 3.3% if healthy cats were positive in one study).13 Mycoplasma spp. are normal commensal organisms of the mucous membranes of multiple species, including cats. M. felis has been associated primarily with conjunctivitis but is suspected as a primary cause of rhinitis in cats as well.31,38,39 There are multiple Mycoplasma spp. of cats, and the pathogenic potential for most is unknown. If other primary diseases are present, even nonpathogenic Mycoplasma spp. may be associated with the disease process. Mycoplasma spp. culture can be difficult and takes longer than routine culture, and antimicrobial susceptibility is not provided by most laboratories. Culture of nasal biopsy samples rather than nasal flush samples may increase yield.39 Mycoplasma spp. PCR assays have at least some clinical utility, with some assays allowing for speciation, which is helpful in assessing the pathogenic potential of the organism. However, because Mycoplasma spp. are common flora, the PPV of the assays is likely to be low. Because the organism is not usually eliminated by treatment, follow-up culture or PCR assay after treatment has minimal benefit. TREATMENT

If primary bacterial infections are suspected, doxycycline 10 mg/kg, administered orally once daily for cats with rhinitis with or without conjunctivitis, is usually effective (Table 30-1). Doxycycline is the treatment of choice for B. bronchiseptica, Mycoplasma spp., and C. felis infections,19,28 and in the last has been shown to be superior to topical administration of tetracycline.90 Sideeffects in young kittens are less of a concern with doxycycline than tetracycline but should still be taken into consideration. Amoxicillin–clavulanate is a good choice in young animals and is effective for most organisms, with the exception of Mycoplasma spp. because these organisms lack a cell wall. Pradofloxacin has been


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TABLE 30-1 Pharmacologic Treatment of Upper Respiratory Tract Disease Class

Drug

Dosage

Antibiotics

Amoxicillin Amoxicillin-clavulanate Azithromycin Cefadroxil Cephalexin Chloramphenicol Clindamycin Doxycycline Enrofloxacin Marbofloxacin Metronidazole Orbifloxacin Pradofloxacin Trimethoprim-sulfonamide

10-22 mg/kg, PO, every 12 hours 13.75 mg/kg, PO, every 12 hours 15 mg/kg, PO, every 24 hours 22 mg/kg, PO, every 12 hours 22 mg/kg, PO, every 8 hours 10-15 mg/kg, PO, every 12 hours 10-12 mg/kg, PO, every 24 hours 10 mg/kg, PO, every 24 hours 2.5-5 mg/kg, PO, every 24 hours 2.5-5 mg/kg, PO, every 24 hours 10-15 mg/kg, PO, every 12 hours 2.5-5 mg/kg, PO, every 24 hours 5-10 mg/kg, PO, every 24 hours 15 mg/kg, PO, every 12 hours

Antihistamines

Cetirizine Chlorpheniramine Clemastine Fexofenadine Hydroxyzine Loratadine

2.5-5 mg/cat, PO, every 24 hours 2 mg/cat, PO, every 12 hours 0.68 mg/cat, PO, every 12 hours 5-10 mg/cat, PO, every 12 to 24 hours 5-10 mg/cat, PO, every 8 to 12 hours 5 mg/cat, PO, every 24 hours

Antifungals

Deoxycholate amphotericin B

Fluconazole Itraconazole Liposomal amphotericin B

1) IV: 0.1-0.5 mg/kg: M, W, F; to 16 mg/kg total cumulative dose 2) SC: 0.5-0.8 mg/kg in 400 mL of 0.45% saline/2.5% dextrose; M, W, F; to 16 mg/kg total cumulative dose 50 mg/cat, PO, every 12 to 24 hours 10 mg/kg, PO, every 24 hours 1 mg/kg IV; Mon, Wed, Fri; to 12 mg/kg total cumulative dose

Antivirals

Cidofovir topical (0.5%) Famciclovir Interferon-alpha Lysine

1 drop OU, every 12 hours 62.5 mg/cat, PO, every 12 hours, 14 days 10 U PO, every 24 hours (chronic); 10,000 U SC, every 24 hours, 21 days (acute) 500 mg/cat, PO, every 12 hours

NSAIDs

Meloxicam Piroxicam

0.025-0.1 mg/kg, PO, every 2 to 3 days 0.3 mg/kg, PO, every 2 days

Glucocorticoids

Beclomethasone (inhaled) Fluticasone (inhaled) Methylprednisolone acetate Prednisolone

1-2 puffs, every 12 to 24 hours 1-2 puffs, every 12 to 24 hours 5-15 mg IM, every 3 to 4 weeks, as needed 2.5-5 mg/cat, PO, every 1 to 2 days

PO, By mouth; IV, intravenously; SC, subcutaneously; OU, each eye; NSAIDs, nonsteroidal antiinflammatory drugs; IM, intramuscularly.

shown to have efficacy against Mycoplasma spp.16,31 Enrofloxacin has also been shown to be effective for C. felis23 but should be used with caution in young cats because of possible adverse effects on cartilage. Although the drug has not been shown to damage chondrocytes in cats, this does occur in several other species. Clindamycin penetrates bone and tissues well and has an excellent anaerobic spectrum. Administering the liquid form of this drug is generally well tolerated if given cold. Azithromycin therapy (15 mg/kg, administered orally once daily) can be tried for cats with suspected resistant bacterial infections.* Doxycycline and clindamycin have been associated with esophagitis and esophageal strictures in cats4,24,61 *References 16, 31, 83, 91, 94, 95.

because of the poor secondary esophageal contractions in this species. The authors recommend never administering dry pills or capsules to cats. Drugs should be compounded into a liquid, administered, and then followed with a 3- to 6-mL liquid bolus or food, administered coated with butter or a product such as Nutri-Cal, or administered in a pill-delivery treat.27,50,111 Cats with acute disease are treated for 7 to 10 days, except for C. felis, in which 28 days of therapy is needed to eliminate infection.31,95 Chronic bacterial disease may require treatment for 6 to 8 weeks to adequately clear the infection if osteomyelitis exists. Pulse therapy may help some chronically affected cats but may induce antimicrobial resistant bacteria in other cats. Most cases of bacterial rhinitis are secondary to other diseases, including trauma, neoplasia, inflammation induced by viral

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infection, foreign bodies, inflammatory polyps, chronic rhinosinusitis, and tooth root abscessation. Thus if routine antibiotic therapy fails, a diagnostic workup should be performed. PREVENTION

The currently available B. bronchiseptica vaccine for intranasal administration can be administered as early as 4 weeks of age, has an onset of immunity as early as 72 hours, and has a minimum duration of immunity of 1 year.81 The American Association of Feline Practitioners (AAFP) Feline Vaccine Advisory Panel, and the European Advisory Board on Cat Diseases (ABCD) recommendations suggest that Bordetella vaccination should be considered primarily for use in cats at high risk for exposure and disease, such as those with a history of respiratory problems and living in humane shelters with culture-proven outbreaks.19,81 However, because the vaccine is administered by the intranasal route, mild sneezing and coughing can result, which may influence case management of kittens housed in shelters or humane societies. Because the disease is apparently not lifethreatening in adult cats, is uncommon in pet cats, responds to a variety of antibiotics, and is considered minimally zoonotic,18 routine use of this vaccine in the majority of client-owned cats seems unnecessary. Killed and modified live C. felis–containing vaccines are available. In recent studies C. felis was amplified from conjunctival swabs of 3.2% of cats with conjunctivitis49 but 0% of nasal discharges from cats housed in a humane society.91 FVRCP vaccines that also contained C. felis were associated with more vaccine reactions in cats when compared to other products.63 Because infection of cats by C. felis generally results only in mild conjunctivitis, is easily treated with antibiotics, has variable prevalence rates, and is of minimal zoonotic risk to humans, some researchers have questioned whether C. felis vaccination is ever necessary in the United States.14 Duration of immunity for Chlamydophila vaccines may be short-lived, so high-risk cats, such as those in multicat environments or where there is a history of chlamydial infection, should be immunized before a potential exposure. Viral Agents DIAGNOSIS

The most common viruses associated with feline res piratory disease are FCV and FHV-1. Both viruses are extremely common in cats, particularly those from crowded environments such as pet stores, catteries, and shelters.14,32 There are many strains of FCV, and mutations resulting in new strains are common. This organism is a common differential diagnosis for cats with clinical evidence of rhinitis, stomatitis, oral ulceration, and conjunctivitis (Figure 30-6). Less commonly, FCV is associated with polyarthritis, lower airway disease in

FIGURE 30-6 Clinical appearance of a kitten with herpesvirus infection.

kittens, and virulent systemic disease.78 Some variants of FCV are thought to induce systemic vasculitis in cats (virulent systemic calicivirus [VS-FCV]), and clinical signs can be severe even in cats previously vaccinated with FVRCP vaccines.10,36,72,87,105 VS-FCV strains arise spontaneously from endogenous FCV strains, and outbreaks have resolved quickly after the initial cases were recognized. Currently, it is unknown how often these outbreaks occur and whether the number of outbreaks is increasing. The VS-FCV strains evaluated to date have been genetically and antigenically diverse.42,71 Virus isolation can be used to document current infection but takes at least several days for results and is not performed by all laboratories. Because of widespread exposure and vaccination, the PPV of serologic tests is poor. Reverse transcriptase (RT) PCR assays can be used to amplify the RNA of calicivirus, and results can be made available quickly. However, these assays also amplify vaccine strains of FCV (Lappin MR: unpublished data, 2010). FCV RNA can be amplified from samples collected from normal carrier cats as well as clinically ill cats, and PCR assays therefore have poor PPV. In addition, amplification of FCV RNA cannot be used to prove virulent systemic calicivirus infection.78 False-negative results of FCV RT-PCR can also occur if inadequate RNA is present on the submitted swab or if the organism has been cleared to levels below the sensitivity limits of the assay by specific immune responses. Because treatment does not eliminate FCV infection, there is no benefit to follow-up culture or RT-PCR testing. FHV-1 is a common differential diagnosis for cats with clinical evidence of rhinitis, stomatitis, conjunctivitis, keratitis, and facial dermatitis. Because of widespread exposure and vaccination, the PPV of serologic tests is poor. FHV-1 infection can be documented by direct fluorescence staining of conjunctival scrapings, virus isolation, or PCR.98 FHV-1 DNA can be amplified

from conjunctival cells of approximately 20% of healthy cats; therefore the PPV of PCR assays for this agent is low.79 Currently used PCR assays also detect vaccine strains of FHV-1, further lessening the PPV.52 Quantitative PCR may ultimately prove to correlate with the presence or absence of disease but failed to correlate to presence of conjunctivitis in one small study in the authors’ laboratory.49 The negative predictive value of the FHV-1 PCR assays is also in question because many cats that are likely to have FHV-1–associated disease are PCR negative. This may relate to clearance of FHV-1 DNA from tissues by the immune reaction. Tissue biopsies have greater sensitivity than conjunctival swabs but do not necessarily have greater predictive value.93 FHV-1 DNA can be amplified from the aqueous humor of some cats, but whether this indicates FHV-1–associated uveitis is unknown.54 Because treatment does not eliminate FHV-1 infection, there is no benefit to follow-up culture or PCR testing. TREATMENT

Therapy for FCV consists mainly of supportive care, which is often needed for cats with VS-FCV infections, and may consist of intravenous fluids, antibiotics for concurrent bacterial infections, and interferon. Interferon may augment immune responses to viral infections by upregulating key cytokines.101 Feline interferon omega (1 to 2.5 million IU/kg, intravenously or subcutaneously, every 24 to 48 hours for up to 5 doses, then reduce to twice weekly and eventually to once weekly, depending on clinical response) (Virbagen Omega, Virbac Animal Health) inhibits FCV replication in vitro, but results of controlled studies evaluating efficacy in clinically affected cats with respiratory disease are not available. If human alpha interferon is used systemically for cats with life-threatening FCV or FHV-1 infections, 10,000 U/kg, administered subcutaneously, can be administered safely once daily, but controlled data concerning efficacy are not available. Recently, use of feline interferon therapy has been used to improve quality of life in cats with FeLV and FIV infections.11 In one study low-dose oral interferon therapy (10 U/kg, orally, daily alternating 7 days on, 7 days off, for 6 months) improved quality of life in cats with FIV infections.73 The effect of oral interferon is thought to be from mediation of inflammatory cytokines. There may also be effects against chronic FHV-1 or FCV infections, but controlled data are not available. Topical administration of alpha interferon in saline to the eyes of cats with conjunctivitis or the nose has been recommended by some veterinarians as an aid in the management of some cats with acute or chronic FHV-1 or FCV infections. Recently, antiviral drugs have become more popular in the management of cats with acute or chronic FHV-1 infections. Currently available antiviral medications are efficacious only for DNA viral infections such as FHV-1,


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and not RNA viruses such as FCV, because they interfere with viral DNA synthesis and thus viral replication. Acyclovir and valacyclovir have been administered to some cats but can induce bone marrow suppression and are minimally effective for FHV-1; therefore they should no longer be used.51,66 Famciclovir is safe and effective and is used for both acute and long-term therapy for cats with FHV-1 infections. One dose that has been used with apparent clinical efficacy is 62.5 mg, orally, every 12 hours for 14 days.58 However, recent pharmacokinetic studies indicate that higher doses may be needed for activity against FHV-1.99 Idoxuridine and trifluridine have been used topically in cats with conjunctivitis or keratitis resulting from FHV-1 infection, but these must be administered multiple times per day and are irritating. Recently, cidofovir was used in a small experimental FHV-1 conjunctivitis study and was shown to lessen clinical signs and FHV-1 shedding.21 Lysine at 250 to 500 mg, orally, every 12 hours may be helpful in some cats with acute or chronic rhinosinusitis caused by FHV-1 infection (not FCV).53 However, in several controlled studies of cats fed a lysine-fortified diet, a significant positive effect was not noted.17,55,80 Intranasal administration of modified live FHV-1 and FCV vaccines may lessen disease in some chronically infected cats, but controlled data are lacking. If there is a positive response to intranasal vaccination in a cat with chronic disease, this form of immunotherapy can be administered up to three times per year. Intranasal vaccination has been shown to potentiate cell-mediated immunity to FHV-1 better than parenteral vaccination.48 Chronic administration of one commercially available probiotic (FortiFlora, Purina Veterinary Diets) was shown to enhance T-helper lymphocyte numbers in cats.106 When this probiotic was administered to cats with chronic FHV-1 infections that were then subjected to mild stress, improved conjunctivitis scores were noted in some of the cats in the treatment group.47 See the section on chronic rhinosinusitis for a discussion of other nonspecific therapies. PREVENTION

Specific pathogen-free (SPF) cats inoculated with one dose of intranasal modified live FVRCP vaccine had significantly less clinical signs than control cats as soon as 4 days when challenged with virulent FHV-1 in one study.45 Administration of the intranasal FVRCP vaccine was also shown to induce FCV antibody responses in SPF kittens more quickly than a modified live FVRCP vaccine administered parenterally.46 Thus the intranasal route of administration may be preferred for the primary or booster immunization of kittens housed in environments at high risk for exposure to FHV-1 or FCV, such as shelters, humane societies, catteries, boarding facilities, and multicat households. However, because

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administration of intranasal FHV-1 and FCV vaccines can induce transient mild sneezing or coughing, the owners should be informed of these potential side effects. Additionally, these vaccine side effects may influence case management of kittens housed in shelters or humane societies. Subcutaneous vaccines are recommended if concerns about the respiratory side effects of intranasal vaccines exist. Currently, yearly revaccination for cats in high-risk environments (e.g., shelters, catteries, multicat household) and a 3-year revaccination interval for cats in low-risk environments (indoor-only with no contact with other cats) are recommended.78,81,98 Inactivated vaccines containing VS-FCV are now available (Calicivax, Boehringer Ingelheim Vetmedica). The product contains a traditional FCV vaccine strain as well as a VS-FCV strain. Cross-neutralization studies show that cats inoculated with more than one FCV strain inactivate more FCV strains in vitro than cats inoculated with one FCV strain.74,75 In addition, a recent challenge study illustrated that kittens vaccinated with the dualstrain product were protected from clinical signs of VS-FCV.35 Fungal Agents C. neoformans and Aspergillus spp. are the most common causes of respiratory tract fungal infection in cats.3,57,68 Cryptococcosis is most common and should be considered a differential diagnosis for cats with respiratory tract disease, subcutaneous nodules, lymphadenopathy, intraocular inflammation, fever, and central nervous system disease.57 Infected cats range from 6 months to 16 years of age, and male cats are overrepresented in some studies.67 Infection of the nasal cavity is reported most frequently and commonly results in sneezing and nasal discharge. The nasal discharge can be unilateral or bilateral, ranges from serous to mucopurulent, and often contains blood. Granulomatous lesions extruding from the external nares, facial deformity over the bridge of the nose, and ulcerative lesions on the nasal planum are common (Figure 30-7). Submandibular lymphadenopathy is detected in most cats with rhinitis. Definitive diagnosis of cryptococcosis is based on antigen testing or cytologic, histopathologic, or culture demonstration of the organism. Cats with cryptococcosis have been treated with amphotericin B, ketoconazole, itraconazole, fluconazole, and 5-flucytosine alone and in varying combinations. Responses have varied among studies, but good to excellent treatment responses are often achieved in cats administered fluconazole or itraconazole.60,67 Because of toxicity and the availability of more efficacious drugs, ketoconazole is no longer recommended by these authors. Fluconazole at 50 mg per cat, orally, once or twice daily is recommended because it results in the fewest side effects, has the best penetration across the blood–brain and blood–ocular barriers of the azoles, and

FIGURE 30-7 Although Cryptococcus and Aspergillus are the most common upper respiratory fungal infections in cats, nasal deformity may also be associated with Sporothrix spp. infection.

has been shown to have good efficacy.60,67 If lifethreatening infection is occurring or the cat is failing to respond to an azole drug, amphotericin B should be used.67 A typical amphotericin protocol involves intravenous infusions on a Monday–Wednesday–Friday schedule until a cumulative dose of 16 mg/kg has been reached. Nephrotoxicity is the most serious side effect, and an initial infusion dose of 0.1 mg/kg is used as a test dose. The dose can be slowly increased to 0.5 mg/ kg if it is well tolerated clinically and if renal values remain stable.26,56 A successful subcutaneous protocol has also been described in which 0.5 to 0.8 mg/kg is added to 0.45% saline/2.5% dextrose, and the total volume is given two to three times weekly to a cumulative dose of 8 to 26 mg/kg.56,67 In addition to the deoxycholate form of amphotericin B, a liposomal formulation is also available. It is thought that less nephrotoxicity is seen with the liposomal product, and a recommended dose regimen is 1 mg/kg, intravenously, on a Monday–Wednesday–Friday schedule until a cumulative dose of 12 mg/kg has been reached.26 Focal nasal and cutaneous cryptococcosis generally resolves with treatment; central nervous system, ocular, and disseminated diseases are less likely to respond to treatment.60,67 Treatment should be continued for at least 1 to 2 months past resolution of clinical disease, or until antigen titers are negative.20,67 People and animals can have the same environmental exposure to Cryptococcus spp., but zoonotic transfer from contact with infected animals is unlikely. Aspergillosis is less common than cryptococcosis but can be equally devastating.3,102,112 Clinical signs of mild disease are similar to those of nasal cryptococcosis. Sinoorbital aspergillosis was recently described in cats and appears to be more aggressive than canine aspergillosis, involving invasion into surrounding structures.3 Ocular

involvement, such as exophthalmos and ocular discharge, can be seen in addition to nasal signs. Diagnosis of aspergillosis is based on visualization of fungal plaques on rhinoscopy or fungal hyphae on cytology or biopsy. Infection can be caused by either Aspergillus spp. or Penicillium spp., which can be difficult to differentiate cytologically. Fungal culture seems less sensitive and specific than visualization on rhinoscopy or biopsy.112 Therapy with oral itraconazole and fluconazole has been documented as 50% to 60% efficacious,102,112 and better efficacy with nasal clotrimazole therapy has been reported in a few cases.102

Chronic Inflammatory Disorders Chronic Rhinosinusitis Lymphocytic–plasmacytic, eosinophilic, and idiopathic rhinosinusitis are a constellation of diagnoses obtained by way of histopathology that are collectively referred to as chronic rhinosinusitis. In many cases this is a diagnosis of exclusion when other etiologies have been ruled out. This syndrome is one of the most significant causes of sneezing and nasal discharge in the cat.33 The nasal discharge is generally serous, but secondary bacterial infections can result in the development of mucopurulent nasal discharge (Figure 30-8), and inflammation can be severe enough to cause intermittent hemorrhage.33 The clinical signs can persist for years. Cats with relatively stable disease that encounter a sudden change in severity should be re-evaluated for the presence of a more severe secondary disease, such as fungal rhinitis or neoplasia. There is a subset of chronic rhinosinusitis cats that have a history of acute FHV-1 or FCV upper respiratory infections at a younger age, and it is postulated that an early severe viral infection may trigger chronic disease.38 In addition, it is estimated that approximately 80% of cats are latently infected with FHV-1,22 and so another possible scenario for chronic viral rhinosinusitis is the

FIGURE 30-8 Mucopurulent nasal discharge is common with chronic rhinosinusitis.


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presence of latent FHV-1 viral infections that are triggered into recrudescence by stressful events. In such cats with a prior history of viral infection, therapies such as lysine, antivirals, and immunomodulators are often tried, as previously discussed. Subjective improvement in clinical signs has been noted in response to cationic liposome DNA complexes (CLDC) immunomodulatory therapy in a small pilot study currently under way at Colorado State University, as well as in a previously published study.107 Stress is thought to play a role in the clinical severity and potential for recurrence of chronic viral rhinosinusitis, particularly if FHV-1 latency or chronic FCV infections are involved. Environmental measures to decrease stress, allocate resources in multicat households, and provide antianxiety therapies such as feline facial pheromone use (Feliway, Ceva Animal Health) may also provide some benefit. Controversy surrounds the use of immunosuppressive therapy in these patients: It may not be beneficial and runs the risk of exacerbating viral and bacterial components of the disease syndrome. In many cases there is no history of viral infection or any other predisposing cause. Generally, idiopathic chronic rhinosinusitis is somewhat refractory to treatment, and palliation of clinical signs, rather than cure, is the goal of medical management. Broad-spectrum antibiotics are often prescribed to manage secondary infections. Administration of antihistamines such as chlorpheniramine at 1 to 2 mg, orally, every 12 hours may lessen clinical signs of disease in some cats. Several newer antihistamines are now available (see Table 30-1), and because response to therapy is variable from patient to patient, an alternative drug should be tried if no improvement is seen with the initial choice. Moistening therapies such as nebulization and saline nasal drops can help loosen secretions and soothe mucosa, particularly in drier climates. The role of immunosuppressive drugs as therapeutic agents in the treatment of chronic idiopathic rhinosinusitis is poorly understood, likely because of the multifactorial nature of this condition. Individual patients will respond variably to this approach. Prednisolone may be used at a maximum dose of 1 to 2 mg/kg, orally, every 12 hours. If a positive response is noted, the lowest dose and the longest dosing interval that is effective should be determined by adjusting the dose over time. Inhaled glucocorticoids can be used as an alternative to decrease the systemic side effects of oral glucocorticoid use and have the benefit of directly affecting the nasal mucosa. Beclomethasone or fluticasone can be administered by metered dose inhaler (MDI) with an inhalation chamber at 1 to 2 puffs once to twice daily. Resistant cases may respond to administration of cyclosporine at up to 7.5 mg/kg, orally, daily or every other day, but controlled data are lacking. Trough blood levels should be checked 2 weeks after initiation of therapy to ensure that

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excessive blood levels are not achieved; this may activate latent infectious diseases.

Neoplasia Neoplasia of the nasal cavity is relatively rare in the cat compared with the dog; lymphoma is the most common tumor type, followed by adenocarcinoma and squamous cell carcinoma.12,33,65 Lymphoma is treated with chemotherapy, often in conjunction with radiation therapy, and has potential for a good long-term prognosis.89 Palliative radiation therapy is indicated for other nasal neoplasms, and surgical debulking is generally not required.62 Prognosis depends on the aggressiveness and extent of the tumor, which is best determined by CT scan. Piroxicam administered at 0.3 mg/kg, orally, every 48 to 72 hours can control inflammation and clinical signs of disease in some cats with nonlymphoproliferative nasal neoplasia. Meloxicam (0.1 mg/kg, orally, every other day) may be another efficacious alternative. However, neither drug may result in antitumor effects against squamous cell carcinoma because it has been shown that there is minimal expression of cyclooxygenase-2 in this cancer type in the cat.15 If nonsteroidal antiinflammatory therapy is used, the cat should be monitored for renal and gastrointestinal side effects (e.g., PCV to assess for gastrointestinal hemorrhage and renal values) because these are potential side effects of this drug family.

Spontaneous Disorders Trauma Trauma to the nasal cavity most commonly results in massive hemorrhage, and thus initial evaluation should include assessment and treatment for hypovolemic shock. Nasal tissue may be easily damaged because of its fragile structure. Placement of a nasal cannula may aid in airflow and allowing healing that maintains a nasal passage. It may take 2 to 3 weeks for healing to occur. Generally, surgical correction of fractures in the nasal cavity is not necessary, although solitary bone fragments should be removed to prevent the formation of sequestra. Trauma may also lead to chronic complications as a result of damage to the nasal passage.33 Foreign Bodies Nasal foreign bodies are more common in cats than generally realized.33,82 In dogs the foreign material is usually inspired into the anterior nares and is found in the ventral meatus just caudal to the nares. Most nasal foreign bodies in cats are plant material that lodges above the soft palate after coughing or vomiting. Clinical signs may include sneezing, reverse sneezing, gagging, and repeated attempts at swallowing. Retroflex rhinoscopic examination of the nasopharynx can sometimes confirm diagnosis and aid in removal of the object. Nasal

lavage under general anesthesia is often more effective. The cuff of the endotracheal tube should be checked for full inflation before performing nasal lavage with saline administered under pressure. In cats lavaging from the anterior nares caudally is recommended. Gauze should be placed in the oropharyngeal area, and then a 20-, 35-, or 60-mL syringe can be used to forcefully flush saline through the nose while the nares are being pinched off to create pressure. Material flushed from the nose (or oropharynx) should be caught on the gauze and examined for foreign material.

DISEASE-SPECIFIC RECOMMENDATIONS: THE LARYNX Laryngeal Paralysis Laryngeal paralysis is a relatively rare condition in the cat compared with the dog, but it may occur as a result of a variety of etiologies.84 Clinical signs include respiratory distress, inspiratory stridor, change in vocalization, coughing, dysphagia, and nonspecific signs such as weight loss and anorexia. Continuous positive airway pressure may be helpful in managing acute cases when intubation is not possible.100 When possible, depending on the stability of the patient, cervical and thoracic radiographs are helpful for ruling out other causes of dyspnea. In a recent study 60% of cats with laryngeal paralysis had evidence of upper airway obstruction on radiographs. Findings included lung hyperinflation; caudal displacement of the larynx; and air in the larynx, pharynx, esophagus, and stomach.84 Insofar as laryngeal paralysis is a functional disease, laryngeal examination provides a definitive diagnosis. In one study 75% of cats examined had bilateral disease.84 In this study medical management was instituted for cats with unilateral disease with good outcome. Surgical management with arytenoid lateralization is reported to be variably successful (50% to 70%) for cats with laryngeal paralysis and is more commonly recommended in cats with bilateral disease. Aspiration pneumonia (with bilateral lateralization procedures), temporary tracheotomy necessitated by laryngeal swelling, and repetition of the surgery have been reported as possible sequelae of surgical management.30

Inflammatory Laryngitis A few cases of inflammatory laryngeal disease have been reported.97 These are clinically and grossly similar in presentation to other causes of laryngeal disease but are apparently non-neoplastic and noninfectious in etiology. Thus a biopsy should always be performed to distinguish inflammatory disease from a neoplastic process. Histopathology of this condition appears to be either


granulomatous or lymphocytic-plasmacytic and neutrophilic. A temporary tracheostomy may be necessary while treatment is initiated, and surgical resection of inflamed tissue may be necessary. Favorable response to glucocorticoids has been reported, with good long-term prognosis in some cases.97

Laryngeal Neoplasia Laryngeal neoplasia most commonly presents with clinical signs similar to those of other laryngeal disorders. A physical examination with special attention to the cervical area may identify a mass originating from tissues adjacent to the larynx. Laryngeal examination may reveal a mass, swelling, or irregularity in the appearance of the larynx. A biopsy is necessary to confirm the diagnosis and differentiate the condition from inflammatory laryngeal disease. The most common laryngeal neoplasms are lymphoma, squamous cell carcinoma, and adenocarcinoma.70 Lymphoma may respond to chemotherapy. Complete surgical excision is usually not possible in this anatomic area, but it can be performed as a palliative measure. The long-term prognosis is poor. Permanent tracheostomy can be performed, but complications are common.29,92

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LOWER RESPIRATORY TRACT DISEASES Randolph M. Baral Lower respiratory tract (LRT) diseases include the following: 1. Bronchial disease (i.e., pathology affecting the airways distal to the tracheal bifurcation) 2. Pulmonary interstitial disease, which is predominantly pneumonia or neoplasia (but also pulmonary edema and pulmonary fibrosis)

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These distinctions are important to make for management purposes, but the clinician should not lose sight of the fact that combinations of these can occur, such as in bronchopulmonary pneumonia. Severe cases of LRT disease usually present for dyspnea or tachypnea. In milder cases cats may present for coughing, wheezing, or “loud breathing.” The diagnostic processes must not only distinguish bronchial from interstitial disease but also LRT diseases from upper respiratory tract (URT) or cardiac disease and other intrathoracic diseases (e.g., those causing pleural effusion or intrathoracic masses). LRT diseases can be classified as infectious or noninfectious, and noninfectious causes can be considered as neoplastic or non-neoplastic. The most common LRT conditions encountered are idiopathic bronchial diseases, commonly described as asthma or chronic bronchitis.

CLINICAL SIGNS The most common presenting signs for cats with LRT disorders are dyspnea, coughing, or other abnormal respiratory sounds or patterns; some cats can present for general malaise, and respiratory signs are first recognized by the clinician rather than the owner. Signs can be intermittent or constant. The clinician must, in the first instance, distinguish LRT signs from those caused by URT, cardiac, or pleural disorders. A recent study of 90 dyspneic cats divided the underlying causes (and proportions) as cardiac (38%), non-neoplastic URT and LRT disease (32%), and neoplasia of the URT, LRT, or pleural cavity (20%).263 Typically, louder (or harsher) expiratory sounds are auscultated with LRT disease compared with the harsher inspiratory sounds auscultated with URT disorders. Disease confined to the pleural space or pulmonary parenchyma does not result in auscultatory change when the airways are not affected. Rapid breathing with decreased depth indicates restrictive disease which can result from alveolar or interstitial infiltrates or masses (LRT) or pleural diseases such as effusion, mediastinal masses, diaphragmatic herniation, or pneumothorax. Auscultation of a murmur usually points toward cardiac disease, but cardiomyopathies do not necessarily result in a murmur. Coughing and wheezing are considered typical signs of LRT disorders such as bronchial diseases or pneumonia and do not typically occur with congestive heart failure (CHF) in cats. Palpably decreased chest wall compliance is considered typical of pleural diseases such as effusion or masses but is certainly recognized with bronchopulmonary disease as well.

DIAGNOSTICS Radiology Radiology is the hallmark modality to diagnose LRT diseases and distinguish them from pleural and cardiac diseases. In acute cases screening images to determine the anatomic location of pathology should be taken in the most comfortable position for the cat; many cats are comfortable sitting sternally, with their elbows stabilizing themselves, which can allow a dorsoventral image. Multiple views of good-quality images are important for precise diagnostics but only after respiratory distress has been relieved. When radiographs are taken for more precise diagnostics, three views should be taken: (1) left lateral, (2) right lateral, and (3) dorsoventral or ventrodorsal. Typically, bronchopulmonary disease is interpreted radiographically by a pattern-based approach of assessment28 (Table 30-2). Bronchial patterns result from fluid or cellular infiltrate within the bronchial walls and peribronchial and perivascular connective tissue of the lung. This leads to increased radiodensity of bronchial walls. When these prominent bronchi are viewed longitudinally, they appear as paired, parallel lines that branch and have been compared to train tracks. In cross-section they appear as tissue-dense circles with radiolucent centers that have been described as resembling “doughnuts” (Figure 30-9). Vascular patterns result from an increase (or decrease) in prominence (i.e., size, shape, number) of pulmonary arteries and veins. Vessels appear as radiodense linear structures running parallel to the main lobar airways that taper. Vascular patterns are more common in cardiovascular disease than LRT disease. Alveolar patterns result from alveolar collapse or flooding of pulmonary acini with fluid. The acini are those parts of the lung distal to each terminal bronchiole. As each acinus becomes flooded, the fluid spreads to the adjoining acinus, resulting in a “fluffy” density. As these “fluffy” densities spread, they coalesce. Any bronchial structures within the density appear as radiolucent lines (known as “air bronchograms”). Alveolar patterns indicate that the disease process is within the end-air spaces and not the lung interstitium (or pleural space or mediastinum) (Figure 30-10). Interstitial patterns result from fluid or cellular accumulation within the lung interstitium (i.e., not airways). The consequence is generally a haze or “veil” over the lung fields that obscures the vascular outlines. Distinct linear densities or nodules are also possible (Figure 30-11). In most cases a combination of patterns (mixed pattern) will result. For example, bronchopneumonia may result in alveolar and bronchial patterns. In all cases


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TABLE 30-2 Radiographic Features of Pulmonary Patterns in Dyspneic Cats Pattern Name

Radiographic Features

Comments

Disease Examples (Not All Inclusive)

Alveolar

Lobar sign; uniform soft tissue opacity; air bronchograms; will not see pulmonary vessels or airways; border effacement of heart or diaphragm

Location is important for formulating a differential list; is the easiest pulmonary pattern to recognize

Aspiration pneumonia; bronchopneumonia; cardiogenic and noncardiogenic pulmonary edema; neoplasia; hemorrhage; smoke inhalation; etc.

Bronchial

Rings and lines are noted within the pulmonary parenchyma; visible in the periphery and away from the pulmonary hilum

Usually generalized; be sure to evaluate in the peripheral lung fields and in the thin areas of lung

Chronic bronchitis; pulmonary infiltrates with eosinophilia; heartworm disease; allergic lung disease; feline asthma

Vascular

Increased in size of the pulmonary arteries, veins or both (left-toright shunting lesions)

Added lung opacity secondary to enlargement of the pulmonary vessels

Pulmonary arteries—heartworm disease or cor pulmonale; pulmonary veins—left-sided heart failure; both—left-to-right PDA, VSD, ASD, or overcirculation secondary to volume overload

Interstitial—nodules or miliary pattern (structured)

Multiple “millet seeds” or small miliary nodules noted throughout the lung fields; variably sized pulmonary nodules

Usually needs to be at least 5 mm in size to be seen as a distinct nodule; “fake-outs” include nipples, end-on vessels, and pulmonary osteomas

Lymphoma, disseminated neoplasia (carcinoma), and fungal disease; parasitic, eosinophilic, or pyogranulomatous pneumonias; nodules can be cavitated

Unstructured interstitial

Increased opacity to the lung fields with decreased visualization of the pulmonary vessels, aorta, and caudal vena cava

Typically generalized and never mild!

Check exposure factors, expiration, lymphoma, fibrosis, fungal infection, edema, hemorrhage, infectious etiologies

PDA, Patent ductus arteriosus; VSD, ventricular septal defect; ASD, atrial septal defect. From Berry CR: Small animal thoracic radiology: the dyspneic cat, in Proceedings, Western Veterinary Conference, 2010.

FIGURE 30-9 Thoracic radiograph (right lateral projection) demonstrating bronchial pattern. Note the increased radiodensity of bronchial walls resulting in “tram tracks” (two, marked with green arrows) and “doughnuts” (one, marked with a red arrow).

the clinician must determine the dominant pattern to help decide the most appropriate next diagnostic step. Although radiography narrows down the possible diagnoses, a precise diagnosis cannot be made without a cytologic assessment. The radiographic pattern can help decide which sampling technique is likely to produce a higher cellular yield. Sampling from airways

FIGURE 30-10 Thoracic radiograph (right lateral projection) demonstrating alveolar pattern. This cat has pulmonary edema subsequent to congestive heart failure. Note the bronchial structure (“air bronchogram”) within the density caused by flooded alveoli appearing as a radiolucent line (marked with green arrow). There is also cardiomegaly, and the stomach is filled with air, as is often the case with dyspneic cats.

(bronchoalveolar washing) is more likely to be successful when bronchial or alveolar patterns are present. Aspiration directly from lung tissue is more likely to aid diagnosis when an interstitial pattern predominates or discrete nodules are present.

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associated with oxygen desaturation of hemoglobin. Pretreatment with terbutaline (0.01 mg/kg subcutaneously) and preoxygenation appear to reduce complication rates.122,132 When bronchial disease is recognized radiographically or suspected despite no radiographic evidence, airway fluid should be collected for analysis by blind or transoral bronchial lavage or by bronchoscopy. Pretreatment with terbutaline (0.01 mg/kg subcutaneously) is recommended for blind sampling as well as with bronchoscopic evaluation.

Bronchoalveolar Lavage

FIGURE 30-11 Thoracic radiograph (right lateral projection) demonstrating interstitial pattern. Note that the radiodensity of the lung fields is increased with a “veil-like” quality. The radiodensity of normal lung fields should approach that of the air surrounding the cat.

Computed Tomography CT is being used more frequently in referral practice. CT eliminates superimposition of overlying structures and offers superior contrast resolution compared with conventional radiography. Most reports of CT, often with CT-guided fine-needle aspiration (FNA), for diagnosis of feline LRT disorders have been for neoplastic disease.106,292 CT is also useful for assessment of airway wall thickening, mucus obstruction, emphysematous changes, secondary bronchiectasis, mucus accumulation in small airways, and air trapping.120,121

Bronchoscopy Bronchoscopy is not yet widely available in general practice but is becoming more so. Bronchoscopy allows examination of patency, color, and character of mucosa; presence and character of secretions; and presence and location of masses or foreign bodies. A major limitation of feline bronchoscopy is the requirement for very narrow bronchoscopes (2.5 to 3.8 mm outer diameter). Even with such narrow scopes, the airways are mostly occluded, requiring intravenous anesthesia for maintenance as well as induction. Oxygen can be supplied through jet ventilation or an oxygen cannula passed adjacent to the scope. In one study of bronchoscopy in 68 cats, complications resulted in approximately one third of cases (26 of 68 cats). In most cases the complications were mild, but in six cases they were serious, with death resulting in four cats. The deaths were considered to be associated with the severity of the underlying pulmonary disease. Complications were predominantly

Bronchoscopic bronchoalveolar lavage (BAL) samples are taken after visual inspection. The bronchoscope is removed from the airway and the biopsy channel rinsed and the outer surface wiped. The bronchoscope is then reintroduced and wedged in the smallest bronchus that accommodates it. Three 10-mL aliquots of warmed, sterile saline are introduced and then retrieved.121 The technique for blind bronchial lavage170,222 is described in Box 30-3 (Figure 30-12). Samples collected should be assessed cytologically and submitted for culture and sensitivity testing. Samples should be evaluated promptly because storage for 48 hours may alter cytologic evaluation.193 Table 30-3 summarizes normal bronchial lavage cytologic findings from several studies. BAL findings are dependent on cell recovery and yield, which is influenced by the distribution and location of lesions in the lung. One study found poor correlation between BAL cytology findings and histology199; however, this is in direct contrast to a prior study that found good correlation.91 A retrospective of 88 BAL specimens from 80 cats with broad-ranging lower respiratory diseases found inconclusive results in 28 cases.79 Series of cats with bronchial disease have mostly shown consistent BAL cytologic findings. Moise and colleagues188 recognized exudates in 58 of 65 bronchial washes. Dye and colleagues63 showed that severely affected cats with bronchial disease had significantly higher percentages of eosinophils or neutrophils (or both) than moderately affected cats compared with normal cats. Corcoran and coworkers45 found that 16 of 24 had BAL cytologic findings consistent with bronchial disease, and the other eight cats had milder radiographic changes. Foster and coworkers75 found no association between BAL cytology or radiographic severity and disease severity, but no direct comparison of cytology to radiologic changes were made. These findings can be summarized as follows: BAL will give helpful clinical information in most (but not all) cases with diffuse bronchial disease. Generalized interstitial disease or focal lesions are less likely to lend themselves to cytologic diagnosis from BAL.


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BOX 30-3 Blind Bronchoalveolar Lavage Technique Equipment 1. Two sterile 10-mL red-top blood collection tubes to submit samples for cytology and culture 2. Sterile endotracheal (ET) tube (usually 4 mm) 3. Two or three sterile 10-mL syringes filled with 5-mL aliquots of warmed sterile 0.9% saline 4. Sterile red rubber feeding tube or polypropylene catheter (usually 8 French). The end of the red rubber feeding tube should be cut off and smoothed so that the sterile saline will flow more easily than through the side holes. The proximal end of the feeding tube may also need to be trimmed so that the syringe will fit. 5. Laryngoscope and topical lidocaine

Procedure 1. Premedicate with an injectable bronchodilator such as terbutaline. 2. Administer a short-acting intravenous anesthetic agent (e.g., propofol, ketamine, midazolam). The entire procedure will only take a few minutes if all the equipment is organized in advance. 3. Desensitize the larynx with topical lidocaine, and use the laryngoscope to insert the sterile endotracheal tube, trying to avoid contamination of the tip of the tube in the oral cavity. 4. Provide a few minutes of supplemental oxygen before the procedure. 5. With the cat in lateral recumbency, the sterile red rubber feeding tube or polypropylene catheter is inserted into the lumen of the endotracheal tube and advanced until resistance is felt when the tip is lodged in a small airway. Do not force the catheter too far into the airway, or trauma may result.

6. A syringe with warmed saline is attached to the end of the red rubber feeding tube or catheter and a 5-mL aliquot is instilled. With gentle suction the fluid is aspirated back from the airways. When negative pressure is felt on the syringe, suction should be decreased, the catheter backed out slightly, and aspiration continued. The hindquarters of the cat can be elevated to facilitate aspiration, and gentle coupage of the chest wall may also be helpful. The presence of foam in the aspirated fluid indicates surfactant and a successful deep alveolar lavage. The volume of saline retrieved is typically less than half of what was instilled. If an inadequate volume is retrieved, a second aliquot can be instilled and the procedure repeated. Typically a total volume of 5 to 10 mL sterile saline is required to retrieve adequate samples, although total volumes of up to 60 mL have been described in cats. 7. The red rubber feeding tube or catheter is removed from the endotracheal tube, and supplemental oxygen is provided until the cat is ready for extubation. Elevating the hindquarters and providing gentle coupage can assist in clearance of remaining fluid from the airways. Once the endotracheal tube is removed, the cat should be closely observed for respiratory distress for the next 15 to 30 minutes. 8. Samples collected should be divided into sterile red-top blood collection tubes and submitted for cytology as well as culture.

Adapted from McCarthy G, Quinn PJ: The development of lavage procedures for the upper and lower respiratory tract of the cat, Irish Vet J 40:6, 1986; Reinero CR: Bronchoalveolar lavage fluid collection using a blind technique, Clinician’s Brief 8:58, 2010.

Fine-Needle Aspiration Focal lesions can be assessed by FNA. Although aspiration is the commonly used term for this technique, it is a misnomer because, when tissue samples are obtained by ultrasound guidance, the needle tip (with attached syringe) should be moved back and forth gently within the lesion 5 to 10 times, instead of using negative pressure to obtain lung tissue. This technique has been described as “woodpeckering”; it decreases sample volume but improves the cellularity of the sample because there is less hemodilution.180 The reported accuracy of samples obtained by FNA compared with histopathology ranges from 83% to 89%.52,266,290

Lung Parenchymal Biopsy FIGURE 30-12 Blind bronchoalveolar lavage. Note that the 8F feeding tube is within the endotracheal tube.

Lung parenchymal biopsy may be warranted when a diagnosis cannot be reached and empiric treatment has

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TABLE 30-3 Bronchial Lavage Cytologic Findings of Normal Cats: Cell Counts and Percentage of Major Cell Types Found Total Nucleated Cell Counts (/µL ± SEM)

Authors (year)

Alveolar Macrophages (%)

Eosinophils (%)

Neutrophils (%)

300

90.5

7.5

0.7

Hawkins et al (1990)

241 ± 101

70.6

16.1

6.7

211

301 ± 126

*

25

*

Lecuyer et al (1995)

280 ± 270

60

11

24

Mills et al (2006)184

185

71

7

6

Dehard et al (2008)54

567 ± 74

89

3.1

7.4

170

McCarthy, Quinn (1986) 102

Padrid et al (1991)

144

SEM, Standard error of the mean. *Unreported. Alveolar macrophages are noted as “cell type most frequently encountered.”

not been successful. A surgical technique of obtaining lung biopsies by a “keyhole” approach has been described. Smaller incisions result in less tissue trauma.200 Nevertheless, the decision to obtain lung biopsy samples should be weighed against the potential additional morbidity that may be created by thoracotomy in a cat with respiratory disease.

LOWER RESPIRATORY TRACT DISEASES LRT diseases may be defined as noninfectious or infectious. Noninfectious LRT disease can be considered as non-neoplastic or neoplastic. By far the most common LRT disorders encountered are idiopathic bronchopulmonary diseases,79 commonly referred to as feline asthma and chronic bronchitis.

ASTHMA AND CHRONIC BRONCHITIS Definition There are no formal definitions of feline idiopathic, inflammatory airway diseases, highlighting the fact that these diseases are still poorly understood. The terms asthma, bronchial asthma, allergic bronchitis, acute bronchitis, and chronic bronchitis have all been borrowed from human medical literature. The cat is the only animal species that commonly develops a syndrome of asthma similar to that experienced by humans, with eosinophilic airway inflammation, spontaneous bronchoconstriction, and airway remodeling.208,227 Despite these similarities, direct comparison between human and feline lower airway disease is difficult because pulmonary function testing is used to help classify bronchial diseases in humans, and this testing is not readily available for cats.188,227 Essentially, asthma is defined as reversible bronchoconstriction, and chronic bronchitis results from airway

remodeling, leading to fixed airway obstruction. Clinically, reversible bronchoconstriction (the defining feature of asthma) can be recognized by the rapid response to treatment with a bronchodilator such as terbutaline, and chronic bronchitis requires the presence of a daily cough (which may be intermittent with asthma).207 Asthma is characterized by predominantly eosinophilic airway inflammation and chronic bronchitis by nondegenerate neutrophilic inflammation.135,192,278 Because the diagnosis, prognosis, and management overlap considerably, these conditions will be considered concurrently.

Epidemiology One study recognized 128 cases of feline bronchial disease compared to 13,831 hospital admissions over the same period, giving a disease prevalence of approximately 1%.188 Cats with idiopathic bronchial disease can present between 4 months and 15 years of age, with a mean age of 4.9 years in one study63 and medians of 5, 5.5, 6, and 9 years reported in others.2,45,75,260 Sex predisposition findings have been inconsistent, with two studies finding two thirds of cases to be female,2,188 another two studies finding two thirds to be male,63,260 and two others finding no sex predispositions.45,75 Two North American studies found Siamese to be overrepresented, accounting for between 16% and 17% of cases, with one of these studies compared to a hospital population of 0.6% Siamese cats over the duration of the study63,188; one European study reported 12 of 22 cats (55%) to be Siamese, compared with a hospital prevalence of 30%.2

Etiopathogenesis The clinical signs of feline bronchial disease can result from bronchoconstriction caused by increased airway reactivity or increased mucus production (or both) and smooth muscle hypertrophy arising from inflammation of the bronchial wall.121,207,208,278 The underlying cause of

airway inflammation is believed to be instigated by antigenic or allergic stimulation causing activation of a T-Helper 2 (Th2) response. A Th2 response instigates secretion of interleukins (IL) 4, 5, and 13, and this cascade results in recruitment of and subsequent degranulation of eosinophils. Degranulation of eosinophils results in damage and destruction of the epithelial lining of the airways.73,201 Cats with predominantly neutrophilic inflammation may have similar toxic damage with subsequent repair processes.121 The consequences of these responses are metaplasia and proliferation of airway epithelium, hyperplasia of mucous glands with production of excess mucus, hypertrophy and hyperplasia of airway smooth muscle, and distal emphysematous changes in the pulmonary parenchyma. Hyperresponsiveness of airway smooth muscle results in airway constriction in response to nonspecific stimuli such as airway irritants, allergens, parasites, and viral particles.121 Experimental models in which cats are first sensitized and then challenged with Bermuda grass antigen, house dust mite antigen, or pig roundworm (Ascaris suum) have been developed. These models have resulted in not only the clinical signs but also the airway hyperreactivity, typical airway cytology, and histologic lesions that are recognized in cats with naturally occurring bronchial disease.133,201

Clinical Signs Cats with bronchial diseases typically present for coughing, wheezing, loud breathing, and rapid or labored respiration. Exercise intolerance can be seen, and some cats present for general lethargy without the owner realizing that the signs are attributable to respiratory disease. Because coughing can be such an active process involving considerable abdominal effort, owners sometimes confuse it with regurgitation or vomiting and may mention gastrointestinal signs to the veterinarian at presentation. The frequency of clinical signs can vary from intermittent (with cats apparently entirely normal between episodes) to daily. Physical examination findings vary markedly. Cats presenting with severe respiratory distress should have only a cursory initial examination, during which the clinician’s aim is to determine if the clinical signs are from LRT disease or pleural effusion. Radiographs in the position most comfortable for the cat may be required to help make this distinction. Oxygen therapy should be instituted as soon as practicable, and a bronchodilator such as terbutaline (0.01 mg/kg subcutaneously) administered if bronchial disease is suspected. At the other extreme, some cats have no specific abnormalities present. In all but emergency situations, it is ideal to observe the cat before handling to watch for tachypnea and any signs of increased or prolonged expiratory


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effort. Auscultation often reveals increased expiratory sounds, which can sound harsh or wheezy. Chronic disease can result in a barrel-chested appearance and decreased thoracic compliance.

Diagnosis Idiopathic, inflammatory bronchial disease is the most common cause of coughing and wheezing in cats. There is no single diagnostic test that is pathognomonic for this diagnosis. Diagnosis is made on the basis of collection of diagnostic clues, the results of which can sometimes be inconsistent, and the exclusion of other known causes of lower respiratory disease, mainly parasitic (e.g., lungworm, heartworm) or other infectious causes. Other causes of respiratory signs, such as pleural effusion, cardiomyopathies, and neoplasia, are mostly distinguished on the basis of radiographic findings. In most cases radiography and bronchial wash analysis, together with clinical history and physical examination findings, will give enough information for a working diagnosis. Response to therapy is also a useful indication; most cats with asthma will respond to corticosteroid therapy within 1 week.207 Lungworm and heartworm can be difficult to rule out definitively; these parasites are considered in subsequent sections. Radiography Radiography is a vital aspect in diagnosis of lower airway disease but cannot provide a definitive diagnosis of the cause of bronchial disease. The radiographic finding of a bronchial pattern helps guide the clinician to determine the cause; however, the absence of such a pattern does not rule out bronchial diseases. Cats with bronchial diseases can have a variety of radiographic findings, including no abnormalities.45 One recent study assessed the radiographic findings of 40 cats with bronchial disease; 37 of 40 cats (92.5%) had a bronchial pattern, but a large number of these cats also had an unstructured interstitial pattern (30 of 40 cats). Nonspecific respiratory signs were also prominent, with lung hyperinflation (31 of 40), hyperlucency (21 of 40), and aerophagia (19 of 40) recognized. Further, lung soft tissue opacities were seen in 11 of 40 cats. This study also found variation in interobserver interpretation; however, there was disagreement in only 2 of 24 cases with severe bronchial disease.83 These findings are similar to one other study in which Foster and coworkers75 found a bronchial or mixed bronchial pattern in 20 of 22 cats (91%). Adamama-Moraitou and coworkers2 recognized a bronchial pattern in 16 of 22 cats (73%), whereas Corcoran and coworkers45 found a bronchial or mixed bronchial–interstitial pattern to be less consistent, occurring in only 17 of 29 cats (59%). Moise and coworkers188 used a bronchial pattern as part of the inclusion criteria but found that 46% also had an

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interstitial pattern and 37% also had a patchy alveolar pattern. The other consistent radiographic finding in cats with bronchial disease is collapsed lung lobes, occurring in 4% to 11% of cases*; the right middle lung lobe is most frequently collapsed because this lobe’s main bronchus has a dorsal-ventral orientation within the bronchial tree, so the accumulated mucus is subject to the effects of gravity.208 With chronicity, miliary broncholithiasis can develop that appears radiographically as a generalized nodular pattern with multiple mineral opacities.264 Figures 30-13 and 30-14 show the progression of radiographic appearance of a cat with bronchial disease over a 9-year period. In summary, a bronchial or bronchointerstitial pattern has a high correlation with idiopathic bronchial diseases, but other findings, including normal radiographs, still allow the possibility of this diagnosis. Airway Cytology and Culture Airway cytology and culture are important in the diagnosis of idiopathic bronchial disease, as well as to rule out specific causes of LRT disease, such as infection. As noted previously, samples can be obtained bronchoscopically (after bronchoscopic examination) or by blind BAL. There are no definitive guidelines for assessment of tracheobronchial wash cytology; contamination of samples is hard to avoid, and up to 75% of cases will result in light growth of bacteria that are not clinically relevant.63,75 Studies of healthy cats have found highly variable nucleated cell counts in BAL fluid, as well as a variation in the proportion of cell types; eosinophils have been reported to make up as much as 25% of the cells retrieved in normal cats (see Table 30-3).184,211 However, comparisons of bronchial wash cytology of cats with bronchial diseases, when directly compared with that of healthy cats, have shown higher cell counts in those cats with airway inflammation.54,63,187 Cell counts from normal cats are typically in the order of 200 to 300 nucleated cells/µL; however, counts as a high as 600/µL can occur. In contrast, cell counts can exceed 1500/µL with airway inflammation.54,102 The predominant cell type in bronchial wash fluid is alveolar macrophages, which can make up as much as 90% of the population of cells retrieved from healthy cats.54,170,171 For asthma and chronic bronchitis, the predominant cell type can be eosinophils or neutrophils.45,63,75,188 It has been suggested that asthma (reversible bronchoconstriction) can be characterized by eosinophilic inflammation, and chronic bronchitis (permanently remodeled airways) may have neutrophils as the predominant inflammatory cell present.278 Although this has not been confirmed clinically, experimental models in which cats are sensitized to an antigen such as Bermuda grass or house dust mites have shown substantial increases in BAL eosinophil *References 2, 45, 75, 83, 188, 260.

proportions from less than 10% to 35% to 45%.145,201 The proportions of inflammatory cells found in wash cytology are not always mentioned in clinical reports, but in one study all eosinophilic exudates comprised more than 60% eosinophils,75 and another noted that mixed cell exudates contained 30% to 50% eosinophils.188 Although a mean of 25% eosinophils was found in one population of healthy cats,211 it could be expected that 25% eosinophils from a wash of 1500 to 3000 nucleated cells/µL would have greater significance than the same proportion found in a wash of only 200 to 300 cells/µL. A large proportion of eosinophils may also reflect other conditions, such as parasitism, which must be ruled out. When the neutrophil population is elevated, the distinction of inflammatory disease from infection must be made. As well as the expectation of a positive culture result (from bacterial infection), the neutrophils associated with infection can be expected to show toxic, degenerative changes, whereas nondegenerate neutrophils resembling those of normal peripheral blood would be expected with inflammatory, noninfectious disease. Not only is culture of Mycoplasma spp. important to rule out pneumonia, but this organism may have an interaction with idiopathic bronchial diseases.35,76,78,273 Mycoplasma spp. infections will be considered with infectious bronchial diseases. Less Routine Diagnostic Interventions BRONCHOSCOPY

Bronchoscopy requires specific training and experience because the procedure carries the risks of bronchospasm and pneumothorax. The consequences of these risks are increased because the patient cannot be intubated. In competent hands bronchoscopy allows direct visualization of airways and a means of guided BAL. However, in most cases, bronchoscopy is not required to make an accurate diagnosis of asthma or bronchitis. COMPUTED TOMOGRAPHY

CT provides more precise imaging information than radiography. Specifically for lower airway diseases, CT can provide precise information about airway thickening, mucus accumulation, and lung lobe consolidation. EXHALED BREATH CONDENSATE ANALYSIS

Exhaled breath condensate (EBC) analysis has been assessed experimentally in cats.136,253 Essentially, increased concentrations of particular biomarkers are recognized in the exhaled air of people, and this technique has been applied to cats to measure exhaled hydrogen peroxide (H2O2). This noninvasive technique involves cats being placed in a chamber similar to an oxygen chamber; the exhaled air is passed through a steel tube that runs through an ice bath for condensation of the exhaled air. The steel tube is disconnected and shaken vigorously to collect the condensate droplets, which are then assessed


A

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B

D C

E

F

FIGURE 30-13 Progression of radiographic appearance (right lateral views) of a cat with bronchial disease over 9 years. A, A bronchointerstitial pattern, with the interstitial change focused about the bronchial tree. Hyperinflation of the lungs is evident. Initially, the cat was diagnosed with Mycoplasma infection. B, Six weeks after the prior radiograph, after treatment with doxycyline during that time. Note improvement in the interstitial pattern, with a bronchial pattern predominating. Bronchoalveolar lavage at this stage showed eosinophils predominating. C, Three years after the initial radiographs. Although the bronchial pattern is less intense, there is evidence of early stage mineralization about the airways. D, Five years after the initial radiographs. Mineralization is more obvious and beginning to organize into nodules. E, Seven years after the initial diagnosis. Note an organized nodular pattern with multiple mineral opacities, typical of broncholithiasis. A collapsed lung lobe is also visible caudoventrally; this is more evident on the dorsoventral view (see Figure 30-14). F, Nine years after the initial diagnosis. Note further broncholithiasias; where lung is visible caudally, a bronchial pattern can be seen. After the initial course of doxycyline, this cat remained on prednisolone and terbutaline, which (for the most part) managed this cat’s clinical signs for the duration of this series.

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criteria for this study); concurrent allergic skin disease and lower airway disease had not previously been reported.190

Treatment Aims Treatment aims are as follows: 1. To reduce airway smooth muscle contraction (bronchodilators) 2. To decrease underlying inflammation (corticosteroids)

FIGURE 30-14 Dorsoventral view of cat with chronic bronchial disease in prior figures. Note that the collapsed lung lobes (marked with green arrows) are dependent lobes. There is also marked broncholithiasis.

to measure H2O2, considered to be a marker of lower airway inflammation.136,253 PULMONARY FUNCTION TESTING

Pulmonary function testing is commonly used in people to determine airway resistance associated with reduced airway diameter caused by bronchoconstriction and mucus accumulation. There are descriptions of pulmonary function testing in cats, but this testing is not widely available.63,111,134 Plethysmography allows pulmonary function testing in conscious cats by calculating expiratory time and peak inspiratory and expiratory flows from a cat in a sealed (and calibrated) Plexiglas box.111,134 IDENTIFICATION OF ALLERGENS

Identification of allergens has been performed for cats with bronchial diseases in both clinical190 and experimental145,198 settings with both intradermal skin testing(IDT)145,190 and IgE serology.145,190,198 These studies show promise, and if specific allergens can be identified, immunotherapy is conceivable as a treatment option. The remaining obstacles for allergy testing of cats with lower respiratory disease are that positive allergen reactions reflect only exposure and may not be clinically relevant. Further, IDT in cats is regarded as problematic to interpret because subtle positive reactions occur and repeatability of both serum IgE and IDT testing cannot always be demonstrated.190 Interestingly, one study found case recruitment difficult because numerous cats had concurrent allergic skin disease (an exclusion

Use of bronchodilators is the primary method of treatment when acute signs develop but are not appropriate as sole therapy. It is important to recognize that human (and most likely feline) airways show evidence of chronic, ongoing inflammation whether the patient is showing clinical signs or not; thus many cats require long-term treatment with corticosteroids.208 Asthma is a chronic disorder without a cure, and even well-controlled patients may experience occasional exacerbations of clinical signs. Although the prognosis for most patients receiving appropriate diagnostic evaluation and treatment is good for control of disease, owners should have realistic expectations about the need for long-term therapy. Emergency Treatment Cats presenting with acute respiratory distress such as open-mouth breathing or abdominal breathing should be handled minimally (to reduce further stress). The clinician’s primary aim should be to distinguish LRT disease from pleural effusion or pulmonary edema; to this end, survey radiographs should be taken in the position most comfortable for the cat (usually dorsoventrally, with the cat supported by its elbows) after the patient has been stabilized as much as possible. It is appropriate to provide the cat with an oxygen-rich environment; details of supplementary oxygen–delivery techniques can be found in Box 30-5 later in the chapter. A bronchodilator such as terbutaline should be administered at 0.01 mg/kg parenterally. A response is usually seen in 10 to 30 minutes. The response to terbutaline alone can aid in the diagnosis of bronchoconstriction as the cause of respiratory distress. Terbutaline can be readministered 30 minutes later at the same dose if minimal effect has been noted. An alternative is to administer salbutamol–albuterol using an MDI (discussed later). The typical dose is 2 actuations every 30 minutes as needed. The drug takes effect rapidly with improvement in clinical signs seen in less than 5 minutes. If oxygen therapy and bronchodilation do not substantially reduce respiratory rate and effort, corticosteroids such as dexamethasone sodium phosphate (0.2 to 1 mg/kg, intravenously or intramuscularly) can be administered. Failure

to respond to these therapeutic measures should alert the clinician to other causes of respiratory distress. Long-Term Treatment Corticosteroids Corticosteroids are the mainstay for treatment of inflammatory airway disease, having demonstrated success in several clinical studies.45,75 Corticosteroids reduce inflammation and migration of inflammatory cells into the airway. However, there have been few studies to determine efficacy or optimal dosing routines for systemic corticosteroids in cats with asthma. One study has shown that prednisolone administered at 5 mg/cat every 12 hours orally for 2 weeks resulted in a significantly lower percentage of eosinophils (mean = 5%) in BAL cytology compared with a control substance (mean eosinophils = 33.7%).226 Typical recommendations are for prednisolone to be administered at 1 to 2 mg/kg every 12 hours for 5 to 10 days before tapering the dose over at least 2 months (e.g., reducing at weekly intervals until 0.5 mg/kg every second day).121,208 Treatment with injectable long-acting corticosteroids (e.g., methylprednisolone acetate, 10 to 20 mg/cat, intramuscularly every 4 to 8 weeks) is the least desirable approach and should be reserved for patients for which no other method of drug administration is possible. Chronic use of these formulations often results in serious side effects, such as weight gain, diabetes mellitus, and an impaired immune response. Owners should be fully informed of the significant risks of this form of therapy. Inhaled corticosteroids have been used to manage feline bronchial diseases for over a decade.204 In veterinary medicine human MDIs containing a propellant rather than dry powder inhalers (e.g., Diskus inhalers) are used. Inhalational delivery of corticosteroids by use of MDI allows for local antiinflammatory activity while minimizing systemic absorption and the potential adverse effects that may arise. Systemic absorption of inhaled medications still occurs with some drugs; one study demonstrated hypothalamic–pituitary–adrenal axis (HPAA) suppression in healthy cats receiving 250 µg flunisolide every 12 hours,223 but another study of cats receiving 220 µg fluticasone every 12 hours showed no suppression.40 Research using nebulized radiopharmaceutical agents has demonstrated that inhaled medications delivered using a face mask and spacer can be distributed throughout the lung fields of cats.242 The most commonly used inhaled corticosteroid is fluticasone, although others are sometimes available (e.g., beclomethasone) and may be less expensive (but potentially less effective). Fluticasone has the longest half-life of the available inhalant corticosteroids, is the most potent, and is the least likely to be absorbed systemically.205 The drug is available in three strengths per actuation, with the labeling varying by country: 44 or 50 µg, 110 or 125 µg, and 220 or 250 µg. In the United States, MDIs are labeled by the amount of drug delivered at the


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mouthpiece, whereas in other countries, they are labeled by the amount of drug delivered from the valve, which accounts for what appears to be different strengths of the same product. Inhaled fluticasone at doses of 44 µg every 12 hours and 110 µg every 12 hours was found to be effective in ameliorating signs and reducing inflammation in experimentally induced eosinophilic airway inflammation.40 Further, 220 µg of inhaled fluticasone every 24 hours reduced the inflammatory response in cats with neutrophilic airway inflammation (but no clinical signs).135 Each MDI delivers a set dose per actuation (a “puff”), and each container has a fixed number of doses. For MDIs that do not include a dose-counting mechanism, the owner must keep track of the doses used so that an empty container is not used. MDIs require slow, deep inhalation on the part of the patient. This type of inspiration is not possible for animals and infants, so a spacer and face mask must be used. Spacers decrease the amount of drug deposited in the oropharynx. A spacer and face mask of appropriate size for cats should be used (e.g., AeroKat, Trudell Medical International). To administer the medication, the MDI is shaken to open an internal valve in the canister and is then attached to the spacer. If the spacer does not contain a valve, the spacer and mask should be applied to the cat’s face before the MDI is actuated. The MDI is then actuated to deliver the drug into the spacer and the owner should observe the cat take 7 to 10 breaths to ensure that the drug has been inhaled. The AeroKat system has an indicator valve that makes it easier for the owner to tell when the cat takes a breath. If a patient is receiving both an inhaled bronchodilator and corticosteroid, the bronchodilator should be administered first and the corticosteroid 5 to 10 minutes later. The owner should follow the manufacturer’s instructions for cleaning and maintenance of the mask and spacer system. It has been stated that the most effective long-term treatment of asthma is systemically administered corticosteroids,208 and it is prudent to start severely affected cats with oral prednisolone with a view to maintenance with inhaled fluticasone when the severity of signs has decreased. It is appropriate to start therapy with inhaled fluticasone in mildly to moderately affected cases. Anecdotal responses indicate that 44/50 µg fluticasone is not always effective clinically but that 110/125 µg every 12 hours is effective in managing most cases of mild to moderate disease and cats with more serious disease require 220/250 µg every 12 hours; it has been suggested that once-daily dosing is occasionally effective and dosing less often is not helpful.208 Inhaled corticosteroid therapy is considerably more expensive than oral therapy, and cost will be a barrier for some owners. The author’s approach to corticosteroid use in severe cases has been to use oral prednisolone, starting at 10 mg/cat every 24 hours or 5 mg/cat every 12 hours

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and tapering weekly until 5 mg/cat every second day is reached. At this point inhaled therapy with fluticasone can be started on the days prednisolone is not given; it should be given daily when the cat has been weaned from prednisolone entirely. It may take 1 to 2 weeks for fluticasone to take effect, so weaning from oral prednisolone should take place over a 2- to 3-week period. Mild to moderately affected cats can be started with inhaled fluticasone (without use of systemic corticosteroids). The author uses an MDI product containing 250 µg fluticasone combined with 25 µg salmeterol and has found that most cats can be managed at dosages between one puff every second day and two puffs twice a day. MDIs containing fluticasone combined with salmeterol are not available in all countries, although they may be available as separate products. Salmeterol is available as 25 µg/ actuation in some countries and as 21 µg/actuation in others. Management appears to be most successful when the dose is started higher and reduced at 1- to 2-week intervals to the lowest effective dose.

Avoidance of oral corticosteroids may be important for certain patients with concurrent diseases, such as diabetes mellitus or herpesvirus infection. In one series of 300 cases,206 80% of 246 cats with mild to moderate disease were weaned from oral corticosteroids and maintained on inhaled fluticasone alone. Of 54 cats with severe disease, 63% were weaned from oral corticosteroids and maintained on inhaled fluticasone. The remaining cats were maintained on a combination of oral and inhaled corticosteroids, but in most cases with a lower oral dose than if inhaled medication was not used. About 85% of owners were able to use a mask and spacer system effectively, and the rate of adverse effects was low, such as 5% of cats with ocular irritation. Box 30-4 provides details of guidelines for the use of inhaled medications in cats (Figures 30-15 and 30-16). BRONCHODILATORS

Because bronchoconstriction is considered a major aspect of inflammatory airway disease, bronchodilators can be

BOX 30-4 Guidelines for Use of Inhaled Medications in Cats Inhaled medications have been successfully used to manage bronchial diseases in cats for more than a decade. Successful therapy depends on habituating the cat (and the owner) to receiving (and giving) medication in this way. There are several commercially available spacers designed for both veterinary and human pediatric use. The clinician should explore available options and become familiar with the equipment. Choices of chamber and mask should be made based on the basis of the following factors: 1. Size of chamber: Ideally, the size of the chamber should be appropriate for a cat’s tidal volume (10 to 20 mL/ kg). Veterinary brands and those designed for human neonates that are approximately 10 to 12 cm long and 3 to 4 cm in diameter are appropriate. 2. Is there a valve present? Presence of a valve between the chamber and the mask allows preloading of the chamber. This reduces the potential stress of the noise of actuating the metered dose inhaler. When using a chamber without such a valve, the owner may need to habituate the cat to the sound of the actuation. 3. Does the mask fit snugly over the cat’s muzzle? Commercial spacers usually have a specially shaped opening that allows only their brand of mask to be fitted. Veterinary systems often include more than one size of mask. Sometimes masks can be cut down to fit better. Habituation: 1. Some cats dislike the mask being placed over their muzzle. These cats can be introduced to the mask slowly by offering food from the mask (just a few kibbles) without the chamber attached for

approximately 1 week and then allowing the cat to breathe air through the mask before attaching the chamber. After a few weeks, medications can be introduced to the chamber. Cats may need oral medication during the period of habituation. 2. When using a chamber without a valve, the owner may need to habituate the cat to the sound of the actuation. Dosing: 1. Anecdotal information indicates that 44 to 50 µg fluticasone is not effective clinically but that 110 to 125 µg every 12 hours is effective in managing most cases of mild to moderate disease and that cats with more serious disease require 220 to 250 µg every 12 hours; it has been suggested that once-daily dosing is occasionally effective and dosing less often is not helpful. 2. The author uses an MDI with 250 µg fluticasone/25 µg salmeterol and has found that most cats can be managed between one puff every second day and two puffs twice day. Management appears to be most successful when the dose is started higher and reduced at 1- to 2-week intervals to the lowest effective dose. 3. Albuterol/salbutamol 90 to 100 µg per actuation can be used before administering fluticasone or, in emergencies, every 30 minutes for up to 4 to 6 hours. Chronic use of albuterol/salbutamol is not recommended. 4. It may take 1 to 2 weeks for fluticasone to take full effect, so some patients may benefit from concurrent administration of oral prednisolone in tapering doses over 2 to 3 weeks.

FIGURE 30-15 Metered dose inhaler connected to chamber and mask ready for delivery of inhaled medication. The mask should fit snugly and comfortably over the cat’s muzzle. The ideal chamber size should approximate the cat’s tidal volume.

FIGURE 30-16 Administration of inhaled medications should be in a relaxed setting where the cat feels comfortable.

expected to be beneficial. Reductions in airway obstruction have been demonstrated with the beta2-receptor agonists, terbutaline (intravenously)63 and a combination of inhaled salbutamol (albuterol) and ipratropium.132 The bronchodilatory effects of inhaled salbutamol, salmeterol, and ipratropium have also been demonstrated against induced bronchoconstriction in healthy cats.148 There are three major classes of bronchodilators: beta2-receptor agonists, methylxanthines, and anticholinergics. BETA2-RECEPTOR AGONISTS The most commonly used beta2-receptor agonists are terbutaline (mostly used through injectable routes or orally) and salbutamol/ albuterol (mostly used as an inhaled medication but available in oral preparations). Beta2-receptor specificity should reduce cardiovascular side effects, but tachycardia


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has been recognized with terbutaline.63 Terbutaline can be given parenterally (subcutaneously, intramuscularly, or intravenously) at 0.01 mg/kg63,64,175 for emergency care and is recommended to be given before bronchoscopy or blind BAL. Oral dosing has been determined to be 0.625 mg every 12 hours.64,175 Terbutaline should be used with care in patients with preexisting cardiac disease, hyperthyroidism, hypertension, or seizures. Salbutamol (International Nonproprietary Name) and albuterol (United States Adopted Name) are different names for the same drug. The drug is available in an MDI as salbutamol (100 µg/actuation) in most of the world and as albuterol (90 µg/actuation) in the United States. In humans salbutamol or albuterol results in significant bronchodilation within 5 to 15 minutes and lasts for 3 to 4 hours.65 Similar results have been found in cats; the longer acting beta2-receptor agonist salmeterol had less effect but lasted for 24 hours.148 There are two forms (enantiomers) of salbutamol or albuterol, the pharmacologically active R-salbutamol or albuterol and inactive S-salbutamol or albuterol; most formulations available are combinations of the two forms, with the proportion of active form varying from 16% to 50%.4,100,117,202,228 Chronic use of the inactive form can result in worsening airway inflammation in humans100,117,202 and in cats.228 Where available, single enantiomer R-salbutamol or albuterol should be used. It is used once daily when needed and is administered before fluticasone. Salbutamol or albuterol should be used with care in patients with preexisting cardiac disease, hyperthyroidism, hypertension, or seizures. The addition of inhaled long acting beta2-agonists to corticosteroids is believed to increase the efficacy of inhaled corticosteroid effects in moderate to severe asthma and chronic obstructive pulmonary disease in humans.36 The author uses 100 µg salbutamol or albuterol as emergency treatment and 25 µg salmeterol (combined with fluticasone) as maintenance therapy for cats with stable disease. METHYLXANTHINES Theophylline and aminophylline are not recommended for routine use; however, propentofylline may show promise. Drugs of this class are generally considered less potent bronchodilators than beta2-agonists209 and remain controversial in human respiratory medicine, with some authors considering these drugs obsolete for airway disease.141 The recommended dose of standard-preparation theophylline is 4 mg/kg orally every 8 to 12 hours; the sustained release preparation dose has been reported at 10 mg/kg orally every 24 hours121 and 25 mg/kg orally every 24 hours.208 However, sustained-release formulations known to have acceptable pharmacokinetics in cats, such as Theo-Dur, were discontinued more than 10 years ago. Extendedrelease formulations from various manufacturers do not have the same pharmacokinetics, preventing

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extrapolation of doses from brand to brand and making routine use of these products impractical. In addition, there are several known drug interactions with theophylline that the clinician must consider. The dose rate for aminophylline is reported to be 5 to 6 mg/kg orally every 12 hours.208 A recent clinical study indicated that cats treated with propentofylline (a methylxanthine derivative marketed for dementia in dogs) improved more on owner and clinician scoring as well as radiographic features than those treated with prednisolone alone.260 This drug’s usefulness could be assessed further by a crossover study (which is not usually practical for a clinical study as was undertaken). ANTICHOLINERGICS Anticholinergics are not widely used in veterinary medicine. Several recent papers have indicated synergistic benefit of inhaled ipratropium bromide when used with salbutamol in healthy cats148 and experimentally allergen-sensitized cats.132 These drugs may prove useful in cats with severe disease in which more routinely used bronchodilators are not sufficiently helpful. Other Therapies ANTIBIOTICS

Antibiotic use is not warranted in a great majority of cases of feline idiopathic airway disease. Antimicrobial therapy should be instituted only on the basis of culture and sensitivity findings from bronchial wash fluid. However, a positive culture result does not always indicate a lower respiratory infection and must be interpreted on the basis of cytologic findings, whether there is pure or mixed growth, and how heavy the growth is. Generally, greater than 105 organisms/mL is consistent with infection.208 LRT infections with Mycoplasma spp. have the strongest association with idiopathic airway disease. Mycoplasma spp. have not been isolated from airways of healthy cats,221 and associations have been made with human asthma and mycoplasma infection.76,78 Treatment with doxycycline 5 mg/kg orally every 12 hours for 3 weeks is effective to clear infection in most cases. More information about mycoplasma infections appears later in this chapter in the section about LRT infections. CYCLOSPORIN-A

An initial study indicated that cyclosporin-A (CsA) inhibits late phase asthmatic responses in experimentally induced allergic airway disease in cats,210 but a subsequent study by the same investigators showed that CsA treatment does not inhibit the early phase asthmatic response or mast cell degranulation.185 No further work appears to have been done, and no recommendations to use CsA for idiopathic lower airway disease can be made as of this writing.

ANTIHISTAMINES

One study has demonstrated that cyproheptadine blocks airway smooth muscle contraction in vitro,212 but the author of this paper has stated that clinical observations do not support these in vitro findings.208 A subsequent study showed minimal reduction in BAL eosinophil percentage compared with a control substance and far less reduction than inhaled or orally administered corticosteroids; however, two of six cats did indicate reduced airway resistance.226 A more recent paper confirmed minimal reduction in BAL eosinophil percentage for both cyproheptadine and another antihistamine, ceterizine, compared with a placebo in experimentally induced allergic airway disease.240 No recommendations to use antihistamines for idiopathic lower airway disease can be made as of this writing. ANTILEUKOTRIENES

Antileukotrienes such as zafirlukast or montelukast have been advocated for the treatment of feline bronchial diseases.165 However, one study failed to show any significant reduction in BAL eosinophil percentage for zafirlukast compared with a placebo in experimentally induced allergic airway disease.226 There is no evidence to support the use of this class of drug for feline bronchial diseases. OMEGA-3 POLYUNSATURATED FATTY ACIDS

A recent study has indicated a significant modulation in the development of allergen-induced airway disease in cats administered a combination of lipid extract of New Zealand green-lipped mussel (providing omega-3 polyunsaturated fatty acids) and lutolein.147 This treatment shows promise as a therapeutic option for feline allergic airway disease. IMMUNOTHERAPY

The identification of allergens responsible for lower airway disease allows the possibility of allergen-specific immune therapy. Several studies from the same investigative group have demonstrated the success of immune therapy in experimentally induced allergic lower airway disease.146,224,225 Because disease was experimentally induced in these cases, the inciting allergen (Bermuda grass allergen) was known; the challenge remains to demonstrate efficacy in natural cases where the inciting allergen (or allergens) must be determined from intradermal skin testing (notoriously difficult in cats) or IgE serology. Nevertheless, immunotherapy holds great promise not only to manage allergic airway disease (as other treatments do) but actually to cure the underlying disease so that ongoing therapy is no longer required. Long-Term Management In the great majority of cases, cats with lower airway disease require chronic, mostly lifelong, treatment.


Cats undergoing long-term therapy (for any condition) should be assessed at regular intervals. Follow-up visits should be scheduled approximately 2 weeks after instituting therapy, 1 month later, and subsequently every 3 to 6 months. The schedules are not fixed and cats should be seen ahead of schedule if the cat fails to respond to treatment. The initial visits are important to assess not only the cat’s response to therapy but also the owner’s ability to administer medication, whether inhaled or oral. As well as the cat’s clinical signs at home at examination, doses and frequency of medication should be assessed and confirmed. Home control measures should be discussed with the clients, such as avoidance of aerosol triggers such as cigarette smoke, fireplace smoke, and dusty cat litters; use of air filters can also help control signs. Cats on long-term systemic glucocorticoid treatment should also have periodic blood glucose assessment. Repeat thoracic radiographs or other investigations may be warranted if a cat’s clinical signs persist, recur, or are not controlled entirely.

OTHER NONINFECTIOUS LOWER RESPIRATORY TRACT DISEASE The diagnosis of noninfectious, non-neoplastic causes of LRT disease in cats is often aided by clinical history. For example, a history of blunt trauma, exposure to smoke inhalation, lipid aspiration from owner administration of mineral oil, or electric shock is often known at the time of admission; likewise, aspiration pneumonia is usually associated with an esophageal disorder and chronic vomiting if not associated with anesthesia. The major exception to this generalization is idiopathic pulmonary fibrosis.

Idiopathic Pulmonary Fibrosis Despite few reports, idiopathic pulmonary fibrosis has been well characterized in one case series of 23 cats41 that included 16 cats from an earlier study,286 which detailed the histologic findings and compared the condition to that in people. Most cats in this study were middle-aged or older, with a median age of 8.3 years (range 1.9 to 15 years). Most cases present for respiratory signs— predominantly labored or rapid respiration but also coughing. Lethargy, anorexia, and weight loss are also prominent (but not always present). Respiratory distress is often recognized at presentation and is often inspiratory or mixed inspiratory and expiratory compared with bronchial disease, in which expiratory signs predominate. Respiratory sounds auscultated were described as harsh or loud in numerous cases and wheezes or crackles, or both were recognized in approximately half of the cases.41

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Radiographic changes affecting the parenchyma resulting in an interstitial or bronchointerstitial pattern are usually marked with diffuse involvement (Figure 30-17), but patchy distribution with greater severity in some regions (particularly caudal lung lobes) was recognized in 10 of 18 cats. BAL findings may show a mild increase in nondegenerate neutrophils or be normal. FNA, when performed, is either nondiagnostic or misleading. Diagnosis depends on histopathologic examination of affected lung tissue; either performed ante mortem by thoracotomy or thorascopic biopsy but usually at necropsy. The characteristic histopathologic finding is interstitial fibrosis with fibroblast or myofibroblast foci, honeycombing with alveolar interstitial smooth muscle metaplasia. Interstitial inflammation is not a prominent feature. As in people, coincident neoplasia may be present.41,286 CT has been used to diagnose idiopathic pulmonary fibrosis presumptively in people with an accuracy of approximately 90%; the key feature is cystic dilation of air spaces leading to peripheral honeycombing. Although this has not been described in cats, it may serve as a useful diagnostic aid.130 There is no known effective treatment. Corticosteroids (e.g., prednisolone at 10 mg/cat, orally every 24 hours) and bronchodilators (e.g., terbutaline) appear to help some cats but have no beneficial effect in many. Cyclophosphamide (12.5 mg orally, on 4 days out of 7) was used for several weeks in the only cat that was alive at the time the report was written. With no definitive cause or known pathogenesis, there can be no definitive treatment. Therapeutic approaches in human patients are aimed at interactions between fibroblasts and other pulmonary cells.41

Aspiration Pneumonia Aspiration pneumonia results from the aspiration of endogenous secretions or exogenous substances into the LRT. The extent of damage depends on the frequency, volume, and character of the aspirated material, as well as the effectiveness of host defense mechanisms. Defense mechanisms include airway closure during swallowing; cough reflex; mucociliary transport apparatus; and pulmonary cellular defenses, which minimize the degree of damage when minimal amounts of material are aspirated.265 Aspiration pneumonia is a potential consequence in cats with esophageal or swallowing disorders, including those that are anesthetized, comatose, or otherwise debilitated. Gastric contents are acidic and therefore result in chemical pneumonitis that can cause necrosis of bronchial and alveolar epithelium, as well as pulmonary edema. Supportive care with oxygen therapy is appropriate, and treatment for pulmonary edema may be required.265

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Aspiration of small amounts of inert substances such as water or barium (or less acidic gastric material) usually results in transient, self-limiting hypoxia. Larger volumes aspirated can result in asphyxia, and solid material aspirated may result in a more severe reaction than gastric fluid alone. Solid material, such as food particles, should be removed by suction or bronchoscopy and must be removed as soon as possible to prevent death from asphyxiation. Oxygen therapy and other supportive care should also be instituted.265 Bacterial pneumonia is a longer-term consequence, and preemptive antibiotics are appropriate. Overnight fasting before anesthesia reduces the risk of aspiration pneumonia as an anesthetic complication. Lipid aspiration pneumonia may result if mineral or paraffin oil is inhaled during oral administration for management of hairballs.34 Because such oils are nonirritating, they do not cause reflex inhibition of aspiration. The resultant pneumonia elicits an extensive macrophage response with fibrosis. A mixed alveolar– interstitial infiltrate is often seen in the middle lung lobe, but diffuse nodular densities that may be confused with metastatic lesions can also be seen.34,265 This condition can be fatal; bronchodilators and corticosteroids may help some cats, but effective treatment may require lobectomy. Endogenous lipid pneumonia can result when underlying obstructive pulmonary disease damages pneumocytes, allowing release of lipid from degenerating cells, which acts as a direct irritant to the lung and triggers an inflammatory response. This condition does not normally result in death, and the underlying condition should be managed.125

A

B

Trauma Thoracic trauma subsequent to automobile accidents or high-rise falls can result in pulmonary contusion (accumulation of blood and other fluids) or bullae (acutely formed pockets of air). Contused lung appears in a patchy alveolar pattern, similar to pulmonary edema; lung cysts appear as isolated air-fluid levels with poorly delineated margins within lung parenchyma and, if they rupture, can result in pneumothorax. Lung cysts and contusions are more obvious radiographically 24 to 48 hours after trauma. These lesions usually resolve with cage rest as other traumatic injuries are managed. Lung cysts sometimes require lobectomy of the affected lobe.6 C FIGURE 30-17 Left lateral (A), right lateral (B), and dorsoventral (C) radiographic views of cat with idiopathic pulmonary fibrosis. Note the diffuse reticular interstitial pattern present throughout all lung lobes. The left caudal lung lobe has consolidation caudally.

Smoke Inhalation Both carbon monoxide intoxication and direct bronc hopulmonary injury result from smoke inhalation. Compromise to surfactant activity causes atelectasis, resulting in necrotizing bronchiolitis and intraalveolar hemorrhage. Radiographic changes include diffuse


peribronchial densities or patchy, interstitial infiltration and, as with trauma, may not be apparent for 24 hours. Cats should be placed in an oxygen chambers (see Box 30-5), and bronchodilators are indicated. Prognosis depends on the degree of damage caused, which is associated with the amount of smoke inhaled.265

NEOPLASIA Primary pulmonary neoplasia is rare in cats179,182,267; no recent prevalence data are available, but the annual incidence was estimated at 2.2 per 100,000 cats approximately 30 years ago.267 Older cats are more likely to be affected, with a mean age of 10 to 14 years reported.13,179 Most tumors are adenocarcinomas of bronchial or bronchoalveolar origin.94 Presenting signs are most commonly referable to the respiratory tract and can include coughing, exercise intolerance, tachypnea, and dyspnea94; however, cats can present for nonrespiratory signs such as lethargy, inappetence, and lameness associated with metastasis to digits; this is also known as “lung–digit syndrome” and carries an extremely poor prognosis.87,189 Metastasis to other locations such as skin,217 skeletal muscle,142,181 and the eye32 has also been reported. Hypercalcemia of malignancy is possible,5,22,238 and hypertrophic osteodystrophy has been reported in 5% to 25% of cases.13,94 In many cases all lung lobes are affected when assessed radiographically, and pleural effusion is present in 35% to 65% of cases. Typical radiographic findings are a mixed bronchoalveolar pattern, an ill-defined alveolar mass, or a mass with cavitation. Some form of bronchial disease is often present and may represent local airway metastasis (Figure 30-18).10,13,179,182

FIGURE 30-18 Right lateral radiographic view of a cat with primary pulmonary adenocarcinoma. As well as the overt lung lobe consolidation and pleural effusion, local osteolysis of the ninth rib (red arrow) is evident and the two crurae of the diaphragm (green arrows) are not aligned. The tumor was adhered to the rib and one diaphragmatic crus.

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In comparison, pulmonary metastasis from other locations appears radiographically as interstitial nodules (either well or ill defined) or a diffuse pulmonary pattern. The latter often consists of an alveolar pattern with or without ill-defined pulmonary nodules or pleural effusion. The most commonly represented primary tumor is mammary gland adenocarcinoma.74 Definitive diagnosis depends on cytologic or histologic assessment. Ultrasound-guided FNA of discrete masses or pleural fluid can provide a cytologic diagnosis in many cases but can lead to missed diagnoses because of poor cell recovery as a result of small sample size, poor exfoliation of certain cell types and minimal exfoliation of certain cell types (e.g., mesenchymal cells), necrosis, or failure to obtain a representative sample.52 Histology of lung biopsy samples may be required for definitive diagnosis.52,199,200 The prognosis for long-term survival with pulmonary adenocarcinoma has been reported to be poor.13 The degree of differentiation of the tumor is the only recognized prognostic factor associated with survival in cats with primary pulmonary neoplasia; cats with moderately differentiated tumors survived a median 698 days (19 to 1526 days) compared with cats that had poorly differentiated tumors at 75 days (13 to 634 days), although all cats eventually died of metastatic disease. The overall median survival time is 115 days.95 Longterm individual treatment success is possible: A recent paper reported that a cat remained well, with no radiographic evidence of disease at 34 months after left-sided pneumonectomy and adjuvant chemotherapy with mitoxantrone, administered every 3 to 5 weeks, for 10 doses after surgery.38

LOWER RESPIRATORY TRACT INFECTIONS In most cases LRT infection results in pneumonia (inflammation of the lung parenchyma) in cats, although occasionally pathology is limited to the airways.17,78,161 Pneumonia is uncommon in cats, which is demonstrated by the scarcity of case series that have been published, including only 39 cases over 10 years161 and 21 cases over 5 years,78 each from teaching hospitals. The potentially serious nature of infectious pneumonia is highlighted by two17,161 of only three case series being postmortem studies; however, early recognition and intervention can lead to successful treatment, as noted in 18 of 20 cats in the only clinical cases series.78 Successful treatment has also been noted in numerous case reports.76,80 Isolation of organisms from BAL fluid or tissue obtained from focal lesions by way of FNA or fuller biopsy forms the basis for diagnosis of infectious pneumonia.78,161 Isolation of bacteria may represent contamination or commensal organisms, although culture of a

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single organism (“pure” culture) implies infection.207 Diagnosis of LRT infection, therefore, is based on identification of an organism with supportive historical, clinical, radiographic, and cytologic findings; further, diagnosis is confirmed only with an unambiguous response to appropriate therapy.78 Clinical signs may not relate directly to the respiratory tract. In one study 14 of 39 cats (36%) did not have respiratory signs,161 although in another, 18 of 20 cats (90%) had coughing (15 of 20) or dyspnea (3 of 20).78 Anorexia, lethargy, and fever were absent in 14 of 39 cats (41%) in one study,161 and pyrexia was noted in only 25% in another.78 Hematologic indication of infection (neutrophilia with or without a left shift) is helpful diagnostically if present but can also be absent.161 Infectious pneumonia is most often associated with an alveolar radiographic pattern, but any pattern is possible; one study found predominantly interstitial patterns (with normal radiographs in 3 of 13 cats),161 and another, although finding 67% with an alveolar pattern, also found 81% with a bronchial pattern.78 Neutrophils with toxic changes can be expected to predominate in bronchial wash fluid. Treatment requires appropriate antibiosis, ideally based on culture and sensitivity findings, as well as supportive care to maintain hydration and electrolyte balance. In some cases of focal pneumonia, pulmonary lobectomy may be required to effect a cure by removing the nidus of infection.191

Viral Until recently, most, if not all, viral causes of LRT infection were diagnosed with lung histopathology and specific viral detection techniques, such as virus isolation by culture, immunofluorescent antibody testing, electron microscopy, or PCR of pulmonary parenchyma obtained, in most cases, post mortem* but in one case ante mortem.124 In one recent paper, influenza A (H1N1), commonly known as “swine flu,” was identified by PCR of BAL fluid.255 Perhaps the increasing availability of PCR testing will allow more ante mortem diagnoses of viral pneumonia in such a manner. Most reported cases of viral pneumonia have been in kittens, but virulent strain calicivirus115,216 and influenza virus† have also been regularly described in adult cats. Additionally, a case series of nine cats with herpesvirus pneumonia included two adult cats.37 Herpesvirus Herpesvirus infections most often result in URT and ocular clinical signs. Necrotizing pneumonia arises in rare cases in kittens or otherwise immune-debilitated *References 17, 37, 115, 137, 157, 160, 161, 216. †

References 55, 137, 139, 157, 252, 255, 268, 291.

cats.* In a recent study, three of nine kittens were also FeLV positive.37 In all but one124 reported case, herpesvirus pneumonia has been fatal. The airways, as well as lung parenchyma, are affected either diffusely or in multifocal distribution with fibrinonecrotic pneumonia. Concurrent infections such as B. bronchiseptica or E. coli may be recognized, and these most likely represent secondary infection. In many cases typical signs of herpesvirus URT infections may be recognized before lower respiratory signs. There may be an overrepresentation of male cats for herpesvirus pneumonia37 (although not for herpesvirus causing only URT signs), but with so few cases recognized, this may be a statistical anomaly. The one reported case of survival from herpesvirus pneumonia also had orthopoxvirus demonstrated by immunohistochemistry and electron microscopy on a sample of lung tissue obtained by Tru-Cut biopsy. The cat was 5 years old, and herpesvirus infection was thought to be as a result of recrudescence. The cat required approximately 2 weeks of hospitalization with supportive care of intravenous fluids and parenteral broad-spectrum antibiotics.124 Calicivirus Pneumonia as a result of calicivirus infection was first described in the 1940s.9 Then, as now, most cases of calicivirus infection resulted in URT signs, often with glossal ulceration. Pneumonia usually cannot be demonstrated ante mortem, but necropsies often reveal grayish, densely consolidated areas in the anterior lobes. The disease is rarely fatal. These findings were confirmed with experimental infection studies in the 1970s that indicated pneumonia was transient and resolved with an appropriate immune response.112,220 Occasional reports of kittens dying with calicivirus pneumonia after natural infection160 were most likely associated with either an inability to mount an appropriate immune response or the pathogenicity of the strain of virus. Outbreaks of virulent strains of calicivirus (named FCV-Ari and FCV-Kaos) in the late 1990s and early 2000s led to new cases of calicivirus pneumonia.115,215,216 Signs referable to pneumonia were not a clinical feature of cats affected with these virulent strains of calicivirus, but severe pneumonia, often with secondary infection, such as with Aspergillus spp., was demonstrated postmortem. Distinctive clinical signs included facial and limb edema in febrile, anorexic, dehydrated cats, with hair loss and ulcerative dermatitis of the face and feet, and sudden death.115,215 In these outbreaks 33% to 50% of infected cats died. Cats need intensive supportive care of intravenous fluids and parenteral antibiotics. Phosphorodiamidate morpholino oligomers (PMOs) are compounds that enter cells to target viral-specific sequences and block viral replication. Use of an *References 17, 37, 69, 82, 113, 159, 247, 256.

anticalicivirus-specific PMO appeared to improve survival in cats affected with virulent calicivirus.249 The virus transmits readily, including by way of fomite dissemination, and sodium hypochlorite solution should be used for disinfection whenever contamination is suspected.115 These outbreaks of virulent calicivirus appeared to be self-limiting, but others may occur in the future given the nature of these organisms to mutate readily. More information on virulent calicivirus infections is found in Chapter 33. Influenza Until this century, clinical signs resulting from influenza viruses were not recognized in cats despite the recognition that cats mount an immunologic response and develop antibodies against experimental infection.110,213,232 The H5N1 avian influenza pandemic in southeast Asia from the early 2000s resulted in sporadic deaths from natural infection in domestic cats. Infection results from ingestion of the carcass of infected birds,139,252 and horizontal transmission to other cats by respiratory and gastrointestinal routes has been demonstrated after experimental infections.139 Infected cats can develop clinical signs, including significant pyrexia, in 1 to 5 days after infection, and virus attachment in the LRT can result in pneumonic signs in only 1 more day.139,230,274 The disease can be fatal, but some cats are asymptomatic, and this wide range of severity of clinical signs is thought to be dose dependent.149 Supportive care with intravenous fluids and parenteral, broad-spectrum antibiotics to treat secondary infection is warranted. There have been no reports of humans contracting the infection from diseased cats.101 The pandemic (H1N1) 2009 influenza virus (swine flu) was first reported in pigs in Canada in May of 2009281 and has subsequently been recognized in multiple species, including humans, on multiple continents. Natural infection has been reported in three domestic cats between the ages of 8 and 13 years; in each case the cats are believed to have been infected by aerosol transmission from their owners.157,255 Pneumonia was recognized radiographically between 1 and 4 days after the onset of clinical signs of inappetence, lethargy, and dyspnea. In one case four other cats in the household had less severe respiratory signs that resolved without any intervention. Two cats died, and H1N1 was diagnosed by PCR of postmortem samples (one of lung tissue and the other of a nasal swab).157 The other cat was diagnosed by PCR of BAL fluid. The BAL fluid comprised 65% macrophages, 25% nondegenerate neutrophils, and 10% small lymphocytes, and radiographs demonstrated opacity of right and left caudal lung lobes. The cat was essentially managed as an outpatient with at-home administration of subcutaneous fluids and oral, broadspectrum antibiotics.255


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Experimental infection of cats with H1N1 influenza resulted in lesions confined to the lungs compared with experimental infection with H5N1 influenza, which also results in extrarespiratory lesions.275 A seroprevalence survey across several states in the United States during the 2009 to 2010 influenza season found that 17 of 78 (21.8%) cats sampled had appreciable antibody titers against the novel H1N1 strain. The high seroprevalence and infrequent reporting of confirmed disease suggest that most infections are clinically inapparent, because there was no increase in pneumonia of undiagnosed cause over the same duration.174 Poxvirus Cowpox, of the genus Orthopoxvirus, is found only in Eurasia, and the reservoir hosts are voles or wood mice.19 Poxvirus-associated pneumonia is rare in cats. This virus typically causes focal cutaneous lesions, with few to no systemic signs.18,218 Experimental infection of domestic cats has been shown to induce fatal pulmonary disease,293 and occasional fatal pneumonia has been reported in natural cases.109,239,243 A recent report described the diagnosis and successful treatment of a 5-year-old cat with cowpox virus and herpesvirus pneumonia. Radiographs demonstrated a consolidated caudal right lung lobe. Neutrophils predominated on BAL cytology. Bacterial culture of the BAL fluid yielded a negative result. Tru-Cut biopsy of the consolidated lung lobe demonstrated severe, acute, necrotizing bronchopneumonia with necrosis affected both the bronchiolar and the alveolar epithelium. Cowpox virus and herpesvirus were demonstrated by immunohistochemistry and electron microscopy. Interestingly, the cat had skin lesions additional to the respiratory signs. The cat improved after nearly 2 weeks of hospitalization with intravenous fluid therapy and parenteral antibiotics. The reason for the prolonged hospitalization was that the owner was concerned about the zoonotic potential.124 The potential of poxvirus infection to veterinary staff and owners should be considered when treating affected cats because cat-tohuman transmission has been reported.103,243 Coronavirus In one study feline infectious peritonitis (FIP) was the cause of pneumonia in 9 of 11 cats with viral pneumonia.161 FIP is unlikely to cause pneumonia in cats without pleural effusion, and there are usually other indicators of infection, such as fever. FIP is covered in detail in Chapter 33.

Bacterial Bacteria represent the most common cause of LRT infections, with postmortem studies recognizing bacterial pneumonia in approximately 50% of infectious pneumonia cases17,161 and a clinical study recognizing 18 of 21

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(86%) LRT infections to be bacterial.78 A postmortem study noted 12 of 20 cases (60%) of pneumonia to be due to hematogenous spread.161 A clinical study used BAL as the major mode to retrieve samples, also finding a bronchial radiographic pattern in 81% of cases78; these findings indicate airway involvement and may suggest inhalation as the primary route of infection. These disparate findings may represent the difference between an antemortem and a postmortem study. Important causes of bacterial pneumonia in cats include Mycoplasma spp.,* Neisseria animaloris (previously described as Eugonic Fermenter 4a or EF-4a),† Pasteurella spp.,17,78,161,186,257 B. bronchiseptica,‡ Streptococcus spp.,17,161,261 Mycobacterium spp.,12,46,80,93,126 E. coli,17,37,108,262 Salmonella spp.,16,72,78,231,258 and Yersinia pestis.67,127 Mycoplasma Mycoplasma spp. deserve special mention in relation to feline LRT infections. In case series, two postmortem studies reported Mycoplasma pneumonia prevalence of 0%161 and 15%,17 respectively, yet a clinical paper found 13 of 17 (76%) of bacterial LRT infections to have mycoplasma infection (and 11 of 13 had purely mycoplasma infection).78 Further, Mycoplasma spp. feature prominently in other reports of feline LRT infections.35,48,76,163,273 This discrepancy between antemortem and postmortem findings may be because Mycoplasma spp. lends itself to more ready diagnosis and successful treatment can be achieved in most cases. Mycoplasma spp. have not been isolated from airways of healthy cats,221 yet mycoplasma LRT infections are often considered to be a consequence of preexisting pulmonary disease, mostly asthma or chronic bronchitis. In human asthma it is recognized that mycoplasma infection can exacerbate asthma and that asthma is induced subsequent to mycoplasma infection; similar associations may apply in feline medicine.76,78 In most cases infection is associated with the airways, but pulmonary parenchymal involvement also may be present (see Figure 30-13).35,76,78,221,273 In some cases pulmonary abscessation may be seen (Figure 30-19).48,78 In most cases treatment with doxycycline 5 mg/kg orally every 12 hours for 3 weeks is often effective to clear infection, but if a cat has underlying airway disease (asthma or chronic bronchitis), management of the concurrent disease is required.78 Neisseria animaloris One of the most frequently reported causes of feline pneumonia is Neisseria animaloris,† which was not formally classified until 2006276 despite reports in cats

*References 17, 35, 48, 76, 78, 163, 273. †

References 33, 43, 44, 58, 92, 118, 161, 176, 284.

‡

References 17, 66, 116, 167, 282, 287.

FIGURE 30-19 Right lateral radiographic view of pulmonary abscess (green arrow) caused by Mycoplasma infection. Note that because the abscess is over the cardiac silhouette, the abscess could not be seen in a left lateral projection.

dating back to 1973.118 N. animaloris is considered to be part of the normal oral flora of the dog and cat and has been recovered from the oral cavity of 30% to 82% of normal dogs8,234; no specific studies appear to have been done in cats, but they are thought to be normal flora in this species also.279 The organism causes fatal necrotizing pneumonia with a multifocal distribution, which suggests hematogenous dissemination. The precise pathogenesis of N. animaloris infection in cats is not well understood. All previous cases have appeared acute clinically, with death occurring within 1 week of onset of clinical signs and often within 2 days, although necropsy and histologic findings were indicative of chronicity. N. animaloris has been shown to have inherently low virulence because experimental inoculation of guinea pigs with low numbers of bacteria did not result in any discernible change, but inoculation with larger numbers resulted in death within 18 hours.156 It has been postulated that prolonged infection overwhelms the host’s defenses, resulting in periodic subclinical bacteremia with hematogenous dissemination to the lungs and an eventual acute on chronic terminal exacerbation.70 Thus the eventual outcome for the patient most likely depends on whether the organism spreads to locations that favor its survival and replication. Because of its small size and Gram stain reaction, the organism is difficult to visualize in cytologic and histologic preparations, necessitating culture of specimens to recognize infection. The organism is susceptible to a broad range of antibiotics, but no successful treatment has been recorded on account of the severity of signs at time of presentation.11 Pasteurella spp. Pasteurella spp. represent approximately one quarter of all LRT infections in two studies17,161 and 32 of 68 (47%) of positive bacterial lower airway cultures in another.257

The organism is recognized as indigenous microflora of the nasopharynx and large airways of dogs and cats.89 Prior respiratory disease such as viral infection89 or potassium bromide–induced airway disease78 contributes to proliferation and then migration to lower airways. Reduced defense mechanisms lead to impaired bacterial clearance from the lung and resultant pneumonia. Pasteurella spp. are usually susceptible to a broad range of antibiotics; however, the pneumonia may be slow to resolve, and abscesses or pleuritis may develop.89 Bordetella Pneumonia as a result of B. bronchiseptica infection has been recognized both experimentally47,116 and as a result of natural infection,282,287 although in most cases disease will be confined to the URT. It is likely that in cases of natural infection other factors may be involved in disease, including environmental factors such as stress or overcrowding or, in some cases, preexisting viral infection.37,66 Multiple cases of LRT disease associated with Bordetella have been reported in breeding catteries, boarding catteries, and in veterinary clinics with boarding facilities. Dogs with Bordetella may spread the infection to cats.21,105,154 Most cases of Bordetella pneumonia are in kittens; a postmortem study of pneumonia in which 65% of cases were kittens younger than 12 weeks of age found 30% of confirmed bacterial infections to be B. bronchiseptica,17 whereas only 1 of 68 (1.5%) of positive lower airway cultures from cats of unspecified age were recognized in another study.257 Antibiotic choice should be based on sensitivity findings; however, almost all isolates of B. bronchiseptica from cats are sensitive to tetracyclines, and doxycycline dosed at 5 mg/kg orally every 12 hours for 21 days is the antimicrobial of choice. Feline isolates of B. bronchiseptica are less susceptible to clavulanate-potentiated amoxicillin, and a high level of resistance has been detected to ampicillin and trimethoprim.254 Supportive care is almost always required initially. Feline vaccines against B. bronchiseptica are available in many countries. Although pneumonia is a severe consequence of this organism, in most cases bordetellosis is a mild disease of low prevalence in the small populations typical of most pet cats, so routine vaccinations are not recommended. Use of this vaccine should be limited to those cats living in or moving into high-density populations of cats with a history of bordetellosis.66 B. bronchiseptica is a zoonosis, and disease has been reported in immunecompromised humans in association with living with cats.283 Others Other bacteria have been recognized as causative agents of pneumonia in cats. Some, such as E. coli,17 Salmonella spp.,72,258 or Streptococcus spp.261 may be recognized in cases of disseminated septicemia. However, these same


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organisms have been recognized in cases of apparent primary respiratory infection17,108,231,262 or in association with viral pneumonia.37 Interestingly, Salmonella pneumonia has been recognized on two occasions with the lungworm Aelurostrongylus abstrusus, and it has been suggested that migrating lungworm larvae may act as carriers for intestinal bacteria.16,78 The pneumonic form of plague, caused by Y. pestis, was found in 10% of cats with this disease in one study.67 The overall mortality of plague in cats is 33%, with pneumonic cases posing the greatest risk.67,127 Various forms of mycobacterial species have been recognized to cause pneumonia both as part of disseminated12,93,126 and localized disease.46,80 In all cases logical approaches to diagnosis by defining organisms from cultures from BAL fluid or FNA or fuller biopsy samples and treatment by antibiotics determined from sensitivity studies with appropriate supportive care should be used.

Fungal Fungal pneumonia is rare in cats, representing 0.8%,17 5%,78 and 15%161 of pneumonia cases in case series. The incidence of fungal infections, generally, depends on whether organisms are endemic to particular regions. Even in endemic areas, fungal pneumonia is not a common consequence of infection, as demonstrated by the fact that there was only one case (Cryptococcus neoformans) among 20 cats with pneumonia in Sydney, Australia,78 where this organism is considered endemic. A diagnosis of fungal pneumonia, therefore, should lead to a high degree of suspicion of immune suppression. Reported causes of fungal pneumonia in cats include Cryptococcus neoformans,* Histoplasma capsulatum,† Aspergillus spp.,‡ Sporothrix schenkii,§ Blastomycosis dermatitides,¶ Coccidioides immitis,90 and Mucor spp.,17,203 and Candida spp.161,172,203 In many cases pneumonia is one manifestation of systemic, disseminated disease.

Parasitic Parasitic infections of the feline LRT include the metastrongyloid A. abstrusus; the capillarid Eucoleus aerophilus; and, in endemic areas, the trematode Paragonimus kellicotti. Collectively, A. abstrusus and E. aerophilus are known as lungworm; P. kellicotti is known as lung fluke. Additionally, the filarioid, Dirofilaria immitis, or heartworm, although a resident of the pulmonary artery in cats, causes predominantly respiratory disease, and the *References 51, 78, 85, 99, 161, 164, 178. †

References 39, 51, 123, 162, 166, 288, 289.

‡

References 17, 29, 51, 81, 104, 172, 203, 236.

§

References 49, 51, 62, 129, 241, 251.

¶

References 3, 24, 25, 51, 86, 119, 183, 194, 233, 245, 246, 251, 290.

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protozoan Toxoplasma gondii can lead to pulmonary involvement in systemic disease. Lungworm A. abstrusus has worldwide distribution.42 Adult A. abstrusus lungworms live in the respiratory bronchioles and alveolar ducts of cats. After mating, the females produce eggs that hatch in this same location. The first stage larvae (L1) then ascend the bronchial tree to the pharynx, from where they are swallowed and subsequently excreted in the feces and into the environment. L1s are then ingested by slugs and snails that act as intermediate hosts, with rodents, frogs, lizards, snakes, or birds acting as paratenic hosts. Cats become infected by ingesting a mollusk or a paratenic host (or both).272 Most infections are subclinical96,244; however, heavy infections can result in clinical signs as a result of damage to the lung parenchyma induced by eggs and larvae. Severe disease can be fatal. Severe clinical disease was reproduced experimentally after kittens were infected with 800 L3 larvae; coughing developed 6 weeks after exposure.97 A. abstrusus infection can mimic allergic respiratory disease because radiographs often demonstrate a bronchointerstitial pattern (although an alveolar pattern predominates during the period of heaviest larval shedding at 5 to 15 weeks post infection) and BAL fluids comprise predominantly eosinophils; further, cats can show an initial positive response to administration of corticosteroids and bronchodilators.88,271 Diagnosis depends on recognition of the organism in feces, BAL fluid, or pleural fluid.140,272 In one study standard fecal examination recognized A. abstrusus in only 21.7% of infected cats.128 Using the Baermann technique to examine feces is considered the most sensitive method for larval detection; however, sensitivity is less than 90%.140,285 A PCR assay for A. abstrusus has recently been validated for use on Baermann sediment, feces, and pharyngeal swabs. This shows great promise to aid in diagnosis, with a reported specificity of 100% and sensitivity of 96.6%.272 Many parasiticides have proved to be effective in treating cats with A. abstrusus infection. Fenbendazole has been used at 20 mg/kg orally every 24 hours for 5 days or 50 mg/kg orally every 24 hours for 15 days.16,88,98 Ivermectin (0.4 mg/kg subcutaneously, repeated 2 weeks later) has been reported to be effective in some reported cases.27,131 Abamectin (0.3 mg/kg subcutaneously, repeated 2 weeks later) was effective in the treatment of one cat.78 A single topical application of imidacloprid/moxidectin reduced larval counts by 100% in one study,269a and topical application of emodopside/ praziquental reduced larval counts by 99.4% in another.272a Two applications of selamectin (6 mg/kg, topical) were effective in the treatment of only one of three cats.88

Eucoleus aerophilus (formerly Capillaria aerophilus) has been recognized worldwide.15,197,270 The life cycle is considered direct. There is, however, some speculation that earthworms may serve as a paratenic or intermediate host. Infection may not result in clinical signs; alternatively, a chronic cough and weight loss may develop. Infection is rarely fatal.42 Definitive diagnosis is by detection of eggs on sugar and zinc sulfate solution fecal flotation270; eggs may also be detected in BAL samples.15 Radiographs typically show a diffuse interstitial lung pattern, and BAL cytology shows an eosinophilic inflammatory response.42 Abamectin (0.3 mg/kg subcutaneously, repeated 2 weeks later) has been reported as effective treatment in one cat.15 Other anthelmintics, such as ivermectin or milbemycin oxime, may also be effective in cats.42 Lung Fluke P. kellicotti is a trematode that can infect the lungs of cats and dogs in the Eastern United States, mainly in areas surrounding the Mississippi River. Other species of Paragonimus can affect cats across eastern Asia and Central and South America. The disease in man is endemic in southeast Asia and portions of central Africa.214 Adult flukes live within cysts inside the lung parenchyma and are about 6 mm long. Eggs are deposited into the lung tissue, where they are coughed up, swallowed, and then passed in the feces. If the eggs enter fresh water, they begin to develop and produce a ciliated miracidium, which hatches and seeks out a young snail host. After asexual multiplication in the snail, the cercarial stage is produced, which penetrates the shell of a crayfish and encysts in an area near the heart of the crustacean. Within the crayfish the cercaria forms a cyst wall and becomes a metacercaria. When the crayfish is ingested by a cat (or dog), the excised metacercariae penetrate the intestinal tract and enter the peritoneal cavity, within which they migrate for 7 to 10 days before entering the pleural cavity through the diaphragm. The lungs are entered approximately 2 weeks after infection.259 Dogs and cats typically become infected by eating metacercariae in crayfish, but rats can serve as paratenic hosts and transmammary or transplacental transmission is also thought to be possible.23 Clinical signs such as occasional coughing are usually mild, although pneumothorax can result from migrating flukes. Early lesions appear radiographically as indistinct nodular densities containing small air cavities and having irregular, sharply defined margins; older cysts are usually air-filled pneumatocysts, but illdefined interstitial nodular densities may also be seen.229,280 Successful treatment has been reported with praziquantel (25 mg/kg orally every 8 hours for a total dose of 150 mg/kg) and albendazole (25 mg/kg orally every 12 hours for 11 to 24 days).23,61,114

FIGURE 30-20 Left lateral radiographic view of cat with Toxoplasma pneumonia. There is a mixed pattern with consolidated ventral lung lobe and pleural effusion.

Toxoplasma Toxoplasma gondii may cause self-limiting small bowel diarrhea but typically causes no disease in cats. However, transplacentally or lactationally infected kittens and immune-suppressed older cats can show severe systemic signs.60 In a study of 100 cases with histologically confirmed toxoplasmosis, 76.7% of 86 lung tissue samples assessed had organisms present, and in the 36 cats considered to have generalized toxoplasmosis, 26 had predominantly pulmonary lesions.59 Retrospective studies of feline LRT infection have found T. gondii in 1 of 20 cats (5%)78 and 6 of 245 cases (2.4%).17 Diagnosis is achieved by recognition of Toxoplasma tachyzoites, which can be found in BAL fluid14 or FNA of affected lung tissue.219,235 Diffuse interstitial to alveolar patterns are typically described,14,219,235 but a bronchial influence is also possible14 (Figure 30-20). Serology can aid diagnosis.60 Recognition of Toxoplasma in an adult cat should instigate investigations to determine a cause of immune suppression, which is often FIV related50,78 but can be iatrogenic (e.g., due to administration of corticosteroids or cyclosporin).14,77 Treatment is covered in detail in Chapter 23 but is typically with clindamycin at 12.5 to 25 mg/kg orally every 12 hours for 2 weeks60; combination therapy with pyrimethamine at 0.25 to 0.5 mg/kg orally every 12 hours may help the prognosis.14 Supportive care such as oxygen therapy maintenance of fluid and electrolyte balance is also important. Successful treatment of clinical feline toxoplasmosis has been described infrequently.14,59,143 Heartworm Despite prevalence studies demonstrating a worldwide distribution and recognizing heartworm infection in up to 18% of cats tested,* the prevalence rate being approximately 5% to 10% of that found in dogs,84,150,153 and the

*References 31, 71, 84, 107, 138, 150, 151, 155, 158, 197, 269, 285.


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prevalence being found similar to that of FIV and FeLV infection,150,151,158 feline heartworm disease remains underdiagnosed in general practice.30,195 This is likely because clinical signs vary dramatically from no signs to sudden death and definitive diagnosis can be difficult.20,30,153,196 Heartworm disease is caused by the filarioid nematode Dirofilaria immitis, which is transmitted by mosquitos and for which dogs are the usual definitive host. Therefore a prerequisite for heartworm infection is a climate with adequate temperature and humidity to support a viable mosquito population and allow maturation of larvae within the intermediate host. The sexually dimorphic adult heartworm mate within an infected dog’s pulmonary artery, producing immature forms called microfilariae. Circulating microfilariae are ingested by mosquitoes feeding on infected dogs. Within mosquitoes, microfilariae transform into larval stages. There are five larval stages (L1 to L5); L1 to L3 transformations occur within the mosquito, and L3 is the form that is transmitted from mosquitos to dogs and cats. Maturation from L3 to other larval stages occurs in subcutaneous tissues and peripheral veins of mammalian hosts; immature worms in peripheral veins are carried in the bloodstream to and through the heart, with adult heartworms ultimately residing at the caudal pulmonary arteries.1 There are significant differences between feline and canine heartworm disease because the parasite is only partially adapted to the cat. The cat is susceptible to heartworm infection but more resistant than the dog. The cat represents a dead-end host because it cannot act as a reservoir for infection. The prepatent period in the cat is 7 to 8 months (1 to 2 months longer than in dogs).169 In dogs, most juvenile worms mature into adults that can live for 5 to 7 years, whereas in cats most juvenile worms die shortly after arriving in the pulmonary arteries, instigating a severe vascular and parenchymal inflammatory response. Pulmonary lesions may be long lasting. The clinical response in the cat has been termed heartworm-associated respiratory disease (HARD). In a small percentage of cats, a few worms develop to mature adults that can live for 2 to 3 years.195 Cats with adult heartworms develop pulmonary changes characterized by intimal proliferation, eosinophilic endarteritis, intimal fibrosis, and disruption of the internal elastic lamina. Arterial wall changes can lead to pulmonary hypertension with resultant pulmonary arterial distention.173 Damage can be caused by juvenile heartworms without development to the adult stage, resulting in increase in thickness of the pulmonary arterial wall that in turn causes occlusion.26,56 There have been suggestions that Wolbachia pipientis, a symbiotic gram-negative intracellular bacterium harbored by D. immitis induces further pulmonary pathology.57 A strong antibody response against Wolbachia surface protein has

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been demonstrated in heartworm-infected cats. Further research is required to define the exact relationship between Wolbachia and HARD in cats. Upon death of heartworms, it has been hypothesized that degenerating parasites may cause an acute anaphylactic reaction and thromboembolism, which can result in fulminant pulmonary failure and sudden death of the cat.152 Even the death of one adult heartworm can be lethal. Adult heartworms are able to suppress pulmonary intravascular macrophage activity and therefore induce little inflammation until they die. Clinical signs can vary from no clinical signs, reported in 28% to 79% of cases,7,84 to acute or chronic respiratory tract signs. Sudden death has been reported in 7% to 47% of naturally infected cats with mature adult heartworm infections.7,68,84,277 Additional signs that may be seen include neurologic signs or vomiting.7,277 On most occasions cats will present clinically with respiratory tract signs mimicking asthma or chronic bronchitis, such as coughing or dyspnea.7,84,277 Physical examination findings are nonspecific. Investigations should follow those for any cats with respiratory signs, but the diagnosis of heartworm disease is sometimes reached only when a high degree of suspicion of this disease is maintained. Cats are rarely microfilaremic, so filtration or immunofluorescent assay for microfilaria is not recommended. No single diagnostic test can detect feline heartworm at all life stages of the worm (Table 30-4). Serologic testing, if positive, is the most straightforward for demonstration of infection, but falsenegative results occur frequently. According to the

American Heartworm Society, the primary reasons for heartworm testing in cats are as follows: 1. To establish a diagnosis in cats that, on the basis of other clinical evidence, are suspected of infection 2. To monitor the clinical course of cats diagnosed with heartworm disease 3. To establish a baseline reference prior to starting prophylaxis Heartworm antigen testing detects mature female heartworm genital parts, so sensitivity increases when more female worms are present. Because heartworm antigen testing is regarded as highly specific, falsepositive results are very rare. One study found 36% sensitivity with only one female heartworm and increasing to 93% sensitivity with seven females present. Cats with only male heartworms test as negative.177 A more recent study comparing antigen tests detected 79.3% to 86.2% of necropsy confirmed heartworm infections. Most cats with false-negative antigen tests had a single male worm.20 On the basis of this study, it can be assumed that antigen testing will detect at least three quarters of cats infected with adult heartworm. However, as previously noted, clinical signs can result from larval infections that do not progress to adult stage heartworms. Antibody tests will help determine exposure, but up to 79% cats with exposure do not become symptomatic.84 A negative antibody test does not rule out infection. The different antibody tests available vary in sensitivity and specificity, insofar as each brand may detect a different stage of larval development. Also, up to 30% of cats on

TABLE 30-4 Interpretation of Heartworm Diagnostic Procedures Tests in the Cat Test

Description

Result

Interpretation

Limitation

Antibody test

Detects antibodies produced in response to heartworm larvae; may detect infection as early as 8 weeks after transmission

Negative Positive

Lowers index of suspicion Increases index of suspicion, confirms cat is at risk of disease; 50% or more of cats will have pulmonary arterial disease

Antibodies confirm infection with heartworm larvae but do not confirm disease causality

Antigen test

Detects antigen produced by adult female heartworms or from >5 dying male or female heartworms

Negative Positive

Lowers index of suspicion Confirms presence of heartworms

Immature or male-only heartworm infections are rarely detected

Thoracic radiography

Detects vascular enlargement, pulmonary parenchymal inflammation, edema

Normal Signs consistent with heartworm disease

Lowers index of suspicion Enlarged arteries greatly increases index of suspicion

Radiographic signs are subjective, affected by clinical interpretation

Echocardiography

Detects echogenic walls of immature or mature heartworms in the lumen of the pulmonary arterial tree

No heartworms seen

Does not change index of suspicion Confirms presence of heartworms

Experience of ultrasonographer influences accuracy

Heartworms seen

Note: In the cat no single test will detect all heartworm cases. Although the antigen tests are highly specific for detecting adult heartworm antigen, they will not detect infections with only live male worms. The clinician must use a combination of test results to determine the likelihood of heartworm disease as the etiology of the cat’s clinical signs. Adapted and reprinted with permission from the American Heartworm Society (www.heartwormsociety.org/veterinary-resources/feline-guidelines.html).

heartworm prophylaxis may become antibody positive, although they are not at risk for HARD. Combining antigen and antibody testing achieves higher sensitivity than either test alone but may generate more falsepositive results.250 Radiographic findings may add to a clinician’s index of suspicion for heartworm disease, but results are inconsistent. Significant enlargement of the central and peripheral caudal lobar pulmonary arteries (greater than 1.6 times the width of the ninth rib) in the ventrodorsal view has been considered a typical radiographic sign of heartworm infection in cats. However, this was recognized in only 53% of cases in one study237 and only 1 of 11 cats in another.277 The latter study found diffuse or focal bronchointerstitial patterns to be most common, with focal changes supporting a better prognosis.277 Echocardiography, in experienced hands, can also aid diagnosis. Adult heartworms typically appear as two echodense parallel lines within the pulmonary artery, one of its branches, or the right ventricle. One study found heartworms in 17 of 43 cats with echocardiography but, it is important to note, allowed a definitive diagnosis to be made in five cats in which antigen test results were negative; four of these five cats had positive antibody test results.53 There is no definitive treatment for heartworm disease in cats. Most cats with infection are asymptomatic, and it is appropriate to start prophylactic treatment in these cats. Heartworm prophylactic treatments have been demonstrated to be slowly adulticidal in dogs,168 and there is no reason to assume that this would not also be the case in cats. Ivermectin has the most potent adulticidal activity, milbemycin the least, with selamectin and moxidectin in between.168 More rapid kill of adult heartworm with arsenical agents such as thiacetarsemide or melarsomine is not recommended. These agents are believed to be less potent in cats and have significant toxicity, and death of heartworms may result in fatal pulmonary embolism.153 Successful surgical removal of heartworms has been reported, although there are substantial risks associated with the procedure. In particular, crushing or transecting the adult heartworms can induce a fatal shock reaction. Trauma to the jugular vein during multiple heartworm retrievals may result in transection of the vein.248 In most cases, in addition to heartworm prophylaxis, it is appropriate to manage the clinical signs of infected cats with corticosteroids and bronchodilators. Prednisolone has been used at 2 mg/kg orally every 24 hours and then tapered at remission of clinical signs.84 If W. pipientis is demonstrated to be relevant to clinical disease, a 3-week course of doxycycline (5 mg/kg orally every 12 hours) would be appropriate.57 Monitoring of heartworminfected cats with radiographic evidence of disease may include repeat thoracic radiographs at 6- to 12-month intervals. Infected cats can also be monitored with repeat


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serologic testing. Recovery is indicated by an improvement in radiographic signs and seroconversion of a positive antigen test to negative. In areas where heartworm is endemic for dogs, all serologic evidence points to the appropriateness of cats (including those confined to indoors) receiving regular prophylactic treatment. There are several macrocytic lactone drugs registered for feline heartworm prophylaxis: ivermectin (Heartguard FX chewables, Merial), milbemycin oxide (Milbemax, Novartis), moxidectin (Advocate/Advantage Multi, Bayer; NB also contains imidacloprid), and selamectin (Revolution or Stronghold, Pfizer).

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THE THORACIC CAVITY Randolph M. Baral

GENERAL CONSIDERATIONS The thoracic cavity is contained within the thoracic wall and the diaphragm caudally. It encloses the lungs and the mediastinum, the potential space located between the right and left pleural cavities. The mediastinum contains numerous vital structures, including the heart, trachea, esophagus, thymus, and great vessels. The pleural space is lined by the visceral and parietal pleura, with visceral pleura covering the surface of the lungs and parietal pleura covering the diaphragm, costal surface, and mediastinum. Diseases affecting the thoracic cavity most commonly result in the following: 1. Fluid accumulation within the pleural space (pleural effusion) 2. Air accumulation within the pleural space (pneumothorax) 3. Solid tissue within the pleural space; such tissue may arise from within the thoracic cavity, such as neoplastic masses, or be introduced, such as abdominal viscera with diaphragmatic herniation In most cases cats with pathology affecting the thoracic cavity will present with dyspnea, but in early stages signs may be so mild that no obvious effect on respiration is evident. Recognition of a disorder affecting the thoracic cavity usually requires radiographic recognition of fluid, air, or masses within the chest or disruption of the diaphragm or chest wall.

CLINICAL SIGNS The presence of fluid, air, or masses within the pleural cavity restricts lung expansion, resulting in rapid, shallow breaths with increased inspiratory effort. Lung volume and expansion are also affected with pathology of the pulmonary parenchyma (e.g., pneumonia, pulmonary edema), so a similar breathing pattern may result. In early stages, signs may be subtle, and cats may simply reduce activity levels. Cats may prefer a sitting or crouched sternal posture with elbows abducted from the thorax, perhaps with head or neck extended to maximize air intake. Coughing is not considered a typical sign with pleural space disease but may result from tracheal compression (e.g., from neoplasia) or pulmonary parenchymal involvement or pleuritis.11,105 Coughing was recognized in 30 of 37 cats with chylothorax in one series.39 Other clinical signs depend on the underlying cause of intrathoracic disease but may include weight loss, anorexia, or fever.

PHYSICAL EXAMINATION Cats presenting in severe respiratory distress should have minimal initial handling and only a cursory examination on presentation because further stress can lead to decompensation. Cats in this situation often need supplemental oxygen (see Box 30-5 later in this chapter). In some circumstances, survey radiographs in the position most comfortable for the cat (often dorsoventral with the cat resting on its elbows) should be taken in lieu of a physical examination. Some authors advocate thoracocentesis (see Box 30-6 later in this chapter) ahead of thoracic radiography when pleural effusion is strongly suspected.42,77 On auscultation, heart and lung sounds may be reduced or absent, particularly ventrally. These signs are obvious in severe cases but may be subtle or absent with milder disease. Thoracic percussion is difficult to perform in cats; tapping against an intercostal space can result in dull, hyporesonant sounds in the case of pleural effusion or pulmonary consolidation; a “drumlike,” resonant sound may be recognized with pneumothorax. Other physical examination findings can be helpful to determine the underlying cause. For example, the presence of a heart murmur, tachycardia, or jugular distention or pulsation can point toward primary cardiac disease (but absence of these signs does not preclude an underlying cardiopathy); hyperthyroidism can result in cardiac disease, so palpation for a thyroid nodule is important in older cats; signs of neoplasia may be present in other locations around the body; abdominal palpation may reveal displaced organs in cats with diaphragmatic hernia. In many cases the signalment of the cat and clinical history will direct the approach. For example, an older cat with a poor body condition score may have neoplasia or hyperthyroidism-associated CHF; a young cat with a fever may have FIP; a cat with known trauma may have diaphragmatic herniation, pneumothorax, or hemothorax.

PLEURAL EFFUSION In normal cats the pleural space contains a tiny amount of fluid (approximately 0.25 mL/kg in dogs) that enables lubrication of intrathoracic organs during respiration. The control of volume and composition of the pleural liquid is affected by a number of mechanisms, including Starling forces (the balance of interstitial and capillary hydrostatic and oncotic pressures), lymphatic drainage through the parietal pleura stomata, as well as the activity of mesothelial cells.90,91,140 Pleural effusions arise when one or more of these factors are altered— that is, fluid formation or accumulation is increased, absorption is decreased, or both. Multiple underlying


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processes can result in pleural effusion, but in most cases the underlying cause is FIP, CHF, neoplasia, pyothorax, or idiopathic chylothorax. A recent review accumulated results from five prior studies ascertaining that of 265 cats with a definitive diagnosis of pleural effusion, 88% to 100% of cases had one of these first four diagnoses11; idiopathic chylothorax is a diagnosis of exclusion and represents 10% to 15% of cats with pleural effusion.23,129,141 Because clinical signs of pleural effusion are essentially the same as for other diseases affecting the pleural space, radiography (or ultrasonography) is required to confirm the presence of pleural fluid.

Radiography Radiography should only be used to confirm the presence or absence of pleural effusion in a dyspneic cat but cannot determine the nature or etiology of the effusion. Multiple radiographic views for precise diagnostics should be attempted only in stable cats. In severe cases, the stress from handling can result in decompensation and death, so some authors advocate thoracocentesis (discussed later and in Box 30-6) before radiography when pleural effusion is suspected.42,77 In many circumstances, cats with pleural effusion present very similarly to cats with pulmonary edema or bronchial disease, and radiography is required to confirm the presence of pleural fluid. Handling should be minimal, and initially only a single radiograph in the position most comfortable for the cat should be taken, with no additional handling to improve symmetry, for example. In most cases dyspneic cats are most comfortable sitting sternally and resting on their elbows, so a dorsoventral view is most appropriate. Supplementary oxygen should be provided by mask or flow-by ventilation if this is not stressful to the cat (see Box 30-5). Horizontal beam radiographs can be used to document fluid lines or distinguish masses from freeflowing fluid; in one study, however, this view did not contribute additional information to that gained from plain radiographs in eight of nine cats.23 Small volumes of pleural effusion are not visible radiographically. It has been shown that 50 mL of effusion is required before radiographic signs are visible in 15-kg dogs,73 but no similar studies appear to have been performed in cats. The first radiographic signs in small volume effusions are interlobar fissure lines, rounding of lung margins at costophrenic angles, separation of lung borders from the thoracic wall, scalloping of lung margins dorsal to the sternum, blurring to absence of the cardiac silhouette, and widening of the mediastinum. With larger volume effusions the visibility of the heart and mediastinum reduces, lung lobes may collapse, the trachea can be elevated dorsally, and the diaphragm and liver may be displaced dorsally42,94,97 (Figures 30-21, 30-22, 30-23, and 30-24).

FIGURE 30-21 For dyspneic cats it is appropriate to take a single radiographic view in the position most comfortable for the cat, even if the radiograph is imperfect. In this poorly aligned dorsoventral radiograph, the lung is separated from the thoracic wall (yellow arrow) and the lung margins are rounded (red arrow). The cardiac silhouette is barely visible. Additionally, pulmonary edema can be seen as patchy opacities in lung lobes on the left side. In this case pleural effusion is more obvious in the lateral view (see Figure 30-22). This cat was subsequently diagnosed with congestive heart failure secondary to hypertrophic cardiomyopathy.

FIGURE 30-22 Right lateral radiographic view of cat from Figure 30-21. Pleural effusion is recognized by interlobar fissure lines, rounding of lung margins at costophrenic angles, separation of lung borders from the thoracic wall, scalloping of lung margins dorsal to the sternum, blurring of the cardiac silhouette, and dorsal elevation of the trachea. This cat was subsequently diagnosed with congestive heart failure secondary to hypertrophic cardiomyopathy.

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FIGURE 30-24 Right lateral radiographic view of severe pleural effusion. Note the distention of the thoracic cavity resulting in extreme dorsal displacement of the diaphragm and liver. This cat had pyothorax.

100

Ultrasonography can be used to detect the presence of small volumes of pleural effusion when radiographic findings are equivocal.72,101 In one study in humans, pleural fluid was recognized by ultrasonography in 93% of cases, compared with only 83% by radiology.53 Ultrasonography can also provide gross estimations of effusion volume and assess effusion characteristics on the basis of echogenicity.72,101

Stabilization Cats (and other animals) with respiratory disease decompensate easily because although the oxygen saturation of hemoglobin is relatively stable, this is only provided the arterial partial pressure of oxygen (PO2) remains above approximately 60 mm Hg. Below this point the amount of oxygen carried by hemoglobin drops dramatically, so for an already respiratory-compromised cat, very small reductions in oxygen intake can result in extreme clinical effects. This is demonstrated by the oxygen–hemoglobin dissociation curve (Figure 30-25), where it can be seen that on the flat (right-hand side) part of the curve, decreases in PO2 from 100 to 60 mm Hg result in only small drops in oxygen hemoglobin saturation. As PO2 decreases below approximately 60 mm Hg, the curve drops to the left steeply, demonstrating the large decrease in the amount of oxyhemoglobin that results from only small drops in PO2; PO2 less

% Hb saturation

FIGURE 30-23 Dorsoventral radiographic view of severe pleural effusion. This cat had pyothorax.

O2 combined with Hb

80

22 18 14

60

10

40

6 20

Dissolved O2

0 20

80 40 60 PO2 (mm Hg)

O2 concentration (mL/100 mL)

Total O2

2

100 600

FIGURE 30-25 Oxygen–hemoglobin dissociation curve demonstrating that as oxygen partial pressure (PO2) decreases below 60 mm Hg, the hemoglobin saturation percentage drops rapidly. (From West JB: Respiratory physiology: the essentials, ed 5, Philadelphia, 1995, Williams & Wilkins.)

than 60 mm Hg is defined as hypoxemic respiratory failure. If a cat is underventilating for any reason, the arterial carbon dioxide (PCO2) will rise; therefore, if the patient is inspiring room air, hypoxia will worsen; PCO2 greater than 45 mm Hg is defined as hypercapnic (ventilatory) respiratory failure.55,77 A patient can have both hypercapnic and hypoxemic respiratory failure occurring to differing degrees simultaneously. Stabilization requires an increase in the patient’s arterial oxygen pressure to enable increased oxygen saturation of hemoglobin—that is, a shift to the right of the oxygen–hemoglobin dissociation curve. The two key components of stabilization are as follows:

1. Oxygen therapy 2. Pleurocentesis Administration of an oxygen-enriched inspired gas mixture will at least partially correct hypoxemia depending on severity of hypoventilation, atmospheric pressure, flow rates, underlying pathology, hemoglobin concentration, cardiac output, and method of administration. The administration of an oxygen-enriched inspired gas mixture improves oxygenation for most respiratory causes of hypoxia. Provision of pure oxygen provides higher concentrations of oxygen than normal air, so a greater amount of oxygen is moved to the alveoli with each breath. Oxygen therapy can be provided in the short term by flow-by delivery (Figure 30-26) or face mask delivery (Figure 30-27). More prolonged oxygen delivery can be achieved with the use of an Elizabethan collar canopy (Figure 30-28) or nasal catheter (Figure 30-29). Oxygen cages are widely used but can be problematic. Many commercially available cages do not permit manipulation of the temperature and humidity within the cage (Figure 30-30); the increasing heat and humidity caused by the presence of the cat in the sealed cage increases the cat’s oxygen demands, thus further reducing the oxygen saturation of hemoglobin. Moreover, each time the cage door is opened to access the patient, the oxygen-rich environment not only is lost (which can lead to decompensation) but takes time to reach the desired oxygen concentration again. Human neonatal incubators (humidicribs) are most appropriate because they do allow manipulation of temperature and humidity, as well as having smaller openings (Figure 30-31). In severe cases intratracheal catheterization may be necessary, and those cats that cannot sustain PO2 greater than 60 mm Hg through their own efforts despite conventional oxygen supplementation will require mechanical ventilation. Further details about oxygen therapy are contained in Box 30-5. Drainage of pleural fluid by pleurocentesis (puncture and aspiration from the pleural cavity) allows improved lung expansion, thereby enabling further oxygen saturation of hemoglobin. Some authors advocate thoracocentesis (puncture and aspiration from the thorax and not necessarily from the pleural space) before imaging when pleural effusion is strongly suspected because it can result in life-saving improvement for the patient.42,77 In experienced hands thoracocentesis is a safe procedure and very well tolerated by cats. The major complications are pneumothorax, hemothorax, pneumohemothorax, or organ laceration, and these risks may be greater in cases when there is a small volume effusion (including no effusion), uncooperative patients, use of a large needle, and the need for multiple needle passes.103 Thoracocentesis is usually performed at the 6th, 7th, or 8th intercostal space, just ventral to the costochondral junction; this site should be clipped and


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surgically prepared. The positioning of the cat will vary from case to case. Sternal recumbency is ideal for maximal drainage of fluid, but access ventrally can be difficult when the cat is in this position; having the cat stand is appropriate, but this requires too much effort for many cats with respiratory distress; lateral recumbency results in the best access but may be too stressful for the cat. Butterfly catheter needles of 19 to 23G are appropriate to use and ideally should be mounted to a three-way stopcock and a 10-mL to 20-mL syringe.42,103 It is important that fluid be collected for assessment as well as drained for therapeutic purposes. Further details about pleurocentesis are contained in Box 30-6 and Figure 30-32.

Pleural Effusion Analysis Assessment of pleural effusion fluid is the key step to determining the underlying cause. Assessments are based initially on the gross appearance (color, turbidity, presence of fibrin), then the protein concentration and cytology. The findings should always take into account the signalment of the cat and clinical findings. Opaque effusion fluid can be milky white or milky pink (chyle), red (hemorrhage, although blood contamination can give a similar appearance); pyothorax often results in green or yellow opaque, malodorous fluid with flocculent material (but this can vary). Translucent effusions can be clear, yellow, or pink tinged and are initially distinguished by protein concentration, with lower protein effusions most typically arising from CHF and higher protein effusions most typically arising from FIP. Neoplasia can result in chylous, hemorrhagic, or translucent effusions of high or low protein concentration; cytology is often, but not always, helpful for diagnosis. More details about pleural fluid analysis can be found in Table 30-5.

CAUSES OF PLEURAL EFFUSION Congestive Heart Failure Effusion Characteristics Effusion fluid from cats with CHF may be translucent (often clear to pale yellow, but blood contamination during pleurocentesis can result in pink or reddish tinge) or chylous (white or pink if blood contamination). The fluid is often a modified transudate (with protein concentrations of 25 to 50 g/L), but transudative or chylous effusion is also possible. Left-sided CHF typically results in pleural effusion in cats associated with increased ventricular diastolic pressure resulting in increased capillary hydrostatic pressure. Right-sided CHF can also cause pleural effusion, and chylothorax is often seen in this circumstance41,68 (Figure 30-33).

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BOX 30-5 Supplemental Oxygen Delivery The fraction of inspired oxygen (FiO2) in normal room air is 0.21 (21%). Providing dyspneic cats with supplemental oxygen (O2) aims to increase FiO2 and thus help increase the patient’s arterial oxygen pressure; this, in turn, enables an increase in the oxygen saturation of hemoglobin—that is, a shift to the right of the oxygen–hemoglobin dissociation curve (see Figure 30-25). Different modes of O2 supplementation provide differing FiO2s and require differing O2 flow rates. Flow-by oxygen (Figure 30-26) • O2 line held 1 to 3 cm in front of the cat’s nose and mouth • O2 flow rate of 6 to 8 L/min used • FiO2 of 0.25 to 0.45 typically achieved • Minimal stress to patient • Requires physical presence of caregiver to hold O2 line in place • High O2 flow rates • Appropriate at initial presentation while carrying out other procedures (e.g., thoracocentesis) Face mask (Figure 30-27) • Well-fitted mask held over cat’s muzzle • O2 flow rate of 6 to 8 L/min used • FiO2 of 0.35 to 0.55 typically achieved (reservoir bag may increase to as high as 0.8) • Poor elimination of carbon dioxide • Stressful for many cats (stress further increases O2 requirements) • Only to be used if tolerated

Elizabethan collar canopy (Figure 30-28) • Elizabethan collar placed snugly around the neck • O2 line placed inside the collar from caudal direction (tip may be taped inside collar) • Front of the collar then covered in plastic wrap with vent holes created or portion left uncovered (to eliminate expired air) • FiO2 of 0.30 to 0.40 • O2 flow rate of 2 to 5 L/min • Mostly well tolerated • Stable patient can be left in cage, affording full accessibility for examination, treatment • Potential heat and humidity, CO2 retention within canopy if vents inadequate • Variability in O2 concentration within the hood, depending on the size of the vent, minute ventilation, exact placement of the oxygen hose within hood

FIGURE 30-27 Face mask oxygen delivery.

FIGURE 30-26 “Flow-by” oxygen delivery.

FIGURE 30-28 Elizabethan collar canopy.


897

BOX 30-5—cont'd Supplemental Oxygen Delivery Nasal catheter (Figure 30-29) • Topical anesthetic (e.g., 2% lidocaine, proparacaine) instilled into one nostril • 5 Fr lubricated, soft rubber catheter (with multiple fenestrations distally) introduced through nostril to the level of the medial canthus then secured to the skin at the nostril with adhesive glue or suture (usually least irritant long term) • Remainder of catheter attached to dorsolateral aspect of nose and head with further sutures or adhesive, then attached to the O2 source • Ideal for in-line bubble humidifier • FiO2 of 0.3 to 0.5 • O2 flow rates of 100 to 150 mL/kg/min • Stable patient can be left in cage, affording full accessibility for examination, treatment • Can be stressful for the patient, so severe respiratory distress may preclude safe placement Oxygen chamber (Figures 30-30 and 30-31) • Most commercially available oxygen chambers/cages inappropriate • Must be able to regulate O2 concentration, eliminate expired CO2, as well as ambient temperature and humidity • Without temperature and humidity regulation, overheating of patient almost inevitable (leading to increased O2 demand) • Human neonatal incubators (humidicribs) most appropriate (see Figure 30-31) • FiO2 of 0.4 to 0.5 • Flow rates variable, determined by unit • Temperature to be maintained ~22°C (~70°F), humidity 40-50%

• Inability to conduct physical examination while animal in O2-rich environment • Loss of O2-rich environment when cage door opened, several minutes to refill with O2

FIGURE 30-30 Cat in an inappropriate oxygen cage with no temperature, humidity, or fraction of inspired oxygen control.

FIGURE 30-31 Cat in a human neonatal incubator (humidicrib). (Courtesy Dr. Peter Best, South Tamworth Animal Hospital, Tamworth, Australia.)

FIGURE 30-29 Nasal catheter oxygen delivery to a recumbent cat. The catheter is marked with a yellow arrow and is glued to the cat’s zygomatic arch. (Courtesy Dr. Peter Best, South Tamworth Animal Hospital, Tamworth, Australia.)

Adapted from Camps-Palau MA, Marks SL, Cornick JL: Small animal oxygen therapy, Compend Contin Educ Pract Vet 21:587, 1999; Drobatz KJ, Hackner S, Powell S: Oxygen supplementation. In Bonagura JD, Kirk RW, editors: Kirk’s current veterinary therapy XII, Philadelphia, 1995, Saunders, p 175; Manning AM: Oxygen therapy and toxicity, Vet Clin North Am Small Anim Pract 32:1005, 2002; Tseng LW, Drobatz KJ: Oxygen supplementation and humidification. In King LG, editor: Textbook of respiratory disease in dogs and cats, St Louis, 2004, Saunders, p 205.

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BOX 30-6 Thoracocentesis • Thoracocentesis should be considered both a therapeutic and diagnostic procedure. • Ultrasound guidance is helpful but rarely necessary for large volume effusions. • Equipment required: • 19- to 23-gauge butterfly needle; larger bore appropriate for thicker secretions such as pyothorax, does not seem more painful to cats • Alternatively, an IV catheter can be used (up to 18 gauge); in this case, the skin is punctured, but the thorax is not penetrated until after tunneling along 1 rib space. The needle is then withdrawn, leaving the catheter in place. This technique may allow further penetration into the thoracic cavity with minimal increased risk of trauma • Three-way stopcock; so only one placement of needle • 10- to 20-mL syringe; 10-mL syringe provides more manual control and can generate more negative pressure but requires more draws

•

•

•

•

•

FIGURE 30-32 Thoracocentesis. Note the milky appearance of the effusion. This chylous effusion was subsequent to right-sided congestive heart failure.

• Extension tubing attached for drainage away from cat Positioning of cat: Different positions have different advantages and disadvantages. • Sternal recumbency ideal for maximal drainage of fluid, but ventral access can be difficult when the cat is in this position • Cat standing appropriate but too much effort for many cats with respiratory distress • Best access in lateral recumbency, but too much respiratory stress for some cats Location for needle insertion: • 6th, 7th, or 8th intercostal space • Ventral to the costochondral junction • Care taken to avoid intercostal vessels and nerves near the caudal rib margin • Necessary to clip and surgically prepare the site Anesthetics/sedation: • Usually not necessary since tolerated well by most cats • Local anesthetic instillation recommended by some; appears to hurt as much (or more) than placement of butterfly needle Samples of pleural fluid (first aliquot) to be collected: • EDTA tube for cell counts and cytology • Plain serum tube for biochemical analysis • Sterile container for aerobic and anaerobic culture (e.g., pediatric BACTEC bottle that will grow both aerobes and anaerobes); must be inoculated without letting air in • Slides with smears should be prepared and subsequently assessed Drainage: • After collection of diagnostic specimens • Stay in one location but continue removing fluid • Three-way stopcock adjusted for syringe filling and emptying • Sometimes slight repositioning of needle necessary to keep fluid flowing because the lungs move in relation to the pleura as fluid drains • After no more fluid retrieved at initial site, repeat on contralateral side

Further Diagnostics

Feline Infectious Peritonitis

The underlying cardiac disease can be determined only by echocardiography; cardiomyopathies such as hypertrophic or unclassified cardiomyopathy are most common. Auscultable changes such as a murmur or gallop rhythm are not necessarily present, and cardiac disease may be secondary to another problem, such as hyperthyroidism. CHF is covered in more detail in Chapter 20.

In one survey of 390 cats with effusive FIP, 17% had thoracic effusions, 62% had ascites, and 21% had effusions in both body cavities57 (Figure 30-34). Effusion Characteristics The effusion fluid found with FIP is typically straw colored to golden yellow (although the shade can vary

Clear

G

73

AD

Early onset blindness

Abyssinian

CRX

n.546delC

64

Polycystic kidney disease

AD

Kidney cysts

Persian

PKD1

C10063A

Pyruvate kinase deficiency‡

AR

Hemopathy

Abyssinian

PKLR

13bp del in exon 6

AR

Muscular atrophy

Maine Coon

LIX1-LNPEP

140kb del, exons 4-6

Progressive retinal atropy Progressive retinal atropy

30

Spinal muscular atrophy

AD, Autosomal dominant; AR, autosomal recessive; ID, incomplete dominance; AS, allelic series. *Mode of inheritance of the non–wild-type variant. †Long fur variants are more or less common depending on the breed. ‡Unpublished test, presented only as abstract.

managing their breeding programs, the phenotypic mutations generally have genetic tests readily available from commercial services. Because most of the mutations for the aesthetic traits are recessive, the mutant alleles must be present in both copies for the effect to be visible, and cats can carry the mutation without detection. Recessive mutations tend to be found in the genes that produce the enzymes of biological pathways. Thus most of the coat color mutations are recessive because they are usually part of disrupting the pigment production pathways. Many genes that affect pathways also tend to have more than one mutation that cause different effects; this is termed an allelic series. The locus for brown color variants, Brown, has two mutations in the causative gene, TRYP1. The wild-type allele, B, which causes normal black pigment, is dominant to the brown allele,

b, which causes a reduced amount of black pigment, producing a more brownish hue to the fur. The brown allele, b, is considered dominant to light brown, whereas bl imparts a cinnamon-color or reddish effect on the fur. The allelic series is written as: B > b > bl to indicate the dominance of one allele over the other. In the case of the Color locus, C, which is also an allelic series, the sepia coloration, cbcb, which is fixed in the Burmese (Figure 44-1) and Singapura (Figure 44-2) breeds, is co-dominantly expressed with the Siamese points, cscs, producing an additive affect. Thus compound heterozygous cats, cbcs, have an intermediate coloration compared with that of the Burmese and the Siamese; this is usually referred to as a mink Tonkinese (Figure 44-3). Complete albinos, which have an additional allele at the Color locus, have been identified. The locus is controlled by the gene

CHAPTER 44 Genetics of Feline Diseases and Traits

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TABLE 44-2 Other Mutations for Inherited Domestic Cat Diseases* Disease

Gene 69

Gangliosidosis 2

HEXB

51

Gangliosidosis 2

HEXB

68

Gangliosidosis 2

GM2A

40

Hemophilia B

F9

40

Hemophilia B

F9

39

Hyperoxaluria

GRHPR 38

Lipoprotein lipase deficiency 9

Mannosidosis, alpha

LPL LAMAN

70

Mucolipidosis II

GNPTA 45

Mucopolysaccharidosis I

102

Mucopolysaccharidosis VI

Mutation

Disease 22,101

inv1467-1491

Mucopolysaccharidosis VI

29

C667T

Mucopolysaccharidosis VII 100

del390-393

Muscular dystrophy 91

G247A

Niemann–Pick C

C1014T

IDUA

del1047-1049

ARSB

T1427C

GUSB

A1052G

DMD

900bp del M promoter -exon 1

SHH

A479G

58

SHH

G257C, A481T

HMBS

c.842_844delGAG

Polydactyla

19-21

Porphyria

C2655T

G1558A

G2864C

Porphyria

del1748-1751

ARSB

NPC

19-21

G1234A

Mutation

58

Polydactyla

G>A I4 acceptor site

Gene

HMBS

c.189dupT

37

CYP27B1

G223A, G731del

42

CYP27B1

G637T

Vitamin D–resistant rickets Vitamin D–resistant rickets

*The presented conditions are not prevalent in breeds or populations but may have been introduced into research colonies.

TABLE 44-3 Simple Phenotypic Traits and Diseases of the Cat and Its Breeds: Mutations Are Unidentified Locus

Phenotype

MOI

Locus

Phenotype

MOI

Bobtail

Curly and kinked tail

AD, variable expression

Orange

Orange hue to pigment

X-linked

Craniofacial Defect

Skull structural closure abnormality common to Burmese

AR

Peterbald

Brush coat, hairless

ID

Ear curl

Pinnae curl rostrally

AD

Rexing

Curly coat

AD

Ear fold

Pinnae folds ventrally

AD

Rexing

Curly coat

AR

Hypokalemia

Potassium insufficiency

AR

Spotting

Bicolor white

AD

Inhibitor

No pheomelanin

AD

Tabby

Type of tabby pattern

AS

Lymphoma

Mediastinal in Oriental breeds

AR

Ticked

Production of a tabby pattern

AD

Dominant white, no pigment

AD

Wired coat

ID

Manx

Tailless, short tail

AD, variable expression

White

Myopathy

Generalized muscle weakness

AR

Wirehair

MOI, Mode of inheritance (of the mutations as compared to the wild-type allele); AD, autosomal dominant; AR, autosomal recessive; ID, incomplete dominance; AS, allelic series. Orange is the only X-linked phenotypic trait.

FIGURE 44-1 Burmese. (Photo copyright 2011 Richard Katris.)

FIGURE 44-2 Singapura. (Photo copyright 2011 Richard Katris.)

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SECTION IX The Feline Genome and Clinical Genetics

FIGURE 44-3 Tonkinese. (Photo copyright 2011 Richard Katris.)

FIGURE 44-5 Devon Rex. (Photo copyright 2011 Richard Katris.)

FIGURE 44-4 Cornish Rex. (Photo copyright 2011 Richard Katris.)

tyrosinase; TYR and the allelic series is written as C > cb = cs > c. The coat color mutations are common to all cats and are effective for genetic typing in all breeds and populations. However, even though long fur is common in pedigreed and random-bred cats, long fur is an exception because four different mutations in the gene fibroblast growth factor 5 (FGF5) can cause a cat to have long fur.25,52 One mutation is common to almost all breeds and populations, which suggests that this mutation is the most ancient and present before breeds developed, but the other long fur mutations are more specific to particular breeds.3 Some cats can have long fur because of two different mutations in the gene FGF5. These cats would

FIGURE 44-6 American Wirehair. (Photo copyright 2011 Richard Katris.)

be considered compound heterozygotes. Thus all four mutations must be genotyped to determine whether a cat carries a mutation for long fur. Rexing is an interesting set of mutations for the domestic cat. At least six different types of rexoid mutations have been noted in the cat, including Cornish Rex (Figure 44-4) and Devon Rex (Figure 44-5), as well as several unpublished varieties, including American Wirehair (Figure 44-6), Selkirk Rex (Figure 44-7), LaPerm (Figure 44-8), and Tennessee Rex. The Devon Rex and


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FIGURE 44-8 LaPerm. (Photo copyright 2011 Richard Katris.)

FIGURE 44-7 Selkirk Rex. (Photo copyright 2011 Richard Katris.) FIGURE 44-9 Sphynx. (Photo copyright 2011 Richard Katris.)

Cornish Rex had been known to be caused by different genes after cross-breeding experiments and genetic studies.85 The genetic studies have ruled out the Devon Rex gene, keratin 71 (KRT71), as causative for the other rexoid cats.35 The Selkirk and LaPerm have dominant mutations, Devon and Cornish are caused by recessive mutations, and the wirehair appears to be a dominant mutation with variable expression and even incomplete penetrance, wherein sometimes cats thought to have the mutation are not wirehaired. Sometimes two traits are not initially known to be caused by the same gene, such as hairlessness of the Sphynx and rexing in the Devon Rex.35,86 Thus the hairlessness of the Sphynx (Figure 44-9)

has had the locus name Hairless with alleles Hr and hr, whereas Devon Rex has had the locus name of Rex with alleles Re and re defining Devon Rex as a separate locus from Rex, with alleles R and r for the Cornish Rex. Both Sphynx and Devon Rex have been proved to be caused by mutations in KRT71.35 Orange is the only trait known to be on the X chromosome for the domestic cat.5,24,46,62 Because the X chromosome is subject to X inactivation in females, female cats that are heterozygous for the Orange and wild-type black alleles will express the coloration associated with the allele that is on the active X chromosome. Because X inactivation is random and occurs early in

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FIGURE 44-10 Manx. (Photo copyright 2011 Richard Katris.) FIGURE 44-11 Scottish Fold. (Photo copyright 2011 Richard Katris.)

embryogenesis, the melanocytes in the skin will have different inactive X chromosomes, leading to the brindled black and orange of a tortoiseshell cat. Combined with the Spotting locus, which affects melanocyte migration and distribution, larger patches of skin will be covered by a clonal melanocyte population that has the same X inactivation, leading to large patches of orange or black or white coloration. Thus only female cats should be tortoiseshell or calico. Calico and tortoiseshell male cats are discovered fairly frequently, but they are usually sterile because they are genetic chimeras, having some cells as XX and some as XY. Chimeras are likely to be caused by the fusion of two embryos very early after fertilization.* Mutations that affect structural traits, such as Manx (Figure 44-10) and ear fold (Figure 44-11) or curl (Figure 44-12), have a tendency to be dominant mutations. Two copies of a dominant mutation are often highly detrimental. Kittens that are homozygous for the Manx mutation die in utero,87 and many cats homozygous for ear fold suffer from osteochondrodysplasia.17,67,80,92 However, cats homozygous for ear curl have no known detrimental health effects, nor do homozygous Japanese Bobtails (Figure 44-13). Most of the dominant mutations have only one known allele, except for polydactylism, in which several causative alleles have been noted in the gene sonic hedgehog (SHH).58 Compound heterozygote cats for polydactylism mutations have not been identified, so the effects of having two different mutations that cause polydactylism are not known. Homozygote cats for a polydactyl mutation have been identified and do not necessarily have a more severe presentation, such as several extra toes or additional abnormalities to the digits (Lyons LA, unpublished data). *References 16, 18, 43, 49, 55, 56, 83, 94.

FIGURE 44-12 American Curl. (Photo copyright 2011 Richard Katris.)

Two genetic mutations of the domestic cat are not associated with a disease or a phenotypic trait. Cats have been shown to have mutations in a gene, TAS1R2, that disrupts the sweet receptors.60,61 This mutation can be used to determine if an unknown DNA sample is of feline origin. Another example is the mutation that causes B blood type in cats.11 Blood type incompati bilities obviously can lead to transfusion reactions and neonatal isoerythrolysis for the cat, but inherently this characteristic is not necessarily a disease. A point mutation and an 18 base pair deletion have both been implicated in the gene CMAH as indicating the presence of the B blood type, or a B blood type carrier. Because both mutations are on the same allele, a clear indication of the

FIGURE 44-13 Japanese Bobtail. (Photo copyright 2011 Richard Katris.)

true causative mutation could not be determined. Thus both mutations should be examined in cats to genetically determine blood type.

Disease Mutations of the Domestic Cat Many cat mutations that cause heritable diseases have been identified by way of the candidate-gene approach. Often, different biomarkers can identify possible inborn errors of metabolism, which lead to lysosomal storage diseases, such as gangliosidosis and mucopolysaccharidosis. Interesting, both gangliosidosis 1, caused by GLB1 mutations, and gangliosidosis 2, caused by HEXB mutations, both found in the Korat breed, were some of the early discoveries of genetic mutations in the cat.23,76 The clinical presentations strongly suggested conditions that were similar to those found in humans and other species. Because causative mutations had already been identified in these other species, the genes became obvious candidates for the cat. These mutations were identified at a time when significant genome sequence was not available for the cat; therefore, although a strong candidate was indicated, the studies were tedious. Dystrophin, the gene that causes Duchenne and many other types of muscular dystrophy, is a significantly large gene, and early studies discovered a feline mutation causing a similar dystrophy in the cat.1,100 Cats having several of the diseases that were discovered early are actively retained in colonies because they are important models for gene therapies and many young children suffer from the same diseases as found in the cat. Many of the disease mutations in the cat were identified in random-bred cats, such as hemophilia B40 and vitamin D–resistant rickets,37 or in a specific individual of a breed and are not a concern to the breed population in general, such as Niemann–Pick type C91 and mannosidosis in Persians.9 These breed-identified genetic mutations should not be part of routine screening by cat


1279

breeders and registries, but clinicians should know that genetic tests are available for diagnostic purposes, especially from research groups with specialized expertise, such as at the University of Pennsylvania (http:// research.vet.upenn.edu/penngen). Unlike coat color mutations, which are common in the random-bred cat, the disease mutations are infrequent and should not be considered for genetic typing unless a clinical presentation is indicative of the disease. Even then, the clinical presentation may be more accurate for defining the disease as a new mutation in a known gene could be as likely in a random-bred population as the rediscovery of an already identified mutation. Several independent mutations have been identified in HEXB for gangliosidosis,14,51,69,76 in ARSB for mucopolysac charidosis VI,22,101,102 and HMBS for porphyria.19-21 A genetic test could rule out these mutations, although other mutations could also be present. Like the Korat with gangliosidosis, the Abyssinian breed has had two different disease forms identified for a specific type of disease: progressive retinal atrophy (PRA). Mutations for both an early-onset, rapidly progressing autosomal dominant PRA, CRX,73 and a lateonset, slowly progressing autosomal recessive PRA, CEP290, have been identified in Abyssinians.72 Abyssinians also have a recessive trait causing deficiency of the enzyme pyruvate kinase in red blood cells, as well as cats in the breed population with different blood types. Therefore Abyssinian breeders commonly use genetic testing in breeding programs. The Abyssinian is one of the oldest cat breeds, present during the early foundations of cat registries. This breed’s genetic heritage is obscure; it is not clearly a cat of eastern or western origins, although some evidence suggests that it may have originated in India. Historically, the breed has been fairly popular around the world, and genetic population statistics do not indicate that the Abyssinian breed is of any more or less concern for inbreeding depression than any other cat breed. Thus the detection of these various diseases in the Abyssinian may be an ascertainment bias or just sporadic bad luck for the breed. Other diseases, such as PKD, are prevalent; PKD in Persians is estimated at 30% to 38% worldwide.7,8,15 Because of cross-breeding with Persians, many other breeds, such as British Shorthair, American Shorthair, and Scottish Fold, also should be screened for PKD.12,26,64 Thus veterinarians need to be aware of cross-breeding practices, which vary among different cat registry organizations, so that genetic tests can be placed as high or low priorities for differentials and diagnostics.

Unidentified Genetic Diseases and Traits of the Domestic Cat Hundreds of traits and diseases that have been recognized to be genetic in other species have been

1280


documented in the domestic cat and its breeds (see Online Mendelian Inheritance in Animals: http:// www.ncbi.nlm.nih.gov/omia). However, an increased incidence and prevalence must be documented before accepting that a single case report or case series of a condition constitutes a genetic problem for a breed or a population. Those traits with as yet unidentified mutations and a strongly suggestive mode of inheritance are presented in Table 44-3. Breed dispositions to diseases, which may be due to genetics, environment, or both, have been reviewed for dogs and cats.41 Common environmental factors are often difficult to identify and consider. Veterinarians should note that populations change genetically over time, and breeders have an impact on undesired traits through selection; thus conditions documented in the past may not be of present concern or risk. As previously mentioned, because breed populations vary greatly in different parts of the world, breed risks for diseases and health conditions vary accordingly. Many cat breeders and registries are proactive and openly list and discuss health concerns for their breeds. Overall, effective genetic studies to find mutations that cause health issues and traits require a sufficient sample size, which generally means active participation from the breed group. Many of the morphologic and structural presentations of the domestic cat breeds may influence the presentation of conditions that are then noted to have a higher prevalence in a breed. Already mentioned are incontinence in the Manx and osteochrondrodysplasia of the Scottish Fold. These health conditions are actually secondary effects of the primary genetic mutation. The brachycephalia of Persian cats and related breeds has caused significant concern on account of the secondary structural abnormalities and chronic health problems caused by the extreme shortening of the skull.57,89,90 Anecdotally, the fine, elegant structures of Abyssinians and Siamese exacerbate patellar luxation. The largest breed, the Maine Coon, may be affected by hip dysplasia, a very common problem in large dog breeds.

GENETIC RISK FACTORS AND COMPLEX TRAITS All the mutations influencing a disease may not be identified at any given time; usually the mutations that influence a condition the most and have the highest heritability are identified first. Because multiple mutations may act additively to cause a disease, each mutation may be said to confer a “risk” for disease development. Thus some mutations may be considered risk factors, predisposing an individual to a health problem. These risk-conferring mutations are neither necessary nor sufficient for causing disease. An excellent example of a mutation that confers

a risk are the DNA variants associated with cardiac disease in cats. Hypertrophic cardiomyopathy (HCM) is a recognized genetic condition in cats.53 In 2005, Meurs, Kittleson, and colleagues reported that a DNA alteration in the gene cardiac myosin-binding protein C 3 (MYBPC3) was strongly associated with HCM in a long-term research colony of Maine Coon cats at the University of California, Davis.75 The DNA mutation is commonly referred to as A31P because this DNA mutation changes codon 31 from an alanine to a proline in the amino acid sequence (i.e., protein) of MYBPC3. The data clearly show that not all cats with the mutation had HCM and that some cats with HCM did not have the DNA mutation. Age of onset, variable expression, and disease heterogeneity were mentioned in this report. These aspects suggest that the identified DNA variant should be considered more of a risk factor than a directly causative mutation. Two recent papers have shown that not all Maine Coon cats with the A31P mutation develop HCM,88,98 and one of those papers has mistakenly interpreted this lack of penetrance as being evidence that the A31P mutation is not causal.98 This interpretation is misleading, causing debate about the validity of the Maine Coon HCM test. To date, most cat genetic tests have been for traits that have nearly complete penetrance, have little variability in expression, and are early in onset. However, some imperfect examples do exist in cats that have not caused as much controversy as the HCM test. The CEP290 PRA mutation in Abyssinians has a late age of onset, and some cats with subclinical disease have been identified.71 Some cats with pyruvate kinase deficiency have very mild and subclinical presentations.54 The interplay of various coat color genes often muddles the determination of the true coat color of cats. As is true in humans with cardiac disease, the finding that not all cats with the A31P mutation in MYBPC3 develop HCM is actually more commonplace in the field of HCM genetic testing. Because disease- or trait-causing mutations may not be 100% penetrant, they do not always cause clinically detectable disease. Presence of clinical disease in an individual cat and the severity of disease (expression) are likely affected by the known genetic aspects presented in the subsequent sections.

Incomplete Penetrance For some traits and diseases, even though a known causative mutation has been identified, an individual with that mutation does not present with the condition. Incomplete penetrance is an extreme of variable expression (discussed in more detail later in this chapter). In general, the reason that a condition associated with a mutation would not be present is unknown, but other genetic, biologic, and environmental interactions

certainly play a role in the overall appearance and health of an individual and its organs. The sensitivity of clinical diagnostics may also influence the determination of penetrance. In the case of HCM, echocardiography can be considered an insensitive tool for detecting mild forms of the disease in cats; thus many cats with mild changes do not clinically appear to have cardiac disease. Experience and bias also play a role in diagnosis. For example, individuals who do not have expertise in the use of ultrasonic examinations for HCM or PKD are less likely to be able to provide an accurate diagnosis for these diseases.

Age of Onset (Age-Related Penetrance) Some diseases have a slow progression and may not present until later in life. In humans HCM caused by MYBPC mutations is clearly a disease that has slow progression and commonly does not express until the individual is over 50 years of age. HCM in Maine Coon cats can also develop in older cats, especially in cats that are heterozygous for the mutation and, for some unknown reason, in females. Often, an autosomal dominant disease may be more severe if two copies of the risk mutation are present in an individual, leading to earlier and more severe disease, which appears to be the case with the A31P mutation. The definitive age as to when a cat is past the risk of developing HCM is not precisely determined.

Variable Expression Most traits and diseases have some amount of variable expression depending on the individual. For example, not all cats with the mutation for blue dilution have the same color of blue–gray fur. Obviously, the background genetics and environment of the individual influence the overall presentations of traits and diseases. Thus the level of presentation can be variable in regard to left ventricular wall thickness in cats with HCM. Cats can have mild, moderate, or severe HCM. Only those cats with severe HCM show clinical signs, although a few cats with lesser severity of disease may die suddenly. Cats with HCM may fall in the “equivocal” range for wall thickness; therefore definitive disease status is difficult to declare. These equivocal cats may progress to more severe disease with time, or the equivocal status may be as severe as the disease gets. Some cats with PKD have only a few cysts and never progress to renal failure while others have severe and fast progression of disease and succumb to renal failure in a few years.

Disease Heterogeneity More than one mutation in the same gene or mutations in different related genes can cause the same disease.


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Genetic heterogeneity for HCM in humans is well established, and there is no reason to think the same situation is not true for cats. Currently, more than 1000 mutations in more than 10 genes are known to cause HCM in humans. Only two mutations have been identified that cause HCM in cats, the A31P mutation in Maine Coon cats and the R820W mutation in Ragdolls,74,75 which also causes disease in humans.84 Both mutations are in MYBPC3, the most commonly mutated gene in humans with HCM (see review by Tsoutsman et al96). Other breeds of cats, including the Bengal, Siberian, Devon Rex, and Sphynx, and random-bred cats either do not have or have an extremely low prevalence of the A31P or the R820W mutation. However, because there are Maine Coon cats that have HCM and do not have the A31P mutation, there must be at least one more cause of HCM, most likely another mutation, in this breed. The long fur mutations in the cat are also examples of trait heterogeneity.

Accuracy of Genetic Testing Even though a specific genetic mutation may be identified for a trait or disease, research laboratories use different methods to assay for the mutation. Errors in genetic assays may produce inaccurate DNA results, leading to confusion in genetic test interpretation. Direct DNA sequencing is considered the most robust method, “the gold standard,” but it is also one of the more costly methods of analysis. Because DNA primers must bind to the DNA sequence flanking a specific mutation, other, unimportant mutations may be in the areas where the primers bind, causing poor or no amplification of one or both alleles for a given individual. This condition is known as allelic dropout, and all testing laboratories are aware of this potential source of error for a genetic test. Even direct DNA sequencing can suffer from allelic dropout, but because a larger portion of the gene that may have other DNA variants is generally amplified, a higher likelihood of detecting allelic dropout is present. Laboratories will place polymerase chain reaction (PCR) primers in different locations surrounding the mutation of interest, which is often proprietary information, in attempts to lower the risk of allelic dropout. Thus some laboratories have better assays than others, even if they are doing the same assay method and testing for the same mutation. The different DNA assay methods are usually developed to reduce cost and fit the laboratory’s expertise and instrumentation. However, some assays may have, in general, an increased risk of test failure. Common methods for DNA testing include real-time PCR (TaqMan), restriction fragment length polymorphism (RFLP), allele-specific oligonucleotides (ASOs), or even mass spectroscopy–based methods. Just as a veterinarian may want to know if a feline immunodeficiency virus (FIV) test is performed by enzyme-linked

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immunosorbent assay (ELISA), PCR, or Western blot because each method has different sensitivities and specificities, this is also true for DNA-testing methods. Veterinarians will need to become familiar with the different genetic testing approaches and not hesitate to ask testing laboratory staff members about their methods and sensitivity and specificity for their approaches.

Inaccurate Clinical Diagnosis Echocardiography is the most common and currently the only useful method for diagnosing cardiac disease in cats. Several studies have evaluated HCM in domestic shorthair and Maine Coon cats.28,44,79 Not all cardiac disease is HCM, and even the definition of HCM can be debated. A consistent definition for HCM is not used by all cardiologists, which creates difficulty when correlating a genetic test result with an ultrasound report, especially if detailed diagnostic criteria are not presented in the report. Misinterpretations in ultrasound examinations may lead to different interpretations with disease status. Overall, the only way to determine the true risk conferred by some mutations is to follow cats over the course of a lifetime with common diagnostic procedures and compare outcomes to the genetic test results. Only time and continued follow-up will help determine the true relative risk that mutations convey for complex diseases. In the case of HCM, various studies have indicated higher or lower risks in different populations of cats, but none has been able to follow cats throughout a lifetime. These studies are important and are of great value to the community. Other mutations must be found, and the cooperation of breeders must be positive and enthusiastic for these studies to succeed.

GENETIC TESTING Breeding Recommendations Cat breeders are very knowledgeable about weighing different factors to produce healthy cats that are of good physical type and temperament. Many genetic tests help a breeder make a clearer, more educated decision. Cats with a positive genetic test for a disease should be screened by another diagnostic method, such as ultrasound in the case of HCM and PKD, to determine disease status, and this overall information should be used in breeding decisions. Other health, physical type, and behavioral attributes should certainly be considered in the overall breeding program. However, breeders should work hard to reduce the risks with any health issue. Every cat that has the HCM A31P mutation is at risk for developing HCM, and every cat with the mutation will pass it on to some or all offspring. Cats that are

homozygous for the A31P mutation will definitely pass the mutation to all offspring. The homozygous cats are at higher risk of developing severe HCM. Cats that are heterozygous for the mutation should not be bred unless they have other qualities that are either highly beneficial or necessary to the breed. Kittens that test negative for the mutation should be used to replace affected parents in the gene pool. A slow eradication of disease is recommended for highly prevalent diseases, such as HCM and PKD, because the quick elimination of a high number of cats could lead to other effects of inbreeding depression. Breeders of cat breeds with very low population sizes, such as the Korat, have learned to manage the gangliosidoses by never breeding carriers together. It is to be hoped that all the disease mutations can eventually be eradicated, but good breeding decisions and balancing population diversity must be considered. Recently, estimated breeding values (EBVs) have been suggested as a means to apply selection to companion animal populations.59,93 EBVs are not a new concept; they are used to assign a value to an animal based on selected qualities. Cat and dog breeders inherently assign EBVs to their breeding stock, but not in a preset and defined numeric fashion. The dairy and beef industries have used EBVs for decades to produce herds that have higher milk yields, milk fat content, or different carcass qualities. Generally, some industry standard has to be developed and routinely followed in the same direction of positive or negative selection for the trait(s) of interest. EBVs usually pertain to traits that are complex and have some quantitative measurement, such as weight, height, or tail length. Thus standard quantitative genetic techniques can be used to estimate the extent of inheritance of the disorder (heritability), followed by the development of a metric that can be used to assess the genetic merit of individual animals for the purpose of selection for reproduction and subsequent breed improvement. In the simplest form, cats that carry undesired traits, such as a disease, should be assigned a low EBV. However, other desired traits may outweigh the negative value of a disease or condition, giving a cat an overall high EBV. EBVs are a concept to consider as more genetic tests are developed because breeders now have more informative data to consider when selecting mating pairs for the propagation of a breed. Standards and a unified effort would need to be developed, as well as retrospective trials to model the effects of the EBVs before they are implemented.

Genetic Testing Concerns in Different Breeds or Populations Once a mutation is identified for a gene that causes a particular coat color or disease, a service laboratory, either in association with the investigator who found the


mutation or an independent commercial laboratory, will establish a genetic test for that mutation to offer to the public (Table 44-4). Over a dozen laboratories around the world now offer genetic testing for PKD in cats. All the laboratories may be technically accurate, but not all of them “know their cats” equally. Some of the concerns with specificity and sensitivity of genetic tests, particularly in regard to testing in hybrid cat breeds, are due to

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a lack of knowledge of how cat breeds are developed and cat evolutionary relationships. Tables 44-1 and 44-2 contain all the currently known genetic mutations in the cat that have been published and may be of concern for genetic testing. Genetic diseases usually present in a specific breed and thus are associated only with that breed. However, some breeds are allowed to outcross with others, and some are legally

TABLE 44-4 Domestic Cat DNA Testing Laboratories University Research Affiliate

Cat Test* ID

Disease

Color

Blood

Coat

Yes

4

Some

Yes

No

Yes

PKD

No

No

No

France

Yes

4

Color

Yes

No

BioAxis DNA Research Centre Ltd. www.dnares.in

India

Yes

PKD

No

No

No

DNA Diagnostics Center www.dnacenter.com

U.S.

No

PKD

No

No

No

GENINDEXE www.genindexe.com

France

Yes

7

5

Yes

No

Genoscoper www.genoscoper.com

Finland

Yes

No

No

Yes

No

Gribbles www.gribblesvets.com

Australia

No

PKD

No

No

No

IDEXX www.idexx.ca

Canada

No

PK def.

No

No

No

Laboklin www.laboklin.de/

Germany

Yes

9

5

Yes

Long

Langford Veterinary Services, Molecular Diagnostics Unit, Langfordvets.co.uk

UK

Bristol

No

3

No

No

No

PennGen research.vet.upenn.edu/penngen†

U.S.

Pennsylvania

No

PK GSD

No

No

No

PROGENUS S.A. www.progenus.be

Belgium

Yes

HCM PKD

No

No

No

Van Haeringen Laboratory www.vhlgenetics.com

Netherlands

Yes

9

5

Yes

Long

Veterinary Cardiac Genetics Lab www.cvm.ncsu.edu/vhc/csds/vcgl

U.S.

North Carolina State

No

HCM

No

No

No

Veterinary Genetics Lab www.vgl.ucdavis.edu

U.S.

California, Davis

Yes

7

All

Yes

All

VetGen www.vetgen.com

U.S.

Michigan

Yes

No

Brown dilute

No

Long

Vetogene www.vetogene.com

Italy

Milan

Yes

HCM PKD

No

No

No

Lab/Website

Region

Animal DNA Testing www.animalsdna.com

Australia

Animal Health Trust www.aht.org.uk

UK

Antagene Immeuble Le Meltem www.antagene.com

Animal Health Trust

PKD, Polycystic kidney disease; GSD, glycogen storage disease; HCM, hypertrophic cardiomyopathy; ID, individual genetic identification; PK def., pyruvate kinase deficiency. *Tests reference to those listed in Table 44-1. If a laboratory offers only one or two tests, those tests are listed. PKD and HCM are the most popular tests to offer. †PennGen also offers tests for diseases in Table 44-2 that are not of concern to the cat breeds or population in general.

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or illegally used to help refine the appearance of another breed. The Siamese and Persian have influenced a host of other cat breeds. Hence any mutation found in one breed can be found in others if cross-breeding has occurred. In addition, cats are bred all over the world, and the rules of various registries and associations are not always the same. An outcross that may be acceptable for The International Cat Association95 in the United States may be unacceptable for the Cat Fanciers’ Association or perhaps the Governing Council of the Cat Fancy36 in the United Kingdom. Thus the personnel of testing laboratories must understand cat breed dynamics to know whether a test is valid for a given breed in any part of the world and to offer the appropriate tests for the breeds at risk. Why does one care if a genetic test developed in one breed is valid in a different breed? The concern is disease heterogeneity. Owners, breeders, and veterinarians may identify a clinical presentation that is abnormal in the cat, but they also may jump to conclusions too quickly. For example, there are many causes of renal failure besides PKD. There are different types of cardiac disease; not all cardiac disease is HCM. Even when a diagnosis of HCM is definitive, not all HCM is caused by the same mutation. Herein lies the concern. An unknowing veterinarian, owner, or breeder may want a cat to have a genetic test for HCM or PKD because the cat has clinical signs consistent with these diseases. If the test shows a negative result, this result does not necessarily mean the cat does not have HCM or PKD, if the test has not been proved effective in that selected breed. The result does imply that the cat does not have the mutation causing Maine Coon or Ragdoll HCM or Persian PKD. A laboratory may very well run the test, but laboratories have different capabilities and skills with genetic counseling. Veterinarians may be on their own when it comes to interpreting the meaning of a negative test. This is why a test is generally listed as pertaining to a specific breed. Until clinical data (e.g., ultrasound diagnoses and genetic test results) is available from a sufficient number of cats, a test cannot be valid for the breed unless clear outcrossing to the risk breeds is apparent.

Genetic Testing Concerns in Hybrid Cat Breeds Some domestic cat breeds are hybrids of two species of cats. According to the biological species concept, organisms are classified in the same species if they are potentially capable of interbreeding and producing fertile offspring. The production of hybrid cat breeds generally has required a female domestic cat to be bred with a male cat from another wild felid species because of temperament concerns. For example, domestic cats have been bred to Asian Leopard cats to produce the

Bengal and to the Serval to produce the Savannah. For the first-generation offspring, or first filial (F1) generation, of hybrid cat breeds, the male F1 is sterile; the subsequent generations cannot be produced by crossing a male F1 with a female F1. Thus the female F1 offspring are generally mated with a full-blooded domestic male or a lower-generation hybrid male that is fertile. Cat breeders will term the subsequent generations of offspring as F2, F3, and so on; however, these designations are actually genetically incorrect, and they should be considered backcross generations (e.g., BC1, BC2). The F1 females are also difficult to mate and may have reduced fecundity. Fertility may take several generations to re-establish in hybrid breeds. The infertility is due to problems with chromosomes aligning during cell reproduction for the production of the gametes, as well as allelic incompatibilities at different genes. Because the inheritance of the allelic incompatibilities is difficult to predict, many hybrid cats can have reproduction problems, even in the lower generations that can be shown in competition. A normal level of genetic variation among cats is expected, typically far less than 1% of a sequence that codes for a protein. Herein lies a problem for hybrid cat breeds. The evolutionary time between the appearances of different cat species is millions of years,50 not the hundreds to thousands of years between the appearance of cat breeds and populations. An Asian Leopard cat had a common ancestor with the domestic cat about 6 million years ago, the Bobcat about 8 million years ago, and the Serval about 9.5 million years ago. The Jungle cat is more closely related to the domestic cat than the Asian Leopard cat is. In addition, for some of these wild felid species, different subspecies have been incorporated into the breed. The DNA sequence of a domestic cat and one of these wild felid species will have many genetic differences, maybe a several percentage difference, less for the jungle cat, more for the Serval compared with that of a domestic cat. The genetic differences are most likely silent mutations, but the variation will interplay with genetic assays and may cause more allelic dropout than what would be normally anticipated. No genetic tests have been validated in the hybrid cat breeds, although they are used frequently. As mentioned, these allelic differences can cause allelic incompatibilities, which could produce reproduction problems and other health issues. Most laboratories recognize that disease mutations are specific to breeds but not the coat colors. The coat color mutations occurred during the early domestication of the cat, before the breeds were developed, so all breeds tend to have the same mutation. This is true for all the coat color tests so far but for the hybrid breeds, such as the Bengal, Chausie (produced from the jungle cat), and Savannah, some oddities in coat color and disease testing may occur. The normal DNA sequence

around each of the mutations for coat colors must be evaluated in many individuals from each wild felid species to find the normal, silent mutations that occur between the wild felids and the domestic cats. At any given gene, in a Bengal, it cannot be determined whether one Asian Leopard cat sequence or two are present. Thus the accuracy for any genetic test is not known for hybrid cat breeds. If the domestic cat alleles are present, the test will perform as expected. However, one never knows when one allele or both are from the Asian Leopard cat. Selection generally favors the wild felid colorations, so inherently the breed is selected for the DNA sequences that may cause the genetic tests to fail.

Inappropriate Genetic Testing Laboratory Procedures Genetic testing laboratories attempt to provide the best service for the lowest cost. Many of the newer technologies allow for higher throughput of samples and also performance of more than one genetic test per assay, greatly lowering costs of reagents and human labor. Many testing laboratories aspire to be as complete as possible, providing all available genetic tests for any given species. However, in the zeal of competition, a few genetic tests that are offered in the cat do not have sufficient scientific support. Any genetic test should be based on a reference publication to determine the genetic sequence surrounding the mutation and provide the statistical support for the accuracy of the mutation for conferring disease or the trait of interest in specific breeds and populations. Published abstracts are not peer-reviewed articles and do not provide sufficient information to determine the accuracy of a test; thus abstracts are not appropriate references for genetic tests. Some universities or researchers own associated companies, the discoveries of which may be protected by licensure or patent, and the data may never be published for competitive advantage. Some genetic tests therefore can be found only with specific testing companies. Currently, the patented tests for cats include PKD, HCM, the mutations for Tyrosinase at the Color locus that confer Siamese and Burmese style “points,” and blood type B.11 However, licensure is available for each of these tests and the patents pertain only to the United States. Some companies will violate these patents because the overall income to the patent holder is generally very low and the likelihood that a university would enforce a patent would be low relative to the prohibitive cost. However, violation of genetic test patents is not encouraged and is generally considered inappropriate. In addition to violating patents, some laboratories offer genetic tests that are not scientifically sound in an attempt to gain a competitive advantage. Another mutation in MYBPC3 for HCM was reported in an abstract


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but was never presented in a peer-reviewed publication. Support for the risk this mutation confers for HCM in cats has not been well documented, but some laboratories nonetheless offer testing for this DNA variant. Laboratories often post disclaimers, leaving the veterinarian, owner, and breeder to speculate about a test’s true diagnostic utility. Some laboratories offer a single method, such as a type DNA array method, to genetically test all mutations for the cat. As noted in Tables 44-1 and 44-2, the mutations that cause traits and diseases of the cat come in a variety of types. Many mutations are point mutations: a single nucleotide difference in the DNA. Others are deletions of one or more bases, and some are very complex alterations that can disrupt several exons of a gene, such as the mutation that causes spinal muscular atrophy in the Maine Coon cat. The genetic sequence surrounding a mutation is also important because some regions may be rich in particular bases, such as a GC-rich region or a region with repeat elements of stretches of similar nucleotides, such as polyadenosine stretches. This information is less important to the veterinarian, but very important to the development of an assay that is sound and efficient. A single testing method, such as size variation, RFLP, real-time PCR (TaqMan), or any array method cannot effectively test all the different mutations. Thus a testing laboratory must be proficient in several methods to test all types of mutations for the cat or any other species. Veterinarians should be skeptical of any laboratory that offers one testing method for all mutations of the cat.

CONCLUSION Genetic testing is an important diagnostic tool for the veterinarian, breeder, and owner. Genetic tests are not 100% foolproof, and the accuracy of the test procedure and the reputation and customer service of the genetic testing laboratory must be considered. Some traits are highly desired, and genetic testing can help breeders determine appropriate pairings more accurately. This may encourage more efficient breeding programs, thereby lowering costs and excessive cat production. Other traits or diseases are undesirable, and genetic testing can be used to prevent and potentially eradicate them from the population. Genetic tests for simple genetic traits are more consistent with predicting the trait or disease presentation, but as genomics progresses for the cat, tests that confer risk will become more common. Veterinarians will have to weigh the relative risks of having a mutation versus having disease as part of the differential diagnosis, and breeders will have to consider risk factors along with the other important attributes of a cat in making breeding decisions.

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References 1. Allamand V, Campbell KP: Animal models for muscular dystrophy: valuable tools for the development of therapies, Hum Mol Genet 9:2459, 2000. 2. American Pet Product Manufacturing Association: National pet owner’s survey, Greenwich, Conn, 2008, The Association. 3. Bach L, Gandolfi B, Grahn R et al: The distribution and possible origins of FGF5 mutations affecting fur length in cats, submitted for publication, 2011. 4. Bamber RC: Correlation between white coat colour, blue eyes, and deafness in cats, Journal of Genetics 27:407, 1933. 5. Bamber RC, Herdman EC: The inheritance of black, yellow and tortoiseshell coat colour in cats, J Genet 18:87, 1927. 6. Banks G, Chamberlain J: The value of mammalian models for duchenne muscular dystrophy in developing therapeutic strategies, Curr Top Dev Biol 84:431, 2008. 7. Barrs VR, Gunew M, Foster SF et al: Prevalence of auto somal dominant polycystic kidney disease in Persian cats and related-breeds in Sydney and Brisbane, Aust Vet J 79:257, 2001. 8. Barthez PY, Rivier P, Begon D: Prevalence of polycystic kidney disease in Persian and Persian related cats in France, J Feline Med Surg 5:345, 2003. 9. Berg T, Tollersrud OK, Walkley SU et al: Purification of feline lysosomal alpha-mannosidase, determination of its cDNA sequence and identification of a mutation causing alphamannosidosis in Persian cats, Biochem J 328 (Pt 3):863, 1997. 10. Bergsma DR, Brown KS: White fur, blue eyes, and deafness in the domestic cat, J Hered 62:171, 1971. 11. Bighignoli B, Niini T, Grahn RA et al: Cytidine monophospho-Nacetylneuraminic acid hydroxylase (CMAH) mutations associated with the domestic cat AB blood group, BMC Genet 8:27, 2007. 12. Biller DS, Chew DJ, DiBartola SP: Polycystic kidney disease in a family of Persian cats, J Am Vet Med Assoc 196:1288, 1990. 13. Biller DS, DiBartola SP, Eaton KA et al: Inheritance of polycystic kidney disease in Persian cats, J Hered 87:1, 1996. 14. Bradbury AM, Morrison NE, Hwang M et al: Neurodegenerative lysosomal storage disease in European Burmese cats with hexosaminidase beta-subunit deficiency, Mol Genet Metab 97:53, 2009. 15. Cannon MJ, MacKay AD, Barr FJ et al: Prevalence of polycystic kidney disease in Persian cats in the United Kingdom, Vet Rec 149:409, 2001. 16. Centerwall WR, Benirschke K: Animal model for the XXY Klinefelter’s syndrome in man: tortoiseshell and calico male cats, Am J Vet Res 36:1275, 1975. 17. Chang J, Jung J, Oh S et al: Osteochondrodysplasia in three Scottish Fold cats, J Vet Sci 8:307, 2007. 18. Chu EHY, Thuline HC, Norby DE: Triploid-diploid chimerism in a male tortoiseshell cat, Cytogenetics 3:1, 1964. 19. Clavero S, Bishop DF, Giger U et al: Feline congenital erythropoietic porphyria: two homozygous UROS missense mutations cause the enzyme deficiency and porphyrin accumulation, Mol Med 16:381, 2010. 20. Clavero S, Bishop DF, Haskins ME et al: Feline acute intermittent porphyria: a phenocopy masquerading as an erythropoietic porphyria due to dominant and recessive hydroxymethylbilane synthase mutations, Hum Mol Genet 19:584, 2010. 21. Clavero S, Haskins M, Giger U et al: Molecular basis of acure intermittent porphyria in the cat, Proc Adv Canine Feline Genomics Inherit Dis, St Malo, France, 2008. 22. Crawley AC, Yogalingam G, Muller VJ et al: Two muta tions within a feline mucopolysaccharidosis type VI colony cause three different clinical phenotypes, J Clin Invest 101: 109, 1998.

23. De Maria R, Divari S, Bo S et al: Beta-galactosidase deficiency in a Korat cat: a new form of feline GM1-gangliosidosis, Acta Neuropathol 96:307, 1998. 24. Doncaster L: On the inheritance of tortoiseshell and related colours in cats, Proc Cambridge Philosophical Soc 13:35, 1904. 25. Drogemuller C, Rufenacht S, Wichert B et al: Mutations within the FGF5 gene are associated with hair length in cats, Anim Genet 38:218, 2007. 26. Eaton KA, Biller DS, DiBartola SP et al: Autosomal dominant polycystic kidney disease in Persian and Persian-cross cats, Vet Pathol 34:117, 1997. 27. Eizirik E, Yuhki N, Johnson WE et al: Molecular genetics and evolution of melanism in the cat family, Curr Biol 13:448, 2003. 28. Fries R, Heaney AM, Meurs KM: Prevalence of the myosinbinding protein C mutation in Maine Coon cats, J Vet Intern Med 22:893, 2008. 28a. Fyfe JC, Kurzhals RL, Hawkins MG et al: A complex rearrangement in GBE1 causes both perinatal hypoglycemic collapse and late-juvenile-onset neuromuscular degeneration in glycogen storage disease type IV of Norwegian forest cats, Mol Genet Metab 90:383, 2007. 29. Fyfe JC, Kurzhals RL, Lassaline ME et al: Molecular basis of feline beta-glucuronidase deficiency: an animal model of mucopolysaccharidosis VII, Genomics 58:121, 1999. 30. Fyfe JC, Menotti-Raymond M, David VA et al: An approximately 140-kb deletion associated with feline spinal muscular atrophy implies an essential LIX1 function for motor neuron survival, Genome Res 16:1084, 2006. 31. Gabor LJ, Canfield PJ, Malik R: Immunophenotypic and histological characterisation of 109 cases of feline lymphosarcoma, Aust Vet J 77:436, 1999. 32. Gabor LJ, Canfield PJ, Malik R: Haematological and biochemical findings in cats in Australia with lymphosarcoma, Aust Vet J 78:456, 2000. 33. Gabor LJ, Malik R, Canfield PJ: Clinical and anatomical features of lymphosarcoma in 118 cats, Aust Vet J 76:725, 1998. 34. Gandolfi B, Bach L, Beresford L et al: Off with the gloves: mutation in KIT implicated for the unique white spotting phenotype of Birman cats, submitted for publication, 2011. 35. Gandolfi B, Outerbridge C, Beresford L et al: The naked truth: Sphynx and Devon Rex cat breed mutations in KRT71, Mamm Genome 21:509, 2010. 36. The Governing Council of the Cat Fancy (GCCF): http:// www.gccfcats.org. Accessed June 22, 2011. 37. Geisen V, Weber K, Hartmann K: Vitamin D-dependent hereditary rickets type I in a cat, J Vet Intern Med 23:196, 2009. 38. Ginzinger DG, Lewis ME, Ma Y et al: A mutation in the lipoprotein lipase gene is the molecular basis of chylomicronemia in a colony of domestic cats, J Clin Invest 97:1257, 1996. 39. Goldstein R, Narala S, Sabet N et al: Primary hyperoxaluria in cats caused by a mutation in the feline GRHPR gene, J Hered 100:S2, 2009. 40. Goree M, Catalfamo JL, Aber S et al: Characterization of the mutations causing hemophilia B in 2 domestic cats, J Vet Intern Med 19:200, 2005. 41. Gough A, Thomas A: Breed predispositions to disease in dogs and cats, ed 2, Oxford, England, 2010, Wiley-Blackwell. 42. Grahn R, Ellis M, Grahn J et al: No bones about it! A novel CYP27B1 mutation results in feline vitamin D-dependent Rickets Type I (VDDR-1), submitted for publication, 2011. 43. Gregson NM, Ishmael J: Diploid triploid chimerism in three tortoiseshell cats, Res Vet Sci 12:275, 1971. 44. Gundler S, Tidholm A, Haggstrom J: Prevalence of myocardial hypertrophy in a population of asymptomatic Swedish Maine coon cats, Acta Vet Scand 50:22, 2008.

CHAPTER 44 Genetics of Feline Diseases and Traits 45. He X, Li CM, Simonaro CM et al: Identification and characterization of the molecular lesion causing mucopolysaccharidosis type I in cats, Mol Genet Metab 67:106, 1999. 46. Ibsen HL: Tricolor inheritance. III. Tortoiseshell cats, Genetics 1, 1916. 47. Imes DL, Geary LA, Grahn RA et al: Albinism in the domestic cat (Felis catus) is associated with a tyrosinase (TYR) mutation, Anim Genet 37:175, 2006. 48. Ishida Y, David VA, Eizirik E et al: A homozygous single-base deletion in MLPH causes the dilute coat color phenotype in the domestic cat, Genomics 88:698, 2006. 49. Ishihara T: Cytological studies on tortoiseshell male cats, Cytologia 21: 391, 1956. 50. Johnson WE, Eizirik E, Pecon-Slattery J et al: The late Miocene radiation of modern Felidae: a genetic assessment, Science 311:73, 2006. 51. Kanae Y, Endoh D, Yamato O et al: Nonsense mutation of feline beta-hexosaminidase beta-subunit (HEXB) gene causing Sandhoff disease in a family of Japanese domestic cats, Res Vet Sci 82:54, 2007. 52. Kehler JS, David VA, Schaffer AA et al: Four independent mutations in the feline fibroblast growth factor 5 gene determine the long-haired phenotype in domestic cats, J Hered 98:555, 2007. 53. Kittleson MD, Meurs KM, Munro MJ et al: Familial hypertrophic cardiomyopathy in maine coon cats: an animal model of human disease, Circulation 99:3172, 1999. 54. Kohn B, Fumi C: Clinical course of pyruvate kinase deficiency in Abyssinian and Somali cats, J Feline Med Surg 10:145, 2008. 55. Kosowska B, Januszewski A, Tokarska M et al: Cytogenetic and histologic studies of tortoiseshell cats, Med Weter 57:475, 2001. 56. Kuiper H, Hewicker-Trautwein M, Distl O: [Cytogenetic and histologic examination of four tortoiseshell cats], Dtsch Tierarztl Wochenschr 110:457, 2003. 57. Kunzel W, Breit S, Oppel M: Morphometric investigations of breed-specific features in feline skulls and considerations on their functional implications, Anat Histol Embryol 32:218, 2003. 58. Lettice LA, Hill AE, Devenney PS et al: Point mutations in a distant sonic hedgehog cis-regulator generate a variable regulatory output responsible for preaxial polydactyly, Hum Mol Genet 17:978, 2008. 59. Lewis T, Rusbridge C, Knowler P et al: Heritability of syringomyelia in Cavalier King Charles spaniels, Vet J 183:345, 2010. 60. Li X, Li W, Wang H et al: Cats lack a sweet taste receptor, J Nutr 136:1932S, 2006. 61. Li X, Li W, Wang H et al: Pseudogenization of a sweet-receptor gene accounts for cats’ indifference toward sugar, PLoS Genet 1:27, 2005. 62. Little CC: Colour inheritance in cats, with special reference to colours, black, yellow and tortoiseshell, J Genet 8:279, 1919. 63. Louwerens M, London CA, Pedersen NC et al: Feline lymphoma in the post-feline leukemia virus era, J Vet Intern Med 19:329, 2005. 64. Lyons LA, Biller DS, Erdman CA et al: Feline polycystic kidney disease mutation identified in PKD1, J Am Soc Nephrol 15:2548, 2004. 65. Lyons LA, Foe IT, Rah HC et al: Chocolate coated cats: TYRP1 mutations for brown color in domestic cats, Mamm Genome 16:356, 2005. 66. Lyons LA, Imes DL, Rah HC et al: Tyrosinase mutations associated with Siamese and Burmese patterns in the domestic cat (Felis catus), Anim Genet 36:119, 2005. 67. Malik R, Allan GS, Howlett CR et al: Osteochondrodysplasia in Scottish Fold cats, Aust Vet J 77:85, 1999. 68. Martin DR, Cox NR, Morrison NE et al: Mutation of the GM2 activator protein in a feline model of GM2 gangliosidosis, Acta Neuropathol 110:443, 2005. 69. Martin DR, Krum BK, Varadarajan GS et al: An inversion of 25 base pairs causes feline GM2 gangliosidosis variant, Exp Neurol 187:30, 2004.

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70. Mazrier H, Van Hoeven M, Wang P et al: Inheritance, biochemical abnormalities, and clinical features of feline mucolipidosis II: the first animal model of human I-cell disease, J Hered 94:363, 2003. 71. Menotti-Raymond M, David VA, Pflueger S et al: Widespread retinal degenerative disease mutation (rdAc) discovered among a large number of popular cat breeds, Vet J 186:32, 2010. 72. Menotti-Raymond M, David VA, Schaffer AA et al: Mutation in CEP290 discovered for cat model of human retinal degeneration, J Hered 98:211, 2007. 73. Menotti-Raymond M, Deckman K, David V et al: Mutation discovered in a feline model of human congenital retinal blinding disease, Invest Ophthalmol Vis Sci 51:2852, 2010. 74. Meurs KM, Norgard MM, Ederer MM et al: A substitution mutation in the myosin binding protein C gene in ragdoll hypertrophic cardiomyopathy, Genomics 90:261, 2007. 75. Meurs KM, Sanchez X, David RM et al: A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy, Hum Mol Genet 14:3587, 2005. 76. Muldoon LL, Neuwelt EA, Pagel MA et al: Characterization of the molecular defect in a feline model for type II GM2gangliosidosis (Sandhoff disease), Am J Pathol 144:1109, 1994. 77. Nakata N, Wang Y, Bhatt S: Trends in prenatal screening and diagnostic testing among women referred for advanced maternal age, Prenat Diagn 3:198, 2010. 78. Orioli I, Castilla E, Scarano G et al: Effect of paternal age in achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta, Am J Med Genet 59:209, 1995. 79. Paige CF, Abbott JA, Elvinger F et al: Prevalence of cardiomyopathy in apparently healthy cats, J Am Vet Med Assoc 234:1398, 2009. 80. Partington BP, Williams JF, Pechman RD et al: What is your diagnosis? Scottish Fold osteodystrophy, J Am Vet Med Assoc 209:1235, 1996. 81. Peterschmitt M, Grain F, Arnaud B et al: Mutation in the melanocortin 1 receptor is associated with amber colour in the Norwegian Forest Cat, Anim Genet 40:547, 2009. 82. Pion P, Kittleson M, Rogers Q et al: Taurine deficiency myocardial failure in the domestic cat, Prog Clin Biol Res 351:423, 1990. 83. Pyle RL, Patterson DF, Hare WCD et al: XXY sex chromosome constitution in a Himalayan cat with tortoiseshell points, J Hered 63:220, 1971. 84. Ripoll Vera T, Montserrat Iglesias L, Hermida Prieto M et al: The R820W mutation in the MYBPC3 gene, associated with hypertrophic cardiomyopathy in cats, causes hypertrophic cardiomyopathy and left ventricular non-compaction in humans, Int J Cardiol 145(2):405, 2010. 85. Robinson R: The rex mutants of the domestic cat, Genetica 42:466, 1971. 86. Robinson R: The Canadian hairless of Sphinx cat, J Hered 64:47, 1973. 87. Robinson R: Expressivity of the Manx gene in cats, J Hered 84:170, 1993. 88. Sampedrano C, Chetboul V, Mary J et al: Prospective echocardiographic and tissue Doppler imaging screening of a population of Maine Coon cats tested for the A31P mutation in the myosinbinding protein C gene: a specific analysis of the heterozygous status, J Vet Intern Med 23:91, 2009. 89. Schlueter C, Budras K, Ludewig E et al: Brachycephalic feline noses: CT and anatomical study of the relationship between head conformation and the nasolacrimal drainage system, J Feline Med Surg 11:891, 2009. 90. Schmidt-Kuntzel A, Eizirik E, O’Brien SJ et al: Tyrosinase and tyrosinase related protein 1 alleles specify domestic cat coat color phenotypes of the albino and brown loci, J Hered 96:289, 2005. 91. Somers K, Royals M, Carstea E et al: Mutation analysis of feline Niemann-Pick C1 disease, Mol Genet Metab 79:99, 2003.

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92. Takanosu M, Takanosu T, Suzuki H et al: Incomplete dominant osteochondrodysplasia in heterozygous Scottish Fold cats, J Small Anim Pract 49:197, 2008. 93. Thomson PC, Wilson BJ, Wade CM et al: The utility of estimated breeding values for inherited disorders of dogs, Vet J 183:243, 2009. 94. Thuline HC: Male tortoiseshell, chimerism and true hermaphroditism, J Cat Genet 4:2, 1964. 95. TICA: The International Cat Association, 2010. http:// www.tica.org/. Accessed June 22, 2011. 96. Tsoutsman T, Bagnall R, Semsarian C: Impact of multiple gene mutations in determining the severity of cardiomyopathy and heart failure, Clin Exp Pharmacol Physiol 35:1349, 2008. 97. Valayannopoulos V, Nicely H, Harmatz P et al: Mucopolysaccharidosis VI, Orphanet J Rare Dis 5:1, 2010. 98. Wess G, Schinner C, Weber K et al: Association of A31P and A74T polymorphisms in the myosin binding protein C3 gene and

99. 100.

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hypertrophic cardiomyopathy in Maine Coon and other breed cats, J Vet Intern Med 24:527, 2010. Wilson TG, Kane F: Congenital deafness in white cats, Acta Otolaryngolica 50:269, 1959. Winand NJ, Edwards M, Pradhan D et al: Deletion of the dystrophin muscle promoter in feline muscular dystrophy, Neuromuscul Disord 4:433, 1994. Yogalingam G, Hopwood JJ, Crawley A et al: Mild feline mucopolysaccharidosis type VI. Identification of an Nacetylgalactosamine-4-sulfatase mutation causing instability and increased specific activity, J Biol Chem 273:13421, 1998. Yogalingam G, Litjens T, Bielicki J et al: Feline mucopolysac charidosis type VI. Characterization of recombinant Nacetylgalactosamine 4-sulfatase and identification of a mutation causing the disease, J Biol Chem 271:27259, 1996.

C H A P T E R

45

Care and Control of Community Cats Brenda Griffin O U T L I N E Safe and Humane Capture, Holding, and Handling, 1292 Differentiating Truly Feral Cats from Reactive Tame Cats, 1299 Special Medical and Surgical Considerations for Free-Roaming Cats, 1299 Pregnant and Lactating Cats, 1304 Small Kittens, 1305 Sick and Injured Cats and the Role of the Caregiver, 1305

Helping Clients Solve Concerns Related to Community Cats, 1306 Relocation of Cats, 1308 Large-Scale Trap-Neuter-Return Programs, 1308 Liability, 1309 Conclusion, 1309

In addition to the estimated 82 million owned pet cats in the United States,6 there are an estimated 30 to 60 million free-roaming stray and feral cats.27,40,48 In fact, these cats may represent as much as 50% of the total cat population in a given community. In addition, they are estimated to produce up to 80% of the kittens born annually in the United States.27 Despite the lack of exact estimates of their numbers, there is no doubt that millions of these cats exist in communities across the United States, and millions of Americans feed them.27 A continuum of lifestyles exists between socialized house cats, free-roaming, previously socialized, or “loosely owned” strays and truly unowned, unsocialized feral cats.36 Feral cats are “wild” offspring of domestic cats and result from pet owners abandoning and/or failing to control their pets’ reproduction.16 Like wildlife species, when raised without human contact, feral cats remain extremely wary of humans and flee if approached. They generally do not allow handling and must be trapped in order to be presented to a veterinarian for care. In contrast, stray cats are at least somewhat socialized to people and include those cats that may have been previously owned as well as those that are “loosely owned” neighborhood or barn cats.36 Free-roaming stray and feral cats form colonies surrounding a “home base,” which includes a source of food and shelter. Locations with garbage dumpsters, such as housing or shopping


complexes, or those with livestock barns, are prime locations in which cat colonies form because they offer a supply of discarded foodstuffs and rodents.16 Cats typically seek shelter in crawl spaces beneath buildings or other nearby structures (Figure 45-1). Because both stray and feral cats frequently co-exist within the same colonies, the term community cats is often used to refer to all of these outdoor-dwelling cats, regardless of socialization status. Unlike wildlife species, cats cannot fully fend for themselves in most instances. Unattended, they survive and reproduce, yet frequently suffer from exposure, disease, and trauma. The mortality rate of kittens born outdoors is high, with fewer than 25% typically surviving beyond 4 to 6 months of age.39,51 However, beyond 6 months of age, the odds of survival are much greater. The life span of free-roaming cats varies depending at least in part on the colony’s location. Trauma is the most common cause of death.39,51 In some cases, these cats become public nuisances, and many are euthanized at animal shelters each year. Because their reproduction frequently goes unchecked, community cats represent not only a result of feline overpopulation, but also a significant source of the problem. Substantial debate surrounds the appropriate response to the presence of community cats. Scientific reviews of their control and its impact on both the cats themselves

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CHAPTER 45 Care and Control of Community Cats

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FIGURE 45-2 A feral cat rests under the shade of a parked car. His cropped left ear tip identifies him as a neutered member of a managed colony. This distinctive mark is the universally recognized symbol of a sterilized free-roaming cat.

FIGURE 45-1 Three feral kittens observe the world from the safety of a crawl space. Such spaces under buildings are typical locations in which feral cats seek shelter and are popular sites for queens to nest and raise kittens.

as well as the environment have been published.27,31,40,43 Numerous stakeholders have issued policy statements regarding this issue, representing many different and often polarized opinions.1,3,5,52 The traditional approach to controlling free-roaming cats has been extermination by trapping and euthanasia. However, large-scale trap and kill programs, which would be necessary for even temporary population control, have not been widely implemented, and even small-scale attempts at trapping and euthanizing cats frequently result in public outcry. There is little doubt that public sentiment is influential in policy making, and numerous examples exist whereby pressure exerted by the public and animal welfare organizations has been instrumental in stopping euthanasia of cat colonies.2 In the author’s opinion, trapping cats for euthanasia perpetuates the message that cats are disposable. In contrast, the provision of affordable services to neuter free-roaming cats raises awareness that cats require and deserve responsible care and enables people to “do the right thing” when cats take up residence on their property or in their neighborhood. In addition to preventing reproduction, neutering cats also serves to promote their welfare. Studies have shown that feral cats roam less and have higher body condition scores following neutering.46,51 In addition, urine marking, fighting, breeding, and roaming are rapidly and dramatically reduced, making these cats less likely to be targeted as public nuisances. Finally, cats in managed colonies are no more likely than pet cats to harbor common infectious and zoonotic diseases.30,34,50

“Trap-neuter-return” (TNR) is a humane, nonlethal method of managing existing colonies of free-roaming cats and represents a legitimate response to existing colonies of cats with caregivers.29,38 Cats are trapped, vaccinated, neutered, and then returned to their “home” for release. The tip of the left ear is cropped to identify the cats as having been sterilized. This is the universal symbol for a sterilized free-roaming/feral cat (Figure 45-2). Caregivers take responsibility for feeding and monitoring the health of the cats in the future. TNR may not be appropriate in all circumstances; for example, colonies should not be located in wildlife refuges or where endangered wildlife species are known to reside. TNR has become an increasingly popular method of managing existing colonies of community cats during the past 2 decades. Neutered cats display fewer “nuisance” behaviors, such as spraying and fighting, and they cannot reproduce. With time, colony size should decrease because of attrition. However, it is crucial to realize that emigration of new cats is always a possibility, and in many cases, a likelihood; thus ongoing vigilance and management are required. Therefore a dedicated caregiver is crucial for long-term cat control, as well as to ensure cat welfare.16,17,51 TNR has also been purported to be more cost effective than trapping and euthanizing cats.21 This is because most states require impoundment and holding of cats prior to euthanasia, and private volunteers are more likely to trap cats for surgery versus euthanasia. Individuals caring for community cats frequently seek veterinary advice and services. The purpose of this chapter is to provide the veterinary clinician with current recommendations for providing care of free-roaming cats during the process of TNR. A general summary of these recommendations is found in Table 45-1.

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SECTION X Population Medicine

TABLE 45-1 General Veterinary Medical Care Protocol for Trap-Neuter-Return of Community Cats Procedure

Rationale

Short-term holding prior to surgery (e.g., 12 to 48 hours)

Provides time for acclimation; some cats that were initially reactive and feral-behaving may be determined to be tame

Balanced anesthesia administered by intramuscular injection

Essential to ensure smooth induction and proper analgesia with minimal handling to decrease stress and optimize staff safety

Physical examination, including scanning for a microchip

To identify any physical problems and to help determine if the cat might be owned

Subcutaneous fluid administration for cats that are pregnant, lactating, or dehydrated

Promotes normal hydration and prevention of complications related to dehydration

Ear tipping

Identifies cats as neutered, vaccinated members of a managed colony

Rabies vaccination (3-year product)

Affords protection against an important endemic disease of public health significance

Modified live FVRCP vaccination

Affords cats protection against common and life-threatening infections

Ivermectin 1% solution (0.3 mg/kg subcutaneously)

Treats ear mite infestations and temporarily limits round and hookworm infestations (cost effective at only pennies per dose)

Holding overnight after surgery prior to release

Ensures cat are fully alert and physically coordinated for safe release

Return to original colony site

Cats possess strong homing instincts, and release to a foreign location is not humane unless careful relocation procedures are followed

FVRCP, Feline viral rhinitis–calicivirus–panleukopenia.

SAFE AND HUMANE CAPTURE, HOLDING, AND HANDLING Because of their lack of socialization, capture and handling is extremely stressful for feral cats. Proper education and equipment are keys to minimizing the feline stress response and keeping caregivers and cats safe. In most instances, cats should be humanely trapped using commercially available live traps (Figure 45-3). For those cats that are elusive, a drop trap is a humane alternative, but generally requires substantial time and patience (Figure 45-4). Once captured, cats should be held securely in their covered traps. Transferring them to larger enclosures is neither necessary nor recommended for short-term holding (e.g., 2 to 3 days), because it increases the risk of human injury as well as cat escape. Indeed, if provided an opportunity, most cats will successfully escape, and serious injury can occur if individuals must recapture them. In addition, escaped cats can be destructive as they attempt to hide and resist recapture. Another advantage of keeping cats confined in traps is that the administration of anesthetics is simple and can be done without extensive handling, minimizing stress, and enhancing safety for both cats and personnel. For all of these reasons, feral cats should not be removed from a trap until heavily sedated or anesthetized. Furthermore, at the completion of surgery and before awakening, they can be returned to their traps for recovery. With this system, cats are never handled while conscious, and there are no opportunities for escape or

FIGURE 45-3 A cat enters a commercially available humane box trap (Tomahawk Live Trap, Tomahawk, Wis.).

injury. And, importantly, they do not sustain any additional stress from unnecessary handling.

Field Capture Before trapping, attaching two small bowls to the back corners of each trap is helpful. Plastic bowls work well and can be secured using zip ties (Figure 45-5). Having these in place before trapping makes it possible to safely feed and water cats without opening the trap once they are captured. Water can be poured into the bowl from a watering can with a long spout, and food can be dropped


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FIGURE 45-4 A drop trap can be used to humanely capture cats that

FIGURE 45-6 Proper holding procedures for feral cats. For safety

will not enter a box trap. Strong-smelling food is placed on the ground beneath the trap, and the caregiver waits covertly nearby until the cat takes the bait. From the remote location, the caregiver pulls a string to remove the prop stick, causing the trap to drop, capturing the cat. A transfer door is used to safely transfer the cat from the drop trap into a regular box trap for transport.

and security, cats remain in their covered traps before and after surgery. Water is poured into the bowl in the trap from a safe distance using a watering can.

FIGURE 45-7 A commercially available box trap (Tomahawk Live Trap, Tomahawk, Wis.). When a cat steps on the spring-loaded footplate to reach the bait, the trap door will close and lock.

FIGURE 45-5 A trap is outfitted with small plastic bowls prior to use. The bowls are secured in place with zip ties. Canned cat food is placed in one of the bowls to bait the trap.

through the wire into the bowl from a safe distance (Figure 45-6). Most live traps are activated by a foot plate: As the cat enters the open door of the trap to reach the food bowl at the opposite end, the footplate is depressed, which, in turn, unhooks the trap door, causing it to drop and lock in the closed position (Figure 45-7). Traps should always be covered with towels or other suitable materials: This serves to make them more inviting, increasing the likelihood of a cat entering and becoming trapped (Figure 45-8). More importantly, covering the trap serves to calm the cat, decreasing stress upon capture.

It is not uncommon for cats to initially panic once trapped. They may lunge and claw in their attempts to free themselves. Torn claws, scraped noses, and nosebleeds are common injuries that can occur in the trapping process. Although minor, these can be disturbing to caregivers, particularly if they are unaware of this possibility. Fortunately, most cats settle down physically within a few minutes of capture. However, emotionally they remain stressed, as evidenced by their tense body posture and dilated pupils. Many trapped cats tuck their feet under themselves and try to hide or back into the farthest corner of the trap. Some freeze, appearing nearly catatonic, while others strike out defensively if approached, particularly feral tomcats. Even the tamest house cats that are trapped or otherwise very stressed may exhibit the same behaviors as feral cats.15

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FIGURE 45-8 Covering the trap serves to make it more inviting. In addition, it helps to decrease the stress response by providing cover and security, helping to calm the cat once it is captured.

Clients planning to implement TNR should be instructed to contact people around the area where they intend to trap to explain their intentions. Caregivers should discontinue feeding of cats for 24 to 48 hours prior to trapping to ensure they are hungry enough to enter baited traps. Setting traps as much as 2 days before a surgery appointment is usually the best approach to ensure successful capture. Trapping further in advance is not recommended, because it leads to prolonged holding times, increasing stress. Every attempt should be made to capture all cats in a colony at the initiation of TNR. Whenever possible, trapping should continue until all members of a colony have been captured. When only a few members of the colony are captured at the outset, the remaining members may prove very difficult to capture in subsequent attempts, prolonging the process and complicating successful management. Clients must be cautioned about the importance of safe handling. Ideally, they should receive rabies pre-exposure vaccination for their own protection. At a minimum, they should be advised that if they are scratched or bitten, they should not release the animal and should immediately contact their physician as well as the local health department or other appropriate agency for advice. Additional client instructions for trapping and holding cats are provided in Box 45-1.

covered traps. From the time they arrive at the clinic, care should be taken not to place cats within spatial, visual, or auditory range of other species, especially dogs. Traps containing cats should be placed in quiet holding areas until the time of surgery. Prior to surgery, injectable anesthetic agents should be administered to the cat while it remains in the trap. This is accomplished by quietly but quickly standing the trap on end and using a commercially available “trap divider” to confine the cat. This allows an intramuscular injection to be administered to the cat between the wire bars of the trap (Figure 45-9). Recommendations for injectable anesthetic agents for feral cats are discussed in Chapter 7. Feral cats should be returned to clean traps following surgery and monitored until they are sternal. A safe heat source, such as warm air or a carefully monitored heat lamp, should be used to ensure adequate body warming during recovery (Figure 45-10). Placing shredded paper in the trap will help to insulate and protect the cats during recovery. Cats should be hospitalized in their traps overnight. At the veterinarian’s discretion, they may be discharged the same day as surgery, but caregivers should be instructed to hold them overnight to allow for a full recovery (e.g., return of normal mental status and motor coordination) prior to being returned to their environments. Additional discharge instructions for caregivers are provided in Box 45-2.

Returning Cats to Their Colonies It is imperative that caregivers understand the crucial importance of returning cats to their original home sites. Release of cats to other areas, even those that may seem protected, such as a private barn site, should only be done as a last resort and with careful consideration and planning (see Relocation of Cats). Releasing a cat in an unfamiliar area is analogous to a person being lost without a map or other method of communication to get home. Originally, the phrase “trap-neuter-release” was commonly used; however, the name quickly changed to “trap-neuter-return” to reflect the importance of returning a cat to its home colony. Emphasizing that the “R” stands for “return” remains important today, because well-meaning caregivers often consider release of cats in novel locations, not understanding the implications of their actions. In addition to creating serious welfare issues for cats, random release of cats constitutes abandonment and is illegal.

In-Clinic Procedures

In Case of Escapes

Most often, the veterinarians’ role in TNR begins with the arrival of a trapped cat at their practice. Caregivers should be required to present cats for surgery in their

When care is taken to adhere to the practices for handling and holding feral cats as described, escapes should not occur. However, accidents do happen and being


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BOX 45-1 Trapping and Holding Instructions for Clients Before Trapping • Establish a routine of feeding the cats at the same time and location each day. Cats that are accustomed to a routine will be easier to capture. If possible, placing traps in the area before trapping begins will allow the cats to acclimate to their presence and facilitate trapping. The door of each trap can be secured in an open position and food placed in the trap so that the cats learn to go inside to eat. • Try to determine the number of cats present and make plans to trap them all. The best trapping success always occurs during the first trapping session. If only a few members of the group are captured, subsequent attempts will be more difficult because cats quickly become savvy to the process. • Prepare a warm, sheltered area (such as a garage) for holding the cats before surgery. Prepare an area to place the traps by spreading newspapers or disposable tarps on the floor to catch urine, stool, and food that will fall from the trap. Bricks or other items can be used to elevate the traps off the ground so that the cats are not sitting in their waste. • Prepare to transport the cats by putting a plastic liner in the vehicle that will be used. This will prevent urine damage in the vehicle while traveling to and from the trap site and veterinary clinic. • Contact neighbors around the area in which trapping will take place. Inform them of the plans and ask them not to feed the cats during this time. In addition, ask that they keep their pet cats indoors during the planned trapping period. • Stop feeding the cats 1 to 2 days before beginning to trap: Hungry cats are much easier to capture.

Setting the Traps • Begin trapping at the established feeding area up to two nights before the surgery appointment. • Weather conditions should dictate when it is safe to trap. Trapping should not be done in temperature extremes. In hot weather, trapping is best accomplished in the evening and early morning hours. In very cold climates, trapping in the daylight hours when it is warmer is generally preferred. • Traps should be set in secure, level areas scattered around the feeding area. Cats are unlikely to enter a

prepared with appropriate equipment and knowledge is essential in order to reduce the chances of injury or damage should a cat escape and need to be contained. When working with cats, exit doors should always remain securely closed to prevent outdoor escapes. Nets are the safest and most humane tool for capture of a

• •

•

•

•

trap if it is unsteady. If the traps are set in a public area, it is best to place them such that they are hidden from view to avoid attracting unnecessary attention. Whenever possible, set at least as many traps as there are cats to maximize the odds of trapping the entire colony at once. The traps should be baited with smelly food such as canned mackerel or the cat food that the cats are accustomed to eating. Most traps have a back door that must be securely latched to prevent escapes and ensure safety during transport of captured animals. Ensuring that this latch is secured is a crucial step. Each trap should be covered with a large towel or other suitable material when it is set. The cover helps to keep the cat calm in the trap. Cats should remain covered in the trap throughout transporting and holding procedures. For safety, wear protective gloves when carrying any animal in a trap. If trapping at multiple colony sites, traps should be carefully labeled in order to ensure that cats are not accidentally returned to the wrong colony site following surgery. Traps should be checked frequently. If a previously neutered cat or a wild animal (such as an opossum) is captured, carefully open the back door of the trap, stand back at a safe distance, and allow the animal to leave.

Holding Procedures • Cats should be held in their traps before and after surgery. Opening the traps or transferring cats to other enclosures poses a safety risk and must be strictly avoided. • Place the traps in the prepared area and keep them covered. If it is more than 12 hours before the surgery appointment, drop a small amount of cat food through the top of the trap into the food bowl and pour a small amount of water into the other bowl from a safe distance outside of the trap. If the surgery appointment is less than 12 hours away, only water should be given. • Check the cats periodically and change dirty newspapers beneath the traps as needed. The cats will likely stay relatively calm and quiet as long as the traps are covered. Be sure the holding area remains at a comfortable temperature with adequate air ventilation.

loose cat indoors. Alternatively, it may be possible or even necessary to use a live trap to recapture a loose cat. However, many cats will resist entering a trap once they have been previously captured this way. When used properly, nets minimize stress, prevent injury of the animal, and ensure staff safety. In contrast,

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A FIGURE 45-10 Carefully monitored heat lamps are used to provide warmth as staff members monitor feral cats during anesthetic recovery at a large-scale TNR clinic.

BOX 45-2 Discharge and Release Instructions for Clients*

B FIGURE 45-9 A, A commercially available “trap divider” (Animal Care and Equipment Services [ACES], Boulder, Colo.) is used to humanely restrain a cat in a box trap to facilitate intramuscular injection of an anesthetic agent. B, The trap is gently and swiftly turned on one end, and the device is inserted, confining the cat for the injection.

the use of control poles to capture cats poses significant risk of injury to the animal and exacerbates stress. For these reasons, their use is considered inhumane and must be strictly avoided.19,22 Several commercially available cat nets are available. In some cases, the design allows the user to close the opening of the net using a special sliding mechanism on the handle (Figure 45-11). This type of net (often called a cage net) is designed for use when a cat is enclosed in a cage or other confined space. Other nets have a flexible rim that will allow the operator to press the opening of the net flat against the floor without placing the handle on the floor, as is required when using a net with a rigid

• Following surgery, cats should be held in their traps overnight prior to return to their colony site. This is essential for their safety. • Keep the cats covered in their traps in a quiet, warm area until the next morning. Check on them periodically during this time. Normal behaviors include sleeping, head bobbing, and wobbly movements. • Some mild oozing of blood from the cropped ear tip may occur, but is not cause for concern unless it continues the day following surgery. • There should be no bleeding from the spay or neuter surgery site. • The morning following surgery, cats should be fed and watered. To feed or water the cats, do not open the traps. Water should be poured into the bowl and food dropped through the wire into the bowl from a safe distance. • If the cats are fully alert the next day, they can be released at the same location from which they were trapped. To release the cat, point the back of the trap away from danger, such as a busy street. Take off the cover, unlock the back door, and lift the door away from the trap. Stand back and patiently and wait for the cat to leave—most run away immediately. *Instructions for the provision of emergency care during the postoperative period should also be provided, as with any surgery patient.

rim. Such nets are more useful for capture in an open space. Although less sophisticated, fishing nets can also be used to humanely capture cats. In this case, the net should be placed over the cat and the rim held firmly against the floor. As the cat backs away, he will step over


the rim of the net. The net can then be lifted and the weight of the cat will effectively close the opening, securing the cat and preventing escape (Figure 45-12). Conversely, leaving the net open at the top with the cat hanging in the bottom will likely result in a second

FIGURE 45-11 A Freeman cage net (Animal Care and Equipment Services [ACES], Boulder, Colo.) is used to humanely capture a cat in an enclosure. The design of the net allows the user to close it using a special sliding mechanism on the handle.

A

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escape and is not safe for the cat or handler (Figure 45-13). Once a cat is securely netted, chemical restraint may be administered through the netting. Covering the cat with a thick towel or blanket will aid in safe and humane restraint while an injectable anesthetic is administered. Once the cat is immobilized, it can be removed from the net. Alternatively, the cat can be transferred in the net to an enclosure without the use of sedatives. Returning a netted cat to a trap can be very tricky. Instead, the cat can be released into a larger cage containing a commercially available cat den. Cat dens are designed as secure hiding boxes for feral or reactive cats. They can be securely closed from a safe distance (Figure 45-14) and used to transport the cat. Alternatively, they have a guillotine door on one end that allows for safe transfer to a trap or other squeeze cage as needed (Figure 45-15). Although it is best to use a net or live trap to capture an escaped cat, in some instances this may not be feasible. It may be physically impossible, for example, to retrieve a cat that has escaped into a narrow space using a net. In this case, commercially available cat tongs can be used to grasp and retrieve the cat (Figure 45-16). However, care must be taken to prevent the use of

B

FIGURE 45-12 A rigid fishing net is used to capture a cat in an

C

open space. A, The net is placed over the cat. B, As the handler moves closer, the cat backs away, stepping over the rim of the net. C, The handler lifts the net, safely entrapping the cat.

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A

FIGURE 45-13 Improper use of a net. The top of the net is open as the cat hangs in the bottom. As he struggles to escape, there is risk of injury for both the cat and handler.

B FIGURE 45-15 A and B, By raising and lowering the guillotine doors, a cat is safely and humanely transferred from a feral cat den to a squeeze cage for restraint.

FIGURE 45-14 A commercially available feral cat den (Animal Care and Equipment Services [ACES], Boulder, Colo.) serves as a secure hiding place for a cat. The circular door can be closed from a safe and nonthreatening distance while the cage is spot cleaned as needed. The cat can also be securely transported in the den.

FIGURE 45-16 Commercially available cat tongs (Animal Care and Equipment Services [ACES], Boulder, Colo.) can be used to capture a cat when a net is not feasible. The cat should be grasped and transferred into a cage or other enclosure as quickly as possible, taking care to avoid injury and unnecessary stress.


unnecessary force when using cat tongs in order to prevent injury.

DIFFERENTIATING TRULY FERAL CATS FROM REACTIVE TAME CATS It is important to remember that cats that are trapped and feral-behaving are not necessarily feral. In reality, it can be challenging to differentiate truly feral cats from those that are tame but very frightened and reactive.15 Indeed, once highly stressed or provoked, cats frequently remain reactive for a prolonged time and may become more reactive if they are stimulated again before they have been allowed a period of time to cool down.7 For this reason, special care should be taken to provide a calm and quiet environment during the time in which cats are being held awaiting surgery. Certainly, it is prudent to determine the cat’s true level of sociability and tractability whenever possible. This information can help caregivers provide the best possible care for cats. Tame cats may be lost, and efforts to reunify them with owners may be warranted. Careful scanning for a microchip should be performed and other measures, such as posting signs in the area where the cat was trapped, should be taken to locate an owner. If an owner is not located, tame cats may be placed in homes rather than returned to their colony. If reunification and adoption efforts are not successful, the best option may be to return the cat to the colony as long as ongoing care will be provided by a caregiver. Relinquishment to an animal shelter may not be in the cat’s best interests because approximately 70% of cats entering shelters in the United States are euthanized.4 If the cat appears to be well adapted to its outdoor life and will receive ongoing care, return is appropriate regardless of socialization status. In order to increase the odds of determining their true socialization status, trapped cats should be allowed “chill out time” to acclimate—preferably at least overnight. Fearful cats, whether feral or tame, may resort to overt aggressive behavior or may “teeter on the edge” of defensive aggression when stressed. Given time, some tame cats will relax. Caregivers can readily recognize these cats, because they will usually stand in the trap, rubbing, mewing, pawing, and chirping as they attempt to solicit attention. However, not all tame cats will relax in a short period of time; some remain reactive and fractious for prolonged periods. Caregivers should be cautioned that even when cats do not exhibit outward aggression in the trap and appear merely “shy” or “nervous,” it is not safe to open the trap or to attempt to touch the cat. These are common behaviors for both fractious and feral cats, and opening the trap will likely result in escape or alternatively, defensive aggression.

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In addition to behavior, certain physical characteristics may be helpful to distinguish feral cats from those that are tame but behaviorally reactive. When cats are not suspected to be feral, based on their physical characteristics, it may be desirable to allow a longer period for acclimation to see if they become less reactive and “show their true colors.” Although it is not often possible to determine a cat’s true status based on physical features alone, careful visual inspection of the cat in the trap may prove helpful. The following features should be noted: • Ear tip: Removal of the tip of one of the ears is the universal symbol for a sterilized free-roaming cat. The presence of an ear tip alone should not be used as a singular designation for feral; the ear tip only truly means that the cat has been spayed or neutered. It likely signifies that the cat is a part of a managed colony. Caution must be taken not to mistake frostbite of the ear for a tipped ear. • Reproductive status: Unless they are ear tipped, feral cats should be assumed to be reproductively intact. Females may be pregnant or lactating, especially between April and October (in the northern hemisphere). A large abdomen on a female may indicate pregnancy. If mature, males will have “tomcat urine odor,” a wide neck, and welldeveloped jowls. In addition, they often have scars on their face and ears or torn ear flaps. In contrast, reactive tame cats may be spayed or neutered. Neutered adult toms will lack the typical secondary sex characteristics. • General body condition: Prior to spaying or neutering, feral cats are usually in lean, wiry body condition. In contrast, reactive tame cats may be overweight, particularly if they have been spayed or neutered. • Age: Feral cats are usually young (frequently less than 3 years of age), unless they are part of a managed colony. In contrast, reactive tame cats may be middle-aged or even geriatric. In fact, pampered adult house cats, including those that are geriatric can become very reactive in stressful situations.12,41 An experienced practitioner may recognize the subtle aging changes that are suggestive of an older cat, especially in the eyes and face.

SPECIAL MEDICAL AND SURGICAL CONSIDERATIONS FOR FREE-ROAMING CATS Patient Selection and Perioperative Care Detailed veterinary medical guidelines for spay-neuter programs have been published.32 Cats undergoing elective surgery should appear to be in reasonably good

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health and body condition. However, veterinarians must weigh the risks and benefits of spaying and neutering patients with apparent physical abnormalities (e.g., evidence of mild infectious disease or decreased body condition). In the context of feral cats, future opportunities for that animal to receive care may not be available, and the alternative outcome may be release without surgical sterilization or euthanasia. Although some conditions may increase the risk of complications, the benefits of neutering likely outweigh these risks in feral cats. Cats that are pregnant, in estrus, or have pyometra, as well as those that are thin or have mild upper respiratory infection, can be safely spayed or neutered.32 Injectable anesthetic protocols with a wide safety margin are preferred, because body weight must be estimated or determined based on an in-trap measurement and because physical examination must be performed following anesthetic induction for feral cats. It is imperative that balanced anesthesia, including proper analgesia, be used. Cats that are pregnant or lactating and those that are dehydrated should receive fluid supplementation. Warmed fluids can be administered subcutaneously postoperatively prior to recovery. Chapter 7 discusses anesthetic recommendations for feral cats.

Surgical Sterilization Aseptic surgical technique is required, and separate sterile instruments must be used for each patient. Surgeries should be performed by experienced veterinarians, because free-roaming cats are returned to their environments the day following surgery and close follow-up is not generally possible. For this reason, most surgeons prefer to make small incisions and ensure that they are securely closed without the use of skin sutures. For spaying female patients, some surgeons prefer a flank approach rather than the traditional ventral midline incision (Figure 45-17).11,24,26,35,53 The flank approach allows caregivers to monitor a cat’s incision from a distance and may help to prevent evisceration should dehiscence of the surgical wound occur. The flank approach has also been recommended for lactating queens, to prevent the possibility of incising mammary tissue and causing leakage of milk into the surgical wound. However, it is not recommended for pregnant cats because of the attendant morbidity associated with a large incision in the lateral abdominal wall. If pregnancy or pyometra is discovered upon entering the abdominal cavity, closing the flank incision and using a ventral midline approach is generally advisable. Another limitation of this approach is that the small size and dorsal location of the incision render thorough abdominal exploration impossible; therefore, if it becomes necessary to locate a dropped pedicle, a ventral midline incision may also be necessary. Increased postoperative pain has also been reported in queens spayed

FIGURE 45-17 Location and landmarks of the flank spay incision. The incision should be located midway between the dorsal and ventral midline and approximately 3 cm cranial to the greater trochanter, or 3 to 4 cm caudal to the last rib.

by a flank approach compared with those spayed using a ventral midline approach.8,20 Depending on the surgeon’s preference, the flank approach can be performed with the patient in either right or left lateral recumbency. Box 45-3 describes the procedure.

Ear Tipping for Identification As previously discussed, removal of the tip of one of the ears (or pinna) is the accepted global standard for marking or identifying a neutered free-roaming community cat. Alley Cat Allies (a national humane organization that serves as a resource on feral cats) recommends removal of the left ear tip, and this standard is widely used. However, some organizations identify cats by removing the right ear tip or by removing the tip on one side or the other, depending on the sex of the cat. Whichever ear is selected for tipping, it is best to be consistent with the standard in your community.18 Ear tipping is performed to clearly and permanently visually identify neutered, vaccinated cats that are being humanely managed by TNR. It is often impossible to get close enough to a feral cat to see a subtle mark or tattoo; thus such methods of identification are not useful because they are frequently ineffective. Similarly, other visual means of identifying cats have not been effective. Collars are impractical, because young cats will continue to grow, and collars are frequently lost with time. Ear tags and bands are also not useful, because they may become infected or be torn out. Microchips are not visible and even if a cat is trapped, proper scanning cannot be performed without removing the cat from the trap because of interference from the metal bars.


BOX 45-3 Lateral Flank Spay Technique • Patient preparation: Shave and prepare the skin beginning at the last rib and extending caudally to the greater trochanter, dorsally to the vertebral transverse processes, and ventrally to the midline. • Positioning: Place the cat in right or left lateral recumbency, according to the surgeon’s preference. A small rolled-up towel may be placed under the lateral lumbar area to remove the concavity of the flank, improving visualization. • Incision location: Midway between the dorsal and the ventral midline and approximately 3 cm cranial to the greater trochanter, or 3 to 4 cm caudal to the last rib (see Figure 45-17). • Incision length and orientation: Approximately 1.5 to 2 cm in length—vertical, horizontal, or oblique. • Entering the abdomen: After making the skin incision, grasp the body wall with thumb forceps and bluntly separate the fibers of the external abdominal oblique, internal abdominal oblique, and transversus abdominus muscles to enter the abdomen. If the left lateral approach is used, special care should be taken to elevate the body wall while separating the muscle layers to avoid trauma to the spleen beneath the incision. Tagging the body wall with a suture will ensure that it can be readily located for closure. • Locating the uterine horn and ovary: The uterine horn should be readily visible and can be gently withdrawn from the abdomen and retracted to identify the ovary. The remainder of the procedure is performed as in the standard ventral midline approach. • Closure: The body wall is closed with one or two cruciate mattress sutures passed through all three muscle layers; the subcutaneous and intradermal layers are closed according to the surgeon’s preference.

When cats are ear tipped, animal control officers, shelter workers, and caregivers can easily and reliably identify cats that are graduates of a TNR program.18 This is important to ensure that all cats in a colony are humanely managed and to prevent shelter euthanasia of feral cats that are part of managed colonies. Ear tipping should be performed even in colonies of cats with dedicated caregivers who believe they “know” all of the cats in their colony by sight, because it is very common for several cats in a colony to possess similar coat colors and patterns, making it difficult, if not impossible, to distinguish which cats have already been trapped and neutered. It is very important that ears be tipped rather than notched, because notching may occur as the result of fighting, especially in tomcats, and may be mistaken as a sign of previous TNR (Figure 45-18, A to C).

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Ear tipping is an antiseptic procedure rather than an aseptic one. It should be performed under clean surgical conditions. Separate sterile scissors and hemostats should be used for each cat. Clean exam gloves or sterile surgical gloves should be worn. Hair removal or shaving of the pinna is unnecessary and is not recommended to avoid abrasion of the tender skin of the earflap. Antiseptic solution, such as chlorhexidine or Betadine, may be used to gently swab both sides of the pinna. Care should be taken to avoid introducing moisture into the ear canal, which could predispose the cat to otitis externa. The distal tip of the pinna may be removed using sharp dissection or, if available, electrocautery or laser, taking precautions not to induce thermal damage. Most veterinarians perform the procedure using a pair of hemostatic forceps and scissors (Figure 45-19). Scissors are preferred rather than a scalpel blade, because their crushing action aids in hemostasis. Straight scissors and straight hemostats should be used to crop the ear in a straight line. This is very important to ensure the desired visual effect: The ear should have a distinct straight edge that is easy to recognize from a distance. Box 45-4 describes the procedure for ear tipping using straight hemostat and straight scissors. Healing is rapid and complications are rare. This procedure is humane and represents a potentially life-saving permanent form of identification for community cats.18

Vaccination Rabies is a core vaccination for all cats and is an absolute necessity for community cats. Rabies is endemic throughout the mainland United States, and vaccination is the most effective method of control. For this reason, all cats should be vaccinated against rabies virus using an approved 3-year vaccine at the time of surgery.44 In addition, the administration of a modified live feline viral rhinitis–calicivirus–parvovirus (FVRCP) vaccine is also recommended. In particular, immunity against panleukopenia is especially important for cats, because of the widespread nature and severity of this disease. Historically, scientists have debated both the effectiveness of vaccines given at the time of surgery and whether or not a single vaccination alone can confer clinically significant immunity. Recent studies have investigated these concerns. In one study of 61 cats undergoing TNR, cats were vaccinated against feline panleukopenia virus, feline herpes virus, feline calicivirus, and rabies virus at the time of surgery.13 Antiviral antibody titers were measured at the time of surgery and again approximately 10 weeks later. The results of this study demonstrated that feral cats had a robust serologic response following vaccination at the time of neutering. The authors concluded that incorporation of vaccination into TNR programs is likely to protect the health of individual cats and possibly reduce the disease burden

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A

B

C

D

FIGURE 45-18 A, Correct appearance of a tipped ear. B, It is very important that ears be tipped rather than notched. This is because notching commonly occurs as the result of fighting or other injury, and may be mistaken as a sign of previous neutering. C, A female cat is anesthetized for ovariohysterectomy, but exploratory surgery revealed she is already spayed. D, Note the small ear notch, which unfortunately was not recognized as an identifying mark of a neutered cat, because it does not adhere to the universal standard.

in the community. Several other independent studies support these findings.23,37,42 Although the exact duration is unknown, immunity against rabies and panleukopenia following a single vaccination may persist for years.14,44,49 Considering the relatively low medical risk and financial cost of vaccination compared with the potential benefits for feline health, community cats undergoing TNR should always be vaccinated against these important feline diseases. Periodically retrapping cats for revaccination is ideal, although it may prove challenging to recapture cats.

Feline Leukemia Virus and Feline Immunodeficiency Virus Testing A common question regarding care of free-roaming cats is whether or not they should be routinely tested for feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV). The American Association of Feline Practitioners recommends testing all cats for FeLV and

FIV and confirming positive test results.28 It is difficult, if not impossible, however, to apply these guidelines intended for pet cats to feral cats. When deciding whether or not to test feral cats, one must consider that based on surveys of thousands of free-roaming and feral cats, the incidence of these diseases is very low (e.g., less than 2% in healthy cats) based on screening tests.30 In addition, community cats are no more likely to test positive than owned pet cats. When cats test positive on screening tests, confirmatory testing requires substantial time and monetary investment and is not generally feasible when cats need to be returned to their colony sites. Furthermore, one should keep in mind that neutering greatly reduces transmission of these viruses by decreasing fighting and preventing kitten births. Finally, one should consider that testing is generally expensive and that for successful cat control, the bulk of financial resources must be used to sterilize as many cats as possible. Although testing all cats for FeLV and FIV may be ideal, considering the cost of testing, the disease incidence, and


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B

C D FIGURE 45-19 Ear tipping procedure. A, A straight hemostat is placed across the left pinna perpendicular to its long axis, exposing approximately 1.3 cm (0.5 inches) of the ear tip. B, Scissors are used to remove the ear tip by cutting over the top of the hemostat in a straight line. C, The hemostat is left in place until after surgical neutering to allow adequate time for hemostasis of the pinna to occur. D, Proper appearance of the ear following removal of the hemostat. Note the distinctive straight edge that is easily recognizable. (Courtesy Brenda Griffin.)

the effects of neutering on transmission, this approach is often not a feasible practice when working with community cats.25,28 Testing is recommended, however, when cats appear unthrifty at the time of presentation for TNR. Sick cats are more likely to test positive than apparently healthy cats. In addition, studies indicate that risk factors for infection include contact with other cats and living outdoors. In particular, intact adult tomcats are often at highest risk.30 For these reasons, positive test results have a higher predictive value in community cats that appear to be in poor health and can be used to help guide decisions for return or euthanasia in the context of TNR programs. Tame cats that are identified as candidates for adoption should also be tested, preferably prior to making substantial investments in their care, because it is often very difficult to place cats in homes. If testing is not performed prior to adoption, adopters should be advised to have their new pet tested and kept separate from other cats prior to doing so.

Parasite Control Both endoparasite and ectoparasite infestations occur frequently in community cats—fleas, ear mites, and roundworms are particularly common culprits.17 To be successful for long-term control, repeated antiparasitical treatments are generally required, especially in the context of outdoor multicat environments where the risk of re-infestation is high. For these reasons, a single antiparasitical treatment at the time of TNR may be of limited or even questionable benefit in most cases. However, in the author’s opinion, treatment may be of particular benefit to some cats, especially unthrifty juveniles, because even temporary reduction in parasite burdens may provide significant support in these maturing cats. When considering products for use in unsocialized cats, selection should be limited to injectable and topical products to ensure safe and reliable administration. Imidacloprid/moxidectin (Advantage Multi, Bayer Animal Health, Shawnee Mission, Kans.) is an excellent

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BOX 45-4 Procedure for Ear Tipping Using a Straight Hemostat and Straight Scissors (See Figure 45-19) • Ear tipping is a quick and simple procedure. It should be performed after the cat has been anesthetized and reached a surgical plane of general anesthesia and prior to surgical sterilization. This will ensure adequate time for hemostasis to occur prior to recovery. • The procedure is performed by placing a sterile straight hemostat across the designated pinna, exposing approximately 1.3 cm (0.5 inches) of the ear tip. The amount of the ear tip removed may be more or less depending on the size of the cat. Proportionately, approximately one third of the distal pinna is removed. • Care must be taken to place the clamp perpendicular to the long axis of the pinna. This is necessary to ensure the desired visual effect—an easily recognizable, straight, cropped ear tip. • Sterile scissors are used to cut the tip off, leaving the hemostat on the ear. The hemostat should remain in place until the cat is in recovery and is removed just prior to returning the cat to the trap. • Some oozing of blood from the ear tip site may occur during recovery especially is the cat rubs or bumps the freshly clotted tissue against the trap. • Gluing or suturing the ear is neither necessary nor recommended. • Profuse, excessive, or prolonged bleeding is abnormal. • Proper placement of the hemostat on the ear tip is critical for proper healing and appearance of the ear. • If the clamp is placed too high, the ear tip will be difficult to recognize from a distance. • If the clamp is placed too low, the skin may retract, exposing the ear cartilage, which may prolong healing and predispose to an incision site infection. • If the clamp is placed at an angle, the pinna will appear pointed from a distance and may be difficult to recognize as a tipped ear. • The use of curved hemostats and/or curved scissors should be avoided. If the ear tip remains curved, it may be difficult to recognize as a tipped ear from a distance. • In very cold climates, mild frostbite of the ear tips is common and may be unilateral or bilateral. Frostbitten ear tips may appear to be cropped but often have a thickened, irregular border. However, it is often difficult to distinguish a frostbitten pinna from a tipped pinna, especially from a distance. In these climates, some programs apply green tattoo ink to the skin margins at the ear tip site to aid in identification.

choice for an effective single broad-spectrum treatment, because it can be administered topically, and a single dose is effective against fleas, roundworms, hookworms, and ear mites. Because of the cost associated with this and similar topical products, it may not be feasible to treat all cats. If flea treatment is desired, the author recommends topical treatment with fipronil (Frontline, Merial, Duluth, Ga.) as a spray or top spot. In particular, the spray is very cost effective. It is safe for use in cats of all ages, including pregnant and nursing mothers. In addition, fipronil also has activity against ear mites, Cheyetiella spp., chewing lice, and ticks.9,45 Because it costs only pennies per dose, the author routinely administers injectable ivermectin to all cats at the time of TNR. A single subcutaneous injection of 1% ivermectin solution at a dosage of 0.3 mg/kg is highly effective against ear mites and also temporarily reduces roundworm and hookworm burdens.

PREGNANT AND LACTATING CATS It is common to capture pregnant and lactating cats, particularly in the springtime. Veterinarians should discuss recommendations for these cats with caregivers before they begin trapping. In the author’s experience, pregnant cats that are captured should be spayed, because it is the most humane course of action. This is for several reasons. First, delivering and raising kittens outdoors is stressful for both the mother and kittens. The mortality rate of kittens is high; often, more than 75% die within the first several weeks of life.39,51 Secondly, pregnant queens frequently migrate prior to queening in order to find a secure nesting site. This is a familiar scenario to anyone who has discovered a mother and her litter on their property. Even if the queen chooses to deliver her litter nearby, it can be very difficult to locate her nest. Furthermore, if she perceives any threat from observation or other disturbance, she will likely attempt to move her kittens. This can make it extremely difficult to locate and capture the litter once they are born outdoors. Some caregivers consider confining pregnant feral cats through delivery of their kittens; however, this is extremely stressful for them and cannot be recommended. Others choose to release pregnant cats that they capture, believing it will be in her best interest to allow her to deliver her kittens. Unfortunately, even if the cat remains in the area, she will likely prove to be difficult to retrap in the future and therefore will continue to reproduce for as long as she survives. Indeed, it is common for cats that have been previously trapped to quickly become “trap savvy” such that they will not enter traps on subsequent occasions. For all of these reasons, caregivers should be advised that pregnant queens should be spayed. This will prevent


unnecessary stress and suffering for the queen and her kittens and will prevent the possibility that she will relocate prior to giving birth. Even for those queens that are in an advanced state of gestation, spaying can be safely and humanely performed. In the author’s experience, cats do not commonly experience signs of maternal loss following late-term spaying and quickly adjust to the less stressful lifestyle of a spayed cat. When a lactating queen is trapped, caregivers should be advised to search for kittens. Even though they may look cute and innocent to caregivers, even small feral kittens can inflict serious injury if proper caution is not taken in their handling and capture. Kittens less than 3 to 4 weeks of age can sometimes be caught without a trap, although they may still be too wild to be easily handled. A thick towel can be used to pick them up, protecting the handler from scratching and biting, until they can be contained in a trap or carrier. Once kittens are coordinated enough to leave the nest (e.g., more than 3 to 4 weeks of age), it is safer and may be easier to trap them. Placing the trapped mother cat next to a baited trap will often facilitate capture of her kittens, because they will be attracted by her presence. Similarly, if small kittens are captured in an area, the mother cat will be attracted by their sound if they are placed near the trap. Obviously, frequent monitoring and common sense must be used to determine how long it is safe to leave trapped cats in an area, depending on such factors as the weather or other threats to their safety. Regardless of whether or not kittens are located, lactating queens should be spayed. Spaying will not interfere with the queen’s ability to produce milk and nurse kittens. Efforts should be made to release mother cats as soon as it is deemed safe for her so that she can return to care for her kittens.

SMALL KITTENS Because of their high mortality rate, if small kittens are captured, the author recommends that they be tamed and placed in homes as pets rather than being returned to their colony sites. If this is not possible, euthanasia may be a more humane option than return considering their poor odds of survival. A study of 70 feral kittens demonstrated that they can become good pets with friendly temperaments and that handling prior to 7 to 8 weeks of age improved socialization success.33 In many cases, it is still possible to tame kittens up to 3 to 4 months of age; however, beyond this age range, taming is often not possible. The process of taming involves confinement with daily handling sessions and requires patient and committed caregivers. Feral kittens can be absolute “spitfires,” and clients should be counseled to wear gloves and use thick towels during handling sessions. In

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addition, they should be advised to contact their local health department and to seek medical care in the event of any bite. Despite the risks and time commitment required, many individuals are eager and willing to provide the care necessary to successfully tame these animals. The taming process may take anywhere from a few days to several weeks to accomplish. In the author’s experience, individual kittens, even within the same litter, may vary tremendously in their acceptance of human handling and their rate of progression in the process. Box 45-5 contains the recommended steps for taming feral kittens.

SICK AND INJURED CATS AND THE ROLE OF THE CAREGIVER Minor physical problems are sometimes discovered once a cat has been anesthetized and a physical examination is performed. In the author’s experience, common ailments include abscesses, wounds, tail tip injuries, dental disease, and Cuterebra infestation.17 These can all be successfully treated at the time of surgical sterilization. In contrast, when cats present with signs of serious illness or injury, humane euthanasia should be considered. Although there are exceptions, ongoing treatment cannot typically be safely, reliably, and humanely administered to a feral cat. However, if treatment is attempted, it is imperative to have proper equipment for safe and humane handling and housing. Feral cat dens and squeeze cages are essential for this purpose (Figure 45-20). In instances where the caregiver has had a long-term relationship with the cat (e.g., the cat has been part of a managed colony for years), the author has witnessed situations where cats accepted care when they were gravely ill despite the fact that they had never before allowed handling of any kind. In these instances, the caregivers found “their” cat in a state of shock (because of trauma or severe infection) and presented them for care. Therapy was initiated, and when the cats regained consciousness they readily accepted handling. Anecdotally, there are numerous stories of this kind because of the fluid nature of cat lifestyles. In the author’s experience, cats that have been neutered and returned and are fed on a regular basis, may increasingly affiliate with their caregivers with time. Although they may not allow handling, they will interact from a closer and closer distance with time. That being said, when cats do not accept handling, the provision of medical care can prove extremely stressful—and is not always in their best interest. In the context of population control efforts, financial resources are best spent by maximizing the number of cats that

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BOX 45-5 Taming Feral Kittens Step 1: Seclusion and Confinement • Select a quiet room and set up a large pet carrier with a litter box, food, and water bowls and comfortable bedding in which to confine the kittens. Arrange the litter box and bowls so that they are within easy reach for cleaning and refilling. • Allow the kittens strict “chill out” time to acclimate to their new surroundings without intrusion or disturbance. Check to be sure they are eating and using their litter box but otherwise do not disturb them for 1 to 2 days.

Step 2: Handling and Hand Feeding • On the second or third day of confinement, begin handling sessions 3 to 4 times daily, or more often if possible. Wear protective gloves and use a towel to pick up each kitten. Start with the one that seems the least reactive and the most likely to accept handling. When one kitten exhibits a stressful response, its behavior may have a negative impact on the responses of the others. Likewise, some kittens may become less reactive as they observe calm and soothing handling of their littermates. • Be sure to approach the kittens slowly; they will be less likely to react when movements are slow and deliberate. Securely wrap and fold the towel around the kitten’s body and limbs, leaving only the head exposed. Holding the kitten so that the head is facing away from the handler will enable it to feel less threatened, making it less likely to struggle or fight to escape. Approaching from the back, carefully attempt to gently touch and rub the top of the kitten’s head. Talk in a soothing tone. Put baby food* on a small spatula and hand feed it to the kitten. • In general, the more often the kittens are handled, the more quickly they will be tamed. Eventually, progress to stroking the kitten’s body during handling sessions.

Step 3: Ensuring and Continuing Progress • Expect to see progress over the next several days. Kittens should begin to relax upon handling and may even begin to greet the caregiver at the front of the carrier. When the kittens are readily accepting handling and greeting caregivers, they can be released in a small

can be sterilized rather than providing heroic care for individual cats. Nonetheless, in some cases, the human–animal bond will call for additional measures. Many caregivers are deeply bonded to the cats they care for despite their lack of direct physical contact with them.

room, such as a bathroom. Prior to their release, the room should be “kitten proofed.” This should include putting away anything that could be broken or damaged or otherwise be harmful to the kittens, securely blocking off any places into which the kittens could crawl and, in the case of a bathroom, closing the toilet lid. Regular handling and feeding sessions should continue, and the kittens should be encouraged to interact with the handler by using toys such as feathers or wands. Play is a very important part of ensuring social bonding. • It is not uncommon for one or more kittens in a litter to progress more slowly than the others. They may resist handling and remain frightened, reactive, or aggressive. In this case, solitary confinement can be extremely helpful. Without littermates for social companionship, the kitten will be more willing to interact with a human caregiver. This will greatly facilitate the taming process and can produce dramatic results.

Step 4: Continuing Socialization • Ensure that the kitten’s world does not “get too big, too fast.” This is crucial to prevent the development of fear, which could hamper the taming process. If allowed too much room in which to explore too quickly, kittens may become stressed and overwhelmed, ultimately seeking a hiding place. They may be difficult to find and even more difficult to catch or retrieve, which, in turn, further induces stress and can compromise the progress they have made. • As kittens progress, it is important to introduce different handlers: They need a healthy daily dose of positive attention from different human caregivers and reasonable amounts of exposure to the sights and sounds of household activities to become properly socialized pets. • If adopted to a new home, new owners must take special care to introduce their new kitten very slowly into the new household. Confinement should be used to ensure the kitten continues to feel secure. Once the kitten is actively seeking to be let out of the carrier or small room, it is usually ready to venture forth. *Baby food that contains onion powder should not be used because of the potential for toxicity from this ingredient.

HELPING CLIENTS SOLVE CONCERNS RELATED TO COMMUNITY CATS When concerns arise regarding the presence of cats in managed colonies, clients sometimes reach out to their veterinarian for advice. In the author’s experience, one


A

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B

FIGURE 45-20 Proper equipment is essential when treating

C of the most common concerns that arise occurs when cats take up residence in a crawl space beneath a home where they are not welcome. Whereas it is important for cats to have shelter available to them, it is sometimes necessary to prevent them from residing in certain locations. This is easy to do by simply eliminating access to this area. However, sealing off access without proper planning can result in accidental trapping of cats without a route for escape, creating serious welfare concerns for the animals. Such situations however can easily and humanely be avoided by using a one-way door: this will allow cats to leave the area, but makes it impossible for them to return to it (Box 45-6). Another common concern arises when cats frequent gardens and/or sand boxes. Efforts to exclude cats from such areas are important for public health, especially because of the zoonotic risk posed from roundworms, hookworms, and toxoplasmosis as a result of contact with contaminated soil. In addition to community cats, pet cats also contribute to this potential risk.10 Covers should be used for children’s sand boxes, and gloves should be worn when gardening. Commercially available motion-activated sprinklers can be helpful in some instances. Spreading prickly textures around the

feral cats. A, B, and C, A cat is safely and humanely transferred from a box trap into a feral cat den. The den can be placed in a larger cage for longer-term holding during treatment. When necessary, transfer from the den into a squeeze cage can be accomplished to facilitate administration of medications.

BOX 45-6 Using a One-Way Door To safely exclude cats from a crawl space where their presence is problematic, use a one-way door. To make a one-way door, simply cut a piece of plywood to fit over the crawl space where cats are entering. Cut a cat-sized door in the board and attach it with a hinge that will only allow the door to open in one direction. Alternatively, attach a thin strip of wood along the bottom of the back of the board to prevent the door from opening inward. Secure the door over the entrance to the crawl space. This allows any cats to exit, yet prevents them from re-entering. After several days, any cats should have departed, and the one-way door can be replaced with a permanent covering. To safeguard the welfare of the cats, it is best to ensure than some alternate shelter is available in the area.

garden, such as pinecones, holly leaves, chicken wire, or purpose-designed prickly mats, especially where there is newly turned dirt, can also be effective. To minimize risks, vegetables should always be washed thoroughly, and excellent hand hygiene should be

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practiced. Additional resources for clients concerning all aspects of community cat care are included at the end of this chapter.

RELOCATION OF CATS On occasion, individuals may wish to relocate feral cats to new sites, or major construction or some other event may necessitate relocation of a colony. However, the process of relocation is difficult and poses significant danger to cats, because they possess strong homing instincts and typically flee when released at a location other than their original colony site. In the author’s experience, when caregivers have released cats at foreign sites, they have either readily disappeared or their remains have been discovered on a nearby roadside. In a few instances, cats have managed to return to their original home sites days or even weeks later. One investigator attempted to establish colonies of feral cats at a farm site in order to study them.47 Following their release, all of the cats disappeared. For this reason, relocation of feral cat colonies must be viewed as a last resort. If relocation cannot be avoided, cats must be confined for several weeks at their new “home” location prior to release. Cats should be confined in enclosures that are large enough to accommodate separate feeding and litter areas as well as a cat den or other suitable purpose-designed box. The enclosure should be situated in a secure location, such as inside a shed, barn, or other protected area. Caregivers should feed and care for the cats daily for a minimum of 3 weeks prior to release. This practice allows cats to acclimate to the new site and become entrained to a routine of feeding at this location. Following release, the cat should continue to be fed at the same location on a regular schedule. It is not unusual for a cat to “disappear” for days or more following release. However, most will come around in time and will ultimately be sighted, usually around the food bowl, as they anticipate feeding times. When more than one cat from a colony is relocated, the presence of familiar cats at the new location facilitates adaptation of others.

LARGE-SCALE TRAP-NEUTERRETURN PROGRAMS Large-scale programs to sterilize community cats in the United States have become increasingly commonplace during the past decade. Caregivers trap community cats for participation in large surgery clinics. In these clinics, cats are sterilized in an assembly line fashion that provides high-quality care to a high volume of patients.

FIGURE 45-21 Veterinarians and volunteers care for cats at a largescale TNR clinic. By using an assembly-line approach, high-quality care is efficiently delivered to a high volume of cats at various dedicated stations throughout the clinic.

FIGURE 45-22 Ear tipping is antiseptically performed at a dedicated ear tipping station at a large-scale TNR clinic.

Most programs use trained volunteers to facilitate patient care and ensure constant monitoring of cats during the process. Following induction of anesthesia, cats are removed from their traps and identified by physically affixing a tag to their body, ensuring they are returned to the correct trap and caregiver at the end of the clinic. Cats are examined, ear-tipped, surgically sterilized, vaccinated, and then returned to their clean traps, where they are monitored until adequately recovered (see Figure 45-10). To maximize efficiency, these programs often establish “stations” that perform each task, using trained volunteers to transport and monitor cats between stations (Figures 45-21 and 45-22). Detailed protocols for establishing large-scale TNR clinics are available online (Box 45-7).


BOX 45-7 Resources for Care of Community Cats Alley Cat Allies: http://www.alleycat.org Neighborhood Cats: http://www.neighborhoodcats.org Operation Catnip: http://www.operationcatnip.org Feral Cat Spay/Neuter Project: http://www.feralcatproject.org Feral Cat Coalition: http://www.feralcat.com

LIABILITY As professionals, veterinarians should always be concerned about liability protection. It is always important to make clients aware of risks associated with any practices or procedures that are recommended and to obtain written consent prior to initiating them. Box 45-8 contains suggested statements for liability forms involving TNR programs, including the loan of traps. Some veterinary practitioners allow clients to “check out” traps as part of the service they provide, to facilitate spaying and neutering of community cats. It is important to discuss these services with your insurance provider to ensure coverage in the event of a claim. Despite the need to be aware of the potential liability concerns, such concerns should not prevent veterinarians from facilitating TNR. In fact, many veterinarians in communities throughout the United States work with individual clients performing TNR as well as with organized TNR programs on a regular basis.

CONCLUSION As a sole measure, TNR programs cannot be expected to solve the problem of free-roaming cats in communities. However, they do hold great merit as a legitimate response to existing colonies of cats with caregivers and raise public awareness of the welfare issues surrounding cats. TNR programs emphasize to communities that cats require and deserve responsible care; including sterilization, vaccination, identification, and regular feeding, watering and shelter. The provision of accessible, affordable spay-neuter services for community cats helps individual cats and people, while promoting veterinary medical care for all cats and providing humane alternatives to sheltering and euthanasia. Where emotions and controversies surround methods of community cat management, the goals of cat control and welfare should not be forgotten. Consideration should always be given to the messages we send with the methods we elect to use. Perhaps the greatest value of TNR is that it promotes both humane care and control

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BOX 45-8 Suggested Statements for Liability Forms Involving Trap-Loan and TNR Services • I understand that this spay/neuter service is for free-roaming community cats, and I certify that to the best of my knowledge these cats are unowned. I accept any liability that may occur secondary to the trapping and treatment of an owned cat. • I understand that all cats will be “ear-tipped” by the surgical removal of the tip of the left ear under anesthesia so that they can be easily identified as having been sterilized and vaccinated. • I recognize the risks feral cats face during handling, anesthesia, and surgery and hold __________ harmless should a cat experience complications, injury, escape, or death. • I understand that trapped animals may be dangerous, and I agree not to open any trap or handle any trapped animal unless specifically instructed. I release ___________ from any liability for any injuries or damages that I may incur or cause while trapping, confining, transporting, or releasing these cats. • I promise to see that, following surgery, spayed/ neutered cats will receive food, water, and necessary care on a regular basis when they are returned to the location from which they were taken. I commit to caring for these cats indefinitely and will secure a substitute caregiver if I am unable to provide adequate care. I acknowledge the possibility that once released, some cats may not return. • I will not use the trap to capture any owned cat, or for any other unlawful act, and will only use it for the purpose of spay/neuter procedures or other necessary medical treatment. Under no circumstances shall this trap be used to capture a healthy animal for destruction or surrender to animal control agencies. I indemnify __________ from any liability based on my use of the trap. • The value of each trap is $____. I will be responsible for said sum to secure its return or replacement. I agree that the traps I am receiving today are in good working order. I understand that if the traps are not returned in similar condition, I will forfeit my deposit for each trap not in good working order.

of cats, setting an important example for responsible stewardship to all animals.

Acknowledgments The author would like to acknowledge “Elmer,” who fearlessly posed as a feral cat to demonstrate the various types of humane capture equipment for many of the illustrations in this chapter. Because of his unflappable good nature, he purred throughout most of his photo session, making it difficult to obtain shots where he actually “looked feral”!

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References 1. American Association of Feline Practitioners (AAFP) position statement on feral cats. Available at http://www.catvets.com/ professionals/guidelines/position/?Id=292, published 2007. Accessed April 17, 2010. 2. Alley Cat Allies: Feral cat activist archives. Available at http:// www.alleycat.org/NetCommunity/Page.aspx?pid=439. Accessed April 8, 2010. 3. American Bird Conservancy: Resolution on free-roaming cats. Available at http://www.abcbirds.org/abcprograms/policy/ cats/Resolution.PDF, published 1997. Accessed April 17, 2010. 4. American Society for the Prevention of Cruelty to Animals: Pet statistics. Available at http://www.aspca.org/about-us/faq/ pet-statistics.html. Accessed January 12, 2010. 5. American Veterinary Medical Association (AVMA): Policy statement on free-roaming abandoned and feral cats. Available at http://www.avma.org/issues/policy/animal_welfare/feral_ cats.asp, published 2009. Accessed April 17, 2010. 6. American Veterinary Medical Association (AVMA): Center for information management: U.S. pet ownership and demographics sourcebook, 2007 ed, Schaumburg, Ill, 2007, AVMA. 7. Beaver BV: Fractious cats and feline aggression, J Feline Med Surg 6:13, 2004. 8. Burrow R, Wawra E, Pinchbeck G et al: Prospective evaluation of postoperative pain in cats undergoing ovariohysterectomy by a midline or flank approach, Vet Record 158:657, 2006. 9. Coleman GT, Atwell RB: Use of fipronil to treat ear mites in cats, Aust Vet Pract 29:168, 1999. 10. Dabritz HA, Atwill ER, Gardner IA et al: Outdoor fecal deposition by free-roaming cats and attitudes of cat owners and nonowners towards stray pets, wildlife and water pollution, J Am Vet Med Assoc 229:74, 2006. 11. Dorn AS: Ovariohysterectomy by the flank approach, Vet Med Small Anim Clin 70:569, 1975. 12. Dybdall K, Strasser R, Katz T: Behavioral differences between owner surrender and stray domestic cats after entering an animal shelter, Appl Anim Behav Sci 104:85, 2007. 13. Fischer SM, Quest CM, Dubovi EJ et al: Response of feral cats to vaccination at the time of neutering, J Am Vet Med Assoc 230:52, 2007. 14. Greene CE, Addie DD: Feline parvovirus infection. In Greene CE, editors: Infectious diseases of the dog and cat, ed 3, Philadelphia, 2006, Saunders, p 78. 15. Griffin B: Scaredy cat or feral cat? Animal Sheltering Nov/Dec:57, 2009. 16. Griffin B: Prolific cats: the impact of their fertility on the welfare of the species, Compend Contin Edu Pract Vet 23:1058, 2001. 17. Griffin B: unpublished data. Scott-Ritchey Research Center, Auburn University, Auburn, Ala, 2004. 18. Griffin B, DiGangi B, Bohling M: A review of neutering cats. In August JR, editor: Consultations in feline internal medicine, ed 6, St Louis, 2009, Saunders Elsevier, p 776. 19. Griffin B, Hume KR: Recognition and management of stress in housed cats. In August JR, editor: Consultations in feline internal medicine, ed 6, St Louis, 2009, Saunders Elsevier, p 717. 20. Grint NJ, Murison PJ, Coe R et al: Assessment of the influence of surgical technique on postoperative pain and wound tenderness in cats following ovariohysterectomy, J Feline Med Surg 8:15, 2006. 21. Hughes KL, Slater MR, Haller L: The effects of implementing a feral cat spay/neuter program in a Florida county animal control service, J Appl Anim Welf Sci 5:285, 2002. 22. Humane Society of the United States: How-to series: how to use a control pole. Available at http://www.animalsheltering.org/ resource_library/magazine_articles/sep_oct_1996/asmSO96_ howto.pdf, published 2006. Accessed April 17, 2010.

23. Kelly GE: The effect of surgery in dogs on the response to concomitant distemper vaccination, Aust Vet J 56:556, 1980. 24. Krzaczynski J: The flank approach to feline ovariohysterectomy (an alternate technique), Vet Med Small Anim Clin 69:572, 1974. 25. Levy JK: Feline leukemia virus and feline immunodeficiency virus. In Miller L, Hurley KF, editors: Infectious disease management in animal shelters, Ames, Iowa, 2009, Blackwell, p 307. 26. Levy J: Feral cat management. In Miller L, Zawistowksi S, editors: Shelter medicine for veterinarians and staff, Ames, Iowa, 2004, Blackwell, p 377. 27. Levy JK, Crawford, PC: Humane strategies for controlling feral cat populations, J Am Vet Med Assoc 225:1354, 2004. 28. Levy JK, Crawford C, Hartmann K et al: 2008 American Association of Feline Practitioners’ feline retrovirus management guidelines, J Feline Med Surg 10:300, 2008. 29. Levy JK, Gale DW, Gale LA: Evaluation of the effect of a long-term trap-neuter-return and adoption program on a free-roaming cat population, J Am Vet Med Assoc 222:42, 2003. 30. Levy JK, Scott HM, Lachtara JL, et al: Seroprevalence of feline leukemia virus and feline immunodeficiency virus infection in cats in North America and risk factors for seropositivity, J Am Vet Med Assoc 228:371, 2006. 31. Longcore T, Rich C, Sullivan LM: Critical assessment of claims regarding management of feral cats by trap-neuter-return, Conserv Biol 23:887, 2009. 32. Looney AL, Bohling MW, Bushby PA et al: The Association of Shelter Veterinarians veterinary medical care guidelines for spayneuter programs, J Am Vet Med Assoc 233:74, 2008. 33. Lowe SE, Bradshaw JWS: Effects of socialisation on the behaviour of feral kittens, Proc Third Int Congress Vet Behav Med, Vancouver, British Columbia, 2001, p 68. 34. Luria BJ, Levy JK, Lappin MR et al: Prevalence of infectious diseases in feral cats in Northern Florida, J Feline Med Surg 6:287, 2004. 35. McGrath H, Hardie RJ, Davis E: Lateral flank approach for ovariohysterectomy in small animals, Compend Contin Educ Pract Vet 26:922, 2004. 36. Miller J: The domestic cat: perspectives on the nature and diversity of cats, J Am Vet Med Assoc 208:498, 1996. 37. Miyamoto T, Taura Y, Une S et al: Immunological responses after vaccination pre- and post-surgery in dogs, J Vet Med Sci 57:29, 1995. 38. Neville PF, Remfry J: Effect of neutering on two groups of feral cats, Vet Record 144:447, 1984. 39. Nutter FB, Levine JF, Stoskopf MK: Reproductive capacity of freeroaming domestic cats and kitten survival rate, J Am Vet Med Assoc 225:1399, 2004. 40. Patronek G: Free-roaming and feral cats: their impact on wildlife and human beings, J Am Vet Med Assoc 212:218, 1998. 41. Patronek GJ, Sperry E: Quality of life in long term confinement. In August JR, editor: Consultations in feline internal medicine, ed 4, Philadelphia, 2001, WB Saunders, p 621. 42. Reese MJ, Patterson EV, Tucker SJ et al: Effects of anesthesia and surgery on serological responses to vaccination in kittens, J Am Vet Med Assoc 233:116, 2008. 43. Robertson S: A review of feral cat control, J Fel Med Surg 10:366, 2008. 44. Richards JR, Elston TH, Ford RB et al: The 2006 American Association of Feline Practitioners Feline Vaccine Advisory Panel report, J Am Vet Med Assoc 229:1405, 2006. 45. Scarampella F, Pollmeier M, Visser M et al: Efficacy of fipronil in the treatment of feline cheyletiellosis, Vet Parasit 129:333, 2005. 46. Scott KC, Levy JK, Gorman SP et al: Body condition of feral cats and the effect of neutering, J Appl Anim Welf Sci 5:203, 2002. 47. Smith RE, Shane SM: The potential for the control of feral cat populations by neutering, Feline Pract 16:21, 1986.

48. Slater MR: Community approaches to feral cats: problems, alternatives, and recommendations, Washington, DC, 2002, Humane Society Press. 49. Soulebot JP, Brun A: Experimental rabies in cats: immune response and persistence of immunity, Cornell Vet 71:311, 1981. 50. Stoskopf MK, Nutter FB: Analyzing approaches to feral cat management—one size does not fit all, J Am Vet Med Assoc 225:1361, 2004. 51. Subacz KB: Impact assessment of a trap-neuter-return program on selected features of Auburn, Alabama feral cat colonies.


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Unpublished graduate thesis: Auburn Univeristy, Ala. Available at http://etd.auburn.edu/etd/handle/10415/1101, 2008. Accessed June 4, 2011. 52. Wildlife Society: Position statement on feral and free-ranging domestic cats. Available at http://joomla.wildlife.org/documents/ positionstatements/28-Feral%20&%20Free%20Ranging%20 Cats.pdf, published 2006. Accessed April 17, 2010. 53. Wilson FD, Balasubramanian NN: The lateral approach for the spaying of canines and felines, Indian Vet J 44:1052, 1967.

C H A P T E R

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Population Wellness: Keeping Cats Physically and Behaviorally Healthy Brenda Griffin O U T L I N E The Components of Wellness, 1312 Goals of a Population Wellness Program, 1313 Health Surveillance (Daily Rounds), 1313 Policy and Protocol Development, 1314 Quality of Life and the Five Freedoms, 1314 Medical Decision Making and Euthanasia, 1315 Problem Prevention, 1315 The Role of Stress, 1315 Considerations Regarding Infectious Disease Transmission, 1316 General Principles of Infectious Disease Control, 1316

Essential Elements of a Population Wellness Program, 1316 Medical Record Keeping and Cat Identification, 1316 Management Oversight, 1320 Developing a Population Wellness Program: Considerations for Physical Health, 1321 Developing a Population Wellness Program: Considerations for Behavioral Health, 1328 Developing a Population Wellness Program: Considerations for Environmental Health, 1346 Conclusion, 1353

Whereas feline practitioners are usually well versed in the creation of wellness programs tailored to individual cats, optimizing the health of a population of cats requires additional knowledge and poses unique challenges. These challenges will vary depending on many factors, including the nature and purpose of the population itself. Indeed, veterinarians may be tasked with developing health care programs for cat populations in a wide spectrum of settings—from facilities housing laboratory animals, to animal shelters, home-based rescue and foster providers, care-for-life cat sanctuaries, breeding catteries, or large multicat households. Regardless of the setting, a systematic approach to the health of the clowder is crucial for success.

THE COMPONENTS OF WELLNESS Merriam-Webster’s Dictionary defines wellness as “the quality or state of being in good health especially as an actively sought goal.”80 Ensuring population health requires careful planning and active implementation of


comprehensive wellness protocols that address both animal health and environmental conditions (Figure 46-1).41 Addressing physical health alone is not sufficient to ensure wellness. For example, a cat may be in proper physical condition and free from infectious or other physical disease, yet suffering from severe stress and anxiety. In this case, the patient cannot be assessed as healthy, because its behavioral (emotional) state is compromising its health and well-being. Thus physical health and behavioral health are both essential components of wellness, and preventive health care must actively address each of these. Addressing the environment of the population is also critically important when considering wellness. Even the best-designed facilities cannot favor good health in a multicat environment without thoughtful implementation of environmental wellness protocols. In small animal practice, environmental wellness is frequently not emphasized simply because many owners are accustomed to providing a reasonably healthy environment for their pets. In contrast, a structured program to address environmental wellness is essential in the

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CHAPTER 46 Population Wellness: Keeping Cats Physically and Behaviorally Healthy Environmental health

Wellness

Physical health

Behavioral health

FIGURE 46-1 The inter-relationship among the components of population wellness. To optimize feline health, wellness programs must be carefully structured to address both the physical and behavioral health of the animals, which are intimately linked to their environment, making it crucial to systematically address environmental conditions as well.

context of a population, regardless of the actual physical facility. Proactive measures to maintain clean, sanitary environments that are not overcrowded—where cats are segregated by age and health status and provided with regular daily schedules of care by well-trained dedicated caregivers—are essential.41

GOALS OF A POPULATION WELLNESS PROGRAM Simply stated, the overarching goals of a population wellness program are to optimize both the physical and behavioral health of the cats as well as preventing transmission of zoonotic diseases. In other words, a population wellness program should be designed to keep animals “healthy and happy” while keeping human caregivers safe.41 It is not difficult to identify a healthy population of cats: When wellness protocols are successful, cats “look healthy” and “act like normal cats.” In other words, they appear in good physical condition and display a wide variety of normal feline behaviors, including eating, stretching, grooming, scratching, playing, rubbing, resting, and if allowed, courtship and breeding. Just as changes in a cat’s physical appearance should alert the clinician to potential problems, so should the absence of such normal feline activities and behaviors by members of the group. Wellness goals must include maintaining the health of individual animals as well as that of the population as a whole. In the context of the population, the individuals that are physically or behaviorally ill serve as indicators or “barometers” of the health care and conditions of the population. When individuals are ill, their health and well-being is always a priority; however, it should also immediately trigger the clinician to ask, “Why is this individual sick? What is the cause of its illness, and how can I prevent this from affecting others?”

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More specific goals will vary depending upon the given population and its purpose. For example, in an animal shelter, specific goals of the wellness program might include decreasing the incidence and prevalence of infectious diseases in the shelter and following adoption, decreasing the incidence of problem behaviors in the shelter, decreasing the rate of return of cats to the shelter for problem behaviors, increasing the adoption rate, and so forth. In the context of a breeding colony, the goals might include increasing kitten birth weights, decreasing neonatal mortality, or improving socialization of kittens. By identifying and tracking measurable factors (often called performance targets in large animal medicine), it is possible to measure progress toward these goals. Once baseline data (such as disease rates) are established, it is possible to measure the impact of protocol changes on population health by evaluating these performance targets. Both medical records and a system for regular surveillance and reporting are required to accurately track and access trends in animal health.41

HEALTH SURVEILLANCE (DAILY ROUNDS) Early recognition is crucial for effective control of infectious disease and problem behavior in a group. Therefore a regular system of health surveillance must be in place to monitor every individual. In a population setting, daily “walk-through rounds” represent the foundation of an effective animal health care program. Rounds should be conducted at least once daily (preferably twice a day or more often, depending upon the needs of individual cats) for the purpose of monitoring and evaluating both physical and behavioral health. Medically trained caregivers should visually observe every animal and its environment, taking note of food and water consumption, urination, defecation, attitude, behavior, ambulation, and signs of illness, pain or other problems. Monitoring should take place before cleaning so that food intake and the condition of the enclosure, including the presence of feces, urine, or vomit can be noted. Alternatively, observation logs can be completed by caregivers at the time of cleaning and reviewed during walk-though rounds. Any cat that is observed to be experiencing a problem, whether it be signs of respiratory infection, diarrhea, anxiety, or obvious pain, suffering, or distress must be assessed and treated in a timely manner. Regardless of length of stay, regular daily assessment is imperative to identify new problems (medical or behavioral) that may develop so that they can be identified and addressed in a timely fashion to ensure the welfare of the individual animal as well as that of the population.

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BOX 46-1 Suggested Topics for Health Care Policies and Protocols41,51 For each disease or problem in question, the following should be included: • Definition or description (including cause, transmission [if applicable], and risk to other animals, including humans) • Description of methods that will be used for diagnosis • Criteria for notification and contact information for individual(s) to be notified • General policy describing the handling and disposition of affected cats

POLICY AND PROTOCOL DEVELOPMENT In addition to early recognition of health problems, timely action is crucial to effectively limit their morbidity. Ideally, all facilities that house multiple cats should have written policies and protocols in place that detail how medical and behavioral problems will be handled.41,51,54 A committee or team of individuals composed of medical staff, managers, and caregivers can establish and oversee these policies and protocols. Such protocols serve as guidelines for systematic triage and care of animals and help to prevent delays in care that may otherwise arise if such plans were not in place. Policies and protocols should be based on medical facts, taking into account the entity’s purpose or mission and the availability of resources for care. They should include a definition or description of the disease or condition in question, a description of the methods that will be used for diagnosis, and a general policy regarding the handling and disposition of affected cats. In addition, protocols should include details on notification, housing, decontamination, treatment, and documentation (Box 46-1).

QUALITY OF LIFE AND THE FIVE FREEDOMS Just as quality-of-life assessment is the responsibility of every veterinarian as they guide the medical care of individual animals, quality-of-life assessment is also a critical part of population health care and monitoring. The factors that affect physical and mental well-being are broad, complex, and often vary substantially among individuals.76 Exacting criteria are lacking for the objective measurement of quality of life of cats. However, subjective assessments can and should be made by

• Description of housing/isolation procedures for affected cats • Description of decontamination procedures, if necessary • Criteria for treatment, if applicable • Who can initiate treatment? • Who is responsible for treatment? • How will recovery be monitored and defined? • How will treatment failure be defined? • Description of medical record keeping and other documentation of cases

BOX 46-2 The Five Freedoms35 1. Freedom from thirst, hunger, and malnutrition by providing ready access to fresh water and a diet that maintains full health and vigor 2. Freedom from discomfort by providing a suitable environment, including shelter and a comfortable resting area 3. Freedom from pain, injury, and disease by prevention or rapid diagnosis and treatment 4. Freedom to express normal behavior by providing sufficient space, proper facilities, and company of the animals’ own kind 5. Freedom from fear and distress by ensuring conditions that avoid mental suffering

medical and behavioral personnel at regular intervals (weekly or even daily, as indicated) considering the most information possible.76,109 The “Five Freedoms,” which were originally described by the Farm Animal Welfare Council in the 1970s, represent a benchmark for ensuring quality of life or animal welfare35 (Box 46-2). These principles provide a useful framework that is applicable across varying situations and species and have been widely accepted and endorsed by animal care experts. Many agencies have used the Five Freedoms as the basis of recommendations for minimum standards of care for many species, including cats housed in catteries, shelters, and research facilities.7,13,54,87 The tenets of the Five Freedoms define essential outcomes and imply criteria for assessment but do not prescribe the methods by which to achieve those outcomes. Regardless of the setting, population wellness programs should ensure the Five Freedoms for all cats.

CHAPTER 46 Population Wellness: Keeping Cats Physically and Behaviorally Healthy

MEDICAL DECISION MAKING AND EUTHANASIA Medical decisions must be weighed in the context of the health of the population as well that of the individual, while considering animal welfare and the availability of resources for care. When large numbers of animals are involved, situations may arise in which animal health and welfare cannot be managed in the case of every individual animal. This may be due to physical or behavioral illness, or environmental conditions that negatively impact animal health, such as crowding. Regardless of the cause, it may be necessary to euthanize affected individuals if no other remedies exist to relieve animal suffering or to protect population health. These decisions can be difficult and emotionally challenging, especially in instances where the individual could easily be treated or otherwise accommodated if adequate resources were available. However, such decisions may be crucial for disease control, animal welfare, and population health. That being said, euthanasia should never be used as a substitute for providing proper husbandry and care. Indeed, a critical need for a comprehensive wellness program exists in every multicat setting. It is unacceptable to house animals under conditions likely to induce illness and poor welfare, and such conditions can be expected when wellness programs are not in place and carefully monitored.41 When facilities elect to house cats with medical or behavioral problems, appropriate veterinary care must be provided. It is imperative that a humane plan for diagnosis, treatment/management, monitoring, and housing be implemented in a timely fashion. When determining if cats with special needs can be humanely cared for in a population setting, the following goals and considerations should be addressed: What measures must be implemented to prevent transmission of disease to other cats or people? Can appropriate care realistically be delivered? Will the care provided result in a cure or adequate management of the disease or problem behavior? Can the facility afford the cost and time for care? How will it impact resources available for other cats? In the case of animal shelters, additional considerations should include Will the cat be adoptable? What steps can be taken to minimize the holding time required for treatment? If the cat is not adopted, do humane long-term care options exist in the shelter? What welfare assessment will be used to measure quality of life in the shelter?41

PROBLEM PREVENTION Both infectious disease and problem behaviors are common in multicat settings. The old adage, “An ounce of prevention is worth a pound of cure” is certainly true.

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Wellness always starts with prevention: It is far more time and cost efficient than treatment, and it is kinder to the animals and their caregivers. With this in mind, population wellness programs should provide broad-based, holistic approaches to preventive care, rather than being based on the control of a single disease or problem, regardless of the setting. Maintenance of good health or wellness is especially challenging in populations with high turnover and interchange of cats of varying ages and susceptibilities, such as animal shelters. Infectious diseases can become endemic in facilities where populations of animals are housed. Even in closed populations, certain pathogens can be difficult to exclude or to eliminate once introduced. Notably, upper respiratory viruses, dermatophytes, and coccidia are among the most difficult pathogenic agents to control because of their persistence in the environment through carrier states and/or resistance to environmental disinfection. In particular, upper respiratory disease is the most common endemic disease in cat populations and is impossible to completely prevent in an open population. Feline herpes virus type 1 (FHV-1) and feline calicivirus (FCV) have been implicated as the causes of most infections: Both viruses induce persistent carrier states and are widespread in the cat population.36 Cats that recover from FHV-1 remain latently infected and shed virus intermittently, especially following periods of stress. FCV carriers shed continuously for months to years following infection. A variety of other viral and bacterial pathogens may also contribute to feline upper respiratory disease, and Bordetella, Chlamydophila, and Mycoplasma are problematic in some populations. Feline infectious peritonitis (FIP) is another disease that is nearly impossible to eradicate from a multicat environment, and sporadic cases can be expected to occur, especially in young cats.93 Fortunately, proper wellness programs can greatly limit the incidence and severity of diseases, even for pathogens that are difficult to control.

THE ROLE OF STRESS The multicat environment also presents enormous opportunities for inducing stress. Because of their unique biology, cats are particularly prone to experiencing acute stress and fear in novel environments. Anything unfamiliar to a cat can trigger apprehension, activating the stress response. Confinement in a novel environment can result in a wide variety of behavioral indicators of stress including hypervigilance, feigned sleep, constant hiding, activity depression, and loss of appetite, among others. In the long term, if cats are unable to acclimate or cope in their environments, chronic stress, fear, frustration, or learned helplessness may result. In group settings, signs of social stress may also manifest with

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increases in problem behaviors, including urine marking, spraying, or other inappropriate elimination; constant hiding; and/or aggression.46 Stress not only has the potential to negatively impact behavioral health but also physical health as well. The intimate link between stress and immunity has been well described. In fact, stress is a leading factor in the development of infectious disease and is particularly important in the pathogenesis of feline upper respiratory infections.37,47 Wellness programs that reduce stress will also serve to minimize the morbidity of infectious disease.

CONSIDERATIONS REGARDING INFECTIOUS DISEASE TRANSMISSION Despite the fact that infectious agents can never be completely eliminated from the environment, it is still possible to maintain good health. This is because the development of disease is determined by a complex interaction of many factors surrounding the host, the infectious agent, and the environment. Keeping these factors in mind provides a rational context for many of the recommendations in this chapter. Some of the host factors that influence health and the development of disease include age, sex and reproductive status, immune status, body condition, stress, and genetics.39 The amount and duration of exposure to an infectious agent (i.e., the “dose effect”), as well as its virulence and route of inoculation, also influence the likelihood and severity of disease. In addition, environmental conditions contribute to the development of infectious disease, including such factors as housing density, sanitation, and fluctuations in temperature or air quality. The fact that disease results from such a large combination of factors underscores the importance of a holistic and broad-based approach to population wellness.

GENERAL PRINCIPLES OF INFECTIOUS DISEASE CONTROL When infectious disease does occur in a population, general principles of infectious disease control should guide the response. These include • • • • •

Removal of infected animals from the population Mass vaccination Mass treatment Quarantine of new arrivals or closure to admission Review of husbandry procedures (animals and environment) • Staff education and communication Coupled with vigilant surveillance to ensure early recognition of disease, these serve as the foundation of all

disease control efforts when disease is present. However, the best method of disease control is always prevention.

ESSENTIAL ELEMENTS OF A POPULATION WELLNESS PROGRAM When creating preventive medicine programs for a population, consideration must be given to all components of wellness: physical, behavioral, and environmental health.41 With regard to promoting physical health, wellness programs should address the following essential elements: • • • • • • • • •

Patient history and physical examination Disease testing Vaccination Parasite control/prevention Spay/neuter Proper nutrition Grooming Periodontal disease prevention Breed-specific care

Likewise, to promote behavioral wellness, programs should include provisions for the following essential elements: • • • • •

History and behavioral care at intake Proper housing Social companionship Mental and physical activity Consistent daily routines

Finally, wellness protocols aimed at creating an environment that promotes health must take into account the following essential elements: • • • •

Population density Cleaning and disinfection Segregation and traffic patterns Facility operations (e.g., heating–ventilation–airconditioning [HVAC], noise and pest control, staff training)

MEDICAL RECORD KEEPING AND CAT IDENTIFICATION Implementing population wellness protocols and ensuring quality and timely care require reliable systems for medical record keeping and animal identification. Regardless of the system used, medical record keeping procedures should comply with state and local practice acts, guidelines provided by state and national veterinary medical associations, and, in the case of laboratory animals, regulations as prescribed by federal law, the


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FIGURE 46-2 A plastic neckband designed for animals is used as an

FIGURE 46-3 Cats in a private cattery wear collars with identifica-

identification collar for this shelter cat (Safeguard 821, Precision Dynamics Corp., San Fernando, Calif.).

tion tags. Visual identification is essential for cats, regardless of the setting, and most cats can safely and reliably wear collars.

Institute for Laboratory Animal Research and Institutional Animal Care and Use Committees. Computerized records are preferred; however, written records may also be used. Computerized records offer the advantage of mechanized reporting, which facilitates detection and monitoring of health trends in the population. A medical record should be prepared for each cat and should include the cat’s entry date, identification (ID) number, date of birth, gender, breed, and physical description, as well as historical and physical/behavioral examination findings. In addition, it should contain the dosages of all drugs administered and their routes of administration, including vaccines, parasite control products, other treatments, and anesthetic agents; the results of any diagnostic tests performed; any surgical procedure(s) performed; and other pertinent information regarding the animal’s condition. Standardized examination and operative reports may be used, but should allow for additions when necessary. Identification of cats in the form of a neckband, collar and tag, tattoo, earband, and/or a microchip is also essential for preventive health care and ongoing surveillance of individuals.45 Whenever possible, some form of identification should be physically affixed to every individual cat. In addition, enclosures should be labeled with the cats’ unique identification number and/or name.

are also a good option (Figure 46-3). Some facilities prefer to use safety collars that are designed to break away should the collar become caught on something. Even for kittens, collars can be used and may be especially beneficial, because they will learn to wear them from an early age.

Identification Collars Contrary to popular belief, most cats can reliably wear collars safely and comfortably.65 Many facilities use disposable collars, including commercially available plastic or paper neckbands made for animals or hospital-type wristbands made for human patients (Figure 46-2). Commercially available cat collars with an ID tag affixed

Microchips Microchips may also be used for identification and are safe and simple to implant (Figure 46-4). The procedure is well tolerated by the vast majority of cats without the need for sedation. Unlike visual means of identification, a scanner is necessary for positive identification of a microchipped animal. For this reason, microchips are often used in conjunction with a visual means of identification and serve as important permanent means of backup identification. Box 46-3 describes the proper technique for scanning for a microchip. During the last 2 decades, microchips of varying radiofrequencies (125, 128, and 134 kHz) have been introduced in the United States.4 The 125-kHz chips have historically been the most common, whereas the accepted standard in the rest of the world is the 134-kHz chip. Because some scanners read only certain radiofrequencies, it is possible to miss detecting a microchip that is present, depending on the scanner being used. Currently, there are efforts to standardize microchipping in the United States, including widespread distribution of universal (global) scanners to ensure that all implanted microchips can be reliably identified. Once global scanners are widely available, the American Veterinary Medical Association (AVMA) recommends adoption of the 134-kHz (ISO) microchip as the American standard, because this frequency is recognized as the international standard for microchips

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A B

FIGURE 46-4 Microchip identification. Small (12- × 2-mm)

C

in the rest of the world. Efforts have also focused on improving, updating, and centralizing microchip registries. This is extremely important in the context of animal shelters. Box 46-4 contains information on the use of collars and microchips as tools for improving cat–owner reunification.

Tattoos In laboratory settings, tattoos may be used as a means of permanent identification of cats (Figure 46-5).45 Tattoos are most commonly applied to the inner pinna of the ear using a tattoo machine with multiple needles. Care must be taken to properly disinfect the needles between patients. A significant disadvantage of tattooing is that tattoos can sometimes be difficult to read because of the presence of hair, fading, or distortion that may occur as the cat grows. In addition, their application requires anesthesia or heavy sedation.

Earbands Small stainless steel ear tags manufactured for wing banding of birds are especially useful for identifying

microchips can be easily implanted in most cats, without sedation, using a needle. Cats may be scanned for reliable permanent identification. (From Griffin B, Hume KR: Recognition and management of stress in housed cats. In August JR, editor: Consultations in feline internal medicine, vol 6, St Louis, 2006, Elsevier, p 717.)

newborn kittens in some settings and are highly economical (Figure 46-6).45 They can be placed without the need for anesthesia or sedation when kittens are less than 10 to 14 days old. Placing earbands requires skill and experience. They must be positioned in such a way as to provide adequate space for growth of the ear, while seating them deeply enough in the ear margin to ensure a secure piercing far enough away from the edge. If placed too close to the ear margin, the ear flap may tear, resulting in loss of the band. Other complications include local inflammation or infection at the site of the piercing. Ear tags are a practical method for identifying individual kittens in institutional or commercial breeding colonies, because when applied skillfully, they are seldom lost and provide reliable, long-lasting visual identification. In contrast, private breeding catteries and animal shelters generally prefer to use methods that will not alter the cat’s cosmetic appearance long term. Colored ribbon, nail polish, or clipping of hair in various areas of the body can all be useful means of temporary kitten identification in the neonatal stage, especially when coat color or patterns do not easily allow individuals to be distinguished.


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BOX 46-3 Microchip Scanning Technique Every cat, including those surrendered by their owners, should be systematically scanned for the presence of a microchip at the time of intake, as well as prior to being made available for adoption or being euthanized. Proper technique and scanning more than once are crucial to avoid missing microchips.67,68 A universal (global) scanner (e.g., one that will read all microchip frequencies that are currently in use) should be used to ensure that all microchip frequencies are detected. At this time, the only universal scanners available in the United States are the new Home Again Global World scanner (Schering Plough, Whitehouse Station, NY) and the iMax Black Label ResQ scanner (Bayer Animal Health, Shawnee Mission, Kans.). One of the most common causes of scanner failure is weak batteries; therefore it is imperative that batteries be checked and replaced regularly. To ensure a thorough scan and avoid missing chips, cats must be removed from carriers or cages prior to scanning. Metal and fluorescent lighting may interfere with chip detection. Metal exam surfaces should be covered with a towel or other material prior to scanning to minimize interference. The entire animal should be scanned using a consistent speed, scanner orientation, scanning pattern, and distance. • Scanner orientation: The scanner should be held parallel to the animal. Rocking the scanner slightly from side to side will maximize the potential for optimal chip orientation and successful detection. The button on the

• •

•

•

scanner should be depressed continuously during the entire scanning procedure. Scanning distance: The scanner should be held in contact with the animal during scanning such that it is lightly touching the hair coat. Scanner speed: The scanner should not be advanced any faster than 0.15 m/second (0.5 ft/second). Scanning slowly is crucial, because universal scanners must cycle through various modes to read all possible chip frequencies. Areas of animal to scan: The standard implant site is midway between the shoulder blades, and scanning should begin over this area. If a microchip is not detected here, scanning should proceed systematically down the back, on the sides, neck, and shoulders—all the way to the elbows in the front and the hindquarters in the rear. Scanning pattern: The scanner should be moved over the scanning areas in an “S”-shaped pattern in a transverse direction (from side to side). If no microchip is detected, the scanner should be rotated 90 degrees, and then the “S”-shaped pattern should be repeated in a longitudinal direction (e.g., the long way) on both sides of the animal. This pattern of scanning will maximize the ability of the scanner to detect the microchip, regardless of its orientation.

BOX 46-4 Use of Identification (ID) Collars and Microchips to Improve Cat–Owner Reunification • Less than 2% of cats are reunited with their owners, compared to as many as 15% to 19% of lost dogs.86 • The use of collars and tags as visually obvious forms of identification is extremely valuable, although overlooked by many cat owners.69 • Cats wearing collars are more likely to be identified as owned and not mistaken for strays. • Even indoor cats require identification in case they escape, and studies clearly demonstrate that visual identification improves the odds of pet–owner reunification.69 • The provision of permanent identification in the form of a microchip represents an important backup, further improving the odds of pet–owner reunification because collars and tags can be lost.66 • Because owners and shelter staff often describe cat coat color and patterns differently, photographs that can be

posted online are a useful method of improving lost-pet matching and enabling owners to look for their pet, even if they are physically unable to come to the shelter. • Adopted animals should be sent home with ID collars and microchips. • Shelter staff should always register microchips before the cat leaves the shelter, because many owners will neglect to do so following adoption, making the microchip an ineffective means of identification.66 • Web-based search engines for pet microchip identification numbers (http://www.checkthechip.com and http://www.petmicrochiplookup.org) have been established in an effort to functionally centralize microchip registries by linking existing national databases.

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A

A

B

B

FIGURE 46-5 Permanent tattoo on the inner pinna of the ear of a

FIGURE 46-6 Earband identification. Small stainless steel bands

laboratory cat. This form of identification requires heavy sedation with appropriate analgesia for placement. (From Griffin B, Hume KR: Recognition and management of stress in housed cats. In August JR, editor: Consultations in feline internal medicine, vol 6, St Louis, 2006, Elsevier, p 717.)

manufactured for wing banding of birds are ideal for identification of young kittens in a laboratory setting. (From Griffin B, Hume KR: Recognition and management of stress in housed cats. In August JR, editor: Consultations in feline internal medicine, vol 6, St Louis, 2006, Elsevier, p 717.)

MANAGEMENT OVERSIGHT The success or failure of a population wellness program hinges in large part on its implementation and oversight. A knowledgeable, cohesive, and dedicated team, where accountability, responsibility, and lines of authority are well defined, is crucial for management success. As a part of the management structure and plan, veterinarians must be involved in the oversight of all aspects of animal care and must be given direct authority for the oversight of medical decisions. This requires that every

facility that houses cats establish a formal relationship with one or more veterinarians who have direct knowledge of their animal population. This is essential to ensure that medical protocols are established with the proper professional oversight, and helps to ensure compliance with local veterinary practice acts that restrict the practice of veterinary medicine to licensed veterinarians. In facilities such as animal shelters, trained shelter staff can carry out preventive health care under the instructions of a veterinarian.6


DEVELOPING A POPULATION WELLNESS PROGRAM: CONSIDERATIONS FOR PHYSICAL HEALTH The clinician should develop a program for physical health for the population that addresses all of the essential elements as noted. None of these should be considered as optional, but their implementation will depend on the setting, purposes, and resources of the group.

History The value of obtaining an accurate medical history on any cat entering a population is immeasurable, because it will often alert the clinician to the presence of potential problems. In a laboratory setting, obtaining cats from commercial purpose-bred colonies or institutional breeding colonies ensures that an accurate history will be available, maximizing the odds that only healthy cats will be added to the population. Likewise, private breeding catteries should always strive to obtain an accurate medical history on any cat that may be accepted into the cattery. The introduction of cats from random sources to closed populations of cats risks the health of the population and should be avoided whenever possible.45 In contrast, by their very nature, animal shelters must frequently receive cats from multiple random sources, and it will not always be possible to obtain accurate histories. In some cases, cats are brought in by animal control officers or good Samaritans who have little if any information about them. Furthermore, some shelters provide a location (e.g., drop-off cages) where cats can be relinquished after business hours. This practice should be discouraged; however, if facilities elect to do this, every effort must be made to obtain a history through questionnaires that can be completed when the cat is left. The presence of staff to directly accept cats and obtain a history at the time of relinquishment is greatly preferred.41 Even so, surrendering owners may or may not provide complete or accurate information, fearing that if they are honest about a pet’s problems, the pet may be euthanized. Nonetheless, when available, a history can be extremely valuable, saving time and money as well as preventing unnecessary stress for cats and staff alike. Intake procedures should be in place to capture basic patient information, including both physical and behavioral data as well as the reason(s) for relinquishment. The importance of obtaining historical information cannot be overemphasized. In many cases, historical information may be used to expedite the disposition of the cat in the shelter.

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Physical Examination Physical examination is the clinician’s single most important tool for evaluating health. Following a standardized physical examination form will ensure a complete and systematic review of all body systems. A veterinarian should carefully examine any new cat entering a closed population prior to admittance. In the context of animal shelters, every cat that is safe to handle should receive a physical examination at or as close to the time of admission to the shelter as possible. In many shelters, a veterinarian may not be available to examine incoming animals. However, staff can and should be trained to perform basic evaluations including sexing, aging, body condition scoring, and looking for evidence of fleas, ear mites, dental disease, overgrown claws, advanced pregnancy, or other obvious physical conditions. Of particular importance in the shelter physical examination are an accurate physical description of the animal and careful inspection for the presence of identification, both of which may aid in pet–owner reunification.41

Disease Testing The gold standard for maintaining the health of a population is through exclusion of pathogens in combination with implementation of comprehensive wellness protocols. This requires that members of a population be free from specific pathogens when the group is established and that the colony be closed to any new individuals that do not meet the health standards of the group.45 This is the foundation of disease control procedures in a laboratory animal setting, and these concepts should be applied to other population settings whenever possible. Consideration should be given to testing for the following: feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), dermatophytosis, intestinal parasites and infections (e.g., Campylobacter, Giardia, coccidia), as well as other endoparasites and ectoparasites. The setting and resources available, as well as the individual’s history and physical examination findings, should guide the clinician’s decisions regarding selection of testing for cats entering a specific population. When new stock is added to a closed colony, disease testing is imperative. Feline Leukemia Virus and Feline Immunodeficiency Virus The American Association of Feline Practitioners (AAFP) maintains detailed professional guidelines for the management of FeLV and FIV infections. Identification and exclusion of infected cats is the most effective method of preventing new infections. Cats and kittens should always be tested prior to entry to a closed population. Those that test negative should be retested, because it

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may take as long as 60 days following exposure for a cat to test positive.62,63 In the context of animal shelters, testing decisions are often influenced by the availability of resources. The AAFP’s guidelines include recommendations specifically for shelters. They state that all cats should ideally be tested at the time of entry and again in 60 days in case of recent exposure. When cats test positive on screening tests (e.g., point-of-care enzyme-linked immunosorbent assay [ELISA] tests), the AAFP recommends that the results be confirmed by additional testing, including testing over an interval of time, because false positives can occur. However, such confirmatory testing requires substantial time and monetary investment and may not be feasible in many shelters. In recognition of this, the Association of Shelter Veterinarians established a policy statement on “Management of Cats Who Test Positive for FeLV and FIV in an Animal Shelter,” which states that the logistics and cost of holding and retesting unowned cats may be an ineffective use of resources.5 In addition, it can be difficult to find homes for retroviruspositive cats, which in many instances translates into stressful, prolonged shelter stays. Such long-term confinement may compromise quality of life and may compound the emotional stress of caregivers who may later be faced with euthanizing cats that have been held for long periods awaiting confirmatory testing or adoption opportunities. For all of these reasons, many shelters elect to euthanize cats that test positive on retrovirus screening tests. Although it may be ideal for shelters to test cats on entry, it is not always feasible because of financial constraints. The next best practice might be to test cats prior to adoption as well as those that are housed in the shelter long term. In addition, cats should be tested prior to placement in group housing with unfamiliar cats and prior to investment, such as foster care, treatment, or spay/neuter surgery. However, given the limited resources of many shelters, the relatively low prevalence in healthy cats and the fact that transmission can be prevented by housing cats separately, it may not be cost effective for all shelters to screen every cat before selection for adoption. Each shelter should evaluate its own resources and determine their best use. When testing is performed, samples must never be pooled, and the negative results of one cat (such as a mother cat) should not be extrapolated to other cats (such as her kittens). These practices are invalid and can falsely lead to misidentification of a cat’s true infection status.62,63 If testing is not performed prior to adoption, adopters should be advised to have their new pet tested and to keep them separate from any other cats they may own prior to doing so. Feline Heartworm Disease Point-of-care heartworm tests for cats have recently become more widely available, but interpreting results

can be problematic.2 In relation to population health, testing is of little value, because infected cats pose no risk to other cats. Nonetheless, a clinician may elect testing as part of an initial database for individual cats, especially if they will be used for breeding. With heartworm tests readily available in combination with pointof-care FeLV/FIV tests, many animal shelters have been faced with determining whether or not to perform routine screening of cats in their care. To answer this question, it is helpful to consider the following: • Infected cats pose no risk to other cats and usually remain asymptomatic. • Even if infection is diagnosed in asymptomatic patients, definitive treatment is neither practical nor safe. • Most infections resolve spontaneously with time and are not associated with a shortened life span.38 • Counseling owners about positive test results poses unique challenges. • Positive test results may alter a cat’s disposition in the shelter. In consideration of these facts, the author does not recommend routine screening of cats for heartworm disease in shelters. Monthly chemoprophylaxis, however, is a safe and effective option for cats sheltered in areas where heartworm infection is considered endemic. Dermatophytosis Dermatophytosis or ringworm, the most common skin infection of cats, is a known zoonosis. It is caused by infection of the skin, hair, and nails with microscopic fungal organisms that cause varying degrees of hair loss and dermatitis. The dermatophyte that causes the majority of cases in felines is Microsporum canis, which is responsible for greater than 96% of all cases.82 If left untreated, most infections will spontaneously resolve within 12 to 14 weeks postinfection. However, during this time, the infected cat will infect the surrounding environment and other animals or humans in the area. Not all cats infected with dermatophytosis develop lesions, and some may become chronic carriers. Control of dermatophytosis is difficult, because the spores formed by M. canis can survive in the environment for up to18 months or longer and are extremely resistant to disinfectants and detergents. In addition, the presence of asymptomatic carriers makes it difficult to readily recognize all infected cats. For this reason, consideration should be given to culturing all cats prior to entry to a closed colony. In particular, Persian cats may be predisposed to dermatophyte infection and can be particularly difficult to clear once infected. In closed colony settings, dermatophyte testing by culture is highly recommended unless the source of the cat excludes the possibility of infection (e.g., specific pathogen-free [SPF] cats, purposebred laboratory cats). To screen cats using cultures,


samples should be collected using the McKenzie toothbrush method, where a new toothbrush is used to brush the cat’s entire body, giving special attention to the face, ears, and limbs. In addition, if skin lesions are present, hair should be plucked around these areas for culture as well. Enteric Pathogens Campylobacter, Salmonella, Giardia, coccidia, Tritrichomonas, and other gastrointestinal parasites and pathogens are common in some cattery situations and can be very difficult to eliminate once they are introduced. In fact, in some settings, these pathogens may become endemic and nearly impossible to eliminate. Treatment of coccidia in shelter kittens is described in Box 46-5. Although clinical signs, such as diarrhea, may be associated with infection, some cats remain asymptomatic. These pathogens have the potential for high morbidity in a population (especially in young kittens), and some possess zoonotic potential. Therefore routine fecal examinations, cultures, and/or empirical treatments should be considered prior to the introduction of new cats.

Vaccination It is well recognized that vaccination plays a vital role in the prevention and control of infectious diseases. Protocols should be established in the context of the population’s exposure risk, which will vary depending upon the setting. In the context of population medicine,

BOX 46-5 Ponazuril for Control of Coccidia in Multicat Environments Ponazuril is a metabolite of toltrazuril that has proven activity against coccidia.* Because there is no approved product for use in cats, the equine product Marquis Oral Paste (15% w/w ponazuril; Bayer HealthCare) may be dosed at 50 mg/kg, PO, once daily for 1 to 5 days. Prophylactic treatment may be instituted in high-risk situations, such as young kittens in environments with documented infection. Proper hygiene, including the use of disposable litter boxes and frequent removal of feces, is also necessary. Oocysts survive in the environment and are not treated by routine disinfectants, such as bleach and quaternary ammonium compounds. Preparation of the equine product for use in cats: 10 mL Marquis Oral Paste added to 20 mL water = 30 mL of 50 mg/mL oral suspension *Data from Lloyd S, Smith J: Activity of toltrazuril and diclazuril against Isospora species in kittens and puppies, Vet Rec 148:509, 2001.

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vaccination protocols are typically applied uniformly to all of the individuals comprising the population. This simplifies their application and helps to afford the best possible protection for the group. Detailed vaccination records should be maintained for each cat, including vaccine name, manufacturer and serial number, date, the initials of the person who administered it, and any adverse reactions.96 Proper vaccination can substantially reduce disease in cat populations, and serious adverse reactions are relatively rare. For this reason, vaccination against certain core diseases is recommended in all population settings. Although exclusion of infectious disease is always a goal of health management, certain pathogens are so widespread that even with careful biosecurity in a closed population, an infection may be introduced to susceptible cats. Only in the case of specific pathogen-free colonies, where there may be a compelling reason not to vaccinate as dictated by the purposes of the research, should vaccination be foregone. The AAFP maintains published guidelines for vaccination of cats in a variety of settings and includes detailed recommendations for cats in animal shelters.96 Core Vaccines for the Population: Feline Viral Rhinotracheitis, Calicivirus, Panleukopenia (FVRCP) Although many vaccines are commercially available for cats, only a few are recommended for routine use in populations. Unnecessary use of vaccines should be avoided to minimize the incidence of adverse reactions and reduce cost. Core vaccines involve diseases that represent significant morbidity and mortality and for which vaccination has been demonstrated to provide relatively good protection against disease. Core vaccines for cats in a population setting include feline parvovirus (FPV or panleukopenia), FHV-1 (feline herpes virus type 1 or feline rhinotracheitis virus), and feline calicivirus (FCV).96 These vaccines are usually given in a combination product commonly referred to as an FVRCP vaccine (feline viral rhinotracheitis, calicivirus, panleukopenia). In most cases, timely vaccination against panleukopenia will prevent the development of clinical disease. In contrast, vaccination against the respiratory viruses (FHV-1 and FCV) does not always prevent disease. In many instances, it affords only partial protection, lessening the severity of clinical signs but not preventing infection. To optimize response, modified live vaccines (MLV) should be used in most cases, because they evoke a more rapid and robust immune response and are better at overcoming maternal antibody interference than killed products. This is especially important in multicat environments in which the risk of infection is high, such as animal shelters, foster homes, as well as any population setting where upper respiratory disease is endemic. A

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single modified live FVRCP vaccine will usually afford protection to cats that are at least 4 months of age. In contrast, killed products require a booster in 2 to 3 weeks to confer immunity, making their use largely ineffective in such environments.96 To ensure rapid protection against panleukopenia, injectable FVRCP vaccines are preferred, but intranasal vaccines may offer advantages for feline respiratory disease, because they have been shown to rapidly induce local immunity at the site of exposure. Furthermore, intranasal vaccines may be better at overriding maternal antibody in young kittens. For this reason, they are often used to reduce the morbidity and severity of upper respiratory infection (URI) in preweaningage kittens. When intranasal vaccines are used in animal shelters, they should be used in combination with injectable FVRCP vaccines to ensure and optimize response against panleukopenia as well as the respiratory infections.96 Ideally, all cats should receive a MLV FVRCP vaccine at least 1 week prior to entering a population. In the context of an animal shelter setting, this is seldom feasible. Vaccination immediately upon entry is the next best practice and can provide clinically significant protection for the majority of cats. If neither maternal antibody nor another cause of vaccine failure interferes, modified live vaccinations against panleukopenia will often confer protection against disease in only 5 days.12 Intranasal vaccines against respiratory infections, including FHV and FCV, typically provide partial protection within 2 to 4 days.18,30 In animal shelters, all incoming cats and kittens 4 weeks of age and older that can be safely handled should receive an injectable MLV FVRCP vaccine immediately upon entry. A delay of even a day or two significantly compromises the vaccine’s ability to provide timely protection. Even injured cats, those with medical conditions, and those that are pregnant or lactating should be vaccinated on entry, because vaccination will likely be effective and the small risk of adverse effects is outweighed by the high risk of disease exposure and infection in the shelter.96 When vaccination of all cats on entry is not financially feasible, the next best practice is to vaccinate all those that are deemed adoptable at the time of entry or that are likely to be in the shelter long term.41 Whenever possible, vaccinated cats should be separated from those that will remain unvaccinated (e.g., those that will be euthanized following a brief holding period) as soon as that determination can be made. In contrast, in lower-risk settings, ensuring that cats are in good health prior to vaccination should be a priority.96 Vaccination of kittens with injectable FVRCP vaccinations may be delayed to 6 to 8 weeks of age. However, when respiratory disease is endemic, administration of intranasal vaccines beginning at 4 weeks of age may be beneficial. In breeding catteries, queens (especially those

with a history of upper respiratory infection) may benefit from vaccination prior to breeding to maximize passage of maternal antibody to their kittens. For pregnant cats in such environments, administration of MLV should be avoided, because the potential risk of injury to the developing kittens may outweigh the risk of infection in this case. Vaccination of lactating queens should also be avoided in a low-risk environment. A series of vaccinations should be administered to kittens less than 4 months of age to minimize the window of susceptibility to infection and ensure that a vaccine is received as soon as possible after maternal antibodies have decreased sufficiently to allow vaccine response.96 For kittens, vaccines should be administered every 2 to 4 weeks until they are 16 weeks (e.g., 4 months) of age or their permanent incisors have erupted. The minimum interval of 2 weeks is recommended in high-risk settings to narrow the window of susceptibility as maternal antibody wanes. A vaccination interval of less than 2 weeks is not recommended, because it may actually blunt the immune response from previous vaccination.40 In the case of an outbreak of panleukopenia, extending vaccination to 5 months of age may be warranted to ensure than no animal remains susceptible. Although the vast majority will respond by 4 months of age, a few may fail to respond, while others are provided with a boost to enhance the immune response. Just as in owned pets, booster vaccines are generally not required until 1 year later for modified live vaccines but should ideally be administered once in 2 to 4 weeks whenever resources permit. This may be especially important for cats that were ill at the time of initial vaccination, as may be the case in an animal shelter. Revaccination in long-term shelter facilities should follow the guidelines set forth for pets: Boost at one year, then every 3 years for FVRCP.96 Rabies Vaccination Vaccination against rabies virus is regarded as a core requirement for pet cats and is required by law in some jurisdictions.96 Thus vaccination against rabies is recommended in the context of private catteries. In contrast, rabies vaccination may be considered optional in most closed laboratory settings, because the risk of exposure should be absent and legal requirements may not apply. In animal shelters, vaccination against rabies is not generally recommended at the time of admission, simply because there is no benefit in terms of disease prevention or public health.96 Vaccination on admission will not provide protection against an infection acquired prior to entry, nor will it limit concern if a cat with an unknown health history bites someone soon after admission. Rabies vaccination is recommended for cats prior to adoption when a veterinarian is available to administer it (or as otherwise legally prescribed by state laws). Alternatively, rabies vaccination may be administered as


soon as possible following adoption.41 The latter may encourage new owners to establish a relationship with a private veterinarian. Rabies vaccination is warranted when cats are housed long term in shelter facilities. In addition, if individual cats must be held for bite quarantines, they should be vaccinated against rabies in accordance with the current Compendium of Animal Rabies Prevention and Control.85 Noncore Vaccines Noncore vaccines include those that may offer protection against disease, but because the disease in question is not widespread or only poses a risk of exposure in certain circumstances, vaccination is only recommended based on the individual risk assessment of a population of animals. Noncore vaccines include FeLV, FIV, Chlamydophila, and Bordetella.96 FELINE LEUKEMIA VIRUS

Vaccination against FeLV is not warranted in a closed population of cats in which there is no risk of exposure (e.g., most laboratory animal settings). In private catteries, a risk assessment should be done to determine if vaccination is warranted (e.g., cats permitted in outdoor enclosures, frequent introduction of cats from external sources, other opportunities for exposure). Special consideration should be given to vaccinating kittens because of their high susceptibility to FeLV infection and the high likelihood that they will become persistently infected if exposed. In general, FeLV vaccination is not recommended in animal shelters when cats are housed short term. However, its use is warranted when cats are group housed when resources permit.96 FELINE IMMUNODEFICIENCY VIRUS

FIV vaccination is not generally recommended in population environments. A confounding feature of FIV vaccination is that vaccinated cats develop false-positive test results on most commercially available tests (see Chapter 33). If FIV vaccination is elected, vaccinated cats should be permanently identified (e.g., by use of a microchip) to help clarify their status.96 CHLAMYDOPHILA AND BORDETELLA

Chlamydophila felis (C. psittaci) and Bordetella bronchiseptica vaccines may be of benefit when clinical signs of these diseases are present in the population and diagnosis is confirmed by laboratory evaluation. Their efficacy is moderate, and reactions are more common than with most other feline vaccines; therefore ongoing use should be periodically reassessed.96 Vaccines Not Recommended Some vaccines are not generally recommended for use because of undemonstrated efficacy, such as the feline infectious peritonitis (FIP) vaccine.96

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Parasite Control and Prevention Control and prevention of internal and external parasites represent another important component of a population wellness program. Common products used for their management are described elsewhere in this book. Of particular importance are roundworms and hookworms, common intestinal parasites with zoonotic potential (see Chapter 23). Although uncommon, the risk of human infection from contaminated environments is real and can result in organ damage, blindness, and skin infections. For this reason, the Centers for Disease Control and Prevention and the Companion Animal Parasite Council strongly advise routine administration of broad-spectrum anthelminthics for their control.17,20 Pyrantel pamoate is one of the most costeffective and efficacious drugs for treatment and control of roundworms and hookworms. In both shelter and cattery settings, the author recommends administration of pyrantel pamoate at a dosage of 10 mg/kg to all cats with re-treatment in 2 weeks and then at monthly intervals.41 In shelters, if it is not possible to treat all cats at the time of entry, at a minimum, all cats that are deemed adoptable should be treated as soon as possible. In addition, kittens should be treated at 2-week intervals until 4 months of age. For cats with diarrhea, fecal examination (e.g., flotation or centrifugation, direct fecal smear and cytology) should be performed with treatment according to results. Even if results are negative, the administration of broad-spectrum anthelminthics should be strongly considered. In animal shelters, ectoparasites, particularly ear mites and fleas, are also very common in cats and kittens. Shelter staff should be trained to recognize infestation and protocols should be established for treatment. In terms of shelter treatment protocols, the author recommends treating ear mites with ivermectin, because it is highly efficacious and costs only pennies per dose. The recommended dosage is 0.3 mg/kg subcutaneously. For fleas, the author recommends topical treatment with fipronil (Frontline, Merial, Duluth, Ga.) as a spray or top spot. In particular, the spray is very cost effective. It is safe for use in cats of all ages, including pregnant and nursing mothers and neonatal kittens. In addition, fipronil also has activity against ear mites, Cheyetiella, chewing lice, and ticks.19,100

Spaying and Neutering Spaying and neutering is another important consideration in the context of population wellness.41 Reproductive stress from estrous cycling in queens and sex drive in tomcats can decrease appetite, increase urine spraying/ marking and intermale fighting, and profoundly increase social and emotional stress in the group. For these reasons, spaying and neutering cats that will not be used

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for breeding is recommended. In animal shelters, spaying and neutering cats prior to adoption will ensure that they do not reproduce and contribute to the surplus of community cats. This will also serve to enhance husbandry, because the procedures rapidly decrease spraying, marking, and fighting; eliminate heat behavior and pregnancy; and greatly mitigate stress. In addition to reducing stress and odor, spaying and neutering sexually mature cats will facilitate group housing, which is often beneficial for cats, especially when housed longer term (see below). The medical benefits of spay/neuter have also been well described, including dramatic reductions in the risk of mammary carcinoma, elimination of cystic endometrial hyperplasia, pyometra and ovarian cancer in queens, and decreased risk of prostate disease in toms.55 Thus spaying and neutering favors both individual as well as population health.

Proper Nutrition Proper nutrition has a profound impact on wellness. Not only is it essential for management of healthy body weight and condition, good nutrition is also known to support immune function. A regular diet of palatable commercial food consistent with life stage should be offered, and fresh water must always be available. Although some cats tolerate changes in food without apparent problems, it is important to recognize that for others, changing from one diet to another can cause loss of appetite and/or gastrointestinal upset. For this reason, it is generally best to provide the most consistent diet possible.49 Whereas this may be relatively easy to do in a laboratory or cattery setting, it can be more challenging in a shelter environment. Some pet food companies offer feeding programs for animal shelters, providing a consistent food for purchase at a special rate for shelters. However, some shelters rely heavily on donations of food. In this case, by requesting donation of certain brands of food, shelters are able to provide a consistent diet whenever possible. It is also feasible to mix donated foods with the shelter’s usual diet to minimize problems caused by abrupt diet changes while taking advantage of other donated products. Free Choice versus Meal Feeding The wild ancestors of domestic cats hunted to eat, feeding up to 30 times in a 24-hour period. This style of feeding behavior is preferred by many domestic cats that would nibble throughout the day and night, consuming many small meals if left to their own devices. Although this is true, most cats are capable of adapting to either free choice or meal feeding as their daily feeding pattern.15,49 There are advantages and disadvantages to each in a population setting. With free choice or ad libitum feeding, food is always available such that a cat can eat as much as he or she

wants whenever he or she chooses. Dry food is used for this method of feeding, because canned products left at room temperature are prone to spoiling. The major advantage of free choice feeding is that it is quick and easy: Caregivers simply need to ensure that fresh dry food is always available. Major disadvantages include the fact that cats that are not eating may remain unrecognized for several days, especially when more than one animal is fed together, and some cats may choose to continually overeat and become obese. Free choice feeding is an excellent method for cats that require frequent food consumption. These include kittens up to 5 to 6 months of age, queens in late gestation, and those that are nursing. Unlike dogs, who are competitive eaters by nature, free choice feeding may benefit cats that are group housed, because it ensures that there will be ample time for all members to eat, provided that dominant members of the colony do not block the access of subordinate cats.49 Meal feeding using controlled portions of dry and/or canned food may be done as an alternative to or in conjunction with free choice feeding. When used alone, a minimum of two meals should be fed per day.49 Meal feeding is ideal for any cat that requires controlled food intake and facilitates monitoring of appetite. Meal feeding also has the benefit of enhancing caregiver–cat bonding and provides a pleasant and predictable experience for cats when done on a regular daily schedule. Using a combination of free choice plus once daily meal feeding takes advantage of the positive aspects of both methods and works well for most cats in a population setting. Typically, dry food is available free choice, and a small meal of canned food is offered once daily. This combination approach accommodates the normal feeding behavior of cats by allowing them to eat several smaller meals throughout the day while allowing caregivers to monitor the cat’s appetite at least for the canned food meal. As necessary for the individual cat, some may be fed additional meals of canned food to ensure adequate nutritional support. Monitoring Good body weight and condition and a healthy hair coat are evidence of an adequate nutritional plane and proper nutritional management. Both appetite and stool quality should be monitored daily. Normal stools should be well-formed and medium to dark brown. Adult cats typically defecate once daily, although healthy adults may defecate anywhere between twice a day and twice a week. Kittens tend to produce a larger volume of stool more frequently, which is often lighter in color and softer in form than that of adults. Simple scales can be used for monitoring appetite (e.g., good, some, none), and fecal scoring charts are available. The author recommends the Purina Fecal Scoring System chart available from Nestlé Purina PetCare Company (Figure 46-7).


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Fecal Scoring System

Score 1 - Very hard and dry; requires much effort to expel from body; no residue left on ground when picked up. Often expelled as individual pellets.

Score 4 - Very moist (soggy); distinct log shape visible; leaves residue and loses form when picked up.

Score 2 - Firm, but not hard; should be pliable; segmented appearance; little or no residue left on ground when picked up.

Score 5 - Very moist but has distinct shape; present in piles rather than as distinct logs; leaves residue and loses form when picked up.

Score 3 - Log-like; little or no segmentation visible; moist surface; leaves residue, but holds form when picked up.

Score 6 - Has texture, but no defined shape; occurs as piles or as spots; leaves residue when picked up.

Score 7 - Watery, no texture, flat; occurs as puddles.

Trademarks owned by Société des Produits Nestlé S.A., Vevey, Switzerland

FIGURE 46-7 Fecal scoring system. (Courtesy Nestlé Purina.)

In addition to appetite and stool quality, it is essential to monitor body weight and condition. Body condition can be subjectively assessed by a process called body condition scoring, which involves assessing fat stores and, to a lesser extent, muscle mass. Fat cover is evaluated over the ribs, down the top line, tail base, and along the ventral abdomen and inguinal (groin) areas. Body condition score charts have been established on scales of 1 to 5 and 1 to 9. The author recommends use of the Purina body condition score chart which is based on a scale of 1 to 9 with 1 being emaciated and 9 being severely obese (see Figure 3-3). Cats should be weighed and their body condition scored at routine intervals. Ideally, body weight should be recorded at entry to the population and then weekly during the initial month of care, after which it could be recorded once a month or more often as indicated based on the individual’s condition. This is especially important for cats, because significant or even dramatic weight loss may be associated with stress or illness during the first few weeks of confinement in a new setting. On the other hand, in long-term–housed cats, excessive weight gain may occur in some individuals. Therefore protocols must be in place to identify and manage unhealthy

trends in body weight, because both weight loss and gain can compromise health and well-being.

Grooming Appropriate grooming is also essential to ensure wellness and must never be considered as optional or purely cosmetic. Most cats require minimal grooming because of their fastidious nature. However, long-haired cats are notable exceptions, often experiencing matting of the hair coat without regular grooming sessions. Matted hair coats are not only uncomfortable for the animal, but may lead to skin infection. Overgrown nails can also be a problem for some cats, particularly those that are geriatric or polydactyl. The provision of appropriate surfaces for scratching will encourage cats to condition their own claws; and a system for regular inspection of the hair coat and nails should be established. In addition to ensuring proper coat and nail maintenance, regular grooming sessions provide an excellent opportunity to monitor body condition; and some cats enjoy the physical contact and attention. In high-risk settings, the use of stainless steel combs or undercoat rakes that can be readily disinfected are generally preferable to the use of

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bristle brushes because the latter are impossible to disinfect and have the potential to spread common skin infections such as ringworm.

Periodontal Disease Prevention Dental health is another component of wellness. In the context of population wellness, it may not be the highest priority; however, it should always be a consideration in terms of individual health care and well-being. This is important because periodontal disease will occur unless it is actively prevented, and plaque and tartar buildup may contribute to serious health concerns, ranging from oral pain to chronic intermittent bacteremia and organ failure. Feline tooth resorption and gingivostomatitis are also common conditions of the feline oral cavity that can lead to chronic pain, affecting the cat’s appetite and ability to self-groom, and negatively impacting quality of life. When painful dental disease is present, a plan for timely treatment should be identified and implemented. Preventive dental care may include tooth brushing, dental-friendly diets, and treats and chew toys in combination with periodic professional dental care.33 These should be tailored to meet the needs of individuals in the population to optimize dental health. Cats with stomatitis should be removed from breeding programs.72

Breed-Specific Care Wellness protocols may also be dictated by the specific needs of certain breeds of cats. For example, Persian, Himalayan, and other brachycephalic cats are predisposed to respiratory disease and tend to be more severely affected than other cats because of their poor airway conformation. Because of the high likelihood of exposure in a shelter setting, these cats should be housed in highly biosecure areas that are well ventilated and should be prioritized for immediate adoption or transfer to foster care or rescue.41 In the author’s experience, even intranasal vaccination of these breeds can result in severe clinical signs of respiratory disease and is best avoided.

DEVELOPING A POPULATION WELLNESS PROGRAM: CONSIDERATIONS FOR BEHAVIORAL HEALTH Just as a physical wellness program must be tailored to the population in question, a behavioral wellness program, composed of all of the essential elements, should be created to meet its specific needs as well. Even when animals will only be housed for short periods, considerations for behavioral care are essential to ensure humane care. Short-term confinement can induce severe stress and anxiety, and when confined long term, cats

may suffer from social isolation, inadequate mental stimulation, and lack of exercise. A behavioral wellness program should strive to decrease stress from the moment cats arrive at a facility until the moment that their stay ends. As previously described, a thorough behavioral history will provide an important baseline for action and follow-up.

Behavioral Care at Intake Understanding the importance of minimizing stress in cats and possessing the ability to recognize and respond to it are essential to facilitate a cat’s transition into a population.42,46 Staff should be trained to evaluate cats beginning at intake and to recognize and respond to indicators of stress. Active daily monitoring of cats for signs of stress or adjustment should be performed, and staff should record their findings daily, noting trends and making adjustments in the care of individual cats and the population as indicated. In animal shelter environments, proper behavioral care of cats also requires an understanding of the wide spectrum of feline lifestyles and an approach tailored to the individual needs of each group. Domestic cat lifestyles and levels of tractability range from the most docile, sociable housecat, to free-roaming strays and truly unsocialized feral cats that will not allow handling. Stray cats include those that may have been previously owned or are “loosely owned” neighborhood or barn cats.79 Because of their lack of socialization, capture, handling, and confinement are especially stressful for feral cats. However, fearful cats may resort to overt aggressive or may “teeter on the edge” of defensive aggression regardless of their socialization status. In fact, even the tamest house cats may exhibit the same behaviors as feral cats when they are highly stressed (Figure 46-8).29,42 These responses can compromise cat welfare and staff safety and hinder adaptation to a new environment. Regardless of their demeanor, all cats and kittens should be provided with a hiding box in their enclosure at the time of entry, because the ability to hide has been shown to substantially reduce feline stress.14 For those cats that are severely stressed or reactive, covering the cage front, in addition to providing a hiding box, and posting signage to allow the cat “chill out” time for several hours or even a few days can facilitate adaptation.42 This is important because, once highly stressed or provoked, cats often remain reactive for a prolonged time and may become more reactive if they are stimulated again before they have been allowed a period of time to calm down.9 Soft bedding should be available for comfort and so that cats may establish a familiar scent, which aides in acclimation to a new environment. Care should be taken during cleaning procedures to minimize stress and noise,


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FIGURE 46-8 The behavioral responses of pampered house cats and

FIGURE 46-9 A commercially available feral cat den (ACES,

feral cats may be indistinguishable at the time of intake to an animal shelter. Two cats exhibit signs of severe stress and fear—crouched and withdrawn in the back of a cage with dilated pupils, feigning sleep. Note the presence of the second cat hiding behind the first. The provision of an appropriate hiding box could greatly aid stress reduction for these cats.

Boulder, Colo.) serves as a secure hiding place for a cat. The circular door can be closed from a safe and nonthreatening distance while the cage is spot cleaned as needed. The cat can also be securely transported in the den.

and cats should be allowed to hide while their cage is quietly tidied and replenished around them as needed. Commercially available “cat dens” are ideal for this purpose, because they can be secured from a safe distance such that the cat is closed inside a secure, familiar hiding place during cleaning procedures (Figure 46-9). Cats should be returned to the same cage and only spot cleaning should be performed to preserve their scent, which is necessary for stress reduction. If it becomes necessary to house the cat in another location, the den and towel should accompany the cat to ease the transition. Finally, the use of commercially available synthetic analogues of naturally occurring feline facial pheromones (Feliway, Veterinary Product laboratories, Phoenix, Ariz.) have been shown to be useful for stress reduction in cats during acclimation to new environments and can be sprayed onto bedding and allowed to dry prior to use or dispersed in the room using plug-in diffusers.48 The way in which cats are handled at intake has a profound impact on their behavior, health, and wellbeing and will impact the cat’s ability to adapt to its new environment. When stress is successfully mitigated, cats are more likely to adapt and to “show their true colors” rather than reacting defensively. During a period of a few days, many cats that did not appear to be “friendly” at intake will become tractable and responsive to their human caregivers, facilitating care.42 Behavioral Evaluation Aside from informally “getting to know” cats during their initial acclimation period in a facility, a systematic

behavioral evaluation may be useful, especially for cats that will be re-homed. Several evaluations have been recommended, but none are scientifically validated for predicting future behavior with certainty.3,103,107 Nonetheless, this form of evaluation may be useful for determining behavioral needs while cats remain in a facility, as well as guiding appropriate placement. Box 46-6 describes common components of a feline behavioral evaluation (Figure 46-10).

Proper Housing Housing design and operation can literally make or break the health of a population.45 Regardless of the species in question, housing should always include a comfortable resting area and allow animals to engage in species-typical behaviors while ensuring freedom from fear and distress.54 It is not sufficient for the design to address only an animal’s physical needs (e.g., shelter, warmth). It must meet their behavioral needs as well, and both the structural and social environment are essential considerations for housing arrangements. Furthermore, the environment must provide opportunities for both physical and mental stimulation, which become increasingly important as length of stay increases.54 A sense of control over conditions is well recognized as one of the most critical needs for behavioral health.77 Thus housing design must provide cats with a variety of satisfying behavioral options. Specifically, housing arrangements must take into account the following feline behavioral needs46: • Opportunities for social interactions with humans and/or other compatible cats

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BOX 46-6 Typical Components of a Formal Behavioral Evaluation for Cats3,103,107 Responses are observed and recorded for each of the following:

Cage Side Evaluation • The tester approaches cage, stands quietly for 20 seconds, then offers verbal encouragement. • If deemed safe to proceed, tester opens the cage door and calmly extends an open hand towards the cat, then attempts to gently touch the cat’s head. • If the caregiver is unsure if this is safe to do, a plastic hand may be used to gauge the cat’s receptiveness to touch (see Figure 46-9). • If the cat allows handling, the cat is gently lifted and carried to a secure, quiet room for further observation.

In-Room Evaluation • The tester sits quietly on a chair and/or the floor; the tester calls and solicits the cat’s attention. • The tester pets the cat on the head. • The tester strokes the cat down the back several times. • The tester picks up the cat and hugs it for 2 seconds. • With the cat standing on the floor, the tester strokes the cat down the back and firmly but gently grasps the base of the tail and lifts the cat off of its hind feet for 1 second. The tester repeats this a second time. • The tester engages the cat in play with an interactive toy.

A

B

• The ability to create different functional areas in the living environments for elimination, resting, and eating • The ability to hide in a secure place • The ability to rest/sleep without being disturbed • The ability to change locations within the environment, including using vertical space for perching • The ability to regulate body temperature by moving to warmer or cooler surfaces in the environment • The ability to scratch (which is necessary for claw health and stretching, as well as visual and scent marking) • The ability to play and exercise at will • The ability to acquire mental stimulation Because these needs will vary depending upon such factors as life stage, personality, and prior socialization and experience, facilities should maintain a variety of housing styles in order to meet the individual needs of different cats in the population (Figure 46-11).46 Feline Social Behavior Managing housing arrangements for a population of cats of varying ages, genders, personality types, social experiences, and stress levels requires knowledge of normal feline social behavior and communication.46 During the past 2 decades, knowledge of feline social structure has evolved from the widespread belief that cats are generally an asocial and solitary species to the realization that they are social creatures.24,25 With the exception of solitary hunting, free-roaming cats perform

C

FIGURE 46-10 In some instances, it is difficult to determine if a cat will accept handling. To prevent injury to staff, a plastic hand (Assess-aHands; Great Dog Productions, Accord, NY) is used to approach this cat. As the hand approaches, the cat appears tense (A) but begins to relax and accepts petting (B and C).


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BOX 46-7 Typical Behavioral Responses of a Cat Caged in a Novel Environment46

FIGURE 46-11 A combination of free-standing runs and condo units are used to house cats awaiting adoption in an animal shelter. The availability of a variety of housing styles facilitates meeting the individual needs of various cats in the population.

most of their activities within stable social groups where cooperative defense, cooperative care of young, and a variety of affiliative behaviors are practiced. Affiliative behaviors are those that facilitate close proximity or contact. Cats within groups commonly practice mutual grooming and allorubbing (e.g., rubbing heads and faces together). This may serve as a greeting or as an exchange of odor for recognition, familiarization, marking, or development of a communal scent. Cats of both genders and all ages may exhibit affiliative behaviors, and bonded housemates often spend a large proportion of their time in close proximity to one another.8 Maternal behavior is the primary social pattern of the female cat, and cooperative nursing and kitten care are common. If allowed, queens form social groups along with their kittens and juvenile offspring.24,25 Tomcats typically reside within one group or roam between a few established groups. Within groups of cats, a social hierarchy or “pecking order” forms.24,90 Once established, this hierarchy helps to support peaceful co-existence of cats within a stable group, minimizing agonistic behaviors between members. Social hierarchy formation occurs within groups of cats that are sexually intact, as well as in those that are neutered. Feline Communication and Behavioral Signs of Stress Knowledge of behavioral signaling is critical for successful management of housing arrangements. Manifestations of both normal and abnormal behavior indicate how successfully an animal is coping with its environment. Common behavioral expressions of feline anxiety may manifest with inhibited or withdrawal behavior, defensive behavior or disruptive behavior.46,90 Inhibited or withdrawal behavior refers to activity depression or

• Fear is typically the initial response, and if threatened by the proximity of unfamiliar caregivers, defensive aggression may be displayed. Alternatively, the cat may freeze or appear catatonic. • If provided with a box for concealment, the cat will hide or otherwise slink against the back of the enclosure, behind the litter box, or disrupt the cage and hide under the paper. • Given time, most cats become more active and engage in greeting behaviors, coming to the front of the cage and pawing or mewing as caregivers approach. • If the cat remains confined with time without adequate periods of exercise, mental stimulation, and social companionship, stress and frustration will manifest with activity depression and withdrawal (lying in the litter box, failure to groom, failure to greet caregivers, and, in some cases, displaying aggression towards caregivers). • Displays of stereotypic behavior (such as pacing) may occur; however, inhibited or withdrawal behaviors are much more common (see Figures 46-12 to 46-15).

the absence of normal behaviors (e.g., grooming, eating, sleeping, eliminating, stretching, greeting people). Defensive behavior may involve characteristic postural and/or vocal responses, and is usually motivated by fear. Disruptive behavior involves destruction of cage contents and creation of a hiding place. Stereotypic behaviors (e.g., repetitive pacing, pawing, and circling) may also develop as a result of stress but generally occur less commonly. As an illustration of these feline behaviors, consider the responses of a typical social domestic cat when caged in a novel environment (Box 46-7 and Figures 46-12 to 46-15). Behavioral signs of stress may be further classified as active communication signals or passive behaviors.46,90 Signals of anxiety, fear, aggression, and submission may be subtle or obvious and include vocalization (growling, hissing), visual cues (facial expression, posturing of the body, ears, and tail), and scent marking (urine, feces, various glands of the skin). Passive signs of stress include the inability to rest/ sleep, feigned sleep, poor appetite, constant hiding, absence of grooming, activity depression (decreased play and exploratory behavior), and social withdrawal. High-density housing exacerbates these signs. Lowsocial-order cats in such an environment may exhibit decreased grooming, poor appetite, and silent estrus.44 Cats that are consistently fearful or anxious may hide,

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A

FIGURE 46-13 A stressed cat exhibits a marked fear response when caged and confronted. Note the frozen stance, dilated pupils, and sideways, flattened ears. If approached more closely, the cat would likely respond with defensive aggression if an escape route were not available. (From Griffin B, Hume KR: Recognition and management of stress in housed cats. In August JR, editor: Consultations in feline internal medicine, vol 5, St Louis, 2006, Elsevier, p 717.)

B FIGURE 46-12 Feline stress commonly manifests with activity depression and social withdrawal. A, A caged cat exhibits signs of acute stress—crouched and withdrawn in the back of a cage with dilated pupils. B, Long-term cage confinement can result in frustration, activity withdrawal, and, in some cases, aggression. This cat lies helplessly in a cage with virtually no other behavioral options. Once friendly to caregivers, it may respond aggressively if handled. (From Griffin B, Hume KR: Recognition and management of stress in housed cats. In August JR, editor: Consultations in feline internal medicine, vol 5, St Louis, 2006, Elsevier, p 717.)

FIGURE 46-14 When caged in a novel environment, a typical

turn their back, huddle, and avert their eyes from the gaze of other cats. Hiding is a normal and important coping behavior; however, when hiding is occurring with increased frequency or in response to stimuli that did not previously cause hiding, it should be recognized as a sign of stress.46,90 In group settings, the complexity of the social structure cannot be overestimated. The internal structure of social groups rarely represents a straightforward linear hierarchy, except in very small groups of less than four to five animals.25 In larger groups of cats, there are usually one or two top-ranking individuals and one or two obvious subordinates, while the remaining cats share the middle space.9,44 Most cats within the group form affiliative or friendly relationships; however, some may fail to form such relationships and remain solitary. Colony members commonly display aggression toward

response for a cat is to disrupt the cage contents and create a hiding place. (From Griffin B, Hume KR: Recognition and management of stress in housed cats. In August JR, editor: Consultations in feline internal medicine, vol 5, St Louis, 2006, Elsevier, p 717.)

unfamiliar or new cats entering the group. Within an established group, however, most social conflicts are not characterized by overt aggression. Instead, the main mode of conflict resolution is avoidance or deference (Figure 46-16).9,46,90 Deference behaviors include looking away, lowering the ears slightly, turning the head away, and leaning backward. Large numbers of cats peacefully co-exist together, using such strategies for avoidance provided ample space and resources are available for all members of the group.10 Signs of social stress within groups of cats may manifest with overt aggression, increased spraying and


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B

A FIGURE 46-15 Hiding is frequently the initial response (A), but after a short period, many cats will solicit the attention of onlookers by pawing at the cage front (B).

A

B

C FIGURE 46-16 The major modes of conflict resolution for cats are deference and avoidance. A, An inquisitive cat (left) approaches a wary cat (right). B, The wary cat exhibits an offensive warning, signaling the approaching cat to stay away. C, Overt combat does not ensue, instead the cat on the left defers by simply sitting down a safe distance away. (From Griffin B, Hume KR: Recognition and management of stress in housed cats. In August JR, editor: Consultations in feline internal medicine, vol 5, St Louis, 2006, Elsevier, p 717.)

marking, or constant hiding.46,90 Lower-ranking cats may spend little time on the floor, remaining isolated on single perches or other locations where they may even eliminate, while higher-ranking cats remain more mobile, controlling access to food, water, and litter resources.44 High-density housing conditions frequently result in such abnormal behaviors and are associated with increases in transmission of infectious diseases and reproductive failure as well.50

Types of Housing Arrangements Cats are commonly housed in three basic arrangements: cage or condo units, multiple runs within a room, or free ranging in a room.45 Cage housing of cats should be avoided unless necessary for short periods for intake observation, legal holding periods in shelters as required by local ordinances, medical treatment or recovery, or to permit sample collection.45 Although space recommendations vary substantially in the literature, common

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FIGURE 46-17 This housing arrangement is inadequate for the

FIGURE 46-18 Traditional cage housing can be enhanced by the

occupant. The small cage does not allow for an appropriately sized litter box, and there is not sufficient space for the cat to rest, move about, or hide.

provision of proper resting perches and hiding places that divide the space into different functional living areas. Placement of a purposemade cardboard box (Hide, Perch and Go Box, British Columbia Society for the Prevention of Cruelty to Animals) improves the quality of the space and the welfare of the cat. This box also folds into a transport carrier.

sense dictates that a determination of necessary housing space should take into account the cat’s length of stay. In the author’s opinion, it is neither appropriate nor humane to house cats in traditional cage housing long term (e.g., more than 1 to 2 weeks). Short-Term Housing The design of short-term housing should include provisions for housing individual animals, litters, families, or bonded housemates for intake evaluation and triage.41 Housing must be easy to clean and sanitize, well ventilated, and safe for animals and caregivers. Short-term housing should provide sufficient space to comfortably stand, stretch, and walk several steps; sit or lay at full body length; and separate elimination, feeding, and resting areas. Litter boxes should be of appropriate size to comfortably accommodate the cats for which they are intended (Figure 46-17). Resting areas should include comfortable surfaces, soft bedding, and a secure hiding place to provide a safe refuge.41 A hiding place is essential, because it reduces stress by allowing cats to “escape,” facilitating adaptation to a new environment. The addition of a sturdy box to a cage will provide a hiding place as well as a perch (Figures 46-18 and 46-19). In addition, cages should be elevated off of the floor by at least 0.5 m (1.5 feet), because this serves to reduce stress as well.73 SIZE OF ENCLOSURES

In most instances, cage or condo style housing is used in most facilities for short-term holding at intake for observation, acclimation, and/or triage. Runs or small rooms are also appropriate for intake housing, and offer cats the obvious benefit of additional space to meet their behavioral needs (Figure 46-20). Regardless of their configuration, enclosures for short-term housing of cats

FIGURE 46-19 A perch and a bed are required for every cat, no matter what the housing arrangement. Portable perch-beds (Kuranda Cat Bed, Glen Burnie, Md.) can accompany the cat from intake cages to long-term housing to ease the transition to a new environment.

should be large enough to allow them to stretch, groom, and move about while maintaining separate functional areas, at least 0.6 m (2 feet) apart, for sleeping, eating, and elimination.41,58,98 Laboratory guidelines in the United States call for a minimum floor area of 0.27 m2 (3 ft2) for cats weighing less than 4 kg and 0.36 m2 (4 ft2) for cats weighing 4 kg or more, with a minimum height 0.6 m (2 ft).54 A resting


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FIGURE 46-20 Single enriched housing in a 4 × 6 ft room for a shy cat during an acclimation period to a new facility. Note the multiple resting areas available and the use of a commercially available feline facial pheromone plug-in diffuser (Feliway, Veterinary Product Laboratories, Phoenix, Ariz.). The screen door facilitates ventilation as well olfactory exchange.

perch is also required. Current guidelines (European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes, ETS123) promulgated by the Council of Europe (http:// www.coe.int) for laboratory cats are similar, but proposed revisions call for substantially more floor space for cats, at 1.5 m2 (16.7 ft2) per adult cat with a height of at least 2 m (6.5 ft).21,22 The revisions, which have not been approved to date, also call for the provision of shelves, a box-style bed, and a vertical scratching surface. Animal shelter facilities in the United States have traditionally been equipped with small perchless cages (e.g., 0.5 to 0.75 m or 1.5 to 2.5 ft long) that are poorly designed for housing cats. The Association of Shelter Veterinarians (http://www.sheltervet.org) recommends a minimum enclosure size of 1 m2 (11 ft2) for adult cats.7 Commercially available cages are typically approximately 0.75 m (2.5 ft) deep (e.g., an arm-length deep so that they can be readily accessed); therefore a cage with a length of 1.2 m (4 ft) is required to provide this approximate square footage, and it will also allow for adequate separation of food, water, and litter (Figure 46-21). Similarly, the Cat Fanciers’ Association (http:// www.cfa.org) recommends a minimum of 0.85 m3 (30 ft3) of space per cat for those weighing 2 kg or more.16 Cubic measurements take into account the use of vertical space in addition to floor space, which is crucial for improving the quality of the environment. For example, a 0.85-m3 (30-ft3) enclosure would measure approximately 0.75 m deep × 1.2 m wide × 1 m high (2.5 ft deep × 4 ft wide × 3 ft high). Larger enclosures also allow for better air circulation, which is an important consideration for control of feline

FIGURE 46-21 Appropriate short-term (e.g., less than 2 weeks) housing for a single cat. Note the large 4-ft long cage, provision of a secure hiding place and perch with bed, separation of litter from resting and feeding areas, and appropriately sized litter box for this large cat.

FIGURE 46-22 A variety of commercially available condo-style housing units are available for cats and serve to separate functional living areas and provide improved opportunities for exercise and exploration. This unit (Tristar Metals, Boyd, Tex.) is constructed of powder-coated stainless steel, which is highly durable and easy to disinfect but less noisy than uncoated stainless steel. Note the elevation from the floor and the grills on both the front and back, which allows flow-through ventilation.

upper respiratory infections. Double-sided enclosures (e.g., cat condos) are ideal for meeting these specifications and have the benefit of easily allowing cats to remain securely in one side of the enclosure while the opposite side is cleaned (Figure 46-22). This helps to minimize stress, prevent exposure to infectious disease,

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A

B FIGURE 46-23 A and B, Conversion of existing cages into condostyle units. A hole is cut through the walls of adjacent cages and a section of polyvinylchloride (PVC) pipe with corresponding rims are used to create a safe portal for passage between the cages.

and preserve staff safety, which are especially crucial for newly arrived cats. Traditional cages can be modified into condo-style enclosures by creating portals to adjoin two or three smaller cages (Figure 46-23). Regardless of the precise specifications of the enclosures, the importance of the overall quality of the living environment cannot be overemphasized. This includes a holistic approach to husbandry, with careful attention to the way in which cats are handled, noise levels, the provision of creature comforts, positive contact with caregivers, and strict avoidance of overcrowding, as well as good sanitation, medical protocols, and careful monitoring to ensure health and welfare. Long-Term Housing For long-term housing (e.g., greater than 2 weeks), consideration should also be given to providing space that

is both mentally and physically stimulating for cats and preferably that which is esthetically pleasing to humans.41 The latter is an important consideration to facilitate adoption in animal shelters. And, even in other types of facilities, it is important to create a pleasant environment not only for the animals, but also for their caregivers. Studies indicate that employee satisfaction improves animal care and staff retention, both of which may positively impact population health and well-being.95 For long-term housing of cats alternatives to traditional cage housing should be afforded.41,45,46 At an absolute minimum, cats that are cage housed must be released each day and allowed an opportunity to exercise and explore in a secure enriched setting. For long-term housing, most cats will benefit from colony-style housing, provided there is sufficient space, easy access to feeding and elimination areas, an adequate number of comfortable hiding, and resting places and careful grouping and monitoring to ensure social compatibility among cats. Not every cat, however, will thrive in a group setting, and certain individuals will require enriched single housing, depending on their unique physical or behavioral needs. These may include cats that bully other cats or are otherwise incompatible and those with special medical needs. It is important to recognize that such singly housed cats will require more regular contact with their human caregivers and higher levels of mental and physical stimulation in order to maintain behavioral health during long-term confinement. Whenever possible, long-term housing of such individuals should be avoided. When cats are housed in amicable groups, it is easier to maintain proper behavioral welfare in the long term, because many of their social and emotional needs can be met by conspecifics. Group Housing (Colony-Style Housing) Group housing affords cats with opportunities for healthy social contact with others, which, in turn, provides additional mental and physical stimulation. When properly managed, this housing arrangement enhances welfare.* Insufficient space and crowding or poor compatibility matching of cats serves to increase stress and negates the benefits of the colony environment. Group housing should never be used as a means of simply expanding the holding capacity of a facility. In animal shelters, the high turnover rate of cats contributes substantially to feline stress levels, especially in the context of groups of unfamiliar animals. Because it may take days to weeks to acclimate to a group environment, enriched individual housing may be preferable when a brief stay is anticipated. However, the benefits of enriched social group housing become evident when stays extend beyond a few weeks.41

*References 28, 45, 46, 57, 59, 70, 71, 74, 90, 98, 99.


SELECTION CRITERIA

Careful attention to groupings of cats is essential for success. Family groups and previously bonded housemates are natural choices for co-housing,11,46 but unfamiliar cats may also be grouped using careful selection criteria. Many cats do have preferences for housemates, necessitating conscientious compatibility matching combined with the provision of a high-quality environment. Groupings of unfamiliar cats should always be given priority for the largest available enclosures. In addition, cats should always receive appropriate health clearances prior to admission to a group. These should be determined by the specific protocols of the facility; but in most cases, minimum requirements would include that cats be free of signs of contagious disease, tested for FeLV and FIV, vaccinated against FVRCP, and treated for parasites. In addition to prior relationships, selection criteria for groupings should include age, reproductive status, and personality. AGE Age is an important consideration regarding housing arrangements.46 To ensure proper social and emotional development, kittens should be housed with their mother at least until they are weaned. Because it can be behaviorally beneficial, it is desirable for them to remain with her for a longer period of time when this is feasible. In fact, queens frequently do not fully wean their kittens until 12 to 14 weeks of age if left to their own devices. If older kittens are housed with their mother, it is important to provide a perch that allows her the option of periodically resting away from them if desired. Most queens will accept the kittens of another cat; therefore young orphan or singleton kittens should be housed with other lactating queens and/or kittens of similar age/size. In a shelter setting where there is a high turnover of cats, it may be beneficial to house young kittens up to 4 to 5 months of age in large cages or condos for biosecurity purposes. Juveniles and adults can be housed in colony rooms or runs but should be segregated by age (e.g., juveniles 5 to 12 months old, young adults, mature adults, geriatrics). Well-socialized juveniles tend to adapt quickly in a group setting with other cats of similar ages and exhibit healthy activity and play behavior. In contrast, mature adults and geriatric cats often have little tolerance for the high energy and playful antics of many younger cats, which can cause them substantial stress. For this reason, adult cats should be kept separate from juvenile cats, and aging or geriatric cats separate from other age groups. In animal shelters, compatible cats that enter the shelter together should be housed together regardless of age, whenever possible. REPRODUCTIVE STATUS Unless cats will be used for breeding, group housing of sexually intact cats of

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breeding age should be avoided whenever possible. At a minimum, mature tomcats should be neutered to prevent intermale aggression, urine spraying, and breeding.41 Reproductively intact females may be co-housed with other intact females or with neutered males. In contrast, in breeding colonies, harem-style housing may be used to facilitate breeding (e.g., a few queens with a tomcat). It is also advantageous to house compatible pregnant queens together before delivery, because they will usually share nursing and neonatal care (Figure 46-24).45 After delivery, pairing of queens becomes more difficult. When tomcats are not breeding, they can usually be co-housed with a spayed female, a neutered male, or a compatible juvenile for companionship. Other recommended groupings in the context of a breeding colony include postweaning family groups, prepubertal juveniles, or compatible single-sex adults. PERSONALITY TYPE There are two basic feline personality types: cats that are outgoing, confident, and sociable and those that are relatively timid and shy.105 Cats with bold, friendly temperaments tend to cope and adapt more readily than shy, timid cats. A subset of the bold, friendly personality type is the “assertive” or “bully” cat.90 Bully cats constantly threaten other cats in a group setting in order to control access to food, litter, perches, or the attention of human caregivers. To maintain harmony, removing cats of this personality type from a colony is usually necessary. Reassignment is possible, but may prove difficult, necessitating single housing. Shy, timid cats sometimes have difficulty interacting successfully with more dominant members of a group or may fall victim to a bully, resulting in chronic stress and increased hiding. Placement of shy cats in smaller groups or with calm juvenile cats, where they will not be intimidated or harassed, is generally rewarding and often helps them to “come out of their shells.”46,90 Similarly, dominant cats will often accept calm, younger cats, as opposed to other adults by whom they may feel threatened. And finally, in the case of some dominant males, the introduction of a female cat will be more likely to be successful.46,64,90 GROUP SIZE AND SPACE

The precise space requirements for long-term housing of cats will vary, because it is dependent on many factors (Box 46-8).46,59 Of paramount importance is that group size must be small enough to prevent negative interactions among cats and to permit daily monitoring of individuals. Cats typically prevent social conflict through avoidance, and adequate space must be available so that cats can maintain social distance as needed. Crowding can make it impossible for animals to maintain healthy behavioral distance, creating situations where individuals may not be able to freely access feeding, resting, or elimination space because of social conflicts over colony

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BOX 46-8 Factors Influencing Spatial Needs of Housed Cats46,59 • Length of stay • Overall quality of the environment, including use of vertical space • Overall quality of behavioral care • Physical and behavioral characteristics of the cat (e.g., age, personality type, prior experience, and socialization) • Individual relationships between cats (e.g., family groupings, previously bonded housemates, versus unfamiliar groupings and degree of social compatibility among cats) • Turnover of cats (e.g., frequency of introduction of new members) • Total room size • Absolute number of cats • Individual needs and levels of enrichment being used to meet these needs

A

B FIGURE 46-24 In breeding colonies, compatible pregnant queens may be housed together prior to delivery. A, Two queens share the care of their litters of kittens. B, Perches should be provided so that mother cats can periodically seek respite if they choose. (From Griffin B, Hume KR: Recognition and management of stress in housed cats. In August JR, editor: Consultations in feline internal medicine, vol 5, St Louis, 2006, Elsevier, p 717.)

resources. Both crowding and constant introduction of new cats induce stress and must be avoided to ensure proper welfare. The addition of new cats always results in a period of stress for the group, and if there is constant turnover within the group, cats may remain stressed indefinitely. High turnover also increases the risk of infectious disease. If cat group numbers are small, disease exposure will be limited, facilitating control. For

all of these reasons, housing cats in small groups is preferred.41,45,46 In most instances, the author recommends housing cats in compatible pairs or small groups of not more than three to four individuals. Housing cats in runs is ideal for this purpose (Figure 46-25). A well-equipped, 1.2- × 1.8-m (4- × 6-ft) run can comfortably house two to three adult cats depending on their familiarity and compatibility, or up to four juveniles (e.g., 6 to 12 months old). Juveniles tend to accept a slightly higher housing density than adults. Likewise, previously bonded housemates and families will generally peacefully co-exist at a higher density than will unfamiliar cats. When runs are used, they must have a top panel and should be at least 1.8 m (6 ft) high to allow caregivers easy access for cleaning and care. If chain-link is used, 2.5-cm (1-inch) mesh is ideal, but larger mesh can be used. Existing dog kennel runs can be converted into areas for cat housing. This is an important and practical consideration in animal shelters, because many shelters have experienced a decrease in dog intake, while the need for improved cat housing is great. Cats and dogs should never be co-housed in the same area; thus conversion should result in an exclusive cat housing area. For colony rooms, the author recommends a minimum enclosure size of approximately 3 to 3.5 m × 5 to 5.5 m (10 to 12 ft × 16 to 18 ft) for colonies of up to a maximum of eight adult cats, or in the case of juveniles, a few more. Doubling the size of an enclosure does not necessarily allow a twofold increase in the number of cats that can be properly housed. Another author recommends 1.7 m2 (18 ft2) per cat as a general guideline for group housing,


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enabling caregivers to better monitor individual appetites and litter box results while allowing cats a period of rest away from one another. Alternatively, individual enclosures may only be used for brief periods for meal feedings of canned food, with dry food available free choice in the colony. This sort of arrangement can also be used to facilitate introduction of new cats to the group and represents a desirable option. If design and biosecurity procedures permit, portable intake enclosures could even be transferred to group rooms to smooth the transition of new cats from intake to long-term housing areas. INTRODUCTION OF NEW CATS

A

B FIGURE 46-25 A, This 4- × 6-ft run has been appropriately outfitted for pair-housing of two adult cats. Note the multiple separate areas for resting, perching, hiding, feeding, eliminating, scratching, and playing. B, Cats enjoy the increased behavioral options provided by run-style housing.

acknowledging that many factors influence the spatial needs of cats, including the overall quality of the environment as well as the relationships of the individual animals.59 In sanctuary and laboratory situations where cats are housed for months to years in stable colonies, larger groupings of cats may be feasible, provided ample space is available.46 Housing arrangements can also be created in which individual enclosures are maintained within a colony room. In this case, cats could be allowed to wander and interact freely in the colony room by day but be confined to their respective enclosures at night,

Tremendous individual variation exists among cats in the context of social relations with other cats. Although introduction of some previously unfamiliar cats will seem effortless and uneventful, introduction of others will result in considerable stress, not only for the new cat but for the entire group as well.46 For this reason, introductions should always be done under supervision, and whenever possible, they should be gradual. To accomplish this, a new cat can be kept in a separate cage within or adjacent to the group enclosure equipped with food, water, litter, and a hiding box. Usually, within a few days, it will be evident by the behaviors of the cats whether or not the new cat can be transferred into the group enclosure without risk of fighting. Wellsocialized kittens and juvenile cats frequently adapt readily to group accommodations, and prolonged introductions may not be necessary unless they are shy or undersocialized. In established groups of cats, the introduction or removal of individuals will require a period of adjustment and may result in signs of social stress for members of the colony. These signs usually subside once a new social hierarchy and territorial limits (usually favored resting places) are established. In some cases, arrangement of incompatible cats, even within visible distance of one another, may create substantial anxiety, necessitating rearrangement (Figure 46-26). In the case of animal shelters, where population interchange is high, it is generally not feasible to maintain consistent groupings of cats. This underscores the absolute necessity of careful selection and compatibility matching, as well as maintaining a variety of housing styles. Even in modestly populated, carefully introduced, environmentally enriched colonies, behavior problems may occur. For this reason, some facilities elect to use an “all in–all out” approach to avoid repeated introductions of new cats into stable groups. In animal shelters, bonded pairs and family groupings of cats frequently enter the shelter together and are usually perfect choices for co-housing.46 Because cats do have strong preferences for new roommates, caregivers must expect to find many that are incompatible as roommates. If only one or two cats are responsible for social destabilization of a group, they can

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FIGURE 46-26 In some instances, arrangement or location of enclo-

FIGURE 46-27 Cats enjoying a sunny window in a colony room at

sures where cats are within visual contact of others may induce stress and anxiety, even though they are not housed in the same enclosure. This caged cat has been isolated from the group, yet remains stressed and threatened by the stares of the on-looking cat.

an animal shelter.

usually be reassigned to another colony, because it is often the social grouping, not the individual, that is the problem. If a cat shows persistent incompatibility with other cats, he or she should be housed singly. Studies indicate that cats that fight at the time of initial introduction are nearly 40 times more likely to continue fighting in the following weeks and months.61 If overt fighting occurs, cats should be permanently separated. Cohousing of incompatible cats or cats that fight is unacceptable. COLONY LIVING ENVIRONMENT

The success of group housing depends not only on selection of compatible cats and the size of the enclosure but also on the quality of the environment.* A variety of elevated resting perches and hiding boxes should be provided to increase the size and complexity of the enclosure and to separate it into different functional areas, allowing a variety of behavioral choices. The physical environment should include opportunities for hiding, playing, scratching, climbing, resting, feeding, and eliminating. Whenever possible, a minimum of 1 litter box and 1 food and water bowl should be provided per 2 to 3 cats and arranged in different locations of the colony space, taking care to separate food and water from litter by at least 0.6 m (2 ft). In addition, placement should allow cats to access each resource from more than one side, whenever possible, without blocking access to doorways. Litter boxes should not be covered, to allow easy access and to prevent entrapment or ambush by other cats. The number of resting boards and perches

*References 28, 45, 46, 57, 59, 60, 70, 71, 74, 89, 90, 97-99.

should exceed the number of cats and should be arranged in as many locations within the enclosure as possible. Open single perches should be separated by at least 0.6 m (2 ft) or staggered at different heights to ensure adequate separation, while larger perches should be available for cats who choose to rest together in close proximity. Many cats enjoy hammock-style perches or semienclosed box-style perches where they can hide. If there are not enough comfortable, desirable resting and hiding places, cats may choose to lie in litter boxes. Comfortable bedding (that is either disposable or can be easily laundered) should be provided. Not only do cats demonstrate preferences for resting on soft surfaces, they experience longer periods of normal deep sleep with soft bedding.23 The environmental temperature should be kept comfortable and constant, and living quarters should be well ventilated, without drafts. By changing location within the colony (e.g., from the cooler surface of the floor to a sunny window), cats should be able to choose the environmental condition they prefer (Figure 46-27).46 In colony rooms, installation of stairs, shelves, and walkways are ideal for increasing the use of vertical space (Figure 46-28). In larger rooms, installation of freestanding towers provides additional living and activity space and contributes to functionally reducing overcrowding (Figure 46-29). Depending on the setting, it may not be desirable for cats to access areas above the level of an arm’s reach so that cleaning is easy and cats can be easily retrieved from the highest perches if needed. Colony room design should also ensure that cats cannot easily escape. In some cases, constructing a foyer at the entrance to the room will be necessary to minimize the risk of escape when the room is entered (Figure 46-30). In addition, ceilings should be constructed of solid surfaces, because cats can easily dislodge the


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A

FIGURE 46-29 In larger colony rooms, free-standing towers (Kuranda Cat Tower, Glen Burnie, Md.) can be used to create additional functional space in the interior of the room.

Social Contact with Animal Care Staff

B FIGURE 46-28 A and B, Installation of stairs, shelves, and walkways can be used to create additional function space and is visually appealing, creating an inviting environment for both cats and humans.

panels typically used for dropped ceilings, and escape into the rafters (Figure 46-31).46

Social Companionship In addition to contact with conspecifics, cats must be afforded time for pleasant daily contact with human caregivers. As previously discussed, daily social contact and exercise sessions with humans are especially important for individually caged cats. Although social contact is usually highly desirable, it is not invariably pleasant for all cats. Personality, socialization, previous experience, and familiarity contribute to whether or not social interactions are perceived as pleasurable, stressful, or somewhere in between.46,77

The importance of a cat-savvy staff that enjoys working with cats cannot be overemphasized. Animal care staff must be willing to spend quality time interacting with cats to assure socialization and tractability.45,46 Whenever possible, caregivers should be assigned to care for the same cats on a regular basis so that they become aware of the personality of each individual cat, which is necessary for detection of health problems, incompatibilities between cats, and, in the case of breeding colonies, estrous cycling. This is also important, because not all cats uniformly enjoy human companionship and will be more likely to be stressed by the presence of different caregivers, rather than becoming familiar and more at ease with one. In general, regular daily contact and socialization is essential to ensure that cats are docile, easy to work with, and have no fear of humans. Caregivers should schedule time each day to interact with “their” cats aside from the activities of feeding and cleaning. Some cats may prefer to be petted and handled, while others prefer to interact with caregivers by playing with toys (Figure 46-32). In particular, human contact is essential for proper socialization of young kittens. A sensitive period of socialization occurs during the development of all infant animals, during which social attachments to members of the same species and other species form easily and rapidly. In kittens, the sensitive period of socialization occurs between 2 and 7 weeks of age, and cats not properly socialized to humans during this time may never permit handling.75,105 Beginning shortly after birth, kittens should be handled daily, talked to in a soothing

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FIGURE 46-31 A solid-surface ceiling is essential in free-range

A

housing rooms to prevent the escape of cats into the rafters. Once in the ceiling, cats may be difficult to recover, and injury and/or damage to the facilities may result. (From Griffin B, Hume KR: Recognition and management of stress in housed cats. In August JR, editor: Consultations in feline internal medicine, vol 5, St Louis, 2006, Elsevier, p 717.)

A B FIGURE 46-30 A, For colony room housing, the construction of a chain-link foyer at the entrance to the room prevents cats from escaping when the room door is opened. B, Inexpensive milk crates attached with zip ties create areas for climbing and perching on the chain-link wall. (From Griffin B, Hume KR: Recognition and management of stress in housed cats. In August JR, editor: Consultations in feline internal medicine, vol 5, St Louis, 2006, Elsevier, p 717.)

B FIGURE 46-32 A and B, Daily social contact with humans aside from cleaning and feeding activities is essential for behavioral welfare. Cats may enjoy petting, grooming, or interaction with toys.


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voice, gently petted, and held. Interactions should include play (stimulated with toys) as the kittens become ambulatory. For kittens housed in a shelter, socialization must always be balanced with infectious disease control, and caregivers should take precautions accordingly.

Mental and Physical Stimulation Other forms of stimulation, including those that engage the various senses, are important methods of enriching the living environment by promoting healthy mental and physical activity. For singly housed cats and longterm residents, appropriate levels of additional enrichment should be provided on a daily basis. FIGURE 46-33 Cats surround a water fountain in this example of enrichment.

Visual Stimulation The provision of birdfeeders, gardens, or other interesting stimuli in the external environment can enhance the internal environment of the colony. Resting perches in view of windows or other pleasant areas of the facility are especially desirable. Other novel and enriching visual stimuli include cat-proof aquariums with fish, water fountains, bubbles, perpetual motion devices, and videos especially designed for cats (Figures 46-33 to 46-35).32 Auditory Stimulation A radio playing soft, low music in the room provides a welcome distraction and important source of

A

B FIGURE 46-34 A and B, Enrichment does not have to be complicated or expensive. In this case, a cat enjoys watching soap bubbles blown by a caregiver.

FIGURE 46-35 A shelter cat watches a specially produced feline video (Video Catnip, Pet Avision, Lyndon Center, Vt.). Provision of adequate mental stimulation is essential for behavioral wellness. (From Griffin B, Hume KR: Recognition and management of stress in housed cats. In August JR, editor: Consultations in feline internal medicine, vol 5, St Louis, 2006, Elsevier, p 717.)

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FIGURE 46-36 Disposable, corrugated cardboard cat scratcher.

FIGURE 46-37 Olfactory stimulation is another important source of

Scratching is an essential need of all cats. It conditions the claws and serves as an important means of feline communication through both visual and scent marking.

sensory enrichment. Many cats like to smell and chew grass, and containers of cat grass or catnip can be introduced for brief periods to stimulate activity.

stimulation. In addition, it may help to habituate cats to human voices and prevent them from being startled by loud noises. Most caregivers also enjoy listening to the radio, and happy caregivers create a relaxed environment.45 Tactile Stimulation The provision of scratching boards is especially important, and a variety of sturdy surfaces, both horizontal and vertical, should be provided for scratching. Sisal rope, the backs of carpet squares, and corrugated cardboard are all useful (Figure 46-36). Olfactory Stimulation Many cats like to smell and chew grass, and containers of cat grass or catnip can be introduced for brief periods to stimulate activity (Figure 46-37). Feeding Enrichment Providing novel sources of food is another important source of stimulation and can be easily accomplished by hiding food in commercially available food-puzzle toys or in cardboard boxes or similar items with holes such that the cat has to work to extract pieces of food (Figure 46-38).46,102

FIGURE 46-38 Cats surround a variety of food puzzle toys (a ball,

Positive Reinforcement–Based Training Obedience training using clickers with food rewards is an excellent form of enrichment, combining social contact with caregivers together with both mental and physical stimulation. Positive reinforcement training using a target stick is a powerful tool for teaching shy cats to approach the front of an enclosure. Teaching cats awaiting adoption to perform tricks is not only stimulating for them, but it often makes them more attractive to potential adopters (Figure 46-39).

Play items that stimulate prey drive and physical activity, such as plastic balls, rings, hanging ropes, springmounted toys, plastic wands, and catnip toys, should also be provided but must be either sanitizable or disposable. Empty cardboard boxes and paper bags are inexpensive, disposable, and stimulate exploration and play behavior as well as scratching. Cats tend to be most stimulated by active toys, including wiggling ropes, wands with feathers, kitty fishing poles, and toys that can be slid or rolled to chase.81 Many cats enjoy chasing

a cardboard tube, and a plastic container with holes). Treats are hidden inside, and they will have to work to extract pieces of food. Novel feeding is an excellent source of enrichment for cats that are housed long term.

Physical Stimulation


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A FIGURE 46-40 “High five!” A trained cat offers its paw to a caregiver. Positive reinforcement–based training combines pleasant social interaction, mental stimulation, and physical activity, making it a profoundly rewarding form of enrichment. It may also enhance the cat’s appeal to adopters in a shelter setting.

B FIGURE 46-39 A and B, A juvenile cat watches and captures the toy at the end of the robotic arm. Commercially available electronic toys (Panic Mouse, Temecula, Calif.) may be used to stimulate mental and physical activity. By turning the toy on at the same time each day, cats can anticipate a predictable pleasant experience in their daily routine.

the beams of laser pointers, small flashlights, or suspended rotating disco balls. Commercially available electronic toys that stimulate play are especially useful in long-term settings (Figure 46-40). Varied toys should be substituted regularly to ensure continued interest.46 Outdoor Access In some climates, cats may be housed comfortably in outdoor enclosures where fresh air, sunshine, and other stimuli can help to create a healthy environment (Figures 46-41 and 46-42).46,60,71 When indoor group enclosures connect to outdoor enclosures, it is important to have ample space for passage between them (e.g., more than one doorway) so that cats can pass freely.

Daily Routine Cats will also benefit greatly from consistent daily routines of care. They become entrained to schedules of care

FIGURE 46-41 An open-air cattery with run-style housing may be feasible in some climates. Benefits include fresh air, sunshine, and a potentially enriching environment for residents.

(e.g., feeding, cleaning, enrichment activities), and unpredictable caregiving has been shown to dramatically increase stress.14 If events that are perceived as stressful (such as cleaning time) occur on a predictable schedule, cats learn that a predictable period of calm and comfort will always occur in between. Cats also respond to positive experiences in their daily routines. For example, feeding and playtime may be greatly anticipated; thus scheduling positive daily events (e.g., a treat at 3:00 PM every day) should also be a priority. Erratic periods of light and darkness are also known to be significant sources of stress for cats. Animals possess natural circadian rhythms and irregular or continuous patterns of light or darkness are inherently stressful. Lighting should be maintained on a regular

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FIGURE 46-43 Signs of stress may be inapparent to the casual or

FIGURE 46-42 Purpose-designed cat fencing (Purrfect Fence, Conshohocken, Pa.) can be used to create outdoor enclosures. A mesh arc facing inward along the top of the fence prevents cats from climbing out.

inexperienced observer. In this 4 × 6 ft room, nine adult cats are seen with only a single litter box. Although they may appear to be resting comfortably at a glance, a skilled observer would quickly realize that the majority are sequestered in place, while more dominant members of the colony move about, accessing colony resources and controlling the most desirable resting areas.

schedule, with lights on by day and off by night. Whenever possible, full-spectrum and/or natural lighting is ideal.

Monitoring Housed cats require active daily monitoring by staff trained to recognize signs of stress and social conflict. To the inexperienced observer, such signs may appear subtle (Figure 46-43). It is often the absence of normal behaviors (such as engaging in grooming or exercise) or subtle social signals (such as covert guarding of resources or dominant staring) that signify problems. Careful observers will note these behaviors and respond accordingly to ensure that stress or conflicts do not persist. When cats are well adjusted and housing arrangements meet their behavioral needs, they display a wide variety of normal behaviors, including a good appetite and activity level, sociability, grooming, appropriate play behavior, and restful sleeping (Figure 46-44).44,46 Ultimately, the success of adaptation of cats to a new environment will depend on both the quality of the environment and the adaptive capacity of the individual. Although most adapt to new environments with time, some never adjust and remain stressed indefinitely, ultimately resulting in decline of physical as well as emotional health. When cats fail to adjust to their environment and remain markedly stressed and fearful despite appropriate behavioral care, every effort must be made to prevent long-term stays. Depending on the circumstances, transfer to another colony room, foster care,

FIGURE 46-44 Group-housed cats in a free-ranging room. The fact that the residents are actively engaged in a variety of normal cat behaviors is evidence of a high-quality environment and a harmonious colony.

adoption, or euthanasia (when no other options exist) may be necessary to ensure cat welfare.

DEVELOPING A POPULATION WELLNESS PROGRAM: CONSIDERATIONS FOR ENVIRONMENTAL HEALTH Achieving population wellness requires a healthy environment. Thus the clinician’s final task in creating a population wellness program is to develop tailored


protocols focused on optimizing environmental conditions that favor cat health. Once again, all essential elements as noted should be addressed.

Population Density Perhaps the most critical aspect of environmental management is to ensure a modest population density. High population density increases opportunities for introduction of infectious disease while increasing the contact rate among members of a group. Both the number of asymptomatic carriers of disease, such as those with upper respiratory infection, as well as susceptible cats in a given group are likely to increase, enhancing the odds of disease transmission among group members through both direct contact as well as fomites. In addition, crowding also increases the magnitude of many environmental stressors (e.g., noise levels, air contaminants) and compromises animal husbandry, all of which induce unnecessary stress and further inflate the risk of disease in the population. Indeed, crowding is one of the most potent stressors recognized in housed animals.77 Although adequate space for animals is essential, it is crucial to recognize that crowding is not solely dependent on the amount of available space. It is also a function of the organization’s ability to provide proper care that maintains animal health and well-being. Every organization has a limit to the number of animals for which it can provide proper care. When more animals are housed than can be properly cared for within the organization’s capacity, caregivers become overwhelmed, and animal care is further compromised.7,54,88 In animal shelters, crowding may also negatively impact adoption rates, because potential adopters often find crowded environments to be overwhelming and uninviting. If disease spread results as a consequence of the environmental conditions, animal adoptions may be further disrupted. Although unexpected shelter intake may occasionally result in temporary crowding, a good wellness program dictates that protocols must be in place to alleviate crowding and maintain a modestly populated environment for the health and protection of the animals and staff.41 Regardless of the setting, facilities must limit the number of animals housed to the number for which they can provide proper space and care. There are three basic methods of reducing crowding: (1) limiting the admission (or births) of new animals into a population, (2) increasing release of animals from a population, and (3) euthanasia. In animal shelters, management practices that minimize each animal’s length of stay and programs that speed or increase adoption, owner reunification, or transfer (e.g., to rescue or foster care) help to minimize crowding and maximize the number of animals that an organization can serve. It is a common misperception that housing more animals in

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a shelter will result in saving more lives. To the contrary, euthanasia rates are highly correlated to intake rates, regardless of the number of animals that a facility houses. In many instances, keeping more animals in the shelter may actually reduce the organization’s ability to help animals, because time and resources are tied up caring for a crowded, stressed population, rather than focusing on adoption or other positive outcomes. In shelter medicine, the term population management is used to refer to an active process of planning, ongoing daily evaluation, and responding to changing conditions as an organization cares for multiple animals.7,88 The major goal of population management is to minimize the amount of time any individual animal spends confined in the shelter, while maximizing the organization’s lifesaving capacity. Moving animals through the system efficiently is the foundation of effective population management. To move animals through the shelter more quickly, delays in decision making and the completion of procedures (e.g., intake processing, transfer from holding to adoption areas, spay/neuter surgery) must be eliminated or minimized whenever possible. In openadmission shelters, even delays of 1 to 2 days can have a dramatic effect on the shelter’s daily census, particularly for shelters handling thousands of animals per year. This, in turn, affects the ability to provide adequate care. It is important to recognize that effective population management does not change the final disposition of an animal. It does mean that determinations are made as soon as possible, which serves both the individual animal as well as the population as a whole.

Cleaning and Disinfection For wellness programs to be effective, a clean and sanitary environment must be maintained. Not only does this promote cat and human health, but it also promotes staff pride as well as public support. In addition to protocols for routine daily cleaning and disinfection procedures, protocols should be in place for periodic deep cleaning and disinfection as well as procedures to be used in the event of disease outbreaks. When crafting protocols, it is important to recognize that cleaning and disinfection are two separate processes. The cleaning process involves the removal of gross wastes and organic debris (including nonvisible films) through the use of detergents, degreasers, and physical action. Although this process should result in a visibly clean surface, it does not necessarily remove all of the potentially harmful infectious agents that may be present. Disinfection is the process that will destroy most of these agents, but it cannot be accomplished until surfaces have been adequately cleaned.27 Disinfection is usually accomplished through the application of chemical compounds or disinfectants. The most commonly used of these are reviewed in Box 46-9.

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BOX 46-9 Key Clinical Information Regarding Use of Common Disinfectants27,53,92 Alcohol Hand Sanitizers (70% Ethanol) • Although commonly used, they must be applied to clean hands and allowed 20 seconds of contact time to be effective. • They are highly effective against bacteria, but have only moderate activity against viral agents, including feline calicivirus (FCV). • They should not be used as a substitute for hand washing or the use of gloves.

Biguanides • Chlorhexidine is the most commonly used biguanide and is relatively expensive. Its major use is as a surgical preparation agent. • Although biguanide compounds have broad antibacterial activity, they have limited efficacy against viruses and are ineffective against nonenveloped viruses, such as panleukopenia and FCV. Therefore they are not recommended as general-purpose environmental disinfectants.

Chlorine Compounds • Household bleach (5.25% sodium hypochlorite) is the most commonly used chlorine compound and is an excellent, safe, and highly cost-effective disinfectant when used correctly. • At a dilution of 1 : 32, bleach is highly effective against bacteria and viruses, including nonenveloped viruses, such as panleukopenia and FCV. • Solutions must be made fresh daily and stored in opaque containers, because bleach is highly unstable once mixed with water and degrades in the presence of ultraviolet light. • Surfaces must be thoroughly cleaned with a detergent, rinsed, and dried prior to the application of bleach, because it is ineffective in the presence of detergents and organic material. • Proper disinfection requires 10 minutes of contact time with a bleach solution. • Although bleach is not effective when mixed with detergents, it can be safely and effectively mixed with quaternary ammonium compounds, which do provide some cleaning activity.101 Therefore this combination can be used for cleaning and disinfection, provided gross organic material is first removed and adequate contact time is allowed. The addition of bleach improves the disinfection properties of the solution, making it effective against nonenveloped viruses, including panleukopenia and FCV.101 • Concentrations stronger than a 1 : 32 dilution can result in respiratory irritation for both animals and people, as well as increased facility corrosion, and are therefore not recommended for routine use.

• At a dilution of 1 : 10, bleach will destroy dermatophyte spores. However, cats must be removed from the environment prior to application of this concentration. • The use of calcium hypochlorite (Wysiwash, St. Cloud, Fla.) is becoming more common and offers the potential advantages of reduced contact time and a neutral pH, which prevents corrosion.108

Oxidizing Agents • Potassium peroxymonosulfate (Trifectant; Vétoquinol, Buena, NJ) is a commonly used oxiding agent. A 1% solution is reliably bactericidal and virucidal (including nonenveloped viruses). • Despite label claims, independent studies have demonstrated that potassium peroxymonosulfate does not effectively inactivate dermatophyte spores.83 • Trifectant contains a detergent; therefore it can be used as the primary agent for both cleaning and disinfection. However, periodic use of a degreaser will be necessary to remove ground-in dirt and buildup of organic debris. • Trifectant retains activity in the presence of small amounts of organic material, making it ideal for use on porous surfaces, such as concrete and laminate. Once mixed, the solution is stable for 7 days. A 10-minute contact time is required to ensure complete disinfection.

Quaternary Ammonium Compounds • Numerous products containing quaternary ammonium compounds are available, many of which contain detergents. At appropriate dilutions, as recommended by the manufacturer of a specific product, these compounds have activity against both bacteria and viruses; however, they do not reliably inactivate panleukopenia or FCV, despite label claims to the contrary.31,34,56 • A 10-minute contact time in the absence of organic material is required for proper disinfection. • Although quaternary ammonium compounds may be safely used in cat housing areas, care should be taken to dry surfaces thoroughly before returning cats. Cats that lick quaternary ammonium compounds may develop ulcers of the tongue that can be severe.

Disinfectants Not Recommended Due to Toxicity The use of products containing phenolic compounds (e.g., products such as Lysol [Reckitt Benckiser, Parsippany, NJ]) or pine oils (e.g., products such as Pine-Sol, The Chlorox Company, Oakland, Calif.) should not be used in areas housing cats. Exposure to these compounds can cause serious neurologic effects and liver damage.


Product selection should take into consideration the conditions present in a given environment (e.g., the type of surface and the presence of organic matter) and the compound’s activity against the pathogens for which the animals are at greatest risk. The nonenveloped viruses, panleukopenia and feline calicivirus, are of particular concern. It is important to note that despite product label claims to the contrary, multiple independent studies have consistently shown that quaternary ammonium disinfectants do not reliably inactivate these important feline pathogens.31,34,56 In addition to selecting effective agents, ensuring adequate contact time followed by thorough drying of surfaces is essential for achieving proper disinfection. Protocols should include detailed methods for achieving both cleaning and disinfection. When performed properly and regularly, these practices decrease both the dose and duration of exposure to infectious agents. Box 46-10 outlines essential considerations for the development of cleaning and disinfection protocols.

Segregation of Cats Segregation refers to the separation of animals from the main group or into subpopulations as necessary to promote health. Segregation of cats by physical and behavioral health status is essential for infectious disease control, stress reduction, and safety.41 In animal shelters, segregation may also be required to ensure compliance with animal control procedures as prescribed by state or local ordinances. Depending on the setting, consideration should be given to separating cats by gender and reproductive status (e.g., intact, neutered, in heat, pregnant, nursing), physical and behavioral health status (e.g., apparently healthy, signs of contagious disease, reactive, feral), and life stage. A variety of separate areas will be necessary, depending on the needs of the given population and the context of the setting. The wellness program should define these areas in order to optimize cat health, while providing for the necessary functions of the facility. Depending on the setting, consideration should be given to establishing areas for quarantine, isolation, general holding, adoption, and long-term housing, as well as to tailoring these by life stage.106 For example, the very young and very old typically require more specialized care than healthy juveniles and adults. Kittens less than 4 to 5 months of age are particularly susceptible to infectious disease, and extra care must be taken to heighten biosecurity and limit their exposure. In particular, geriatric cats require comfortable, quiet quarters with careful attention to stress reduction91 (e.g., the provision of a secure hiding place and a dedicated caregiver to enhance bonding and comfort). If cats are used for breeding, functional areas will be required to facilitate mating, queening, and kitten care.45 And, as previously

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discussed, behaviorally fearful, highly reactive cats and feral cats should be separated from others—the stress responses of these cats can create fear in others.42 Quarantine Quarantine involves the holding of healthy-appearing animals. It is most useful when animals enter a closed population to ensure that they are not incubating disease when they are introduced into the general population. Quarantine areas, with rigid biosecurity procedures in place, should be used to segregate healthy animals for observation. The use of such areas not only allows apparently healthy animals to be observed for developing signs of infectious disease, but it also allows time for response to vaccination in a highly biosecure environment where exposure risks are minimized. The use of quarantine is a mainstay of effective infectious disease control programs and is intended to prevent the introduction of disease into a population. It should be used whenever it is feasible to implement effectively, such as in a laboratory setting, a private cattery, or a low-volume, limited-admission sanctuary setting. However, quarantine practices are not effective in most animal shelters, because the high volume and turnover of animals precludes proper implementation of a true quarantine where an “all in–all out” system is used.41 Instead, incoming animals are usually added to the “quarantine group” on a daily basis, effectively defeating the purpose of true quarantine and simply prolonging the animal’s stay. This is especially concerning given the fact that a cat’s length of stay in a shelter is a major risk factor for development of upper respiratory infection.26 For this reason, the use of quarantine is not recommended in most shelter settings. Instead, high biosecurity areas are recommended for housing the most susceptible animals (e.g., kittens less than 4 to 5 months of age). On the other hand, quarantine is warranted when a serious disease is discovered in a shelter population. If healthyappearing animals are exposed during a serious outbreak, quarantine procedures should be used to stop the movement of animals and prevent further spread of disease. If possible, temporary closure to admittance is also recommended. Quarantine may also be required in bite cases to ensure compliance with state rabies laws.41 The particular population setting will guide the clinician’s determination regarding implementation and length of quarantine, if any. A 14-day quarantine is sufficient to determine that cats are not incubating many common infectious diseases, including feline panleukopenia. However, other diseases, including feline leukemia virus and dermatophytosis, can have longer incubation periods and will therefore require a longer quarantine period.63,82 In breeding colonies, early weaning and quarantine have been advocated to prevent infection of kittens with feline coronavirus.1 Pregnant queens are isolated, and

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BOX 46-10 Key Considerations for Cleaning and Disinfection Protocols27,53,92 • Staff must wear personal protective equipment, as necessary, to prevent exposure to chemicals and/or pathogens. • Thorough cleaning and disinfection of enclosures should occur between occupants and as part of periodic deep cleaning procedures. • Cats must be removed from enclosures during these procedures. • “Spot cleaning” is generally sufficient for apparently healthy cats that will continue to occupy the same enclosure. • The cat remains in the enclosure while it is cleaned and soiled material is removed. • This method is often less stressful for cats (see Figure 46-8). • Separate staff should clean and care for animals in areas with highly susceptible or sick animals, whenever possible. • At minimum, attention should be given to the order of cleaning. • The least contaminated areas should be cleaned before those that are the most contaminated. • The most vulnerable animals should be cleaned before the least vulnerable. • Long-term residents that are housed in the same enclosure require less frequent disinfection of their enclosure, but daily cleaning remains essential. • Protocols should always include practices to control fomite transmission. • Dedicated cleaning equipment should be available for each area. • Protective clothing should be worn to prevent cross-contamination. • Hand sanitation should be achieved through a combination of hand washing, hand sanitizers, and the use of gloves. • Protocols should include cleaning and disinfection of all equipment that comes into contact with cats and that cannot be discarded after use. • Scratched and porous surfaces are difficult to impossible to completely disinfect and should be used with caution or discarded (e.g., litter boxes, carriers, or bowls made of plastic).

kittens are weaned as early as possible (e.g., 4 to 5 weeks of age) and placed in strict quarantine. In this manner, as maternal antibody wanes and kittens become susceptible to the virus, exposure and infection are prevented. However, it is important to note that the level of bio security required for success is difficult to achieve.

• Equipment known to be contaminated by virulent or resistant pathogens (e.g., parvoviruses, ringworm) and that cannot be completely disinfected should be discarded. • Protocols should include instructions for cleaning and disinfection of the following: • Transport cages and vehicles • Commonly touched surfaces (e.g., door knobs, cage handles, light switches) • Food and water bowls • Litter scoops • Buckets, squeegees, and other cleaning implements • Vacuuming (with high-efficiency particulate air [HEPA] filtration) should be used whenever possible, to minimize airborne particles and dust. • Mops should always be rinsed to remove organic debris before being returned to a bucket of disinfectant. • Laundry/bedding should be discarded if heavily soiled; otherwise, it should be washed in hot water and thoroughly dried in a commercial washer and dryer. • Periodic deep cleaning should be performed on a regularly scheduled basis (e.g., weekly, monthly, or quarterly, depending on the setting). • Cats must be removed for deep cleaning. • All disposable items in the room should be discarded. • Cages or enclosures should be removed or pulled out from the walls. • Thorough vacuuming should be done to remove all particles, dander, and hair present in the environment. • A degreaser should be used to remove organic buildup. • After a thorough mechanical scrubbing, everything should be rinsed prior to application of a disinfectant. • Adequate contact time with disinfectants must be allowed (e.g., usually 10 minutes). • All air-exchange filters should be changed at the time of deep cleaning. • The area must be thoroughly dried and ventilated before returning cats.

Furthermore, eventual exposure and infection are highly likely because of the ubiquitous nature of coronaviruses.93 In addition, because of the importance of the mother–kitten relationship to normal social and emotional development, this management practice may not always be desirable.


General Holding, Housing, Adoption, and Other Areas In many settings, general holding areas are used for housing healthy juvenile and adult cats at intake. In animal shelters, it is important to consider that length of stay is associated with an increased risk of feline upper respiratory disease and that vaccination against core diseases often rapidly confers immunity. For these reasons, holding periods should be minimized whenever possible. In some cases, holding times will be influenced by legally required holding periods prescribed by state laws that allow owners a chance to reclaim lost pets. Legal holding periods are usually not required for owner-relinquished pets and preweaning-age animals, but a brief medical hold (e.g., 1 to 2 days) for evaluation and triage is usually warranted. Regardless, management practices that reduce length of stay are generally best for population health in a shelter setting. Immunity is often strengthened with time through a combination of both active and passive immunity resulting from vaccination and exposure. Upper respiratory disease is often endemic in cat populations, and in open populations, constant introduction of large numbers of carriers and susceptible cats make exposure likely. As length of stay increases, many cats develop and recover from respiratory disease. As animals acclimate to their environment and gain immunity, less stringent biosecurity requirements may be required for long-term housing areas, depending on the particular setting. In animal shelters, the public is usually allowed to interact with cats in adoption areas, which is another management consideration. Isolation Isolation areas are used to segregate sick animals from the general population. Immediate isolation of animals with signs of infectious disease is critical to effective control. Isolation should be targeted by age and disease. For example, separate isolation areas should be available for cats and kittens with respiratory disease and those with gastrointestinal disease, whenever possible. In populations where upper respiratory infection is problematic, having two isolation areas for cats with respiratory infections is ideal: one area for those cats with moderate to severe signs that will require more intensive monitoring and treatment, and a separate area for those cats with only mild clinical signs and those that have been treated and are nearly recovered.43 When mildly symptomatic cats can be housed separately from those that are very ill, staff compliance with isolation procedures are often improved. Cats with non-infectious conditions should also be housed in separate areas for treatment, and, in some cases, housing in the general population is appropriate.

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Healthy environmental conditions in isolation areas promote recovery, and their importance cannot be overemphasized.43 Crowding, noise, and stress must be avoided, and facilities must be easy to clean and disinfect. Room temperature should be warm and comfortable with good air quality. Windows are ideal, because natural sunlight is always beneficial to animal health and healing. Biosecurity and Traffic Patterns Strict biosecurity in quarantine and isolation areas, with attention to traffic patterns and the use of protective clothing, such as gowns and shoe covers, is essential. Footbaths are insufficient to prevent transfer of infectious agents on shoes. This is because disinfectants typically require 10 minutes of contact time and may be poorly effective in the presence of organic debris. In fact, footbaths may even contribute to the spread of disease. Dedicated boots or shoe covers should be used when entering contaminated areas.84,104 In addition, separate, designated staff should care for animals in high biosecurity areas whenever possible. By design, traffic patterns should move from the healthiest and most susceptible groupings to the least susceptible, and finally to isolation areas housing sick animals. Observation windows and signage are useful to reduce traffic flow into high-risk areas. Staff hygiene is extremely important, and the importance of diligent hand washing cannot be overemphasized. Where space or facilities are not available, foster care may represent a viable and medically sound option for quarantine or isolation in some settings. For instance, in animal shelters, foster care is particularly useful for the care of preweaning-age kittens. Foster homes must be monitored to ensure that cats receive proper care and that resident animals are protected from disease exposure.41

Other Facility Operations In addition to ensuring proper population density, segregation, and sanitation procedures, there are several other essential aspects of facility operations that must be incorporated into a population wellness program. These include heating, ventilation, and air conditioning (HVAC) considerations, noise and pest control, general facility maintenance, and staff training.41 Heating, Ventilation, and Air Conditioning Extremes or fluctuations in temperature and humidity, as well as poor ventilation and air quality, can compromise animal health. Poor ventilation and high humidity favor the accumulation of infectious agents, while dust and fumes may be irritating to the respiratory tract. Many cats are particularly sensitive to drafts and chilling, both of which can predispose to upper respiratory

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infection. Heating, ventilation, and air conditioning (HVAC) specialists are uniquely qualified to help establish and maintain the environmental conditions required for animal health. When facilities are designed specifically for housing animals, these specialists should be consulted beforehand to ensure installation of the most effective and efficient systems possible. In reality, many facilities that house cats, including private catteries and shelters, among others, were not originally built for this purpose. Retrofitting existing facilities with the ideal HVAC system is often neither logistically nor financially feasible. Regardless, consultation with HVAC specialists is recommended in order to maximize the potential of the facility’s existing system. The recommended temperature range for cats is between 18° C and 29° C (64° F and 84° F) with a temperature setting in the low- to mid-20s Celsius (70s Fahrenheit) being typical.54 The temperature setting should be determined according to the specific animals’ needs. For example, neonatal kittens are more susceptible to hypothermia and generally require warmer temperatures than healthy adult cats. The location of the cats may also be a consideration. For example, enclosures located closer to floor level are often a few degrees cooler than those at higher levels. The exact temperature setting may also vary somewhat based on the season of the year. For instance, power companies typically recommend keeping the temperature between 25° C and 26° C (78° F and 79° F) during hot weather to conserve electricity and reduce power bills.41 Laboratory guidelines recommend 30% to 70% humidity for cats.54 Higher humidity (e.g., 70%) may be advantageous in areas housing cats with respiratory disease because moist air may be beneficial to the respiratory passages, whereas lower humidity (e.g., 40% to 50%) may be beneficial in other areas in order to reduce survival of infectious agents in the environment. Although the range considered acceptable is large, a given room should have a relatively constant humidity (i.e., it should not have large fluctuations). Hosing or even mopping a room usually results in temporary spikes in humidity, but these will be short lived in a well-ventilated room.41 Adequate ventilation is crucial for good air quality. This is especially important for cats, because good air quality is essential for control of upper respiratory disease. Ten to fifteen air changes per hour is the standard recommendation for an animal room, but more or less airflow may be acceptable or necessary depending on the housing density.54 Theoretically, the best case scenario, and what is typical in laboratory animal settings, is for the HVAC system to allow for 100% fresh (e.g., nonrecycled) air in each room so that the air entering a given room is exhausted out of the building and not recirculated to another room. Maintaining separate ventilation systems for various rooms or areas of a facility

prevents exchange of air among them and is recommended, because air pressure gradients that recirculate or cause exchange of air between rooms have been associated with the spread of disease by aerosols. When applying these standard recommendations to a particular setting, there are some practical considerations that should be taken into account.41 First, even when ventilation systems provide 10 to 15 room air changes per hour, airflow may be restricted inside of cages or other enclosures within the room. In other words, the body of the room may be well ventilated, yet inside the cages, the air may remain relatively stagnant. In this case, ventilation may be improved by altering the housing design or arrangement; for example, the use of flow-through cages, runs, free-range rooms, or outdoor access may result in improved air quality. When considering the recommendations for 100% fresh, nonrecycled air with separate ventilation systems in various areas of the facility, consideration should be given to the fact that respiratory pathogens in cats are not aerosolized because of the cats’ small tidal volume.36 Although droplet transmission is possible, droplet spray does not extend more than 4 feet, and most transmission of respiratory disease in cats is through direct contact with infected cats, carriers, or fomites.94 Although this recommendation seems prudent to consider, especially for isolation areas, it is very expensive to install and operate this type of ventilation system throughout a facility, especially in very cold or very hot climates. If air quality remains good and the facility maintains effective comprehensive wellness protocols, it may not be necessary for animal health.41 More research is needed on the impact of such air exchange, but in the meantime, the author recommends consulting with an HVAC specialist to establish effective and efficient settings to suit the specific needs of the given population. In addition to ensuring good ventilation, it is imperative to use other strategies for maintaining good air quality, including regular maintenance of filters, control of dust and dander through routine vacuuming and periodic deep cleaning, and the use of dust-free litter.52 Noise and Pest Control Noise control is another important consideration. It is crucial to keep cats out of auditory range of dogs, because many are profoundly stressed by the sounds of barking. Also, staff should be trained to reduce or avoid other sources of noise whenever possible. The installation of sound-proofing systems may be necessary for noise abatement and stress reduction. Routine pest control may also be required, depending on the setting. It may be necessary to treat the environment for fleas, ticks, or other insects or ectoparasites. Products used to treat the environment must be selected carefully, because cats are extremely sensitive to the toxic effects of many insecticides.78 In many instances, it will


be necessary to remove cats during their application and only return them to the environment once it is thoroughly dried and ventilated. If rodent control is necessary, the use of rodenticide baits should be avoided, because cats can be exposed even if the bait is not within their reach. Rodents that have ingested the poisonous bait may enter an animal enclosure and, if the animal ingests the rodent, the poison will affect that animal. Humane live traps can be used to capture rodents for removal from a facility. Food containers should be kept tightly sealed, and clutter should be minimized to discourage pests in the environment. General Facility Maintenance General building maintenance procedures (e.g., regular inspection and servicing with repairs as needed) are also important considerations for the maintenance of a healthy environment. For example, periodic resealing of floors may be required as well as maintenance of plumbing fixtures to repair leaks or other problems. Developing and following written standard operating procedures and daily, weekly, monthly, and quarterly checklists will ensure that systematic schedules of maintenance are carried out in a timely fashion.41 Staff Training Regular staff training is essential for implementing effective population wellness programs. Simply stated, staff caring for animals must be qualified to do so. To a large extent, their knowledge and skill will determine the success or failure of the wellness program. Embracing a culture of training promotes high-quality animal care as well as human safety. Both formal and on-thejob training should be provided to ensure that a staff has the knowledge and skills required to perform their assigned tasks. Protocols should be established for all levels of training, and a system should be in place to ensure proficiency. Staff training should be documented, and continuing education should be provided to maintain and improve skills. Finally, training must include the provision of information about zoonoses and other occupational health and safety considerations.54

CONCLUSION Regardless of the setting, maintaining population health is essential for animal welfare as well as to meet the goals of the particular population. Population health depends on implementation of comprehensive wellness protocols, systematic surveillance, and excellent management. Facilities must establish goals for animal health, and wellness protocols must be regularly evaluated and revised to ensure that these goals are met. The bulk of efforts must focus on preventive strategies to

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ensure both the physical and behavioral health of cats, as well as a healthy environment. A proactive, holistic approach coupled with compassion is required. When these are combined with careful attention to the unique needs and stress responses of cats, the result will be “healthy, happy cats.”

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108. Wysiwash Product Information, St Cloud, Fla. Available at: http://www.wysiwash.com. Accessed June 8, 2010. 109. Wojciechowska JI, Hewson CJ: Quality-of-life assessment in pet dogs, J Am Vet Med Assoc 226:722, 2005.

Index

A AAFCO. See Association of American Feed Control Officials (AAFCO) AAFP. See American Association of Feline Practitioners (AAFP) AAs. See Amino acids (AAs) Abamectin, 882 Abdomen involvement in feline infectious peritonitis, 1041, 1042f physical examination of, 35-36 in senior cat, 1179 Abdominal distention due to ascites, 538-539, 539f, 540t causes of, 540t Abdominal ultrasonography (AUS), 528-529 Abdominocentesis, 541 Abelcet. See Amphotericin B ABK. See Acute bullous keratopathy (ABK) Abrin, 924 Abscess anal sac, 409-410, 410f, 490 orbital, 813 Absolute erythrocytosis, 673 ABVP. See American Board of Veterinary Practitioners (ABVP) Abyssinian cat, 1256-1258, 1256t-1257t disease gene mutations in, 1279 erythrocyte membrane fragility in, 662 pyruvate deficiency in, 661-662 Acanthocyte, 649-650, 649f Accessory cephalic vein for intravenous catheterization, 70 ACE. See Angiotensin-converting enzyme (ACE) inhibitors ACE inhibitors. See Angiotensinconverting enzyme (ACE) inhibitors Acepromazine, 113-114, 113b, 114t for geriatric patients, 139 for hypertension with chronic kidney disease, 1122t in neonatal anesthesia, 1248-1249 for opioid-associated vomiting, 97 for urethral obstruction, 1003 in feline idiopathic cystitis, 992t Acetabular fracture, 708 Acetaminophen metabolism of, 41t oxidative damage to erythrocytes due to, 665 toxicity of, 916t, 928, 931t Acetate tape in skin disease diagnosis, 374-375, 375f Acetazolamide, 738 Acetylcysteine, 916t Acetylsalicylic acid. See Aspirin Acid-base disorders, fluid therapy for, 62 Acid-base status, fluid therapy planning and, 80 Acidemia in urethral obstruction, anesthesia and, 142 Acid-fast staining in Mycobacterium infection, 1076 Acidic food, taste receptors for, 237 Acidic urine, 941 Acidifying crystalloid fluids, 62

Adhesions in symblepharon, 823-824, 824f Adhesive tape in skin disease diagnosis, 375, 375f Adhesive tape muzzle for mandibular fracture, 706 Adiponectin in progression of obesity to diabetes, 1105t Ad libitum feeding, 243 chronic kidney disease and, 973 in population wellness program, 1326 Adnexal disease of eye, 813-817 Adrenalectomy for hyperadrenocorticism, 598-599, 599t, 601 for hyperaldosteronism, 601f, 605 Adrenal gland disorders, 592-610 hyperadrenocorticism as, 592-602 clinical features of, 592-594, 593f-594f, 593t diagnosis of, 594-598, 596t, 598f prognosis for, 602 screening tests for, 594-597 treatment of, 598-602, 599t hyperaldosteronism as, 602-606 hypoadrenocorticism as, 606-609 tumors as catecholamine secreting, 602 hyperadrenocorticism due to, 592, 593f sex hormone secreting, 602 Adrenocortical suppression, etomidate-related, 124 Adrenocorticotropic hormone (ACTH) in hypoadrenocorticism, 606, 608 Adrenocorticotropic hormone (ACTH) response test, 596-597, 596t, 608 Adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas, 611 Adriamycin. See Doxorubicin ADRs. See Adverse drug reactions (ADRs) Adult cat behavior needs of, 163 nutrition in, 244-246, 245t Adult-onset motor neuron disease, 762 Adult-onset (spontaneous) hypothyroidism causes of, 584-585 clinical features of, 585, 586t Advantage. See Imidacloprid Adverse drug reactions (ADRs), 1144-1149 with chemotherapeutic drugs, 774-776 classification of, 1144-1145 diagnosis of, 1146-1147 with glucocorticoids, 1136 incidence of, 1144 with long-term pain management, 1152-1153 management of, 1147-1148 prevention of, 1145-1146 reporting of, 1148, 1148t in senior and geriatric cats, 45 Adverse reaction to food, 251-253, 269-270, 269b to vaccination, 173 Aelurostrongylus abstrusus, 881-882

Acidosis in chronic kidney disease, 969-970 in diabetic ketoacidosis, 87 fluid therapy and, 77, 80 in urethral obstruction, 999 Acne, chin, 398-399, 399f Acquired immunodeficiency syndrome (AIDS), 1057 Acrocentric chromosomes, 1263 Acromegaly, 611-618 causes of, 612 clinical features of, 612-615, 613b, 613f-614f diagnosis of, 615-616, 615b, 616f differential diagnosis for, 616-617 insulin therapy resistance due to, 563t prognosis of, 618 treatment of, 617-618 Acromelanism, 407 ACT. See Activated clotting time (ACT) ACTH. See Adrenocorticotropic hormone (ACTH) Actin-actin depolymerizing F as biomarker in human acute renal failure, 966t Actinic dermatitis, 398 Activated charcoal for toxicosis, 916t, 932 due to cholinesterase inhibitors, 920 Activated clotting time (ACT), 683-684 Activated partial thromboplastin time (aPTT), 683-684 Acupuncture technique for neonatal resuscitation, 1213 Acute bullous keratopathy (ABK), 827, 827f Acute onset diarrhea in unwell cat, 464 in well cat, 462 Acute renal failure (ARF), 957-960, 957f, 958t biomarkers in, 966, 966t fluid and electrolyte loss assessment in, 79t healing phase of, fluid therapy and, 83-84 Acyclovir for ocular herpesvirus infection, 821-822 for upper respiratory tract disease, 855 Additives in fluid therapy, 62-64, 63f, 63t Adenitis, sebaceous, 396 Adenocarcinoma intestinal, 475-476, 475f pancreatic, 517-518, 518f pulmonary, 877, 877f renal, 949 thyroid, 584 Adenoma adrenocorticotropic hormone-secreting pituitary, 611 growth hormone-producing, 612 hepatocellular, 527t pancreatic, 517 Adenomatous intestinal polyps, 476 Adequan. See Polysulfated glycosaminoglycan ADH. See Antidiuretic hormone (ADH)

Pages followed by “f” indicate figures, “t” tables, “b” boxes.

1357

Aesculapian authority, 1160-1161 AF. See Atrial fibrillation (AF) Aflatoxin, 269 African wildcat, 1254-1255 Agar-gel immunodiffusion test (AGID), 1023 Age factors in genetic disease, 1272, 1281 in group housing, 1337 in skin disease, 372 Agenesis eyelid, 813-814, 814f renal, 946 Age of kitten, assessment of, 1231, 1231b Agglutination of erythrocytes, 650 Aggregate reticulocyte, 648, 648f Aggregation, 679 Aggression as behavior problem, 219-224 body postures in communication of, 5-6, 5f directed toward owners, 222-223 early spay and neuter and, 1247 facial signals in communication of, 5f, 6 fear, 220 due to hyperthyroidism, 572t idiopathic, 224 intercat, 220-221, 221f maternal, 221 pain, 223-224 petting, 223 play, 221 predatory, 224 redirected, 222 signs of, 219, 219f territorial, 223 at veterinary visits, 3, 7b AGID. See Agar-gel immunodiffusion test (AGID) Aging, impact of, 1166-1168. See also Senior cat Aglepristone for control of estrus and reproduction, 1200t, 1202 for cystic endometrial hyperplasiapyometra complex, 1222 for mammary hyperplasia, 1203-1204 AGP. See Alpha-1 acid glycoprotein (AGP) AHMS. See Aqueous humor misdirection syndrome (AHMS) AIDS, 1057 Air conditioning for environmental health in population wellness programs, 1351-1352 Air righting, 184 Airway cytology and culture, 868 Airway disease, lower, 866-875 Alanine aminotransferase (ALT) in liver disease, 522-523 neonatal values, 1237t Alaria marcianae fluke, 501 Albendazole, 882 Albinism, genetics of, 1273-1276 Albon. See Sulfadimethoxine Albrus precatorius toxicity, 924

1358

INDEX

Albumin in hypocalcemia, 637t neonatal values, 1237t testing of in liver disease, 522-524 urinary, 942t, 944 Albumin replacement, 67-68, 67b Albumin to globulin ratio n feline infectious peritonitis, 1043-1044, 1043b Albuterol for inflammatory airway disease, 873 Albuterol-salbutamol for bronchial disease, 870-871, 872b Alcohol hand sanitizers, 1348b Aldactone. See Spironolactone Aldara. See Imiquimod Aldosterone antagonists for hypertension with chronic kidney disease, 1122t Aldosterone concentration in hyperaldosteronism, 604-605 Aldosterone-renin ratio in hyperaldosteronism, 605 Alendronate, 727 Alfaxalone, 920b Alfaxan. See Alphaxalone Alfentanil, side effects of, 96 Alinia. See Nitazoxanide Alizin. See Aglepristone Alizine. See Aglepristone Alkaline phosphatase (ALP) in hyperadrenocorticism, 594 in liver disease, 522-523 neonatal values, 1237t Alkaline urine, 941 Alkalinizing crystalloid fluids, 62 Alkylating agents for chemotherapy, 776-778, 777t Allele defined, 1271b-1272b dominant, 1271b-1272b mutant, 1271b-1272b recessive, 1271b-1272b Allelic series, 1273-1276 Allergens human allergies to cats and, 419-424 identification of in asthma and bronchitis, 870 in feline atopic dermatitis, 388-389 in immunotherapy, 390-391 major versus minor, 420 Allergy to blood products transfusion, 67-68, 656 flea bite, 381, 383f dermatitis due to, 385, 385b food, 251-253 human, to cats, 419-424 insect bite, eosinophilic lesion due to, 405 otitis due to, 413 pruritus due to, 385-391 atopic dermatitis, 387-391, 388f-389f, 390t flea allergy dermatitis, 385, 385b food allergy, 386-387 insect bite hypersensitivity, 385-386, 386f Allergy testing in feline atopic dermatitis, 388-389, 389f Alloantibodies anti-A, neonatal isoerythrolysis and, 662 cross-match testing for blood transfusion and, 646-647, 651 Allogrooming, 195 Alopecia, 399-402, 401f-402f assessment during physical examination, 36-37 due to chemotherapy, 775 in dermatophytosis, 392, 392f diagnostic flow chart for, 400f in feline lower urinary tract disease, 982, 982f

Alopecia (Continued) feline paraneoplastic, 795, 795f in hyperthyroidism, 572t due to overgrooming, 214 Alopecia areata, 402 ALP. See Alkaline phosphatase (ALP) Alpha-1 acid glycoprotein (AGP) in feline infectious peritonitis, 1044 Alpha2-adrenergic agonist agents for analgesia, 104-105 for sedation and premedication, 115-116, 116b Alpha1 blocker for hypertension with chronic kidney disease, 1122t Alpha cells, 548t Alpha-lipoic acid, 1172 AlphaTRAK glucometer, 559 Alphaxalone for induction of anesthesia, 118t, 125-126, 125b for total intravenous anesthesia, 132 Alprazolam for behavior-modification therapy, 232t for learning, 9 ALT. See Alanine aminotransferase (ALT) Aluminum, drug compounding and, 46-47 Aluminum carbonate for intestinal phosphate binding, 974 Aluminum hydroxide for intestinal phosphate binding, 974 Aluminum salts, pharmacodynamic monitoring of, 1140t, 1142 Alveolar artery, 335 Alveolar bone expansion, 344, 346, 346f Alveolar macrophages, bronchial lavage, 866t, 868 Alveolar nerve block, 341-342, 342f Alveolar radiographic patterns in lower respiratory tract disease, 862, 863f, 863t Amantadine, 105, 1151t Ambient temperature in population wellness program, 1352 in veterinary hospital, 23-24 Ambiguous genitalia, 1189, 1189f genetics of, 1264 AmBisome. See Amphotericin B American Association of Feline Practitioners (AAFP) on management of FeLV and FIV infections, 1321-1322 American Board of Veterinary Practitioners (ABVP), 20 American curl cat, 1277-1278, 1278f American Society of Anesthesiologists Physical Status Classification System (ASA-PS), 112, 113t, 1167-1168, 1167t American Veterinary Medical Association (AVMA) on declawing, 225 on palliative care, 1159 reporting of adverse reactions to, 269, 269b American wirehair cat, 1276-1277, 1276f Amikacin, 48 Amino acids (AAs) dietary requirements for, 238-239, 244 in parenteral nutrition, 277-278, 277f taste receptors for, 237 Aminoglycosides dosage adjustment in renal insufficiency, 42-43, 42f, 42t nephrotoxic effects of, 959 ototoxic effects of, 415-416 pharmacokinetic monitoring of, 1142, 1143t Aminophylline for anaphylaxis, 699-700, 699t for inflammatory airway disease, 873-874 stability of suspensions of, 47t

Aminophyllin ligands, 1136 Amino-terminal probrain natriuretic peptide (Nt-proBNP), 1110 Amitriptyline for behavior-modification therapy, 232t for feline idiopathic cystitis, 991-992 for pain management, 1151t transdermal administration of, 48 Amlodipine for hypertension, 309, 309t in chronic kidney disease, 970, 1122-1123, 1122t pharmacodynamic monitoring of, 1140, 1140t transdermal administration of, 48 Amlodipine besylate, 605 Ammonia values in liver disease, 524 Ammonium urate uroliths, 998f Amoxicillin for Helicobacter gastritis, 454 for neonatal sepsis, 1244t for nocardiosis, 1080 for small intestinal bacterial overgrowth, 480 for upper respiratory tract disease, 853t Amoxicillin-clavulanate for Campylobacter diarrhea, 478-479 for Clostridium diarrhea, 479 for eosinophilic granuloma complex, 353 for Escherichia coli diarrhea, 479 for neonatal sepsis, 1244t for osteomyelitis, 725 for skin disease, 384t for upper respiratory tract infection, 852-853, 853t Amphotec. See Amphotericin B Amphotericin B, 1024-1025, 1024t for upper respiratory tract disease, 853t, 856 Ampicillin for hepatoencephalopathy, 535t for neonatal sepsis, 1244t Amylase activity, 240 Amyloidosis, 527-528 hepatic, 528 renal, 948-949 ANA. See Antinuclear antibody (ANA) test Anaerobiospirillum sp., 480 Anafen. See Ketoprofen Analgesia/analgesics, 90-111 alpha2-adrenergic agonist agents for, 104-105 for degenerative joint disease, 715 drug dosages for, 97t individual variation in response to, 106 local anesthetic agents for, 102 local anesthetic blocks for, 103-104, 103f mixed, for pain management, 1152 multimodal, 105 n-methyl-d-aspartate receptor antagonists for, 105 nonsteroidal antiinflammatory drugs for, 100-105 in oncologic palliative care, 802-803 opioids for, 96-100 pain recognition and assessment and, 90-94, 91b, 92f-93f postoperative neonatal, 1249 routes and methods of drug administration for, 94-96, 97t “send home” medications for, 105-106 for special populations, 106 Anal glands, palpation of, 36 Anal sac disease, 409-410, 409f-410f, 490-491, 491f Anaphylaxis, 698-700, 699t in adverse drug reactions, 1147-1148

Anaplasmosis, 1025-1027 molecular assays for diagnosis of, 1087 Ancestry, common, 1271b-1272b Ancillary testing, ophthalmic, 811-812, 811f-812f Ancylostoma braziliense, 499-500 Ancylostoma spp., 171 diarrhea due to, 477t prevalence of, 170t Ancylostoma tubaeforme, 499-500 Anemia acute blood loss in, 657 aplastic, 672 due to blood loss or hemolysis, 672 blood transfusion for, 654-656 due to bone marrow disease, 672-673 of chronic renal disease, 670-671, 974-975 concurrent with heart failure, 1114 clinical evaluation of, 651-653, 654f cytauxzoonosis in, 663-664, 664f defined, 656, 668 diagnostic plans in, 656-657, 668 early release of immature erythrocytes due to, 648 due to feline hemoplasmosis, 666-668, 667f due to feline leukemia virus, 671-672, 1051 flea bite, 381 Heinz body, 664-666, 665b due to onion toxicity, 250 history and physical examination in, 656, 668 due to hypophosphatemia, 666 immune-mediated hemolytic, 657-661, 659t of inflammatory disease, 669-670 iron-deficiency anemia versus, 669t inherited erythrocyte abnormalities in, 661-662 iron deficiency, 668-669, 669t neonatal isoerythrolysis in, 662-663 nonregenerative (nonresponsive), 668-673 paraneoplastic, 796 in pure red cell aplasia, 672 regenerative (responsive), 656-668 supportive care in, 653-656 Anesthesia equipment, monitoring and fluid therapy during, 133-136, 133f-135f esophagitis due to, 443-444 for feral cats, 133 hepatic lipidosis and, 142-143 hyperthyroidism and, 139-141, 139b hypertrophic cardiomyopathy and, 143-145, 144b induction agents for, 118-127 alphaxalone as, 125-126 etomidate as, 123-125 inhalant anesthetics as, 126-127 intravenous doses for, 118t ketamine as, 119-121 propofol as, 122-123 telazol as, 121-122 thiopental as, 118-119 intravenous fluid therapy during, 82 intubation and, 127 local and regional in oral and dental disease treatment, 341-342, 341f-342f maintenance of, 127-132 balanced anesthetic techniques for, 129-132 inhalant anesthetics for, 127-129 in neonates, 137-138 for neonatal patients, 137-138, 137b, 1248-1249 risk assessment for, 112, 113b, 113t sedation and premedication for, 112-127 anticholinergics for, 117-118

INDEX Anesthesia (Continued) in neonates, 137 opioids for, 116-117 tranquilizers and sedatives for, 113-118 in senior cats, 138-139, 138b, 1167-1168 total intravenous, 132 for upper respiratory disease diagnostics, 849 urethral obstruction and, 141-142, 141b Anesthetic creams, 102 Anesthetics dissociative, 116-118, 117b inhalant for induction, 126-127, 126f for maintenance, 127-129, 131 local, for pain, 102 steroid, 125-126 Anestrus, 1196 persistent, 1217 primary, 1217 secondary, 1217 vaginal cytology changes in, 1216b Angiotensin-converting enzyme (ACE) inhibitors for cardiorenal syndrome, 1110-1112 for congestive heart failure, 312 dosage adjustments in renal insufficiency, 43 for hypertension, 309 with chronic kidney disease, 1122t, 1124 for hypertrophic cardiomyopathy, 312 Animal factors in nutritional management of disease cancer, 267 cardiovascular, 255-256, 256f chronic renal disease, 278 chylothorax, 268-269 in critical care, 272 dental and oral, 256-257 diabetes mellitus, 264 gastrointestinal, 259 hepatic, 260 herpesvirus, 268 hyperthyroidism, 265-266 idiopathic cystitis, 281 obesity, 261-262, 262b osteoarthritis, 266 skin, 258 urolithiasis, 279-281 Animal hazards, 927-928 Anipryl. See Selegiline Anisocoria due to feline leukemia virus, 1051, 1052f with spastic pupil syndrome, 832, 832f Anisocytosis, 649-650 in hemoplasmosis, 667f Ankylosis, temporomandibular joint, 364-365 Anomalies, 1232-1236, 1233b-1234b, 1233f-1236f breed-specific data regarding, 1230t of female reproductive system, 1204, 1205f infertility due to, 1218 of palate, 356 renal, 946-948 of spinal column, 751-752, 752f Anorectal disease, 490-492, 491f-492f constipation due to, 485, 486t Anorexia fluid and electrolyte loss assessment for, 79t in hyperthyroidism, 572t due to lily toxicosis, 922t linear foreign body under tongue and, 480 paraneoplastic, 799 Anovaginal fistula, 1233f Ant bait toxicity, 924-925

Anterior uveitis, 808-810, 827-828 Anthelmintics, 172t, 499t for neonatal diarrhea, 1242 for roundworms, 498 Anthracycline chemotherapy agents, 777t, 778 Anti-A alloantibodies, 662 Antibiotics. See also specific types for airway disease, 874 for esophagitis and esophageal strictures, 445 for Helicobacter gastritis, 454 for hepatoencephalopathy, 535t indwelling catheterization and, 1002 for neonatal sepsis, 1243, 1244t for neutropenia, 677-678 for osteomyelitis, 725 for pancreatitis, 516 concurrent with inflammatory bowel disease, 1117-1119, 1118t for panleukopenia/parvovirus, 478 for pyothorax, 904 for skin disease, 384t for stomatitis, 349-350 for upper respiratory tract disease, 853t Antibodies maternally derived, response to vaccination and, 173-174 against recombinant human erythropoietin, 670-671 for therapeutic immunomodulation, 1137 Antibody testing feline coronavirus, 1044-1045 feline immunodeficiency virus, 1058 in heartworm, 884-885, 884t revaccination and, 173 Anticholinergics for inflammatory airway disease, 874 for premedication, 117-118, 117b in neonates, 137 in urethral obstruction, 142 Anticholinesterase for myasthenia gravis, 758 Anticoagulant rodenticide toxicity, 915-917, 916t Anticoagulants in bone marrow sampling, 644 in donor blood, 655 Anticonvulsants, 763, 764t for pain management, 1150-1151, 1151t Antidepressants for behavior problems, 232-233, 232b for cognitive dysfunction in senior cat, 1172-1173 for feline hyperesthesia syndrome, 763-764, 764t for feline idiopathic cystitis, 991-992 monitoring of long-term therapy with, 1139t for pain management, 1150 Antidiuretic hormone (ADH) in regulation of water balance, 57 Antiemetics, 431-433, 432t in chronic kidney disease therapy, 973, 973t in hepatic lipidosis therapy, 532-533, 532t in pancreatitis therapy, 516 Antiepileptics, 763, 764t for pain management, 1150-1151, 1151t Antifreeze toxicity, 926-927 Antifungal therapy, 1024-1025, 1024t for dermatophytosis, 393-394, 394f for Malassezia dermatitis, 384 monitoring of long-term therapy with, 1139t for skin disease, 384t for upper respiratory tract disease, 853t Antigens in food hypersensitivity, 251 in systemic anaphylaxis, 698

Antigen testing in feline immunodeficiency virus infection, 1058 in heartworm, 884, 884t SNAP Giardia, 504 Antihistamines for anaphylaxis, 700 for asthma and bronchitis, 874 for immune-mediated adverse drug reactions, 1148 monitoring of long-term therapy with, 1139t for pruritus in atopic cat, 390, 390t for upper respiratory tract disease, 853t Antihypertensive treatment, renal function during, 1123-1124 Antileukotrienes for asthma and bronchitis, 874 Antimetabolite chemotherapy agents, 777t, 778-779 Antimicrobials. See also specific types for diarrhea, 436-438, 437t effects on urine, 938b for infection in immunocompromised cat, 1127-1128 for pyelonephritis, 967-968 for slow-growing mycobacterial infections, 1078t for urinary tract infection, 1005 Antinuclear antibody (ANA) test, 697, 712 Antioxidants for chronic kidney disease, 973 for cognitive dysfunction in senior cat, 1172 Antiparasitics for diarrhea, 436-438, 437t Antiprotozoal drugs, 502t for Giardia infection, 505 Antirobe. See Clindamycin Antisedan. See Atipamezole Antiseptic agents in preparation for venous access, 71 Antispasmodics for urethral obstruction, 1003 in feline idiopathic cystitis, 991, 992t Antithrombin (AT), 680 Antitoxin, tetanus, 764-765 Antitubulin chemotherapy agents, 777t, 779 Antivirals. See also specific types for Chlamydophila felis conjunctivitis, 820-822, 821b monitoring of long-term therapy with, 1139t for upper respiratory tract disease, 853t, 855 Anuria, due to lily toxicosis, 922t Anus, imperforate, 1233f Anxiety behavior problems associated with, 212-213 elimination outside litter box associated with, 218 examination and, 13-14, 14f learning and, 9 misbehavior and aggression at veterinary visits due to, 7 separation, 215-216 Anxiety-related disorders, 213-219 elimination in unacceptable locations, 217-218 excessive vocalization, 216-217 obsessive-compulsive disorder, 213-214 overgrooming, 214 pica, 214-215, 214f separation anxiety, 215-216 urine spraying, 218-219 Anxiolytics for cognitive dysfunction in senior cat, 1172-1173 for excessive vocalization, 216-217 for fear aggression, 220

1359

Anxiolytics (Continued) for intercat aggression, 221 for learning, 9 for overgrooming, 214 for pica, 215 for redirected aggression, 222 for separation anxiety, 216 for urine spraying, 219 Anzemet. See Dolasetron Apathetic hyperthyroidism, 575 APC. See Atrial premature contraction (APC) Apical delta, 331, 335 Aplastic anemia, 672 A31P mutation, 1282 Apnea, propofol-associated, 122-123 Apocrine hidrocystoma, 416, 416f, 816, 817f Apomorphine for toxicosis, 916t transmucosal administration of, 49t Appearance in acromegaly, 612-613, 613f in hyperthyroidism, 574-575 Appendage temperature for monitoring of fluid therapy for hypovolemia, 77 Appetite decreased in hyperthyroidism, 572t in hypothyroidism, 586t in senior cats, 1179-1180, 1179f monitoring of in population wellness program, 1326 Appetite stimulants in chronic kidney disease therapy, 973 in critical care setting, 272-273 monitoring of long-term therapy with, 1139t in palliative care for cancer, 804 for senior cats, 1180, 1180b for treatment of cardiovascular disease, 256 Apresoline. See Hydralazine aPTT. See Activated partial thromboplastin time (aPTT) Aquaporins, 57 Aqueous flare, 808-810 Aqueous humor misdirection syndrome (AHMS), 836-837, 837f ara-C. See Cytosine arabinoside Arachidonic acid, 244 deficiency of, 250t Arachnoid cyst, intracranial, 739 Arava. See Leflunomide Arginine intake in cancer, 267b intake in hepatic disease, 260b nutritional requirements, 238 Arginine vasopressin for diabetes insipidus, 621 Arrhythmias, 319-322, 319f-320f atrioventricular blocks as, 321, 321f auscultation of in physical examination, 34-35 conduction disturbances as, 320-321 in hypertrophic cardiomyopathy, 310 isorhythmic dissociation as, 321, 322f in physical assessment of cardiovascular disease, 302 treatment of, 321-322, 322t Arrhythmogenic right ventricular cardiomyopathy (ARVC), 315-316 Arterial blood pressure chronic kidney disease and, 1120-1121, 1121t for monitoring of fluid therapy for hypovolemia, 75-76 Arterial thromboembolism (ATE), 316-319, 316f-317f clinical signs of, 316-317, 317f recurrence and prevention of, 318-319 treatment of, 317-318

1360

INDEX

Arthridities, 709-716 autoimmune, 711-713, 715-716 degenerative joint disease, 709-710, 709b, 713-715, 715b erosive, 711-712 idiopathic polyarthritis, 712-713, 712b infectious, 710-711 periosteal proliferative polyarthritis, 711, 711b rheumatoid, 711-713, 712b Scottish Fold arthropathy, 713, 713f systemic lupus erythematosusassociated, 712 therapy for, 713-716 Arthrodesis for carpal hyperextension, 717-718, 717f Articular cartilage, degenerative joint disease of, 709-710 Artificial tear formulations for conjunctivitis, 823, 824f ARVC. See Arrhythmogenic right ventricular cardiomyopathy (ARVC) ASA-PS. See American Society of Anesthesiologists Physical Status Classification System (ASA-PS) Ascarids treatment of, 172t zoonotic, 1094, 1094f Ascencia Elite glucometer, 559 Ascites, 526-527, 538-546 causes of, 543-545 clinical evaluation of, 538-541, 539f, 541f due to feline infectious peritonitis, 1040 fluid analysis and classification in, 541-543, 542t due to overhydration, 58 pathophysiology of, 538 Asclepias spp. toxicity, 923-924 Ascorbic acid for acetaminophen toxicity, 916t ASD. See Atrial septal defect (ASD) Asian lily toxicosis, 921-923, 958t Asian wildcat, 1254-1255 Aspergillus spp., 856-857 Aspiration for bone marrow collection, 645-646 fine needle in cancer staging, 769 in high-grade intestinal lymphoma, 474-475 in liver disease, 529-530 in pancreatitis, 515 pulmonary, 865 splenic, 687 hepatic, 529-530 Aspiration pneumonia, 875-876 Aspirin, 101 for arterial thromboembolism prevention, 318 metabolism of, 41t toxicity of, 929, 931t Assays, 1082-1089, 1083f, 1085f bloodborne agents, 1086-1088 feline coronavirus, 1044-1045 gastrointestinal agents, 1086 ocular agents, 1088 respiratory agents, 1084-1086 Assessment tool for pain assessment, 91, 92f Association of American Feed Control Officials (AAFCO), 245-246, 291, 296 Asthma, 866-875 clinical signs of, 867 definition of, 866 diagnosis of, 867-870, 869f-870f epidemiology of, 866 etiopathogenesis of, 866-867 treatment of, 870-875, 872b, 873f AT. See Antithrombin (AT) Atarax. See Hydroxyzine Ataxia in myelopathies, 750 ATE. See Arterial thromboembolism (ATE)

Atenolol for hypertension, 309t with chronic kidney disease, 1122t transdermal administration of, 48 for ventricular tachyarrythmias, 322, 322t Atipamezole for dexmedetomidine reversal, 104 in neonatal anesthesia, 1248-1249 Atopecia. See Cyclosporine Atopic dermatitis, 387-391, 388f-389f, 390t Atopic reactions to pet dander, 420 Atovaquone, 664 Atresia ani, 491 Atrial enlargement in arterial thromboembolism, 316 electrocardiography for detection of, 303-304 Atrial fibrillation (AF), 320 Atrial premature contraction (APC), 319-320 Atrial septal defect (ASD), 323 Atrial standstill, 316, 320 Atrial tachyarrhythmias, 322t Atrioventricular blocks, 321, 321f Atrioventricular valvular malformations, 323 Atrophy, progressive retinal, 841 DNA testing for, 1274t genetics of, 1284 Atropine for anaphylaxis, 699t for cholinesterase inhibitor toxicity, 920 for pain of uveitis, 831 for sedation and premedication, 114t, 117-118 for toxicosis, 916t Auditory stimulation in population wellness program, 1343-1344, 1344f Auriculonasocephalic reflex, 184 AUS. See Abdominal ultrasonography (AUS) Auscultation of heart, 34-35, 35f of lungs, 34, 862 Autoagglutination, 647, 647f, 650 Autoimmune disease arthridities as, 711-713 therapy for, 715-716 systemic lupus erythematosus as, 696-697, 696b Avian influenza, 1034-1036 zoonotic, 1093-1094 AVMA. See American Veterinary Medical Association (AVMA) Avulsion, lip, 358, 358f Azalea toxicity, 923 Azapirones, 232b, 233 Azathioprine, 716 3’Azido-2’3’-dideoxythymidine (AZT), 1053 Azithromycin for chlamydial conjunctivitis, 822 for Cryptospordium felis, 508 for mycobacterial infection, 1078t for protozoal disease, 502t for upper respiratory tract infection, 852-853, 853t Azole antifungals, 1025 Azotemia chronic kidney disease and, 963-966, 964t fluid therapy in, 82-84 hypertrophic cardiomyopathy and, 313-314, 314f with urethral obstruction, 999 AZT. See 3’Azido-2’3’-dideoxythymidine (AZT); Zidovudine (AZT) B Bacteria in food-related illness, 269

Bacteria (Continued) with raw food diets, 290-291, 291t pancreatitis concurrent with inflammatory bowel disease and, 1115-1116 pleural effusion fluid, 899t Bacterial arthritis, 710 Bacterial enteritis, 478-480 Bacterial infection, 1070-1082, 1071t associated with hepatopathy or hepatic inflammation, 534b bartonellosis as, 1070-1073 lower respiratory tract, 879-881, 880f in meningomyelitis, 752-753 metritis as, 1214 mycobacterial, 1073-1080, 1074t, 1078t feline leprosy as, 1077-1079 Mycobacterium avium complex as, 1075-1077, 1075f-1076f Mycobacterium tuberculosis complex as, 1073-1077 rapidly growing, 1079-1080 nasal, 852-854, 853t nocardiosis as, 1080, 1080f paronychia as, 408 pregnancy loss due to, 1223b, 1224 pyelonephritis as, 950-951 pyoderma as, 381-383 urinary tract, 1004-1005 Bacterial zoonotic disease, 1091-1093, 1092f Bacteriuria in urinary tract diagnosis, 936t Bain coaxial system, 133, 133f Bait ant, 924-925 fly, 915 mole and gopher, 918-919 roach, 924-925 slug, 914-915, 915f snail, 914-915, 915f BAL. See Bronchoalveolar lavage (BAL) Balanced anesthesia, 129-132, 129t in hypertrophic cardiomyopathy, 144 Balancing on ledges, 185, 185f Balloon catheter dilation for esophageal strictures, 445-446 BARF diet, 289, 291 Barium contrast radiography for gastric emptying assessment, 456-457 Barium impregnated polyspheres (BIPS), 457 Barrett esophagus, 444 Bartonellosis, 1070-1073 molecular assays for diagnosis of, 1087-1088 of upper respiratory system, molecular testing for, 848 uveitis with, 828-830 zoonotic, 1091-1092, 1092f Base pair, genetic, 1271b-1272b Bathing of cat for reduction of allergens, 422 for toxicity decontamination, 930-931 B cells, 690 Beclomethasone, 853t Bedding in veterinary hospitals, 16, 23, 24f Behavior(s) evaluation of in population wellness program, 1329, 1330b, 1330f of kitten feeding as, 186-187 grooming as, 187-188 learning as, 188 maternal and in utero factors in, 183 play as, 185-186, 185f, 186t social, 186, 186f, 188-189 toileting as, 187, 187f mating, of male cat, 1185-1186 normal biology of cats and, 191 communication as, 193-195 grooming as, 195

Behavior(s) (Continued) hunting and feeding as, 195, 237, 243 learning as, 195 sense organs and, 191-193 social organization and density and, 195-196, 196f time budgets and, 196 preventive health care associated with, 156t, 160-164 for adult and mature cat, 163 environmental enrichment in, 161-163, 162f for geriatric cat, 164 indoor versus outdoor lifestyle and, 161, 161f internet resources for, 177t for juniors, 163 for kittens, 163, 163f for senior cat, 164 self-maintenance, 209 Behavioral care in population wellness program, 1328-1346 daily routine in, 1345-1346 at intake, 1328-1329, 1329f-1330f, 1330b mental and physical stimulation in, 1343-1345, 1343f-1345f monitoring in, 1346, 1346f proper housing in, 1329-1341 feline communication and signs of stress and, 1331-1333, 1331b, 1332f-1333f feline social behavior and, 1330-1331 group, 1336-1341, 1338b, 1338f-1342f long-term, 1336 short-term, 1334-1336, 1334f-1336f types of arrangements in, 1333-1334 Behavioral changes in clinical history for vomiting cats, 428t due to hyperthyroidism, 574-575 in senior cat, 1169-1170 Behavioral development in kitten, 182-190 after birth, 183-184 influence of parental factors on, 182-183 sensitive periods in, 184-185 Behavioral history, 29, 206-210 basic patient information in, 208-209 counseling skills in, 206-207 empathy in, 206 formulation of treatment plan and, 210 interview questions for, 28b organization of consultation for, 207-208 “problem behavior” in, 210 questionnaire for, 208b of self-maintenance behaviors, 209 for senior cat, 1171b social environment in, 209 Behavioral pain indicator, 91, 92f Behavioral questionnaire, 207, 208b Behavioral stress response in feline idiopathic cystitis, 986 Behavioral therapeutics, 226-234 behavior modification as, 226-227 environmental management as, 227-230, 227f of hunting and foraging behavior, 228-229, 229f novelty in, 230 resting places in, 229, 229f scratching and, 229 social interaction in, 230 viewing places in, 230 psychotropic medication as, 230-233, 232b, 232t Behavior modification, 226-227 drugs used for, 232t

INDEX Behavior problems, 211-225 aggression as, 219-224 directed toward owners, 222-223 fear, 220 idiopathic, 224 intercat, 220-221, 221f maternal, 221 pain, 223-224 petting, 223 play, 221 predatory, 224 redirected, 222 signs of, 219, 219f territorial, 223 anxiety as, 212-213 anxiety-related disorders as, 213-219 elimination in unacceptable locations, 217-218 excessive vocalization, 216-217 obsessive-compulsive disorder, 213-214 overgrooming, 214 pica, 214-215, 214f separation anxiety, 215-216 urine spraying, 218-219 environmental enrichment for prevention of, 162, 162f fear as, 212 onychectomy and, 224-225 phobia as, 212 problem behaviors versus, 211 in senior cat, 1170-1173 treatment of (See Behavioral therapeutics) Belly up as play behavior, 185, 186t Benadryl. See Diphenhydramine Benazepril for cardiorenal syndrome, 1112 dosage adjustments in renal insufficiency, 43 for hypertension, 309t Bence Jones protein, 942t Bengal cat, 1258 Benzimidazoles, 172t, 498 Benzodiazepines for behavior problems, 232b, 233 for sedation and premedication, 114-115, 115b Beta blockers for heart rate control in hyperthyroidism, 326 for hypertension with chronic kidney disease, 1122t for hypertrophic cardiomyopathy, 312 with congestive heart failure, 312 for ventricular tachyarrythmias, 322 Beta cells, 548t in normal glucose metabolism, 549f Beta-hydroxybutyrate, elevation of in diabetes mellitus, 548 Betamethasone for immunosuppression, 1135t Beta2-receptor agonists, 873 Bethanechol for bladder management following spinal trauma, 756 for urethral obstruction in feline idiopathic cystitis, 992t Biguanides for disinfection, 1348b Bile acid concentration assessment in liver disease, 524 Bile duct extrahepatic obstruction of, 525 neoplasia of, 527t Bile peritonitis, ascites due to, 545 Biliary cystadenoma, 527-528, 527t, 528f Biliary tree, 523f Bilirubin neonatal values, 1237t testing of in liver disease, 522-524 urinary, 941 Billinghurst, Dr. Ian, 289, 291t Binocular headset for ophthalmic examination, 808-810, 810f

Binocular vision, 192 Biochemistry findings in ascites, 539 in hyperthyroidism, 575-576 in hypoadrenocorticism, 607, 607t in hypothyroidism, 587 in liver disease, 522-523 Biomarkers in diagnosis of heart disease, 306-307 abuses of, 306-307 in congestive heart failure, 311 in human medicine for early detection of acute renal failure, 966, 966t Biopharm. See Pentosan polysulfate Biopsy for bone marrow collection, 645-646 for cancer diagnosis, 769-770 conjunctival, 811-812, 811f in diarrhea, 465 liver, 529-530 lung parenchymal, 865-866 muscle in muscular dystrophies, 759 in polymyositis, 758 in oral and maxillofacial cancer, 366 renal, 945, 945f centers for full assessment of, 945, 952, 952b in glomerulonephritis, 952-953, 952b in urinary tract diagnosis, 936t skin, 376-377, 377f equipment for, 373b in upper respiratory system disease, 849-850 in vomiting, 430 Biosecurity in population wellness programs, 1351 Biotin deficiency, 250t BIPS. See Barium impregnated polyspheres (BIPS) Birman cat, 1256-1258 hypotrichosis in, thymic atrophy and, 678 neutrophil granulation anomaly in, 678 Birth weight, 1231, 1232b Bis-acryl in jaw fracture repair, 360, 361f-362f, 362 Bisecting angle technique in dental radiography, 338-339, 339f Bismuth subsalicylate, 454 Bisphosphonates for hypercalcemia, 634, 634b-635b, 636 Bites cat, 1090-1091 osteomyelitis following, 725 flea dermatitis due to, 385, 385b hypersensitivity, 381, 383f insect hypersensitivity, 385-386, 386f eosinophilic lesion due to, 405 mosquito, hypersensitivity to, 405 snake, 927 spider, 927-928 Bladder. See also Lower urinary tract disease management of following spinal trauma, 756 neoplasia of, 1005-1007 pancreatic, 516-517 rupture of, 1007-1008 Blastomycosis, 1022-1023, 1022f Bleeding time, buccal mucosa, 683 Blind bronchoalveolar lavage technique, 864, 865b, 865f Blindness due to enrofloxacin toxicity, 839-840 due to hyperaldosteronism, 603 Blinking in communication, 6 Blister cell, 649-650 Blocks atrioventricular, 321 local anesthetic

Blocks (Continued) brachial plexus, 103f dental, 103 distal paw, 103-104, 104f intercostal nerve, 104 for pain, 103-104 wound infusion catheters, 104 Blood erythrocytes in, 647-653, 648f blood types and, 650-651, 651t-652t qualitative parameters, 649-650, 649f-650f quantitative parameters, 648-649, 649f hemostasis and, 679 fibrinolysis in, 680 primary, 679 secondary, 679-680 leukocytes in, 675 Bloodborne agents, polymerase chain reaction in detection of, 1086-1088 Blood disorders anemia as blood transfusion for, 654-656 clinical evaluation in, 651-653 nonregenerative, 668-673 regenerative, 656-668 diagnostic techniques for, 643-647 bone marrow collection as, 643-646, 644b cross-match as, 646-647 slide agglutination test as, 647, 647f erythrocytosis as, 673-675, 674f of hemostasis, 679-685 of leukocytes, 675-679 Blood flow through spleen, 685-686 Blood gas analysis during anesthesia, 136 Blood glucose in diabetes mellitus, 548 home monitoring of, 555-557, 559-562 glucometers for, 559 in hyperthyroidism, 576 insulin therapy for control of, 552-562 in stress hyperglycemia, 3 Blood glucose curve, 557, 557f, 558t home monitoring of, 559-560, 560f Blood loss anemia and nonregenerative, 672 regenerative, 657 fluid loss due to, 59t Blood pressure in chronic renal disease diagnosis of, 964-966 International Renal Interest Society (IRIS) classification of, 964, 964b, 966f effects of alpha2 agonists on, 116 in hypertension diagnosis and classification, 307-308, 307t chronic kidney disease and, 970 hypertensive chorioretinopathy and, 838 measuring of, 15, 15f in minimum database, 165t for senior cats, 1169 monitoring during anesthesia, 134-135, 134f in neonate, 138 for monitoring of fluid therapy for hypovolemia, 75-76 normalizing of in cardiorenal syndrome therapy, 1112 Blood products, 66-68 intraoperative administration of, 136 Blood sample collection, 15, 16f Blood testing in ascites, 539 in diarrhea, 463-465 in gastrointestinal disease, 464-465, 464t before prescribing psychotropic medication, 231 in vomiting, 429

1361

Blood transfusion, 66-68 adverse reaction to, 656 for anemia, 654-656 cross-matching testing for, 646-647 for hemostatic disorders, 684 hepatic insufficiency and, 44, 44f neonatal, 1240 Blood types/typing, 650-651, 651t neonatal isoerythrolysis and, 663, 1244 in preventive health care, 167 Blood urea nitrogen (BUN) in cardiorenal syndrome, 1110 in hyperthyroidism, 575-576 as renal function test, 935-936, 936t testing of in liver disease, 522-524 Blood volume, fluid therapy for hypovolemia and status of, 74-75 Blunt trauma, chest wall, 909-910 BMBT. See Buccal mucosa bleeding time (BMBT) Body condition scoring (BCS), 29, 30f in cancer cachexia and anorexia, 799 in nutritional planning, 245t in obesity diagnosis, 261 in population wellness program, 1327 Body fluid balance, 52 perfusion and, 55 sodium balance in, 55-56 steady state and concept of maintenance in, 52-53 terminology of, 58 water balance in, 56-57 Body fluid compartments, 53-55, 53f fluid movement between intracellular and extracellular, 54-55 fluid movement in extracellular, 54, 54b Body fluid losses, 57-58, 59t fluid therapy planning and, 80 Body language, 193-194, 193f Body mass index, 37, 37b, 37f-38f Body postures in communication, 5-6, 5f Body temperature acepromazine’s effects on, 114 monitoring during anesthesia, 134 neonatal, 1212-1213, 1232b anesthesia and, 137 assessment of, 1231 opioids associated with elevation of, 96 Body weight changes in different life stages, 1168t documentation of in medical record, 261 drug dosages and, 46 fluid losses and, 57-58 in medical history, 29 normal, 191 in obesity, 261 Boldenone undecylenate for appetite stimulation, 257t Bolus feeding, 267, 273f Bonazepril, 1122t Bone(s) changes with acromegaly, 614 fluid in, 54 of skull, 332-333, 334f Bone marrow anemia due to disease of, 672-673 collection of, 643-646, 644b, 644f-645f decreased (See Thrombocytopenia) Bone mineralization schedule for prediction of due date, 1206, 1207t Booster vaccination, 173 Bordetella bronchiseptica molecular assays in diagnosis of, 1086 pneumonia due to, 881 in upper respiratory infection, 852-853 vaccination against, 176, 854 in population wellness programs, 1325 recommendations for, 174t Bordetella spp., zoonotic, 1091t Bornavirus, 744, 1061-1062

1362

INDEX

Bottle for feeding of orphan kittens, 1245, 1246f Bougienage for esophageal strictures, 445-446 Bovine lactoferrin for feline herpesvirus-1, 1031 for feline immunodeficiency virus, 1060 for stomatitis, 350 Box trap, 1293f Brachial artery, 704, 705f Brachial plexus block, 103, 103f Brachycephalic cat, 332-333 entropion in, 814-815, 815f nasolacrimal system disease in, 817, 818f upper respiratory difficulties in, 851 Bradyarrythmias, 302, 320, 322 Brain in glucose metabolism, 549 tumors in, 740-742, 741f-742f Breath sounds auscultation in physical examination, 35 Breed factors in congenital defects, 1234 in cryptorchidism, 1189, 1189t in diabetes mellitus, 551 in female puberty, 1195-1196 in genetic testing, 1282-1285 in skin disease, 372 Breeding management in female, 1198-1200, 1199b Breeds of domestic cats, 1255-1259, 1256t-1257t, 1258f blood types and, 652t genetic testing and, 1282-1284 origins and health of, 1259-1261, 1260f Breed-specific reproduction data, 1229t-1230t Brewer’s yeast, 510 Bromethalin toxicity, 917 Broncheoalveolar washing, 863 Bronchial radiographic patterns in lower respiratory tract disease, 862, 863f, 863t airway disease, 867-868, 869f idiopathic pulmonary fibrosis, 875 Bronchitis, 866-875 clinical signs of, 867 definition of, 866 diagnosis of, 867-870, 869f-870f epidemiology of, 866 etiopathogenesis of, 866-867 treatment of, 870-875, 872b, 873f Bronchoalveolar lavage (BAL), 864, 865b, 865f, 866t Bronchodilators for asthma and bronchitis, 872-874 for bronchial disease, 870 emergency treatment of, 870-871 Bronchoscopy, 864 in asthma and bronchitis, 868 Brown recluse spider bite, 928 Brown trait, 1273-1276 DNA testing for, 1274t Brushing for environmental enrichment, 230 Buccal drug formulations/route, 48-49 for analgesia, 94-95 Buccal mucosa bleeding time (BMBT), 683 Budesonide for inflammatory bowel disease, 439 for intestinal small cell lymphoma, 473 for pancreatitis with inflammatory bowel disease, 1118t Buffers in crystalloid solutions, 61t, 80 Bufo toad exposure, 927 Bulk laxatives for constipation, 487t Bulla osteotomy for nasopharyngeal polyps, 851 Bullous keratopathy, 827, 827f BUN. See Blood urea nitrogen (BUN)

Bupivacaine, 102, 341 Buprenex. See Buprenorphine Buprenorphine butorphanol versus, 98 for degenerative joint disease, 715 epidural administration of, 100 in neonatal anesthesia, 1248-1249 for pain management, 98, 1151t, 1152 dose ranges and route of administration for, 97t in feline cholangitis syndrome, 534 in feline idiopathic cystitis, 991 in pancreatitis, 516 as “send home” medication, 105-106 for pancreatitis with inflammatory bowel disease, 1118t for sedation and premedication, 114t side effects of, 96 transmucosal administration of, 48, 49t for urethral obstruction in feline idiopathic cystitis, 992t Burettes, 59, 60f Burmese cat, 1256-1258 hypokalemic polymyopathy in, 729-730 phenotypic mutations in, 1273-1276, 1275f Burning mouth syndrome, 355 Burr cell, 649f “Burrito wrap”, 11, 11f Buserelin, 1202-1203 Buspirone for behavior-modification therapy, 232t, 233 for cognitive dysfunction in senior cat, 1172t Butorphanol, 97-98 in balanced anesthetic technique, 130 buprenorphine versus, 98 dose ranges and route of administration for, 97t in neonatal anesthesia, 1248 for pain management in feline idiopathic cystitis, 991 in pancreatitis, 516 side effects of, 96 for urethral obstruction in feline idiopathic cystitis, 992t Butterfly catheter, 71t C Cabergoline, 1200t, 1202 Cachexia cancer, 799 cardiac, 255 Cage, oxygen, 896b-897b, 897f for pleural effusion, 895 Caging in veterinary hospitals, 16-17, 17f, 23, 1333-1334, 1334f Calcaneal tendon rupture, 723-724, 723f-724f Calcipotriene toxicity, 632 Calcipotriol toxicity, 632 Calcitonin in calcium regulation, 625 for hypercalcemia, 634, 634b Calcitriol in calcium regulation, 625-626 for hyperparathyroidism in chronic kidney disease, 974 renal secondary, 630 for hypocalcemia, 639-640 Calcium addition of in fluid therapy, 61t, 63t, 64 deficiency of, 250t disorders of, 625-642 hypercalcemia as, 626-627, 629-636 hyperparathyroidism as, 629 hypocalcium as, 636-640 feline idiopathic cystitis and, 996 homeostasis of, 625-626, 625f neonatal values, 1237t

Calcium carbonate for hypocalcemia, 639 for intestinal phosphate binding, 974 Calcium channel blockers, 1122-1124, 1122t Calcium gluconate for dystocia, 1211 for eclampsia, 1213 for hypocalcemia, 639 Calcium oxalate toxicity, 924 Calcium oxalate uroliths, 279-281, 955-956, 996-997, 996f-998f prevalence of, 993, 993f radiographic appearance of, 985t Calcium phosphate ureteral stones, 955-956 Calcium salts, pharmacodynamic monitoring of, 1140t, 1142 Calcivirus stomatitis due to, 349 vaccination against, 174t, 175 Calculi. See also Urolithiasis/uroliths renal, 955-956, 955f ureteral, 955-956 Calicivirus. See Feline calicivirus (FCV) Calla lily toxicity, 924, 925f Calluses, digital pad, 408 Caloric content of centrally administered parenteral nutrition, 277-278 Caloric intake for hyperthyroidism, 266b in medical history, 29 neonatal, 1232b for obesity, 262-264 in palliative care, 1157t for slowing progression of chronic kidney disease, 969 Calories in crystalloid solutions, 61t Calvarial thickening in acromegaly, 614, 614f Campylobacter diarrhea due to, 477t, 478-479 food contamination with, 251 in raw food diets, 291, 291t molecular assays for diagnosis of, 1086 Cancer. See also Neoplasia biopsy techniques in, 769 chemotherapy for, 770-782 injection-site sarcoma as, 787-791 lymphoma as, 782-786 mammary, 791-794 nutritional management of, 266-268, 267f oral and maxillofacial, 365-366, 365f, 367f palliative care in, 802-806 paraneoplastic syndromes in, 794-802 screening diagnostics for, 768 signs of, 768 staging of, 769 ten common signs of, 1173b thyroid gland, 584 Cancer cachexia, 799 “Candidate-gene” approach, 1273 Candidatus Mycoplasma haemominutum, 666-668 molecular assays for diagnosis of, 1086-1087 Candidatus Mycoplasma turicensis, 666-668 molecular assays for diagnosis of, 1086-1087 Cane toad toxicity, 927 Canine parvovirus-2 (CPV-2), 1036, 1038 Canine teeth, 329, 330t, 332f Caninsulin insulin, 553t Canned foods, 245 chronic kidney disease and, 972t hyperthyroidism associated with, 571 for obstipation, 488 Canned versus dry carbohydrates, 294 Cannibalization of kittens by queen, 221 CAP. See Carpal arthrodesis plate (CAP)

Capillaria aerophilus, 882 Capillary refill time (CRT) assessment of in cardiovascular disease, 302 for monitoring of fluid therapy for hypovolemia, 76 Capital femoral physeal fracture, 707-708, 707f-708f Capnocytophaga canimorsus, 1091t Capnography during anesthesia, 135, 135f Caprofen, 101 for degenerative joint disease, 714 metabolism of, 41t Capstar. See Nitenpyram Capsule drugs given as, 46-47 esophageal damage due to, 444-445 Capture of community cats, 1292-1299, 1292f-1293f field capture, 1292-1294, 1293f pregnant and lactating, 1304-1305 small kittens, 1305 Carbamate pesticide toxicity, 919-920, 931t neurologic signs of, 745 treatment of, 916t Carbergoline, 1203-1204 Carbimazole adverse effects of, 581 for hyperthyroidism, 581-582 pharmacodynamic monitoring of, 1141 transdermal administration of, 48 Carbohydrates alterations in metabolism of, cancer and, 267 canned versus dry, 294 excess of, 249t in idiopathic hepatic lipidosis, 532 intake of in cancer, 267b diabetes mellitus, 265b, 562-563 novel diet, for vomiting, 434 nutritional requirements, 239-240 as nutrition controversy, 292-295, 293t obesity and, 262 in palliative care, 1156-1157 therapeutic renal diets and, 972t Carbon dioxide monitoring during anesthesia, 135-136 Carbonic anhydrase inhibitor for glaucoma, 837 Carbon monoxide intoxication, 876-877 Carboplatin as chemotherapy agent, 777t, 779-780 Carcinoma. See also Neoplasia bile duct, 527t hepatocellular, 527t lower urinary tract transitional cell, 1005-1006 mammary, 791, 791f renal, 949 squamous cell esophageal, 448 eyelid, 816, 816f-817f hypercalcemia associated with, 631 oral and maxillofacial, 365-366, 365f orbital, 813 thyroid gland, 584 Cardiac glycoside toxicity, 923-924 Cardiac output effects of alpha2 agonists on, 116 improving of in cardiorenal syndrome therapy, 1112-1113 for monitoring of fluid therapy for hypovolemia, 76 in oxygen delivery, 55 Cardiac signs in hyperthyroidism, 573 Cardiac sounds assessment during physical examination, 34-35, 35f Cardiac troponin I (cTnI), 967 Cardiomegaly, 304

INDEX Cardiomyopathy, 310-319 with acromegaly, 614 arrhythmogenic right ventricular, 315-316 arterial thromboembolism as complication of, 316-319, 316f-317f dilated, 314, 314f taurine deficiency in, 250, 301, 314 DNA testing for, 1274t excess moderator band, 316 hypertrophic (See Hypertrophic cardiomyopathy (HCM)) unrestrictive and unclassified, 314-316, 315f Cardiorenal syndrome (CRS), 1108-1114, 1111b classification in humans, 1109b diagnosis of, 1110 pathophysiology of, 1109-1110, 1109f prevalence of, 1108-1109 prognosis for, 1114 therapy for, 1110-1114, 1111t Cardiovascular disease, 300-328 arrhythmias as, 319-322, 319f-320f atrioventricular blocks as, 321, 321f conduction disturbances as, 320-321 isorhythmic dissociation as, 321, 322f treatment of, 321-322, 322t cardiomyopathies as, 310-319 arterial thromboembolism as complication of, 316-319, 316f-317f dilated, 314, 314f hypertrophic, 310-314, 310f-313f unrestrictive and unclassified, 314-316, 315f congenital heart disease as, 322-325, 1233b atrial septal defect as, 323 patent ductus arteriosus as, 324-325 peritoneopericardial diaphragmatic hernias as, 324, 324f supravalvular mitral stenosis (cor triatriatum sinister) as, 323 ventricular septal defect as, 322-323, 323f congestive heart failure as clinical signs of, 302 fluid therapy for, 84-86 glucocorticoid-associated, 325 N terminal-proBNP in diagnosis of, 306 diagnosis of, 303-307 biomarkers in, 306-307 echocardiography in, 305-306 electrocardiography in, 303-304 radiography in, 304-305, 304f-305f endocarditis as, 326 history and physical examination in, 301-303 hypertension as, 307-309, 307t hyperthyroidism and, 325-326 myocardial infarction as, 319 nutritional management of, 255-256, 256f, 257t prevalence of, 300-301 risk factors for, 301 Cardiovascular system alphaxalone in depression of, 125 anesthesia and geriatric, 138 hyperthyroidism and, 139-140 neonatal, 137 effects of acromegaly on, 614 effects of alpha2 agonists on, 116 Caregiver. See also Owner(s) caring for after death of cat, 1162-1163 Carnassials, 329 Carnitine for cognitive dysfunction in senior cat, 1172

Carnitine (Continued) for diabetes mellitus, 265 dilated cardiomyopathy associated with deficiency of, 256 for hepatic lipidosis, 532-533, 532t intake in hepatic disease, 260b Carnivores, cats as, 168 Carnivorous adaptations, 243-244 Carotenoids, 240 Carpal arthrodesis plate (CAP), 717-718 Carpal hyperextension injury, 717-718, 717f Carprofen dose ranges and route of administration for, 97t use in neonates, 106 Carrier examination of cat in, 11, 11f getting cat out of, 10-11, 11f getting cat used to, 9-10, 10f housing of cat in, 23, 24f for kitten socialization classes, 200 for transportation to veterinary hospital, 9-10 Cartilage, articular, degenerative joint disease of, 709-710 Cartrophen. See Pentosan polysulfate Case example of fluid therapy plan, 81, 81t Castor bean plant toxicosis, 924 Castration chemical, 1187 mating behavior following, 1186 surgical, 1186 Cat breeds of domestic, 1255-1259, 1256t-1257t, 1258f communication of, 5-6, 5f dogs and, 163f growing population of, 20 history of, 4 hypoallergenic, 422 learning in, 8-9, 8f origins and health of breeds of, 1259-1261, 1260f origins of domestic, 1254-1255 ownership of by immunecompromised persons, 1095 receiving of, 10 removal of due to human allergy, 422 understanding of, 4-5 CATalyst Counsel, 20 CATalyst Summit, 20 Cataract, 834, 834f due to uveitis, 831-832 Cat bites, 1090-1091 osteomyelitis following, 725 Catecholamine(s) adrenal tumor secretion of, 602 anesthesia in hyperthyroid patient and, 141 diabetes mellitus development and, 551 Caterwall, 194 Cat-friendly practice, 20-25 feline veterinarians and, 21 foundations of, 21 physical features of, 21-24 equipment, 23, 23f examination rooms, 21-22, 22f housing, 23-24, 23f-24f public areas, 21, 21f-22f treatment areas, 22-23, 22f Cathartics for toxicosis, 932 Catheters/catheterization gauge of, 70 intravenous for fluid therapy, 69-70, 71t neonatal, 1239-1240, 1239f placement of, 70-73, 72f urethral for lower urinary tract trauma, 1007-1008

Catheters/catheterization (Continued) for urethral obstruction, 1000-1002, 1000b, 1001f for urine collection, 938 in feline lower urinary tract disease, 983, 983t for vascular access, 70, 71t wound infusion, 104 Cat identification ear tipping for, 1300-1301, 1302f-1303f, 1304b in population wellness program, 1316-1318, 1317f, 1319b, 1320f Cat scratch disease (CSD), 1091-1092 CBC. See Complete blood count (CBC) CCH. See Cholangitis/cholangiohepatitis complex (CCH) CCL. See Cranial cruciate ligament (CCL) CCNU. See Lomustine CD. See Cognitive dysfunction (CD) CD4+ lymphocytes, 1057 CD8+ lymphocytes, 1057 CD134 molecules, feline immunodeficiency virus binding through, 1056-1057 CeeNU. See Lomustine Cefadroxil for skin disease, 384t for upper respiratory tract infection, 853t Cefazolin for neonatal sepsis, 1244t for panleukopenia/parvovirus, 478 Cefotaxime, 516 Cefovectin, 479 Cefpodoxime, 384t Ceftiofur, 1244t CEH. See Cystic endometrial hyperplasia (CEH) Ceiling in colony-style housing, 1340-1341, 1342f Cellulitis, orbital, 813 Cementoenamel junction, 330-331 Cementum, 330-332 Centers for Disease Control and Prevention on food-related illness, 269 Centrally administered parenteral nutrition, 277-278 Central nervous system (CNS) borna disease virus in, 744 feline infectious peritonitis infection in, 742-743, 743f, 1040-1041, 1041t fungal infection in, 744, 745f hydrocephalus of, 738 Toxoplasmosis gondii in, 743-744, 744f vomiting mediated by, 426-427 Central venous catheter, 70, 71t Central venous partial pressure of oxygen (CvO2), 77 Central venous pressure (CVP) monitoring of during anesthesia, 136 monitoring of during fluid therapy, 69, 69f for anaphylaxis, 699 for hypovolemia, 75 Central vestibular disease (CVD), 415 Centrifugal feces flotation, 463b Centrifugation of urine sediment, 939, 943 Cephalexin for neonatal sepsis, 1244t for skin disease, 384t for upper respiratory tract infection, 853t Cephalic vein for intravenous catheterization, 70-71 Cephalosporins dosage adjustment in renal insufficiency, 41-42 for osteomyelitis, 725

1363

Cephalothin, dosage adjustment in renal insufficiency, 41-42, 42t Cerebellar hypoplasia, 738-739, 739f Cerebrospinal fluid (CSF) analysis in Cryptococcus neoformans central nervous system infection, 744 in seizure disorders, 735-736, 735f in spinal lymphoma, 754, 754f in Toxoplasmosis gondii infection, 743-744 Cerebrovascular accident (CVA), 746, 746f Cerenia. See Maropitant Cervical spine involvement in myelopathies, 750 Cesarean section, 1212-1213, 1212b, 1213f Cestodes, 171, 172t, 500-501 Cetirizine for pruritus in atopic cat, 390t for upper respiratory tract disease, 853t Ceva. See Feliway Cevovecin, 1005 Chamber induction, 126, 126f Charcoal, activated, for toxicosis, 916t, 932 due to cholinesterase inhibitors, 920 Chase as play behavior, 185, 186t CHD. See Congenital heart disease (CHD) Checklist for wellness services, 153, 154f Chédiak-Higashi syndrome (CHS), 1125t leukocytic disorders associated with, 678-679 Cheeks, anatomy of, 333 Cheek teeth, 329, 332f Chemical castration, 1187 Chemistries in hypothyroidism, 587 in minimum database, 165t neonatal, 1237t Chemokines, keratin-derived, as biomarker in human acute renal failure, 966t Chemoreceptor trigger zone (CTZ), vomiting and, 426 Chemotherapy, 770-782 adverse effects of, 774-776 dosing and administration of, 772-774 drugs used for, 776-781, 777t for high-grade intestinal lymphoma, 475 for injection-site sarcoma, 789-790 for lymphoma, 784-785, 784t for mammary tumors, 793 for osteosarcoma, 725 preparation for, 771-772, 772b resources regarding, 771 for spinal lymphoma, 754 Chemotherapy spill kit, 771, 772b “Cherry eye”, 817 Chest tubes placement of, 902b-903b, 902f-903f for pyothorax, 901-904 Chest wall compliance, decreased in lower respiratory tract disease, 862 Chest wall pathology, 909-910 congenital, 1234-1236 Cheyletiella mites, 379, 1091t identification of acetate tape preparation for, 374 skin scrapings for, 373-374 treatment for, 379-380 CHF. See Congestive heart failure (CHF) Chiggers, 379 Childbirth. See Parturition Children, attendance of at kitten classes, 199 Chin acne on, 398-399, 399f physical examination of, 33 in assessment of skin diseases, 372

1364

INDEX

Chinese desert cat, 1254-1255 Chin furunculosis, 398-399 Chitosan/calcium carbonate, pharmacodynamic monitoring of, 1140t, 1142 Chlamydophila felis in conjunctivitis, 819-823, 820t, 821b molecular assays in diagnosis of, 1086 pregnancy loss due to, 1224 in upper respiratory infection, 852-853 vaccination against, 176, 854 in population wellness programs, 1325 recommendations for, 174t zoonotic, 1092 Chlorambucil adverse effects of, 473 as chemotherapy agent, 776, 777t for feline cholangitis syndrome, 534 for immune-mediated hemolysis, 659t, 660 for immunosuppression, 1137 for inflammatory bowel disease, 438t, 439 with pancreatitis, 1118t, 1119 for intestinal small cell lymphoma, 472-473, 472t for pemphigus foliaceus, 397-398 stability of suspensions of, 47t for systemic lupus erythematosus, 697 Chloramphenicol metabolism of, 41t for upper respiratory tract infection, 853t Chlordiazepoxide, 257t Chlorine compounds for disinfection, 1348b Chlormadinone, 1200t, 1201 Chlorpheniramine monitoring of long-term therapy with, 1139t for pruritus in atopic cat, 390t for upper respiratory tract disease, 853t Chlorpromazine in chronic kidney disease therapy, 973t for sedation and premedication, 114 for vomiting, 432t Chlor-Tripolon. See Chlorpheniramine Cholangiocarcinoma, 527t Cholangitis, pancreatitis with, 513 Cholangitis/cholangiohepatitis complex (CCH), 533-534, 533f-534f, 534b Cholecalciferol toxicity, 916t, 917-918 Cholestasis, 525, 526f Cholesterol neonatal values, 1237t testing of in liver disease, 522-524 Cholinesterase inhibitors toxicity, 919-920 Chondroitin sulfate for degenerative joint disease, 715 Chondroprotectives for degenerative joint disease, 715 CHOP chemotherapy protocol, 784-785, 784t Chorioretinal disease, 837-841 due to enrofloxacin toxicity, 839-840, 839f hypertensive chorioretinopathy, 837-839, 838f progressive retinal atrophy, 841 taurine-deficient retinopathy, 840, 840f Chromium supplementation for diabetes mellitus, 265 Chromosomes, 1263-1265, 1264f Chromosome painting, 1264-1265, 1264f Chronic bronchitis, 866-875 definition of, 866 diagnosis of, 867-870, 869f-870f epidemiology of, 866 etiopathogenesis of, 866-867 treatment of, 870-875, 872b, 873f

Chronic disease management, 1134-1163 adverse drug reactions in, 1144-1149, 1148t concurrent (See Concurrent disease management) immunosuppressive drug therapy in, 1134-1138, 1135t monitoring of long-term drug therapy in, 1138-1144 clinical, 1139, 1139t pharmacodynamic, 1140-1142, 1140t pharmacokinetic, 1142-1143, 1143t palliative care for pain assessment and management in, 1149-1155 quality of life and euthanasia decisions in, 1155-1163 Chronic inflammatory nasal disease, 857-858, 857f Chronic kidney disease (CKD), 962-976, 962b anemia of, 670-671, 974-975 associated with feline immunodeficiency virus, 1057-1058 clinical findings in, 963 diagnosis of, 964-967, 966t fluid and electrolyte loss assessment in, 79t fluid therapy for, 84 heart failure concurrent with, 1108-1114, 1109b, 1109f, 1111b, 1111t hypercalcemia with, 630 hyperparathyroidism with, 974 hyperphosphatemia with, 973-974, 974t hypertension and, 970, 1120-1124, 1121t-1122t, 1123f hyperthyroidism with, 575-576, 579-580, 580f, 1099-1101 hypokalemia with, 968-969, 975 International Renal Interest Society classification of, 963-964, 964b, 964t, 965f-966f metabolic acidosis with, 969-970 nutritional management of, 278-279, 279b, 279f prognosis for, 975-976 proteinuria in, 970-971, 1121-1122, 1122t pyelonephritis with, 967-968 therapy for, 967-975, 968t hydration in, 969, 969b nutrition and dietary protein in, 971-973, 972t-973t, 973b slowing progression of disease in, 969, 969b urine culture and sensitivity in, 943-944 Chronic renal disease. See Chronic kidney disease (CKD) Chronic renal insufficiency (CRI), 962-963. See also Chronic kidney disease (CKD) CHS. See Chédiak-Higashi syndrome (CHS) Chylothorax, 904-905, 904f nutritional management of, 268-269, 268f Chylous effusions in peritoneal fluid, 543 Cidofovir for ocular herpesvirus infection, 822 for upper respiratory tract disease, 853t Cimetidine, 916t C1 in crystalloid solutions, 61t Circulation lymph, 689f splenic, 685 Circumferential wiring for mandibular fracture, 705, 706f for mandibular symphyseal separation, 360-361, 361f

Cirrhosis, drug therapy considerations in, 44 Cisapride for esophagitis and esophageal strictures, 445 for obstipation, 488 for obstructing feces, 487 for vomiting, 432t, 433 Cisplatin, 780 CK. See Creatine kinase (CK) CKD. See Chronic kidney disease (CKD) Clarithromycin for Helicobacter gastritis, 454 for mycobacterial infection, 1078t for nocardiosis, 1080, 1080f Class curriculum for kitten classes, 202-205, 202f-205f Classical conditioning in behavior modification, 226-227 Clavicle anatomy, 704, 705f Claw care internet resources for, 159b in preventive health care, 163f, 164 Cleaning in population wellness program, 1347-1349, 1348b of soiled areas, 218-219 Clear adhesive tape in skin disease diagnosis, 375, 375f Clef lip and/or palate congenital, 356, 1233f traumatic, 356, 357f Clemastine for pruritus in atopic cat, 390t for upper respiratory tract disease, 853t Clicks, systolic, 302 Client communication with in preventive health care, 152, 178 perspective of on veterinarian visits, 2 receiving of, 10 Client education in feline-friendly veterinary visits, 9, 10b regarding retrovirus-infected cats, 1053-1054, 1053b Climbing lily toxicity, 958t Climbing on ledges, 185, 185f Clindamycin drug compounding and, 46, 47f esophageal damage due to, 444, 852-854 for infectious myopathies, 758-759 for infectious polymyositis, 729 for meningoencephalitis, 744 for protozoal disease, 502t for skin disease, 384t for upper respiratory tract infection, 853t Clipping of hair coat for dermatophytosis, 393 Clofazimine, 1078t Clomipramine for behavior-modification therapy, 232t, 233 for feline hyperesthesia syndrome, 763-764, 764t Clonazepam for behavior-modification therapy, 232t for cognitive dysfunction in senior cat, 1172t Clopidogrel, 318 Cloprestenol, 1214 Closed mouth vocalization, 194 Closed pneumothorax, 906 Closed tooth extraction, 351 Clostridium difficile diarrhea due to, 477t, 479 in raw food diet-related illness, 291t

Clostridium perfringens diarrhea due to, 479 in raw food diet-related illness, 291t, 477t Clostridium piliforme, 480 Clostridium spp., molecular assays for diagnosis of, 1086 Clostridium tetani, 764 Clot dissolution, 680 Clotting factors deficiencies of, 680-682, 680t, 681b in hemostasis, 679 Cluster seizures, 734-735 CMAH gene mutation, 1278-1279 CNS. See Central nervous system (CNS) Coagulation, 679 disorders of, 680-682, 680t, 681b fresh whole blood transfusion for, 66-67 disseminated intravascular, 680t, 682 paraneoplastic, 797 Coagulation factors deficiencies of, 680-682, 680t, 681b in hemostasis, 679 Coat examination of in assessment of skin diseases, 373 grooming of, 164 Coat color mutation, 1276 Coaxing in enteral nutrition, 272 Cobalamin (vitamin B12) for appetite stimulation in cardiovascular disease treatment, 257t diarrhea and, 435-436, 464-465, 464t in exocrine pancreatic insufficiency treatment, 520 in hepatic lipidosis therapy, 532-533, 532t in inflammatory bowel disease treatment, 468 monitoring of long-term therapy with, 1139t Coccidia, 501-503, 501f, 502t control of in population wellness program, 1323 ponazuril for, 1323b Coccidiocidal drugs, 502-503 Coccidioidomycosis, 1020-1022 Coccygeal separation, 756, 756f Codocyte, 649f Cognitive dysfunction (CD) environmental enrichment and onset of, 228 perioperative in geriatric patient, 138 in senior cat, 1170-1173, 1171b, 1172t Colectomy for megacolon, 489 Collagen in hemostasis, 679 type I, defects of in osteogenesis imperfecta, 727 Collar, identification, 1317, 1317f, 1319b Collection site for bone marrow, 644-645, 645f Colloids, 59, 66-69 blood products as, 66-68 general characteristics of, 66 for hypovolemia, 74 intraoperative administration of, 136 natural, 66-68, 67b synthetic, 68-69, 69f Coloboma, eyelid, 813-814 Colony-style housing, 4, 196, 1336-1341, 1338b, 1338f-1341f Color of coat, genetic mutations of, 1276 of effusion in feline infectious peritonitis, 1043, 1043b, 1043f of urine, 939, 939f Color trait, 1273-1276 DNA testing for, 1274t Colostrum, 246 Combing, flea, 374

INDEX Comfort, optimizing of in palliative medicine, 1158-1159, 1159f Common ancestry, 1271b-1272b Common calcaneal tendon (CCT) rupture, 723-724, 723f-724f Communication, 5-6, 193-195 body language in, 193-194, 193f client, in preventive health care, 152 housing in population wellness program and, 1331-1333 odor signals in, 194-195 olfactory, 6 tactile, 6 visual, 5-6, 5f vocal, 6, 194 Community cats anesthetic options for, 133 care and control of, 1290-1311, 1291f feral versus reactive tame cats, 1299 helping clients resolve issues related to, 1306-1308, 1307b liability regarding, 1309, 1309b pregnant and lactating, 1304-1305 relocation of, 1308 resources for care of, 1309b returning of to colonies, 1294 safe and humane capture, holding and handling of, 1292-1299, 1292f-1293f escapes in, 1294-1299, 1297f-1298f field capture in, 1292-1294, 1293f in-clinic procedures in, 1294, 1296b, 1296f sick and injured, 1305-1306, 1307f small kittens, 1305 surgical and medical procedures for, 1299-1300 ear tipping for identification, 1300-1301, 1302f-1303f, 1304b feline leukemia virus and feline immunodeficiency virus testing, 1302-1303 parasite control, 1303-1304 patient selection and preoperative care, 1299-1300 surgical sterilization, 1300, 1300f, 1301b vaccination, 1301-1302 trap-neuter-return of, 1291, 1292t large scale, 1308, 1308f Compazine. See Prochlorpromazine Complaint in medical history, 29-31 Complementary therapies in long-term pain management, 1153 in palliative care for cancer, 803 Complete blood count (CBC) in cancer, 768 in feline infectious peritonitis, 1044 in hyperadrenocorticism, 593t in immune-mediated hemolysis, 658 in minimum database, 165t in regenerative anemia, 656-657 in upper respiratory system disease, 848 Complexed calcium, 625 Complex partial seizure, 734-735 Compliance preventive dental care, 167 psychotropic drug therapy, 231-232 Computed tomography (CT) in intervertebral disk disease, 751 in lower respiratory tract disease, 864 asthma and bronchitis, 868 in meningioma, 741, 741f in oral and dental disease, 340-341, 340f in otitis, 413 in peripheral vestibular disease, 749, 749f in upper respiratory tract disease, 849-850, 849f

Concurrent disease management, 1098-1133 chronic kidney disease and hypertension, 1120-1124, 1121t-1122t, 1123f diabetes mellitus and feline lower urinary tract disease, 1106-1108 diabetes mellitus and obesity, 1103-1106, 1105f, 1105t heart failure and chronic kidney disease, 1108-1114, 1109b, 1109f, 1111b, 1111t hyperthyroidism and chronic kidney disease, 1099-1101 hyperthyroidism and diabetes mellitus, 1101-1103 immune deficiency, stress, and infection, 1124-1128, 1125f, 1125t pancreatitis and inflammatory bowel disease, 1114-1120, 1118t for senior cat, 1174 Condominium, cat, 17f, 23, 24f, 1335-1336, 1335f Conduction disturbances, 320-321 Congenital anomalies/disorders, 1232-1236, 1233b-1234b, 1233f-1236f breed-specific data regarding, 1230t of female reproductive system, 1204, 1205f infertility due to, 1218 of palate, 356 renal, 946-948 of spinal column, 751-752, 752f Congenital heart disease (CHD), 322-325 atrial septal defect as, 323 patent ductus arteriosus as, 324-325 peritoneopericardial diaphragmatic hernias as, 324, 324f supravalvular mitral stenosis (cor triatriatum sinister) as, 323 ventricular septal defect as, 322-323, 323f Congenital hypothyroidism causes of, 585 clinical features of, 586, 586t Congenital hypotrichosis, 401, 401f Congenital myotonia, 728t Congenital polyneuropathy, 760-761 Congestive heart failure (CHF) ascites due to, 545 biomarkers in diagnosis of, 311 clinical signs of, 302 fluid and electrolyte loss assessment for, 79t fluid therapy for, 84-86 glucocorticoid-associated, 325 in hyperthyroidism, 572t in hypertrophic cardiomyopathy, 310-311, 311f-312f N terminal-proBNP in diagnosis of, 306 pleural effusion due to, 895-898, 900f radiographic diagnosis of, 305, 305f secondary to arterial thromboembolism, 317 Conjunctiva examination of, 33-34 sample collection from, 811-812, 811f Conjunctival disease, 817-818 Chlamydophila felis, 819-823, 820t, 821b eosinophilic keratoconjunctivitis, 826, 826f feline herpesvirus, 818-819, 818f-819f, 820b symblepharon, 823-824, 824f Conjunctivitis, 823, 823f-824f Chlamydophila felis, 819-823, 820t, 821b neonatal, 1241-1242, 1241f Connective tissue, fluid in, 54 Conn’s syndrome, 603

Constant rate infusion (CRI) of analgesic drugs, 94, 95b of dexmedetomidine, 104-105 of furosemide for cardiorenal syndrome, 1112 of insulin, 566f, 631-632 of lidocaine, 102 of potassium, 63, 63f Constipation, 484-489, 486t-487t in hypothyroidism, 586t in senior cat, 1169-1170 Consultation for behavioral history taking, 207-208 Contaminants, food, 251 in raw food diet, 290-291, 290b, 291t Contracture, tendon, 727, 727f Contrast cystography in feline idiopathic cystitis, 988 in feline lower urinary tract disease, 983-984, 983b, 984f Contrast esophogram, 443, 444f Contrast radiography for gastric emptying assessment, 456-457 in gastric neoplasia, 457 in intestinal foreign body, 482 Convallaria majalis toxicity, 923-924 COP chemotherapy protocol, 784-785 Copper deficiency of, 250t skin disease associated with, 258 excess of, 249t Coral snakes, 927 Core biopsy for bone marrow collection, 646 Core vaccines, 174, 174t in population wellness program, 1323-1324 Cornea, 191-192 disease of, 817-818 acute bullous keratopathy as, 827, 827f corneal sequestration as, 825-826, 825f-826f eosinophilic keratoconjunctivitis as, 826, 826f due to feline herpesvirus, 818-819, 818f-819f, 820b symblepharon as, 823-824, 824f ulceration as, 824-825, 825f examination of, 811 scrapings of, 811-812, 811f Cornish Rex cat, 1276-1277, 1276f Coronal in oral anatomy, 335 Coronavirus. See Feline coronavirus (FCoV) Corticosteroids adverse effects of, 473 for asthma and bronchitis, 871-874, 872b for chlamydial and herpesvirus conjunctivitis, 822-823 for hydrocephalus, 738 for hypercalcemia, 636 indwelling catheterization and, 1002 for inflammatory bowel disease, 468 nonsteroidal antiinflammatory drugs contraindicated with, 101 for pancreatitis, 516 with inflammatory bowel disease, 1119 for pruritus in atopic cat, 390t for spinal trauma, 755 for uveitis, 831 Cortisol in hyperadrenocorticism, 595-597 Cortisone for immunosuppression, 1135t Cor triatriatum sinister, 323 Cost(s) of desmopressin, 622 of hyperthyroidism therapy, 581 of preventive health care, 158, 159b Cough in lower respiratory tract disease, 862

1365

Counseling skills in behavioral history taking, 206-207 Counterconditioning in behavior modification, 227 Covinan. See Proligesterone Cowpox, 1063 pneumonia due to, 879 COX. See Cyclooxygenase (COX) enzymes Coxibs dosage adjustment in renal insufficiency, 43-44 Coxiella burnetii, 1091t CPV-2. See Canine parvovirus-2 (CPV-2) Cr. See Creatinine (Cr) Crandell-Rees feline kidney (CRFK), 962-963 Cranial cruciate ligament (CCL) injury, 721-723, 722f Creams, anesthetic, 102 Creatine kinase (CK) in hyperaldosteronism, 604 in myopathies, 729 Burmese hypokalemic polymyopathy, 729-730 inflammatory, 758 Creatinine (Cr) assessment in liver disease, 524 in chronic kidney disease classification, 963-964, 964t drug dosage adjustment and, 41 neonatal values, 1237t as renal function test, 935-936, 936t urine protein to, 942-943 in systemic lupus erythematosus, 697 Creatinine (Cr) clearance test, 937 Creatinine (Cr) ratio, 944 CRFK. See Crandell-Rees feline kidney (CRFK) CRI. See Chronic renal insufficiency (CRI); Constant rate infusion (CRI) Critical care/illness, nutrition during, 270-278, 271f animal factors in, 272 dietary factors in, 272 enteral, 272-277 parenteral, 277-278, 277f Crossmatch testing, 646-647 before blood transfusion, 655 Crotalid snakes, 927 Crowding in animal shelters, 1347 Crown of tooth, 330-331 amputation of, 353, 354f for tooth resorption, 347-348 intentional reduction of, 348 CRS. See Cardiorenal syndrome (CRS) CRT. See Capillary refill time (CRT) Cruciate ligament anatomy of, 704 injury to, 721-723 Crushing of medications, 46 Crusting, 391 Cryoepilation for eyelid agenesis, 814, 814f Cryohypophysectomy for acromegaly, 617 Cryptococcosis, 1016-1019, 1017f-1018f, 1018b of central nervous system, 744, 745f in otogenic encephalopathy, 748-749, 748f seizures due to, 735, 735f of spine, 752-753 Cryptococcus gatti, 1016-1017 Cryptococcus neoformans, 1016-1017 pneumonia due to, 881 in upper respiratory infection, 856-857 Cryptorchidism, 1189-1191, 1189t-1190t, 1190b, 1191f Cryptosporidium felis, 507-509, 508f enzyme-linked immunosorbent assay for, 463 molecular assays for diagnosis of, 1086

1366

INDEX

Cryptosporidium parvum, 477t Crystalloids, 59-66, 61t acidifying and alkalinizing, 62 calculation worksheet for, 62t for chronic kidney disease, 278-279, 279f combination of high- and low-sodium, 65-66 composition of, 61t for congestive heart failure, 85 hypertonic saline solutions, 66 hypotonic low-sodium, 64-65 for hypovolemia, 74 intraoperative administration of, 136 isotonic high-sodium, 60-64 supplements in, 62-64, 63f, 63t Crystalluria, 943 in feline idiopathic cystitis, 987-988 in feline lower urinary tract disease, 981f CSD. See Cat scratch disease (CSD) CSF. See Cerebrospinal fluid (CSF) CT. See Computed tomography (CT) Ctenocephalides felis flea vector in Rickettsia felis, 1027 cTnI. See Cardiac troponin I (cTnI) CTZ. See Chemoreceptor trigger zone (CTZ) Cuff, blood pressure, 134-135 Culture in bronchial disease, 868 in cryptococcosis, 1018 dermatophyte, 376, 376f fecal in diarrhea, 462-463 in Tritrichomonas foetus, 507 in otitis media, 414 in upper respiratory system disease, 849-850 urine, 943-944, 944b Curette, 343, 344f Curriculum for kitten classes, 202-205, 202f-205f Cushing’s disease, 611 Cushing’s syndrome, 592-602 clinical features of, 592-594, 593f-594f, 593t diagnosis of, 594-598, 598f fragile skin with, 406, 406f insulin therapy resistance due to, 563t prognosis for, 602 screening tests for, 594-597, 596t treatment of, 598-602, 599t Cutaneous Cryptococcus nodule, 1017-1018, 1018f CVAs. See Cerebrovascular accident (CVA) CVD. See Central vestibular disease (CVD) CvO2. See Central venous partial pressure of oxygen (CvO2) CVP. See Central venous pressure (CVP) Cyanosis, fluid therapy for hypovolemia and, 76 Cyanuric acid acute renal failure due to, 959 food contamination with, 251 Cycad palms (cycas, zamia species) toxicosis, 924 Cyclooxygenase (COX) enzymes, 100-101 Cyclophosphamide as chemotherapy agent, 776, 777t for injection-site sarcoma, 789-790 for lymphoma, 784-785, 784t for immune-mediated arthritis, 716 for immune-mediated hemolysis, 659t, 660 monitoring of, 716 stability of suspensions of, 47t Cyclosporin-A for allergic induced airway disease, 874 for asthma, 874

Cyclosporine for chronic rhinosinusitis, 857-858 for cytokine inhibition, 692-694 for eosinophilic granuloma complex, 353 for immune-mediated hemolysis, 659t, 660 for immunosuppression, 1136 for inflammatory bowel disease, 438t, 439 pancreatitis with, 1118t for insect bite hypersensitivity, 386 for pemphigus foliaceus, 397-398 pharmacokinetic monitoring of, 1142, 1143t for plasma cell pododermatitis, 408 for pruritus in atopic cat, 390-391, 390t for stomatitis, 350 Cyclosporine modified for food allergy dermatitis, 387 Cyproheptadine for allergic induced airway disease, 874 for appetite stimulation in cardiovascular disease treatment, 257t monitoring of long-term therapy with, 1139t in palliative care, 1157 for pancreatitis with inflammatory bowel disease, 1118t Cystadenoma biliary, 527-528, 527t, 528f renal, 949 Cysteine, nutritional requirements of, 238 Cystic disease, renal, 946-948, 946f-947f Cystic endometrial hyperplasia (CEH), 1219-1222, 1220f Cystin C as biomarker in human acute renal failure, 966t Cystine uroliths, 281 radiographic appearance of, 985t Cystitis, idiopathic, 985-992 clinical signs of, 986-987 diagnosis of, 987-988, 988f management of, 281-282, 988-992, 989b-990b, 990f, 992t prevalence of, 985 signalment and risk factors in, 985-986 Cystocentesis for urine collection, 15-16, 16f, 938 in feline lower urinary tract disease, 982-983, 983t for urethral obstruction, 1000 Cystography, contrast in feline idiopathic cystitis, 988 in feline lower urinary tract disease, 983-984, 983b, 984f Cystorelin. See Gonadotropin-releasing hormone (GnRH) Cystoscopy in feline idiopathic cystitis, 988, 988f in lower urinary tract disease, 984-985 for urolith removal, 994t Cystotomy for urolith removal, 993-994, 994t Cyst(s) intracranial arachnoid, 739 ovarian, 1218, 1218f pancreatic, 516-517 renal acquired, 948 in polycystic kidney disease, 946-948, 946f Cytarabine. See Cytosine arabinoside Cytauxzoonosis anemia due to, 663-664, 664f molecular assays for diagnosis of, 1087 Cytochrome P450 activity, 45 Cytogenetics, 1263-1265, 1264f

Cytokines, 692-696 as biomarker in human acute renal failure, 966t definition of, 692 in degenerative joint disease, 709-710 for feline immunodeficiency virus, 1060 feline infectious peritonitis and, 1040 hematopoietic growth factors as, 695 inflammatory skin disease and, 258 interleukins as, 694-695 investigational use of, 695-696 physiology of, 692, 693b, 693f-694f in systemic anaphylaxis, 698 therapeutic uses of, 692-694 Cytology in cancer staging, 769 ear swab, 374 mineral oil, 374 exfoliative in Helicobacter gastritis, 454 in lower respiratory tract disease, 863-864, 866t in minimum database, 165t nail bed, 374-375, 375f in otitis media, 414 skin, 374-375 Cytosar-U. See Cytosine arabinoside Cytosine arabinoside, 777t, 778-779 Cytostatic drugs, 1137 Cytotec. See Misoprostol Cytotoxic drugs for immune-mediated arthritis, 716 Cytotoxic T lymphocytes, feline infectious peritonitis and, 1039-1040 Cytoxan. See Cyclophosphamide D Daily energy requirement (DER), 244-245 for senior and geriatric cats, 246 Daily rounds, 1313 Daily routine in population wellness program, 1345-1346 Dander, allergic reactions to, 419-424 “Dandruff”, 391 Dantrolene for urethral obstruction, 1003 in feline idiopathic cystitis, 992t Darbepioetin for anemia of chronic renal disease, 671 pharmacodynamic monitoring of, 1140t Daylily toxicosis, 921-923, 958t D cells, 548t DCM. See Dilated cardiomyopathy (DCM) DDAVP. See Desmopressin (DDAVP) D-dimer test, 684 Death anesthesia-related, 112, 113b, 127 due to feline immunodeficiency virus, 1060 fetal, 1205-1206, 1206f following renal transplantation, 962 kitten, 1228-1229, 1229t-1230t due to lily toxicosis, 922t Deciduous teeth, eruption of, 329, 330t Decision making in population wellness program, 1315 Declawing. See Onychectomy Decontamination environmental, for control of feline calicivirus, 1034 for toxicity, 930-932 Décor of veterinary hospital, 21, 21f-22f Defecation outside of litter box, 217-218 Deficiencies, nutritional, 249-250, 250t Degenerative joint disease (DJD), 709-710, 709b with acromegaly, 614 following cranial cruciate ligament rupture, 722 in senior cat, 1173-1174, 1173f, 1174b therapy for, 713-715, 715b

Degenerative myelopathies, 750-751 Degenerative neurologic disorders, 737-738, 737f Degranulation in systemic anaphylaxis, 698 Dehydration, 58, 59t assessment of, 58 associated with chronic kidney disease, 969 crystalloid solutions for, 61 due to feline panleukopenia virus, 1037-1038 fluid plan for, 78, 79t due to lily toxicosis, 922t low-sodium crystalloids for, 65 neonatal, 1239, 1239f in sepsis, 1243b in senior cat, 1169-1170 subcutaneous fluid calculation for, 969b treatment in palliative care, 1155-1156, 1155b in urethral obstruction, anesthesia and, 141-142 7-Dehydrocholesterol, 240 Delayed gastric emptying, 456-457 Delirium, perioperative in geriatric patient, 138 Delivery cesarean, 1212-1213, 1212b, 1213f normal, 1207-1209, 1208f, 1209b postpartum problems following, 1213-1215 problems with, 1209-1213, 1210b Delta cells, 548t Delvosteron. See Proligesterone Demadex. See Torsemide Demerol. See Meperidine Demodex mites, 380-381, 380f skin scrapings for identification of, 373-374 Demodicosis, 380-381, 380f with feline immunodeficiency virus, 1057-1058, 1058f otitis due to, 412 Dendritic corneal ulcers, 818, 819f Dental anatomy, 236, 329-335 bones and joints in, 332-333, 334f common terminology in, 335, 336f muscles, cheeks, and lips in, 333 oral mucosa in, 332, 333f palate in, 333-334, 334f periodontium in, 331-332 teeth in, 330-331, 332f eruption of, 329, 330t formulas of, 329-330, 330f-331f, 330t tongue in, 334, 335f Dental block, 103 Dental care, 167-168, 167f at home, 168 internet resources for, 159b, 177t in population wellness program, 1328 in preventive health care, 156t, 167-168, 177t Dental disease dentoalveolar trauma as, 348-349 diagnostic imaging in, 338-341 computed tomography in, 340-341, 340f radiography in, 338-340, 338f-339f jaw fractures as, 359-362, 360f-362f local and regional anesthesia in treatment of, 341-342, 341f-342f nutritional management of, 256-257 periodontal, 342-344, 343f of temporomandibular joint, 362-365, 363f-364f tooth extraction for, 350-353, 351f-354f tooth resorption as, 344-348 Dental examination, 335-338 diagnostic imaging in, 338-341 extraoral, 336 intraoral, 336-338, 337f laboratory, 338

INDEX Dental examination (Continued) patient history and clinical signs in, 335-336 Dental explorer, 337-338, 337f Dental film, 338, 338f Dental luxator, 350-351, 351f Dental radiographs, 167 Dentin, 331 Dentoalveolar trauma, 348-349, 348f-349f Deoxycholate amphotericin B, 853t, 856 Deoxyribonucleic acid (DNA) defined, 1271b-1272b feline immunodeficiency virus, 1057 feline leukemia virus, 1048, 1050, 1050t in molecular assays, 1082-1083 polymerase chain reaction, 1083-1084 Deoxyribonucleic acid (DNA) array, 1266-1267 Deoxyribonucleic acid testing, 1273, 1274t Depigmentation, 407 Depression in hyperthyroidism, 575 due to lily toxicosis, 922t DER. See Daily energy requirement (DER) Dermacentor variabilis tick vector, 1026 Dermanyssus gallinae, 379 Dermatitis actinic, 398 atopic, 387-391, 388f-389f, 390t feline herpesvirus-1 in, 1030, 1030f flea allergy, 385, 385b granulomatous, 392-393 herpetic periocular, 815-816, 815f Malassezia, 383-384 miliary, 404, 404f paraneoplastic exfoliative, 398, 795 perineal, 492, 492f solar, 398 Dermatologic signs of food hypersensitivity, 252, 252f of hypothyroidism, 585, 586t of nutritional deficiencies, 258 of paraneoplastic syndrome, 795, 795f Dermatology, 371-424 human allergies to cats, 419-424 skin disease alopecia as, 399-402, 400f chin acne and chin furunculosis as, 398-399 diagnosis of, 371-377, 372f diseases of paw pads, paronychia, and anal sacs, 407-410 eosinophilic lesions as, 403-406 fragile skin as, 406, 406f hard skin as, 406-407, 407f nonhealing wounds as, 416-417, 416b otitis as, 410-416 pigmentary changes, 407 pruritus as, 377-391 scaling, crusting, and greasy skin as, 391-398 ulcers and erosions as, 402-403 Dermatology kit, diagnostic, 371, 372f Dermatophyte culture, 376, 376f Dermatophytosis, 385, 391-396, 392f, 394f management in animal shelters, 395-396 testing for in population wellness programs, 1322-1323 in preventive health care, 166 Desensitization for behavior modification, 227 for petting aggression, 223 Desflurane, 129 Deslorelin, 1200t Desmopressin (DDAVP) adverse effects of, 622

Desmopressin (DDAVP) (Continued) cost of, 622 for diabetes insipidus diagnosis and therapy, 619, 620t, 621-622 transmucosal administration of, 49t Desoxycorticosterone pivalate (DOCP), 609 Detemir insulin, 554-555 Developmental myelopathies, 751-752 Devon Rex cat moyopathy in, 728t, 730, 730f multifactorial clotting factor defect in, 682 phenotypic mutations in, 1276-1277, 1276f DEXA. See Dual-energy x-ray absorptiometry (DEXA) Dexamethasone for hypoadrenocorticism, 609 for immune-mediated hemolysis, 659t, 660 for immunosuppression, 1135t for inflammatory bowel disease, 439 for otitis media, 414 for spinal trauma, 755 for uveitis, 831 Dexamethasone sodium phosphate for anaphylaxis, 699t, 700 for emergency treatment of bronchial disease, 870-871 Dexamethasone suppression test in hypoadrenocorticism, 596 high-dose, 596t, 597-598 low-dose, 596-597, 596t Dexdomitor. See Dexmedetomidine Dexmedetomidine in balanced anesthetic technique, 129t, 131-132 for pain management, 104-105 for sedation and premedication, 114t, 115-116 Dexrazone, 775-776 Dextrose in crystalloid solutions, 61t, 63t for diabetic ketoacidosis, 87 for dystocia, 1211 in fluid therapy, 80 in parenteral nutrition, 277, 277f DHA. See Docosahexaenoic acid (DHA) DI. See Diabetes insipidus (DI) Diabetes insipidus (DI), 618-622 cause of, 618 clinical features of, 618 confirming diagnosis of, 619-621, 620t diagnostic workup for, 619 fluid and electrolyte loss assessment for, 79t prognosis of, 622 treatment of, 621-622 Diabetes mellitus (DM), 547-567 with acromegaly, 612-614, 613f carbohydrates and, 294-295 clinical signs and diagnosis of, 548-549 complications and concurrent conditions with, 564 feline lower urinary tract disease, 1106-1108 hyperthyroidism, 1101-1103 obesity, 1103-1106, 1105f, 1105t pancreatitis, 513 definition of, 1103 diabetic crisis in, 564-567, 566f epidemiology of, 547-548, 548f fluid and electrolyte loss assessment for, 79t nutritional management of, 264-265, 265b due to pancreatic adenocarcinoma, 518 pathophysiology of, 549-550, 549f-550f prevalence of, 548f treatment of, 556b diet in, 562-563

Diabetes mellitus (DM) (Continued) insulin resistance and, 563-564, 563t insulin therapy for, 552-562, 553t, 557f-558f, 558t oral hypoglycemic agents for, 562 underlying causes of, 550-551 Diabetic crisis, 564-567, 566f Diabetic ketoacidosis (DKA), 565-567 as diabetic crisis, 564-567 fluid therapy for, 86-87 low-carbohydrate diets and, 295 treatment and management protocol for, 565b Diabetic neuropathy, 564, 761, 761f pain of, 1150 Diagnostic dermatology kit, 371, 372f Diagnostic imaging. See Imaging Dialysate, 960 Dialysis, 960-961, 960f Diamox. See Acetazolamide Diaphragmatic hernia, 907-909, 908f-909f peritoneopericardial, 324, 324f Diarrhea, 459-465 biopsy in, 465 blood and urine testing in, 463-465 Campylobacter, 478-479 Clostridium difficile, 479 defined, 459 diagnostic approach to, 460f in exocrine pancreatic insufficiency, 519 fecal assessment and culture in, 462-463, 463b fluid and electrolyte loss assessment in, 79t fluid loss due to, 57, 59t in hyperthyroidism, 572t, 575 imaging in, 465 infectious causes of, 477-480, 477t in kitten, 1242 physical examination in, 462 signalment and clinical history in, 460-462, 461t treatment of antimicrobials and antiparasitics for, 436-438, 437t dietary modifications for, 435 immunosuppressive therapies for, 438-439, 438t probiotics and prebiotics for, 436 vitamin supplementation for, 435-436 Tritrichomonas foetus, 506 Diastolic blood pressure for monitoring of fluid therapy for hypovolemia, 75-76 Diazepam for appetite stimulation in cardiovascular disease treatment, 257t in critical care setting, 272-273 for behavior-modification therapy, 232t, 233 for sedation and premedication, 114-115, 114t administered with ketamine, 119-121 neonatal, 1248 for seizures, 736, 736t for toxicosis-associated seizures, 916t due to permethrin, 920b transmucosal administration of, 49t for urethral obstruction, 1000, 1003 in feline idiopathic cystitis, 992t Dibenzyline. See Phenoxybenzamine Dieffenbachia spp. toxicity, 924, 925f Diestrus, 1196-1197 vaginal cytology changes in, 1216b Dietary factors in cancer, 267 in constipation, 486t in dental and oral disease, 257 in gastrointestinal disease, 259, 260b in hepatic disease, 260

1367

Dietary factors (Continued) in hyperthyroidism, 265-266 in idiopathic cystitis, 282 in skin disorders, 258 in urolithiasis, 280-281, 280b Diet/dietary therapy cancer and, 267, 267f for cardiorenal syndrome, 1113 cardiovascular disease and, 256, 256b changing of, 169, 263b chronic kidney disease and, 278-279, 279b, 279f, 971-973, 972t-973t hypertension and, 970 chylothorax and, 268-269 in critical care, 272 “dental”, 257 diabetes mellitus and, 264-265, 265b, 562-563 with feline lower urinary tract disease, 1107-1108 for diarrhea treatment, 435 elimination, 259 in food hypersensitivity diagnosis, 252-253, 252b, 387 for gastrointestinal disease, 259 for feline lower urinary tract disorders, 1108 fiber-enhanced, 259 gastrointestinal, 258-259 for geriatric or senior cat, 247 gluten-free, 259 hepatic disease and, 260, 260b herpesvirus and, 268 homemade, 295-297 for hypercalcemia, 635b hyperthyroidism and, 265-266, 266b, 581-582 for idiopathic hepatic lipidosis, 532 for impacted feces management, 487-488 for inflammatory bowel disease, 468 pancreatitis with, 1116-1117 low-fat, 259 maternal, effects on kitten, 183 in medical history, 29 for obesity, 262-264, 263b, 263f-264f osteoarthritis and, 266 in preventive health care, 168, 177t raw foods, 289-292, 290b, 291t for senior cats, 1177-1178 for urolithiasis, 280-281, 280b-281b, 995-996 for vomiting treatment, 433-434 Diet history, 262b Diet in clinical history in cat with diarrhea, 461t for vomiting cats, 428t Diffuse iris melanoma (DIM), 832-833, 832f Digestive system disease. See also Gastrointestinal disease anorectal, 490-492 blood testing in, 464-465, 464t diarrhea in, 436-439, 459-465 biopsy in, 465 blood and urine testing in, 463-465 fecal assessment and culture in, 462-463, 463b imaging in, 465 overview of, 459-460, 460f physical examination in, 462 signalment and clinical history in, 460-462, 461t treatment of, 435-439, 437t-438t esophageal, 441-450 clinical presentation of, 441-442, 441t diagnostic approach to, 442-443, 442f esophagitis and esophageal strictures as, 443-446, 444f, 445t foreign bodies as, 446-447, 447f hiatal hernia as, 449, 449f megaesophagus as, 447-448, 448f

1368

INDEX

Digestive system disease (Continued) neoplasia as, 448 vascular ring anomaly as, 448 intestinal, 466-496 constipation as, 484-489, 487t infectious enteritis as, 477-480 inflammatory bowel disease as, 466-469 megacolon as, 488-489 neoplasia as, 469-477 obstruction as, 480-484 of liver, 522-537 amyloidosis as, 527-528 ascites as, 526-527, 538-546 aspirates and biopsies in, 529-530 cholestasis and icterus as, 525, 525b, 526f clinical signs of, 522 feline cholangitis syndrome as, 533-534, 533f-534f, 534b hepatobiliary imaging in, 528-529 hepatobiliary neoplasia as, 527-528, 527f-528f, 527t idiopathic hepatic lipidosis as, 530-533, 531b, 531f-532f, 532t liver function tests in, 524-525 of peritoneal cavity, 538-546 portal hypertension and hepatic encephalopathy, and acquired protosystemic shunting as, 526-527, 534-535, 535t-536t routine laboratory testing in, 522-524, 523f therapy for, 530-535 pancreatic, 513-522 cysts, pseudocysts, and bladders as, 516-517 exocrine pancreatic insufficiency as, 518-520 neoplasia as, 517-518 nodular hyperplasia as, 517 pancreatitis, 513-516 parasites as, 496-512 cestodes, 500-501 nematodes, 496-500 protozoa, 501-511 trematodes, 501 of stomach, 450-459 clinical presentation of, 451-452 gastric motility disorders and delayed gastric emptying as, 456-457 gastritis as, 452-455, 452f-453f, 455f neoplasia as, 457-458, 457f-458f ulceration as, 455-456 vomiting in, 426-431, 427f biopsies in, 430 blood and urine testing in, 429 imaging in, 430 pathways in stimulation of, 426-427, 426f physical examination in, 429 signalment and clinical history in, 428-429, 428t therapies for, 431-435, 432t Digital dental radiography, 338 Digital pad calluses, 408 Digital thermometer, 33f Digits, tumors and other swellings of individual, 409 Dignity, dying with, 1159-1162 Digoxin, 322t Dihydrostreptomycin, 1078t Dilated cardiomyopathy (DCM), 314, 314f taurine deficiency in, 250, 256, 256f, 301, 314 Dilation for esophageal strictures, 445-446 DIM. See Diffuse iris melanoma (DIM) Dimenhydrinate, 973t Dimethyl sulfoxide (DMSO), 775-776 Dinotefuran, 382t

Diphenhydramine for anaphylaxis, 699t, 700 for blood transfusion reactions, 68 in chronic kidney disease therapy, 973t for pruritus in atopic cat, 390t Diphyllobothrium lactum, 500-501 Dipylidium caninum, 170t, 171, 500-501 Direct Coombs’ test in immunemediated hemolysis, 659 Direct ophthalmoscopy, 810f Direct wet preparation for fecal analysis, 462, 463b Dirofilaria immitis, 171-172, 883 Disaster preparedness, 160 internet resources for, 159b Discharge nasal assessment of, 33 in chronic rhinosinusitis, 857, 857f differential diagnosis for, 847b in nasal disease, 846-847 postpartum, 1209 Discomfort, alleviating of in palliative medicine, 1158-1159, 1159f Disease carbohydrates and, 294-295 environmental enrichment and rates of, 228 genetic heterogeneity for, 1281 raw food diets and, 291-292 testing in population wellness program, 1321-1323 DISHA mnemonic, 1171 Disinfection in population wellness program, 1347-1349, 1348b Disseminated intravascular coagulation (DIC), 680t, 682 paraneoplastic, 797 Dissociative anesthetics, 116-118, 117b Dissolution therapy for struvite uroliths, 995-996 Distal, oral anatomy and, 335 Distal paw block, 103-104, 104f Diuresis following urethral obstruction, 1002-1003 for nephrotoxicity, 932 postobstruction and in healing phase of acute renal failure, fluid therapy and, 83-84 Diuretics for cardiorenal syndrome, 1112 effects on urine, 938b for hydrocephalus, 738 for hypercalcemia, 634-636, 634b-635b resistance in heart failure, 1112 DJD. See Degenerative joint disease (DJD) DKA. See Diabetic ketoacidosis (DKA) DMSO. See Dimethyl sulfoxide (DMSO) DNA defined, 1271b-1272b feline immunodeficiency virus, 1057 feline leukemia virus, 1048, 1050, 1050t in molecular assays, 1082-1083 polymerase chain reaction, 1083-1084 DNA array, 1266-1267 DNA testing, 1273, 1274t accuracy of, 1281-1282 Dobutamine, 699-700 Docosahexaenoic acid (DHA), 1113 DOCP. See Desoxycorticosterone pivalate (DOCP) Documentation of body weight in medical record, 261 Dog, hyperadrenocorticism in cats versus, 592-594 Döhle bodies, 676 Dolasetron in chronic kidney disease therapy, 973t

Dolasetron (Continued) in hepatic lipidosis therapy, 532-533, 532t for vomiting, 432t, 433 in pancreatitis, 516 Dolichocephalic cat, 332-333 Domestication of cat, 1255 Domestic cat breeds of, 1255-1259 origins of, 1254-1255 Dominant allele, 1271b-1272b Donor for blood transfusion, 655 Dopamine agonists for acromegaly, 618 Dopamine for anaphylaxis, 699-700, 699t Doppler ultrasound monitoring during anesthesia, 134-135, 134f Dopram, 849 Dorsal, oral anatomy and, 335 Dorsal scapular luxation, 717 Dorzolamide, 837 Dosing adjustments for renal insufficiency, 40-44, 42f, 42t adjustments in senior cats, 1167 analgesic drug, 97t chemotherapy, 772-774 insulin therapy, 555-557 psychotropic drugs, 231-232 Double contrast cystography in feline idiopathic cystitis, 988 in feline lower urinary tract disease, 984, 984f Doxil. See Liposomal-encapsulated doxorubicin Doxorubicin as chemotherapy agent, 777t, 778 extravasation due to, 775-776 hypersensitivity to, 776 for injection-site sarcoma, 789-790 for lymphoma, 784-785, 784t for mammary tumors, 793 Doxycycline for anaplasmosis, 1027 for Bordetella pneumonia, 881 for chlamydial conjunctivitis, 822 drug compounding and, 46 for ehrlichiosis, 1026 esophageal damage due to, 444, 852-854 for heartworm prophylaxis, 885 for hemoplasmosis, 667-668 for mycobacterial infection, 1078t for Mycoplasma lower respiratory tract infection, 880 for plasma cell pyodermatitis, 408 for rickettsial disease, 1026 for skin disease, 384t for stomatitis, 350 for upper respiratory tract infection, 852-853, 853t Drainage for pyothorax, 901-904 Dramamine. See Dimenhydrinate Dried solidified blood (DSB) uroliths, 997-998 Drontal Plus. See Febantel Drooling, 336 Drop trap, 1293f Drug(s)/drug therapy adverse reactions to (See Adverse drug reactions (ADRs)) analgesic (See Analgesia/analgesics) for behavior problems, 230-233, 232b, 232t chemotherapeutic, 776-781, 777t effects on urine pH, 941 effects on urine samples, 937, 938b in hepatic insufficiency, 44, 44b, 44f infusion, fluid administration as vehicle for, 65 metabolism of, 40, 41t in neonates and kittens, 44-45 for pain management, 1150-1153 routes of administration alternative, 47-49, 49t

Drug(s)/drug therapy (Continued) for analgesic drugs, 94-96 for fluid therapy, 69-73 transdermal, 47-48 transmucosal, 48-49 in senior cats, 45-46, 45f, 46b, 1167-1168, 1167t toxicity of, 928-929 Drug compounding, 46-47, 47f, 47t Drug dosages adjustments for renal insufficiency, 40-44, 42f, 42t adjustments in senior cats, 1167 analgesic drug, 97t insulin therapy, 555-557 psychotropic drugs, 231-232 Drug interactions, opioid, 97 Dry foods, 168-169, 245 chronic kidney disease and, 972t dental disease prevention and, 257 Dry kibble, 245 DSB. See Dried solidified blood (DSB) uroliths Dual-energy x-ray absorptiometry (DEXA), 1103-1104 Due date, prediction of, 1206, 1207b, 1207f, 1207t Dupuytren’s contracture, 727 Dwarfism disproportionate in hypothyroidism, 586, 586t pituitary, 611 Dying with dignity, 1159-1162 Dynamic murmur, 301 Dynamic testing in hyperthyroidism, 578-579, 578t Dysautonomia, 762, 762f Dysostoses, 725-726 Dysphagia, 336 Dysplasia hip, 718, 719f patellar luxation and, 719 physeal, 707-708 Dyspnea in hyperthyroidism, 572t Dystocia, 1209-1212, 1210b Dystrophin-deficient myopathy, 728t Dystrophin gene mutation, 1279 E Ear bands for identification in population wellness program, 1318, 1320f Ear fold genetic mutation, 1275t, 1277-1278, 1278f Early spay and neuter (ESN), 1246-1249 Ear mites, 377-379 otitis due to, 412 Ear(s), 192, 192f in body language, 193 in communication, 5f, 6 congenital defects of, 1233b examination of, 34 in assessment of skin diseases, 372 for home blood glucose monitoring, 561, 561f otitis of, 410-416 Ear swab cytology, 374 mineral oil, 374 in otitis diagnosis, 411 Ear tipping for identification, 1300-1301, 1302f-1303f, 1304b Easter lily toxicosis, 921-923, 922f acute renal failure due to, 958, 958t Eating. See Feeding EBC. See Exhaled breath condensate (EBC) analysis EBVs. See Estimated breeding values (EBVs) Eccentrocyte, 649f ECF. See Extracellular fluid (ECF) Echinococcus multilocularis, 500-501 Echinocytes, 649-650, 649f

INDEX Echocardiography in arterial thromboembolism, 316, 316f-317f in diagnosis of heart disease, 305-306 in dilated cardiomyopathy, 314, 314f in heartworm, 884t, 885 in hypertrophic cardiomyopathy, 311, 311f in peritoneopericardial diaphragmatic hernia, 324f in unclassified cardiomyopathy, 314-315, 315f in ventricular septal defect, 323f Eclampsia, 1213 hypocalcemia with, 638 Edema, pulmonary, 58 EDS. See Ehlers-Danlos syndrome (EDS) EDTA. See Ethylenediaminetetraacetic acid (EDTA) Education, client in feline-friendly veterinary visits, 9, 10b in prevention of behavioral problems, 160-161 transportation to veterinary hospital in, 9-10 Effective plasma volume, 55-56 Effusion(s) due to feline infectious peritonitis, 1040, 1043, 1043f peritoneal fluid, 540t chylous, 543 hemorrhagic, 543 pleural (See Pleural effusion) EG. See Ethylene glycol (EG) EHBDO. See Extrahepatic bile duct obstruction (EHBDO) Ehlers-Danlos syndrome (EDS) collagen defect of, 680 fragile skin with, 406, 406f Ehrlichiosis, 1025-1027 Eicosapentaenoic acid (EPA) for cardiorenal syndrome, 1113 Elapid snakes, 927 Elderly persons, cat ownership for, 1095 Electrical cord oral injury, 358-359, 359f Electrocardiography (ECG) during anesthesia in patient with hypertrophic cardiomyopathy, 144-145 in arrhythmias, 319f-320f in atrioventricular blocks, 321, 321f in heart disease, 303-307 in hypoadrenocorticism, 608 in isorhythmic dissociation, 322f in neonate, 1238 as screening test, 303-304 Electrolytes addition of in fluid therapy, 62-64 administration of during anesthesia in hepatic lipidosis, 143 in hyperthyroid patient, 141 in cardiorenal syndrome, 1114 in fluid balance, 53 monitoring and correction of in diabetic ketoacidosis, 86-87 normalization of in liver disease, 530-531 for urethral obstruction, 999 Electrolyte disorders assessment in minimum database, 165t in azotemia, fluid therapy in, 83 central nervous system signs of, 739-740 constipation due to, 485-487, 486t in urethral obstruction, 999 Electronic identification, 158 Elemental zinc for appetite stimulation, 257t Elimination licking of anogenital area by queen for stimulation of, 187, 187f preventive health care and, 156t in unacceptable locations, 217-218

Elimination diet, 259 in food hypersensitivity diagnosis, 252-253, 252b, 387 for gastrointestinal disease, 259 for vomiting, 434 ELISA. See Enzyme-linked immunosorbent assay (ELISA) Elizabethan collar canopy for oxygen delivery, 895, 896b-897b, 896f Embryogenesis, 1233 Emergency treatment of asthma and bronchitis, 870-871 of urethral obstruction, 999-1000 Emesis induction for toxicosis, 916t, 931 EMLA cream, 15, 102 Emodepside, 498, 499t Emollient laxatives, 487, 487t Emotional Subjective Assessment Plan, 38f Empathy in behavioral history taking, 206 Enalapril for cardiorenal syndrome, 1112 dosage adjustment in renal insufficiency, 42t for hypertension with chronic kidney disease, 1122t Enamel on tooth, 330-331 resorption of, 344 Encephalopathy feline ischemic, 746-747, 747f hepatic, 526-527, 534-535, 535t metabolic and nutritional, 739-740 vascular, 746-747, 746f Endemic dermatophytosis, 395-396 Endocardial cushion defect, 323 Endocarditis, 326 Endocrine factors in physeal dysplasia, 708 Endocrine pancreatic disease, 547-571 diabetes mellitus as, 547-567 clinical signs and diagnosis of, 548-549 complications and concurrent conditions with, 564 diabetic crisis in, 564-567, 566f epidemiology of, 547-548, 548f pathophysiology of, 549-550, 549f-550f treatment of, 551-564 underlying causes of, 550-551 gastrinoma as, 567 insulinoma as, 567-568 overview of, 547, 548t Endocrinologic disease, 547-642 of adrenal glands, 592-610 catecholamine secreting tumors as, 602 hyperadrenocorticism as, 592-602 hyperaldosteronism as, 602-606 hypoadrenocorticism as, 606-609 sex hormone secreting tumors as, 602 of calcium metabolism, 625-642 calcium homeostasis and, 625-626, 625f hypercalcemia as, 626-627, 629-636 hyperparathyroidism as, 629 hypocalcemia as, 636-640 central nervous system signs of, 739-740 diabetes mellitus as, 547-567 carbohydrates and, 294-295 clinical signs and diagnosis of, 548-549 complications and concurrent conditions with, 564 diabetic crisis in, 564-567, 566f epidemiology of, 547-548, 548f nutritional management of, 264-265, 265b, 562-563 pathophysiology of, 549-550, 549f-550f treatment of, 551-562

Endocrinologic disease (Continued) underlying causes of, 550-551 gastrinoma as, 567 insulinoma as, 567-568 obesity as, nutritional management of, 260-264, 262b-263b, 263f-264f pancreatic, 547-571, 548t paraneoplastic, 797-798 of pituitary gland, 610-625 acromegaly as, 611-618 anatomy and physiology and, 611 Cushing’s disease as, 611 diabetes insipidus as, 618-622 dwarfism as, 611 macrotumors as, 611 of thyroid gland, 571-592 adenocarcinoma as, 584 hyperthyroidism as, 571-584 hypothyroidism as, 584-588 Endogenous adrenocorticotropic hormone (ACTH) concentration in hyperadrenocorticism, 598 in hypoadrenocorticism, 608 Endometrial hyperplasia, 1219-1222, 1220f Endoparasitic prophylaxis, 172 for kittens, 172 Endoscopy in esophageal disease, 443, 446-447 in gastric neoplasia, 457 in gastric ulceration, 456 in gastrointestinal disease diagnosis, 430 Endothelial disorders, 679 Endotracheal intubation, perioperative, 127 End-tidal carbon dioxide partial pressure monitoring during anesthesia, 135 Enema for obstipation, 488 phosphate, hypocalcemia due to toxicity, 638 Energy deficiency of, 250t in skin disorders, 258 excess of, 249t intake for hepatic disease, 260b Energy requirements, 168, 244, 245t in critical care, 272 daily fluid needs and, 58 in idiopathic hepatic lipidosis, 532 obesity and, 262 during pregnancy, 246 for senior cat, 1168 Enilconazole, 393 Enrofloxacin for Campylobacter diarrhea, 478-479 dosage adjustment in renal insufficiency, 43 for senior and geriatric cats, 45 for Escherichia coli diarrhea, 479 for feline cholangitis syndrome, 534 for hemoplasmosis, 667-668 for mycobacterial infection, 1078t for neonatal sepsis, 1244t for skin disease, 384t toxicity, chorioretinal disease due to, 839-840, 839f for upper respiratory tract infection, 852-853, 853t Enteral nutrition, 271-277 appetite stimulants in, 272-273 enterostomy feeding tube in, 277 esophagostomy feeding tube in, 274-276, 275f-276f forced feeding in, 273, 273f gastrostomy feeding tube in, 276, 276f nasoesophageal feeding tube in, 273-274, 273f-274f nursing care and coaxing in, 272 orogastric feeding tube in, 273, 273f in palliative care for cancer, 803-804 tube feeding in, 273

1369

Enteric pathogens feline coronavirus as, 1039 testing for in population wellness programs, 1323, 1323b Enteritis, infectious, 477-480, 477t Enteritis agents, 1061 coronavirus as, 1038-1047 Enterochromaffin cells, 548t Enterostomy feeding tube, 277 Enterotomy for intestinal foreign body removal, 483, 483f Enthesopathies, 711 Entropion, 814-815, 815f Environmental decontamination for control of feline calicivirus, 1034 Environmental enrichment in behavioral problem prevention, 161-163, 162f for cognitive dysfunction in senior cat, 1173 in colony housing, 1340-1341, 1340f-1342f for feline idiopathic cystitis, 988-991, 989b, 990f internet resources for, 159b in long-term pain management, 1153 in population wellness program, 1343-1345, 1343f-1345f preventive health care and, 160-161 resources for, 990b Environmental factors in constipation, 486t in hyperthyroidism, 571 Environmental health in population wellness program, 1346-1353 cleaning and disinfection in, 1347-1349, 1348b general facility maintenance in, 1353 heating, ventilation, and air conditioning in, 1351-1353 population density in, 1347 segregation of cats in, 1349-1351 for senior cats, 1169 staff training in, 1353 in preventive health care, 156t, 177t Environmental management of behavioral problems, 227-230, 227f novelty in, 230 resting places in, 229, 229f social interaction in, 230 viewing places in, 230 of diabetes mellitus with feline lower urinary tract disease, 1107-1108 of human allergies to cats, 421-422 of hunting and foraging behavior, 228-229, 229f in palliative care for cancer, 803 of scratching, 229 Environmental manipulation for management of urine spraying, 219 Environment in clinical history for vomiting cats, 428t Enzootic disease, feline coronavirus, 1039 Enzyme-linked immunosorbent assay (ELISA) Cryptosporidium felis, 463 in feline immunodeficiency virus infection, 1058 in feline leukemia virus, 1052 in feline panleukopenia virus, 1037 Enzymes liver, elevated in liver disease, 522-524 pancreatic, for exocrine pancreatic insufficiency, 519-520 Eosinophilia, paraneoplastic, 797 Eosinophilic granuloma, 404-405 Eosinophilic granuloma complex, oral, 353, 355f Eosinophilic keratoconjunctivitis (FEK), 826, 826f

1370

INDEX

Eosinophilic lesions, 403-406 familial, 406 granuloma as, 404-405, 405f indolent ulcer as, 403-404, 403f miliary dermatitis and eosinophilic plaques as, 404, 404f due to mosquito and insect bite hypersensitivity, 405 Eosinophilic meningomyelitis, 753 Eosinophilic plaque miliary dermatitis and, 404, 404f in pyoderma, 381-383, 383f Eosinophilic sclerosing fibroplasia, gastrointestinal, 476 Eosinophils bronchial lavage, 866t in bronchial disease, 868 neonatal values, 1236t EPA. See Eicosapentaenoic acid (EPA) Epakitin, 974 Ependymoma, 742 EPI. See Exocrine pancreatic insufficiency (EPI) Epidural administration of analgesic drugs, 95-96 of ketamine, 105 of opioids for analgesia, 100 in balanced anesthesia, 130-131 Epidural lymphoma, 753, 753f Epilepsy. See also Seizures idiopathic, 734-735 Epinephrine for anaphylaxis, 699-700, 699t in adverse drug reactions, 1147 hypokalemia due to release of, 3 transmucosal administration of, 49t Epistaxis, 846-847 Epitheliotropic lymphoma, 398, 398f EPO. See Erythropoietin (EPO) Epsiprantel, 499t Epulis, 365 Equilibrium dialysis, 578, 587 Equipment and supplies for anesthesia, 133-136, 133f for blind bronchoalveolar lavage technique, 865b for bone marrow collection, 643-644, 644f in cat-friendly practice, 23, 23f for chemotherapy, 772b for dermatology mini laboratory, 373b for kitten socialization and training classes, 200, 200f for neonatal spay and neuter, 1248 for resuscitation of neonatal kittens, 1212, 1212b for skin biopsy, 373b for thoracocentesis, 898b for urethral catheterization, 1000, 1000b Erosions, 402-403 Erosive arthritis, 711-712 Eruption of deciduous and permanent teeth, 329, 330t Erythrocytes, 647-653, 648f blood types and, 650-651, 651t-652t disorders of (See Erythrocyte disorders) inherited abnormalities of, 661-662 neonatal values, 1236t oxidative damage to, 664-666, 665b qualitative parameters, 649-650, 649f-650f quantitative parameters, 648-649, 649f splenic storage of, 685-686 Erythrocyte disorders anemia as blood transfusion for, 654-656 clinical evaluation of, 651-653, 654f nonregenerative, 668-673 regenerative, 656-668 supportive care in, 653-656 erythrocytosis as, 673-675, 674f membrane fragility as, 662

Erythrocytosis, 673-675, 674f Erythromycin for Campylobacter diarrhea, 478-479 for nocardiosis, 1080 Erythrophagocytosis, 650 Erythropoietin (EPO) deficiency of, anemia of chronic renal disease and, 670 in erythrocyte production, 647-648 erythrocytosis and, 673-675 for feline immunodeficiency virus, 1060 pharmacodynamic monitoring of, 1140t, 1141 recombinant human for anemia of chronic renal disease, 670-671, 974-975 pharmacodynamic monitoring of, 1140t, 1141 Escape of captured community cat, 1294-1299, 1297f-1298f Escherichia coli food contamination with, 251 in raw food diets, 291, 291t gastrointestinal, 477t, 479 resistant, 479 in urinary tract infection, 1005 Escherichia coli 0157:H7 food contamination, 291 ESN. See Early spay and neuter (ESN) Esophageal disease, 441-450 clinical presentation of, 441-442, 441t diagnostic approach to, 442-443, 442f drug-induced, 852-854 esophagitis and esophageal strictures as, 443-446, 444f, 445t foreign bodies as, 446-447, 447f hiatal hernia as, 449, 449f megaesophagus as, 447-448, 448f neoplasia as, 448 nutritional management of, 259 vascular ring anomaly as, 448 Esophageal feeding tube, 531-532, 532f Esophageal strictures, 443-446, 444f, 445t Esophagitis, 443-446 Esophagostomy feeding tube in critical care setting, 274-276, 275f-276f in palliative care for cancer, 803-804 Esophagus, Barrett, 444 Esophogram in esophagitis and esophageal strictures, 443, 444f in megaesophagus, 447-448, 448f Essential amino acids, 238 Essential fatty acids. See Fatty acids Essential oils toxicity, 925-926, 926f Estate planning, 159b, 160 Estimated breeding values (EBVs), 1282 Estradiol levels during estrous cycle, 1196-1197 in ovarian remnant syndrome, 1202 Estrogen in anestrus, 1196 for termination of pregnancy, 1201 Estrous cycle, 1196-1197, 1196b, 1196f seasonality of, 1195 Estrus, 1196, 1196f control of, 1200-1202, 1200t hormonal events of, 1197-1198 infertility with abnormal, 1217-1218, 1218f infertility with normal, 1218-1219, 1219f length of, 1196b vaginal cytology changes in, 1216b Ethambutol, 1078t Ethanol for ethylene glycol toxicity, 916t Ethylenediaminetetraacetic acid (EDTA), 644 Ethylene glycol (EG) hypocalcemia due to ingestion of, 638 toxicity, 916t, 926-927, 931t acute renal failure due to, 959-960

Etomidate, 118t, 123-125, 124b Eucoleus aerophilus, 882 Europe, history of cats in, 4 European wildcat, 1254-1255 Euthanasia, 1155-1163 in population wellness programs, 1315 Eutrombicula, 379 Examination. See Physical examination Examination room, cat-friendly, 21-22, 22f Excesses, nutritional, 248-249, 249t hypervitaminosis A, 248-249 hypervitaminosis D, 249 polyunsaturated fatty acids, 249 Excessive vocalization, 216-217 Excess moderator band cardiomyopathy, 316 Excisional biopsy for cancer diagnosis, 770 Excretory urography, 944-945 Exercise for pain management, 1153 Exfoliative cytology in Helicobacter gastritis, 454 Exfoliative dermatitis, paraneoplastic, 398, 795 Exhaled breath condensate (EBC) analysis, 868-870 Existing complaint in medical history, 29-31 Exocrine pancreatic disease, 513-522 cysts, pseudocysts, and bladders as, 516-517 exocrine pancreatic insufficiency as, 518-520 neoplasia as, 517-518, 518f nodular hyperplasia as, 517, 517f pancreatitis as, 513-516, 514f-515f Exocrine pancreatic insufficiency (EPI), 518-520 in diabetic cat, 564 Exon, 1271b-1272b Exophthalmos, 813 Expiratory sounds in lower respiratory tract disease, 862 Exploratory rhinotomy, 850-851 Explorer, dental, 337-338, 337f Extracellular fluid (ECF) calcium, 625 Extracellular fluid (ECF) compartment, 53-55, 53f fluid movement in, 54, 54b movement between intracellular fluid compartment and, 54-55 Extracellular fluid (ECF) volume depletion of crystalloid solutions for, 60-64 in diabetic ketoacidosis, fluid therapy for, 86 fluid therapy plan for, 78 sodium balance in disorders of, 55-56 Extraction, tooth, 350-353, 351f-354f for stomatitis, 350 for tooth resorption, 347-348 Extradural spinal tumor, 753 Extrahepatic bile duct obstruction (EHBDO), 525 Extramedullary spinal tumor, 753 Extraneous skeletal mineralization, 726-727, 726f Extraoral examination, 336 Extrasystoles, ventricular, 302 Extravasation, due to chemotherapy, 775-776 Extreme neutrophilic leukocytosis, 676-677 Extrinsic coagulation pathway, 680 Exudates abdominal distention due to, 540t in feces, 461t peritoneal fluid, 542-543 septic, 544-545 in pleural effusion, 899t

Eyes, 191-192 in body language, 193-194 in communication, 5f, 6 physical examination of, 33-34 neonatal, 1232 in senior cat, 1179 toxic exposure, 931 Eye disease. See also Ophthalmologic disease feline calicivirus in, 1033 feline herpesvirus-1 in, 1029-1030 feline immunodeficiency virus in, 1057-1058, 1058f feline infectious peritonitis in, 1040-1041, 1041t Eyelid disorders agenesis, 813-814, 814f congenital, 1233b entropion, 814-815, 815f herpetic dermatitis, 815-816, 815f neoplasia, 816, 816f-817f third eyelid disease, 817, 817f F Fabric eating, 214-215, 214f Face, examination of in assessment of skin diseases, 372 Face mask oxygen delivery, 896b-897b, 896f for pleural effusion, 895 Face off as play behavior, 185, 186t Facial expression, pain assessment based on, 91, 93f Facial nerve, 335 Facial paralysis, 761-762 Facial pheromone, synthetic, 22 Facial signals, 5-6, 5f Facilitating incision for catheter placement, 71 Facility maintenance for environmental health in population wellness programs, 1353 Factor I (fibrinogen) clinical evaluation of, 684 deficiency of, 680t Factor IX deficiency, 680-681, 680t Factor VII deficiency of, 680t in hemostasis, 679-680 Factor VIII deficiency, 680t Factor V in hemostasis, 679-680 Factor X deficiency of, 680t in hemostasis, 679-680 Factor XII deficiency, 680-681, 680t Factor XIII in hemostasis, 679-680 “Fading kitten” syndrome, 586 Failure of passive transfer of immunity (FPT), 1240-1241 Famciclovir, 853t, 855 Familial eosinophilic lesions, 406 Family attendance at kitten classes, 199 Famotidine in chronic kidney disease therapy, 973 for gastrointestinal ulcers, 434, 434t for hepatoencephalopathy, 535t for nutritional care in cancer patients, 805t Fat lip syndrome, 404-405, 405f Fat mass changes in different life stages, 1168t Fats cancer and alterations in metabolism of, 267 deficiency of, 250t diabetes mellitus and intake of, 265b digestibility of in different life stages, 1168t hyperthyroidism intake of, 260b inflammatory bowel disease and intake of, 260b nutritional requirements, 239 obesity and, 262 restriction of, 259 for chylothorax, 268-269

INDEX Fatty acids deficiency of, skin disease associated with, 258 nutritional requirements, 239, 244 omega-3 polyunsaturated for asthma and bronchitis, 874 of cardiorenal syndrome, 715, 1113 for chronic kidney disease, 279b of diabetes mellitus, 265 excessive intake of, 249 for skin disease, 258 for pruritus in atopic cat, 390 FAVN. See Fluorescent antibody virus neutralizing (FAVN) FBMI. See Feline body mass index (FBMI) FCoV. See Feline coronavirus (FCoV) FCV. See Feline calicivirus (FCV) FCV-Ari, 878-879 FCV-Kaos, 878-879 FDA. See Food and Drug Administration (FDA) Fear aggression due to, 220 behavior problems associated with, 212 body postures in communication of, 5-6, 5f examination and, 13-14, 14f facial signals in communication of, 5f, 6 misbehavior and aggression at veterinary visits due to, 7-8 Febantel, 499t for Giardia infection, 504-505 for protozoal disease, 502t Febendazole, 505 Fecal assessment in diarrhea, 460-463, 461t, 463b for parasites, 170-171 in population wellness program, 1326 Purina Fecal Scoring System for, 1327f Fecal culture in diarrhea, 462-463 in Tritrichomonas foetus, 507 Fecal flotation techniques, 170, 463b for Cryptospordium felis diagnosis, 508, 508f for Giardia diagnosis, 503-504, 504f Fecalith, anal sac distention due to, 491, 491f Fecal polymerase chain reaction, 1086 Fecal smear for Cryptospordium felis diagnosis, 508, 508f for Giardia diagnosis, 503-504, 504f FECV. See Feline enteric coronavirus (FECV) Feeding cancer and, 268 in cardiovascular disease, 256, 257t in chronic renal disease, 279 in chylothorax, 269 in critical care, 272-278 in dental disease, 257 effects on urine pH, 940 forced in critical care setting, 273, 273f in gastrointestinal disease, 259 in hepatic disease, 260 in herpesvirus, 268 in hyperthyroidism, 266 in idiopathic cystitis, 282 in idiopathic hepatic lipidosis, 532 kittens and, 186-187 as normal behavior, 195, 237, 243 nutrition and, 237, 243 obesity and, 262-264, 263b, 263f-264f of orphan kittens, 1245-1246, 1245f-1246f in osteoarthritis, 266 in population wellness program, 1326 in skin disease, 258 tube (See Feeding tube) in urolithiasis, 281, 281b

Feeding enrichment, 228-229, 229f in population wellness program, 1344, 1344f Feeding regimens in preventive health care, 168-169 Feeding tube in chronic kidney disease therapy, 973 consideration for, 973b in critical care setting, 273 enterostomy, 277 esophagostomy, 274-276, 275f-276f gastrostomy, 276, 276f for idiopathic hepatic lipidosis, 531-532, 532f for liver disease, 531b nasoesophageal, 273-274, 273f-274f orogastric, 273, 273f for orphan kittens, 1245-1246, 1246f in palliative care, 1157, 1157f FEK. See Eosinophilic keratoconjunctivitis (FEK) Fel d 1 allergen, 420-421 reduction of, 422 Fel d 2 allergen, 420 Fel d 3 allergen, 420 Fel d 4 allergen, 420 Felicola subrostratus, 379 Feline atopic dermatitis, 387-391 Feline body mass index (FBMI), 37, 37b, 37f-38f Feline calicivirus (FCV), 1031-1034, 1032f molecular assays in diagnosis of, 1084 stomatitis due to, 349 upper respiratory disease due to, 854-856 vaccination against, 174t, 175, 1034 Feline cholangitis syndrome, 533-534, 533f-534f Feline coronavirus (FCoV), 1038-1047 clinical signs of, 1040-1042, 1041f-1042f, 1041t diagnosis of, 1042-1045, 1043b, 1043f, 1044t enteric, 477t, 478 in feline infectious peritonitis, 742 molecular assays in diagnosis of, 1087-1088 pneumonia due to, 879 pregnancy loss due to, 1224 prevention and control of, 1046-1047, 1046b, 1046t transmission and pathogenesis of, 1039-1040 treatment of, 1045 Feline enteric coronavirus (FECV), 478 in feline infectious peritonitis, 742 molecular assays in diagnosis of, 1087-1088 Feline-friendly veterinary visit, 9-18 a better way, 3 cat’s perspective on, 3 client education in, 9, 10b client’s perspective on, 2 first veterinary visit and kitten classes in, 10 getting cat out of carrier in, 10-11, 11f handling during examination in, 11-14, 12f-14f handling for laboratory sample collection in, 15-16 hospitalization in, 16-17, 17f receiving cat and client in, 10 returning home in, 17-18 the situation today, 9 transportation to veterinary hospital in, 9-10, 10f veterinary team’s perspective on, 3 Feline genome project, 1266 Feline hemoplasmosis, 666-668, 667f Feline herpesvirus-1 (FHV-1), 1029-1031, 1030f Chlamydophila felis versus, 819-823, 820t in corneal and conjunctival disease, 817-819, 818f-819f, 820b, 824

Feline herpesvirus-1 (FHV-1) (Continued) conjunctivitis, 823 corneal ulceration, 824 eosinophilic keratoconjunctivitis, 826 in feline orbital pseudotumor, 813 in lower respiratory tract infection, 878 molecular assays in diagnosis of, 1085-1086 nutritional management of, 268 in periocular dermatitis, 815-816, 815f pregnancy loss due to, 1224 stomatitis due to, 349 stress and, 1126-1127 upper respiratory disease due to, 854-856, 854f chronic rhinosinusitis, 857 vaccination against, 174t, 175 virologic considerations in, 820b Feline hyperesthesia syndrome (FHS), 763-764, 764t Feline idiopathic cystitis (FIC), 985-992 clinical signs of, 986 diagnosis of, 987-988, 988f management of, 988-992, 989b-990b, 990f, 992t nutritional management of, 281-282 pathophysiology of, 986-987 prevalence of, 985 signalment and risk factors in, 985-986 Feline immunodeficiency virus (FIV), 1056-1061 clinical signs of, 1051b, 1057-1058, 1058f diagnosis of, 1058-1059 genetics of susceptibility to, 1267 lymphoma associated with, 782-783 molecular assays for diagnosis of, 1087 pregnancy loss due to, 1224 prevention and control of, 1061 seroprevalence of, 1048, 1048t testing for, 1021, 1055b in community cats, 1302-1303 false-positive results, 166 in minimum database, 165t in population wellness programs, 1321-1322 transmission and pathogenesis of, 1056-1057 treatment of, 1059-1061 in uveitis, 829t vaccination against, 176, 1059, 1061 in population wellness programs, 1325 recommendations for, 174t Feline infectious peritonitis (FIP), 1038-1047 ascites due to, 543-544 central nervous system, 742-743, 743f clinical signs of, 1040-1042, 1041f-1042f, 1041t diagnosis of, 1042-1045, 1043b, 1043f, 1044t intestinal granulomatous inflammation due to, 484 pleural effusion due to, 898-900, 900f prevention and control of, 1046-1047, 1046b, 1046t renal involvement with, 949 transmission and pathogenesis of, 1039-1040 treatment of, 1045 uveitis due to, 828-830, 828f, 829t vaccination against, 176 Feline interferon omega for stomatitis, 350 for upper respiratory viral infections, 855 Feline ischemic encephalopathy, 746-747, 747f Feline ischemic neuromyopathy, 761

1371

Feline leprosy syndromes, 417, 1077-1079 Feline leukemia virus (FeLV), 1048-1056, 1049t anemia due to, 671-672 clinical signs of, 1050-1051, 1051b, 1051f-1052f diagnosis of, 1052 lymphoma associated with, 782-783 myelopathy associated with, 752-753 neutropenia with, 677 prevention and control of, 1054-1056, 1054b-1055b seroprevalence of, 1048, 1048t spinal lymphoma and, 754 subgroups of, 1048-1049, 1049t testing for, 29 in community cats, 1302-1303 in minimum database, 165t molecular assays in, 1087 in population wellness programs, 1321-1322 transmission and pathogenesis of, 1049-1050, 1050t treatment of, 1052-1054, 1053b-1054b vaccination against, 175-176, 1055-1056 in population wellness programs, 1325 recommendations for, 174t Feline lower urinary tract disease (FLUTD), 980-1013, 981f diabetes mellitus concurrent with, 1106-1108 diagnosis of, 981-985, 982f cytoscopy in, 984-985 imaging in, 983-984, 983b, 984f, 985t physical exam and clinical signs in, 982, 982f urinalysis and urine collection in, 982-983, 983t idiopathic cystitis as, 985-992 incontinence as, 1008-1009, 1008b, 1008f neoplasia as, 1005-1007, 1006f traumatic, 1007-1008 urethral obstruction as, 998-1004, 1000b, 1001f, 1003f urethral plugs as, 998 urolithiasis as, 992-998, 993f, 994t, 995f-998f Feline multisystem granulomatous mycobacteriosis, 417 Feline ocular sarcoma (FOS), 832, 834-835, 835f Feline odontoclastic resorptive lesion (FORL), 344 Feline orbital pseudotumor (FOP), 813 Feline orofacial pain syndrome (FOPS), 355 Feline pancreatic lipase immunoreactivity (fPLI), 514 in diarrhea assessment, 464-465, 464t in inflammatory bowel disease with pancreatitis, 1116 Feline panleukopenia virus (FPV), 1036-1038, 1037f pregnancy loss due to, 1224 vaccination against, 174t, 175 Feline paraneoplastic alopecia (FPA), 795, 795f Feline restrictive orbital sarcoma, 813 “Feline scabies”, 379 Feline symmetrical alopecia (FSA), 399, 401f Feline synctium-forming virus (FeSFV), 711 Feline trypsin-like immunoreactivity (fTL1) in exocrine pancreatic insufficiency, 519 testing of in diarrhea assessment, 464-465, 464t Feline veterinarian, 21

1372

INDEX

Feline viral rhinotracheitis, calcivirus, panleukopenia (FVRCP) vaccine in population wellness programs, 1323-1324 for upper respiratory infection prevention, 855-856 Felis bieti, 1254-1255 Felis catus, 4, 1254-1255 Felis libyca, 4 Felis lybica, 1254-1255 Felis ornata, 1254-1255 Felis silvestris, 191 Feliway, 216-217, 222, 991 FeLV. See Feline leukemia virus (FeLV) Female call, 194 Female reproduction, 1195-1227 clinical problems with, 1202-1204, 1205f control of, 1200-1202, 1200t determining status of, 1204 estrous cycle in, 1196-1197, 1196b, 1196f fertility and breeding management in, 1198-1200, 1199b gestation and parturition in, 1204-1209 care of queen in, 1206-1207 normal labor and delivery in, 1207-1209, 1208f, 1209b postpartum problems with, 1213-1215 prediction of due date in, 1206, 1207b, 1207f, 1207t pregnancy diagnosis in, 1204-1206, 1205f-1206f problems with labor and delivery in, 1209-1213, 1210b hormonal events of estrous and pregnancy in, 1197-1198 infertility and, 1215-1224, 1215b-1216b with abnormal estrus, 1217-1218, 1218f cystic endometrial hyperplasiapyometra complex in, 1219-1222, 1220f-1221f with normal estrus, 1218-1219, 1219f due to pregnancy loss, 1222-1224, 1222b-1223b vaginal cytology in, 1216-1217, 1216b, 1216f puberty and, 1195-1196 seasonality in, 1195 spontaneous ovulation in, 1198 Femoral head and neck excision (FHNE), 708 Femoral neck, resorption and remodeling of, 707-708, 708f Femur, bone marrow collection from, 644-645, 645f Fenbendazole for Aelurostrongylus abstrusus infection, 882 for diarrhea, 436-437, 437t for Giardia infection, 504-505 for protozoal disease, 502t for roundworms, 498 Fencing, 1346f Fentanyl, 98-99 in balanced anesthetic technique, 129t, 130 dose ranges and route of administration for, 97t for pain management in feline idiopathic cystitis, 991 transdermal administration of, 48 for pain management, 1151t, 1152 side effects of, 96 for urethral obstruction in feline idiopathic cystitis, 992t Feral cat, 1290, 1291f, 1299. See also Community cats anesthetic options for, 133 reactive tame cat versus, 1299 Feral kitten, capture of, 1305, 1306b Ferritin, iron-deficiency anemia and, 669

Ferrous sulfate for iron-deficiency anemia, 669 Fertility, control of in female, 1198-1200, 1199b FeSFV. See Feline synctium-forming virus (FeSFV) Fetus development of, 1233 heart rate in, 1205-1206 in dystocia, 1209-1210 palpation of, 1205 ultrasonic evaluation of, 1205-1206 Fever in blood transfusion reactions, 656 in immunocompromised cat, 1128 Fexofenadine, 853t FFP. See Fresh frozen plasma (FFP) FGF5. See Fibroblast growth factor 5 (FGF5) gene mutation FHNE. See Femoral head and neck excision (FHNE) FHS. See Feline hyperesthesia syndrome (FHS) FHV-1. See Feline herpesvirus-1 (FHV-1) Fiber-enhanced diet, 259 for constipation, 487-488 for diabetes mellitus, 265b for diarrhea, 435 for hypercalcemia, 635 for large intestinal disease, 259 for obesity, 262-263 Fiber intake for hyperthyroidism, 266b for inflammatory bowel disease, 260b Fibrillation, atrial, 320 Fibrin, pleural effusion fluid, 899t Fibrinogen (factor I ) clinical evaluation of, 684 deficiency of, 680t Fibrinolysis, 680, 684 Fibroblast growth factor 5 (FGF5) gene mutation, 1276 Fibrodysplasia ossificans, 731 Fibrodysplasia ossificans progressiva, 759, 760f Fibroplasia, gastrointestinal eosinophilic sclerosing, 476 Fibrosarcoma, hepatic, 527t Fibrosis, idiopathic pulmonary, 875, 876f FIC. See Feline idiopathic cystitis (FIC) Fiddle or fidget as fear response, 8 Field capture, 1292-1294, 1293f-1294f, 1295b Fight as fear response, 8 Film, dental, 338, 338f Fine needle aspiration (FNA) in cancer staging, 769 in high-grade intestinal lymphoma, 474-475 in liver disease, 529-530 in pancreatitis, 515 pulmonary, 865 splenic, 687 FIP. See Feline infectious peritonitis (FIP) Fipronil for flea control, 382t toxicity, 921 “FIP test”, 1044 First veterinary visit, 10 FISH. See Fluorescence in situ hybridization (FISH) Fish hook in esophagus, removal of, 447 Fistula anovaginal, 1233f oronasal, 356 Fitergol. See Nicergoline FIV. See Feline immunodeficiency virus (FIV) Five Freedoms, 1314, 1314b Flagyl. See Metronidazole Flap for cleft lip and/or palate congenital, 356 traumatic, 356-357, 357f Flat chest defect, 1234-1235, 1234f-1235f

Flea allergy dermatitis, 381, 383f, 385, 385b Flea combing, 374 Flea infestation, 381 control of in feline atopic dermatitis, 389-390 products for, 382t neonatal, 1242-1243 Flehmen reaction, 1185-1186 Flexible endoscopy in esophageal disease, 443 Flight as fear response, 8 Floor, examination of cat on, 11-14, 12f, 22 Flow-by oxygen delivery, 896b-897b, 896f for pleural effusion, 895 Flubendazole, 499t Fluconazole, 1024t, 1025 absorption of in neonates and kittens, 45 for dermatophytosis, 393-394 for fungal central nervous system infection, 744 for Malassezia dermatitis, 384 for otitis media, 414 for skin disease, 384t for upper respiratory tract disease, 853t, 856 Flucytosine, 1024t, 1025 Fluid. See also Body fluid entries peritoneal analysis and classification of, 541-543, 542t normal, 538b pleural, 892-893 in congestive heart failure, 895 in feline infectious peritonitis, 898-900 in idiopathic chylothorax, 904-905 Fluid bags, sizes of, 59, 60f Fluid excess, assessment of, 58 Fluid pump, 59, 60f Fluid therapy, 79t acid-base and, 80 additives in, 62-64, 63f, 63t for anaphylactic shock, 699 during anesthesia and surgery, 82, 133-136 in urethral obstruction, 142 for arterial thromboembolism, 318 for azotemia and renal disease, 82-84 calculation worksheet for, 62t of cardiorenal syndrome, 1113-1114 for chronic kidney disease, 278-279, 969, 969b for congestive heart failure, 84-86 concurrent with cardiac disease, 85-86 development of plan for, 77-81 case example for, 81, 81t dextrose in, 80 for diabetic ketoacidosis, 86-87, 565b, 566 effects on urine, 938b for extracellular fluid volume depletion, 78 general considerations for, 59, 60f for hypercalcemia, 634-635, 634b for hyperglycemic hyperosmolar syndrome, 87-88, 566 for hypernatremia, 82 for hypoadrenocorticism, 608-609 for hypovolemia, 73-77 for intracellular fluid volume depletion, 78-80 for liver disease, 88-89 maintenance fluid intake and, 80 neonatal, 1239 ongoing fluid losses and, 80 in palliative care, 1155-1156, 1155b-1156b for pancreatitis, 516 routes of administration for, 69-73

Fluid therapy (Continued) intravenous, 69-73, 71t subcutaneous, 69 types of fluid for, 59-69 colloids, 66-69 crystalloids, 60-66, 61t with urethral obstruction, 999 Fluid thrill in ascites, 538-539 Fluke Alaria, 501 lung, 882 Platynosomum, 501 Fluorescein dye, 811, 811f Fluorescence in situ hybridization (FISH), 1083 Fluorescent antibody virus neutralizing (FAVN), 1048 Fluoroquinolones for Campylobacter diarrhea, 478-479 dosage adjustment in renal insufficiency, 42t, 43 for Escherichia coli diarrhea, 479 for hemoplasmosis, 667-668 monitoring of long-term therapy with, 1139t 5-Fluorouracil (5-FU) as chemotherapy agent, 779 toxicity of, 929 Fluoxetine for behavior-modification therapy, 232t for cognitive dysfunction in senior cat, 1172t for feline hyperesthesia syndrome, 763-764, 764t monitoring of long-term therapy with, 1139t for pain management, 1150 Flurazepam for appetite stimulation, 257t Flush, nasal, 850, 850f FLUTD. See Feline lower urinary tract disease (FLUTD) Fluticasone for inflammatory airway disease, 871, 872b transmucosal administration of, 48, 49t for upper respiratory tract disease, 853t Fly bait toxicity, 915 FNA. See Fine needle aspiration (FNA) Focal alopecia inflammatory, 402 noninflammatory, associated with treatments, 402 Focal seizure, 734-735 Focusing and structuring, in behavior history taking, 207 Folate nutritional requirements, 241 testing of in diarrhea assessment, 464-465, 464t Folinic acid for Toxoplasmosis gondii infection, 510 Food Heinz bodies in, 665 introduction of new, 169 preferences for, 237, 243 temperature of, 237 Food and Drug Administration: Center for Veterinary Medicine, reporting of adverse drug reactions to, 1148t Food and Drug Administration (FDA), reporting of food-related illness to, 269, 269b Food component nutritional disorders, 248-250 deficiencies, 249-250, 250t taurine, 250 thiamine, 249 vitamin E, 250 excesses, 248-249, 249t hypervitaminosis A, 248-249

INDEX Food component nutritional disorders (Continued) hypervitaminosis D, 249 polyunsaturated fatty acids, 249 inappropriate, 250 Food contaminants, 251 in raw food diet, 290-291, 290b, 291t Food hypersensitivity, 251-253, 252b, 252f skin disease due to, 386-387 Food intolerance, 253 Food puzzle, 263-264, 263f Food-related illness nutritional management of, 269-270 reporting of, 269b Foot pads for home blood glucose monitoring, 561 FOP. See Feline orbital pseudotumor (FOP) FOPS. See Feline orofacial pain syndrome (FOPS) Foraging, environmental management of, 228-229, 229f Forced feeding in critical care setting, 273, 273f Forceps, tooth extraction, 351, 351f Foreign bodies caught under tongue, 480 esophageal, 446-447, 447f gastritis due to ingestion of, 452-453, 452f-453f intestinal, 480-483, 481f-483f nasal, 858 tongue caught under, 429 in urolith formation, 998 Forelimbs, physical examination of, 34 FORL. See Feline odontoclastic resorptive lesion (FORL) Fortekor. See Bonazepril FOS. See Feline ocular sarcoma (FOS) Foxglove toxicity, 924 Foyer in colony-style housing, 1340-1341, 1342f FP. See Frozen plasma (FP) FPA. See Feline paraneoplastic alopecia (FPA) fPLI. See Feline pancreatic lipase immunoreactivity (fPLI) FPT. See Failure of passive transfer of immunity (FPT) FPV. See Feline panleukopenia virus (FPV) Fracture(s), 704-709 capital femoral physeal, 707-708, 707f-708f mandibular and maxillary, 359-362, 360f-362f, 705-706, 706f nonunion, 709 due to osteogenesis imperfecta, 727 patellar, 706-707, 707f pelvic, 708-709, 708f radial and ulnar, 707 rib, nontraumatic, 910 spinal, 755-756, 755f tooth, 348 Fragile skin, 406, 406f Fragile X site, 1263 Francisella tularensis Free choice feeding. See Ad libitum feeding Free fatty acids, 239 Freeman cage net, 1297f Free-roaming cats. See Community cats Free thyroxine concentration by dialysis (FT4D), 1103 Free thyroxine (FT4) in hyperthyroidism, 578 in hypothyroidism, 587 Freeze as fear response, 8 Fresh frozen plasma (FFP), 66-67 for hepatoencephalopathy, 535t Fresh whole blood (FWB) transfusion, 66-67 for anemia, 654-655 for hemostatic disorders, 684

Front limb, musculoskeletal conditions of, 717-718 Frontline. See Fipronil Frozen plasma (FP), 66-67 Fructokinase activity, 240 Fructosamine in diabetes mellitus diagnosis, 548 home monitoring of, 556-557 in hypothyroidism in diabetic cat, 1103 Fructose-1-phosphate, 239-240 FSA. See Feline symmetrical alopecia (FSA) FT4. See Free thyroxine (FT4) fTL1. See Feline trypsin-like immunoreactivity (fTL1) 5-FU. See 5-Fluorouracil (5-FU) Fundus anatomy of, 838f examination of, 808-810, 810f Fungal infection, 1016-1025 antifungal therapy for, 1024-1025, 1024t associated with hepatopathy or hepatic inflammation, 534b blastomycosis as, 1022-1023, 1022f in central nervous system, 744, 745f coccidioidomycosis as, 1020-1022 cryptococcosis as, 1016-1019, 1017f-1018f, 1018b histoplasmosis as, 1019-1020, 1019f lower respiratory tract, 881 nasal, 856-857, 856f sporotrichosis as, 1023-1024, 1023f urinary tract, 1004 Fungal zoonotic disease, 1094-1095, 1094f Fur mites, 379-380 Furosemide for cardiorenal syndrome, 1112 dosage adjustment in hepatic insufficiency, 44 in renal insufficiency, 42t, 43 for hydrocephalus, 738 for hypercalcemia, 634-636, 634b-635b Furunculosis, chin, 398-399 FVRCP. See Feline viral rhinotracheitis, calcivirus, panleukopenia (FVRCP) vaccine FWB. See Fresh whole blood (FWB) transfusion G GABA. See Gamma-aminobutyric acid (GABA) receptors Gabapentin, 105 for degenerative joint disease, 715 for feline hyperesthesia syndrome, 763, 764t for pain management, 1150-1151, 1151t GAG. See Glycosaminoglycan (GAG) Gait analysis in degenerative joint disease, 710 of Devon Rex and Sphynx myopathy, 730 Galastop. See Cabergoline Gallop heart sound, 302 fluid therapy in heart disease and, 86 in hyperthyroidism, 572t Gamma-aminobutyric acid (GABA) receptors, 115 Gamma cells, 548t Gamma globulin, effusion fluid, 1044t Gamma glutamyltransferase (GGT) in liver disease, 522-523 neonatal values, 1237t Gangliosidosis, 1274t-1275t, 1279 Gas accumulation, abdominal distention due to, 540t Gastric emptying, 451 assessment of, 455-457 delayed, 456-457 Gastric lavage for toxicosis, 931-932

Gastric motility disorders, 456-457 Gastric pH, oral absorption of drugs in neonates and kittens and, 45 Gastric ulcer, 455-456 Gastrinoma, 567 Gastritis, 452-455 acute uncomplicated, 452 chronic, 454-455, 455f due to foreign body ingestion, 452-453, 452f-453f Helicobacter, 453-454 Gastroesophageal reflux disease (GERD), 443-444 Gastrointestinal diet, 258-259 Gastrointestinal disease anorectal, 490-492 blood testing in, 464-465, 464t due to chemotherapy, 774-775 diarrhea in, 436-439, 459-465 biopsy in, 465 blood and urine testing in, 463-465 fecal assessment and culture in, 462-463, 463b imaging in, 465 overview of, 459-460, 460f physical examination in, 462 signalment and clinical history in, 460-462, 461t treatment of, 435-439, 437t-438t esophageal, 441-450 clinical presentation of, 441-442, 441t diagnostic approach to, 442-443, 442f esophagitis and esophageal strictures as, 443-446, 444f, 445t foreign bodies as, 446-447, 447f hiatal hernia as, 449, 449f megaesophagus as, 447-448, 448f neoplasia as, 448 vascular ring anomaly as, 448 intestinal, 466-496 constipation as, 484-489 infectious enteritis as, 477-480 inflammatory bowel disease as, 466-469 megacolon as, 488-489 neoplasia as, 469-477 obstruction as, 480-484 of liver, 522-537 amyloidosis as, 527-528 ascites as, 526-527, 538-546 aspirates and biopsies in, 529-530 cholestasis and icterus as, 525, 525b, 526f clinical signs of, 522 feline cholangitis syndrome as, 533-534, 533f-534f, 534b hepatobiliary imaging in, 528-529 hepatobiliary neoplasia as, 527-528, 527f-528f, 527t idiopathic hepatic lipidosis as, 530-533, 531b, 531f-532f, 532t liver function tests in, 524-525 of peritoneal cavity, 538-546 portal hypertension and hepatic encephalopathy, and acquired protosystemic shunting as, 526-527, 534-535, 535t-536t routine laboratory testing in, 522-524, 523f therapy for, 530-535 nutritional management of, 258-259, 260b pancreatic, 513-522 cysts, pseudocysts, and bladders as, 516-517 exocrine pancreatic insufficiency as, 518-520 neoplasia as, 517-518 nodular hyperplasia as, 517 pancreatitis, 513-516 parasites as, 496-512 cestodes, 500-501

1373

Gastrointestinal disease (Continued) nematodes, 496-500 prevalence of, 169-170, 170t protozoa, 501-511 testing for in population wellness programs, 1323, 1323b trematodes, 501 polymerase chain reaction for detection of agents in, 1086 of stomach, 450-459 clinical presentation of, 451-452 gastric motility disorders and delayed gastric emptying as, 456-457 gastritis as, 452-455, 452f-453f, 455f neoplasia as, 457-458, 457f-458f ulceration as, 455-456 ulcers as, vomiting associated with, 434-435, 434t vomiting in, 426-431 Gastrointestinal signs of food hypersensitivity, 252 of hyperthyroidism, 575 Gastrostomy feeding tube in critical care setting, 276, 276f in palliative care, 1157 Gastrotomy for gastric foreign body, 453 Gauge, catheter, 70 G-CSF. See Granulocyte colonystimulating factor (G-CSF) Gemcitabine, 777t, 779 Gender factors in social practices, 196 Gene, defined, 1271b-1272b Gene interaction, 1271b-1272b Gene locus, 1271b-1272b Gene mutation, 1271b-1272b General anesthesia. See Anesthesia General appearance in acromegaly, 612-613, 613f in hyperthyroidism, 574-575 Generalized seizure, 734-735 Genetic disease hallmarks of, 1270-1273 inaccurate clinical diagnosis of, 1282 Genetic factors in behavioral development of kitten, 182 in diabetes mellitus, 551 in feline infectious peritonitis, 1039-1040 in hypertrophic cardiomyopathy, 310 Genetic map, 1265-1266 Genetic polymorphism, 1271b-1272b Genetic risk factors, 1280-1282 Genetics, 1263-1265, 1264f future of, 1267-1268 glossary of terms, 1271b-1272b Genetic terms, 1271b-1272b Genetic testing, 1282-1285, 1283t accuracy of, 1281-1282 in hypertrophic cardiomyopathy, 311-312 inappropriate, 1285 in polycystic kidney disease, 947 in preventive health care, 166-167 Genetic traits age of onset, 1281 complex, 1280-1282 disease heterogeneity, 1281 disease mutations, 1279 incomplete penetrance, 1280-1281 with known mutations, 1273, 1274t-1275t phenotypic mutations, 1273-1279, 1275f-1279f, 1275t simple, 1273-1280 unidentified, 1279-1280 variable expression, 1281 Genetic variance, 1271b-1272b Genitalia, ambiguous, 1189, 1189f genetics of, 1264 Genome, defined, 1271b-1272b Genome project, feline, 1266

1374

INDEX

Genome-wide association studies (GWASs), 1266-1267 Genomics, 1263-1269 Genotype, 1271b-1272b Gentamicin toxicity, 959 Geographic distribution of blood types in domestic cats, 651, 651t GERD. See Gastroesophageal reflux disease (GERD) Geriatric cat. See Senior cat Germ cells, testicular, 1184 Gestation. See Pregnancy Gestational age, ultrasound for prediction of, 1206, 1207b, 1207f GFR. See Glomerular filtration rate (GFR) GGT. See Gamma glutamyltransferase (GGT) GH. See Growth hormone (GH) Giardia duodenalis, 503-505, 504f, 504t Cryptospordium felis with, 508 Trichomonas foetus versus, 504t Giardia spp. diarrhea due to, 477t molecular assays in diagnosis of, 1086 Gingiva, 331 enlargement of, 342-343 Gingival sulcus anatomy of, 331 examination of, 337-338 Gingivitis, 342-343, 343f Gingivostomatitis with feline immunodeficiency virus, 1057-1058, 1058f pain management in, 1153 Glargine insulin, 554-555 Glass slide impression smear in skin disease diagnosis, 374 Glaucoma, 836-837, 836f-837f due to uveitis, 831-832, 831f Gleevac. See Imatinib Gliadin-free foods, 259 Glioma, 742 Glipizide, transdermal administration of, 48 Globe, anatomy of, 827f Glomerular filtration rate (GFR) drug absorption in neonates and kittens and, 45 drug dosage adjustment and, 41 in hyperthyroidism, 575-576 with chronic kidney disease, 1100 Glomerulonephritis (GN), 951-954, 951b-952b, 953f Glomerulosclerosis, 951 Gloriosa lily toxicity, 958t Glory lily toxicity, 958t Gloves, protective, for chemotherapy, 771 Glucagon, endocrine pancreas production of, 548t Glucagon-like peptide-1, 1105, 1105t Glucocorticoids, 1135-1136, 1135t adverse reactions of, 1136 for anaphylaxis, 700 congestive heart failure associated with, 325 for cytokine inhibition, 692-694 for degenerative joint disease, 715 diabetes mellitus development and, 551 dosage adjustment in hepatic insufficiency, 44 for eosinophilic granuloma complex, 353 fragile skin due to excessive, 406 for hypercalcemia, 634b-635b, 635-636 for hypoadrenocorticism, 609 for immune-mediated hemolysis, 659-660, 659t for inflammatory bowel disease, 438-439, 438t for nasopharyngeal polyps, 851 for pruritus in atopic cat, 390-391

Glucocorticoids (Continued) for stomatitis, 350 for upper respiratory tract disease, 853t Glucokinase activity, 239-240 Glucometer, 559 Gluconeogenesis in diabetes mellitus, 548 Glucosamine for feline idiopathic cystitis, 992 Glucose addition of in fluid therapy, 64 elevated in diabetes mellitus, 548 home monitoring of, 555-557, 559-562 glucometers for, 559 in hyperthyroidism, 576 insulin therapy for control of, 552-562 neonatal values, 1237t normal metabolism of, 549, 549f plasma osmolality and, 56 in stress hyperglycemia, 3 testing of in liver disease, 522-524 urinary, 941 Glucose transporter proteins (GLUTs), 549 diabetes mellitus and, 549-550, 550f Glucosuria, due to lily toxicosis, 922t Glucotest granules, 562 Glucuronidation, drug metabolism and, 40, 41t Gluten-free foods, 259 GLUTs. See Glucose transporter proteins (GLUTs) Glycemic control in diabetes mellitus, 552-562 Glycogen storage disease (GSD) type IV in Norwegian Forest cat, 728t, 730-731 DNA testing for, 1274t Glycopyrolate for sedation and premedication, 114t, 117-118 Glycosaminoglycan (GAG), feline idiopathic cystitis and, 987, 992 Glycosides, cardiac, toxicity of, 923-924 Glycosuria in diabetes mellitus diagnosis, 549 in hyperadrenocorticism, 594 GM-CSF. See Granulocyte monocyte colony-stimulating factor (GM-CSF) GN. See Glomerulonephritis (GN) GnRH. See Gonadotropin-releasing hormone (GnRH) Goiter, 579 in hypothyroidism, 586t “Golden Rules” of nutrition, 271-272 Gonadectomy. See Spay and neuter Gonadotropin-releasing hormone (GnRH) for control of estrus and reproduction, 1200-1201, 1200t in cryptorchidism diagnosis, 1190b for ovarian remnant syndrome diagnosis, 1202 in ovulation, 1197 Gopher bait toxicity, 918-919 “GOSH DARN IT” mnemonic, 627, 628b G proteins, 572 Graft, gingival, 343-344 Grand mal seizure, 734-735 Granulocyte colony-stimulating factor (G-CSF), 695 for feline immunodeficiency virus, 1060 Granulocyte monocyte colonystimulating factor (GM-CSF), 695 Granuloma, eosinophilic, 404-405, 405f Granuloma complex, eosinophilic, 353, 355f Granulomatous dermatitis, 392-393 Granulomatous inflammation hypercalcemia due to, 631-632 intestinal obstruction secondary to, 484 Grapes, nephrotoxic effects of, 959 Grass eating, 229, 229f

Gravol. See Dimenhydrinate Grayanotoxins, 923 Greasy seborrhea syndromes, 396, 396f Griseofulvin, 1139t Grooming kittens and, 163f, 187-188 as normal behavior, 195 over-, 188, 214 in feline symmetrical alopecia, 399 in palliative care, 1158 in population wellness program, 1327-1328 in preventive health care, 164 as sign of stress, 188 for yeast dermatitis, 384 Group A streptococcus, zoonotic, 1092 Group housing, 1336-1341, 1338b, 1338f-1342f Growling, 194 Growth energy requirements and, 245t nutrition and, 246 Growth factors, hematopoietic, 695 Growth hormone (GH) concentration in acromegaly, 615-616 congenital deficiency of, 611 Growth hormone (GH) receptor antagonist for acromegaly, 618 Growth hormone (GH)-secreting pituitary tumor, 611-618 Growth plates, delayed closure of, in hypothyroidism, 586t GSD. See Glycogen storage disease (GSD) Gunshot oral trauma, 359 GWASs. See Genome-wide association studies (GWASs) H Hair coat clipping of for dermatophytosis, 393 examination of, 36-37 greasy, 396 grooming of, 164 matting of, 36-37, 37f unkempt, in hyperthyroidism, 572t, 574 Hairless locus, 1276-1277 Hair loss. See Alopecia Hair trichogram, 375, 376f Halitosis, 336 Handling of community cats, 1292-1299 during examination, 11-14, 12f-14f for laboratory sample collection, 15-16 socialization and training classes for kittens and, 201-202 Hand-raised kittens, socialization and, 188, 189f Hand sanitizers, 1348b HARD. See Heartworm-associated respiratory disease (HARD) Hard palate, 333-334, 334f defects of, 355-357 midsagittal split of, 705-706 Hard skin, 406-407, 407f Harelip, 356 Havana Brown cat, 1259 Haw’s syndrome, 817, 817f H2 blockers. See Histamine 2 (H2) blockers hCG. See Human chorionic gonadotropin (hCG) HCM. See Hypertrophic cardiomyopathy (HCM) HDLs. See High-density lipoproteins (HDLs) HDO. See High-definition oscillometric (HDO) system HE. See Hepatic encephalopathy (HE) Head, physical examination of, 33-34, 33f Headache, due to dehydration, 58

Head tilt, due to vestibular disease, 747, 747f Health, breeds of cats and, 1259-1261, 1260f Health Canada: Veterinary Pharmacovigilance, 1148t Health care cats receiving of, 20 preventive (See Preventive health care) Health insurance, pet, 158 Health surveillance, 1313 Hearing, 4, 192, 192f Heart, size of, radiographic assessment of, 304, 304f-305f Heart block, atrioventricular, 321, 321f Heart disease. See also Cardiovascular disease concurrent with renal disease, fluid therapy in, 85-86 congenital, 322-325 atrial septal defect as, 323 patent ductus arteriosus as, 324-325 peritoneopericardial diaphragmatic hernias as, 324, 324f supravalvular mitral stenosis (cor triatriatum sinister) as, 323 ventricular septal defect as, 322-323, 323f nutritional management of, 255-256 Heart failure ascites due to, 545 biomarkers in diagnosis of, 311 clinical signs of, 302 concurrent with chronic kidney disease, 1108-1114, 1109b, 1109f, 1111b, 1111t fluid therapy for, 84-86 glucocorticoid-associated, 325 in hyperthyroidism, 572t in hypertrophic cardiomyopathy, 310-311, 311f-312f pleural effusion due to, 895-898, 900f radiographic diagnosis of, 305, 305f Heart murmur in hyperthyroidism, 572t, 573, 580 in hypertrophic cardiomyopathy, 310, 310f localization and characterization of, 302-303 in physical assessment of cardiovascular disease, 301-302 prevalence of, 300 Heart rate control of in hyperthyroidism, 326 fetal, 1205-1206 neonatal, 1232b anesthesia and, 137-138 Heart sounds assessment during physical examination, 34-35, 35f in cardiovascular disease, 302 Heartworm, 171-172, 883-885, 884t testing for in population wellness programs, 1322 treatment of, 172t Heartworm-associated respiratory disease (HARD), 883 Heating for environmental health in population wellness programs, 1351-1352 Heats, silent, 1217 Heatstroke, fluid and electrolyte loss assessment for, 79t Heinz bodies, 649f-650f, 650 Heinz body anemia, 664-666, 665b due to onion toxicity, 250 Helicobacter gastritis, 453-454 Helmet cell, 649f Helper T cells in airway inflammation, 866-867 cytokines in regulation of, 692, 695 feline immunodeficiency virus replication in, 1056-1057 feline infectious peritonitis and, 1039-1040

INDEX Hemangiosarcoma hepatic, 527t intestinal, 477 Hematemesis in gastric ulceration, 455 Hematochezia, 461t Hematocytopenia, 692-694 Hematologic findings in chemotherapy, 775 in hyperthyroidism, 575 in hypoadrenocorticism, 607, 607t in hypothyroidism, 587 in paraneoplastic syndrome, 795-797 Hematology cytokines in, 692-696 definition of, 692 hematopoietic growth factors as, 695 interleukins as, 694-695 investigational use of, 695-696 physiology of, 692, 693b, 693f-694f therapeutic uses of, 692-694 diagnostic techniques in, 643-647 bone marrow collection as, 643-646, 644b cross-match as, 646-647 neonatal, 1236, 1236t slide agglutination test as, 647, 647f erythrocytes in, 647-653, 648f blood types and, 650-651, 651t-652t disorders of, 651-675 qualitative parameters, 649-650, 649f-650f quantitative parameters, 648-649, 649f hemostasis in, 679 disorders of, 679-685 fibrinolysis in, 680 primary, 679 secondary, 679-680 leukocytes in disorders of, 675-679 evaluation of, 675 lymph nodes in anatomy and function of, 688-690, 689f disease of, 688-692 spleen in disorders of, 686-688 function of, 685-686 microanatomy and circulation, 685 Hematopoiesis cytokines in, 692, 693f growth factors in, 695 Hematuria, 942 in feline idiopathic cystitis, 987-988 in urinary tract diagnosis, 936t Hemimelia, radial, 726, 726f Hemobartonellosis, hemolytic anemia due to, 666-668 Hemodialysis, 960-961, 960f Hemodynamically stable patient, fluid therapy planning and monitoring in, 77-82 Hemoglobin, 648 mean corpuscular concentration, 648-649 urinary, 941-942, 942t Hemoglobin beta polymorphism, 1265 Hemoglobinuria, 941-942 Hemolysis, liver disease associated with, 522-524 Hemolytic anemia Heinz body, due to onion toxicity, 250 hypophosphatemia-associated, 666 immune-mediated, 657-661, 659t due to inherited erythrocyte abnormalities, 661-662 nonregenerative, 672 Hemophilia, 682 Hemophilia A, 680t Hemophilia B, 680t genetics of, 1275t Hemoplasmosis, 666-668, 667f

Hemorrhage acute hemolysis due to, 672 due to hemostatic abnormalities, 682 Hemorrhagic effusions, peritoneal fluid, 543 Hemorrhagic shock, 79t Hemostasis, 679 disorders of clinical evaluation in, 682 diagnostic plans for, 682-683 etiology of, 680-682, 680t, 681b laboratory evaluation of, 683-684 supportive care in, 684 thrombocytopenia as, 684-685 nonsteroidal antiinflammatory drugs’ effect on, 101 primary, 679 secondary, 679-680 HEPA. See High-efficiency particulate arresting (HEPA) filters Heparin therapy for arterial thromboembolism, 318 Hepatic cytochrome P450 activity, 45 Hepatic disease, 522-537 amyloidosis as, 527-528 ascites as, 526-527, 538-546 aspirates and biopsies in, 529-530 cholestasis and icterus as, 525, 525b, 526f clinical signs of, 522 feline cholangitis syndrome as, 533-534, 533f-534f, 534b fluid therapy for, 88-89 hepatobiliary imaging in, 528-529 hepatobiliary neoplasia as, 527-528, 527f-528f, 527t idiopathic hepatic lipidosis as, 530-533, 531b, 531f-532f, 532t liver function tests in, 524-525 nutritional management of, 259-260 portal hypertension and hepatic encephalopathy, and acquired protosystemic shunting as, 526-527, 534-535, 535t-536t routine laboratory testing in, 522-524, 523f therapy for, 530-535 Hepatic encephalopathy (HE), 526-527, 534-535, 535t, 739 Hepatic insufficiency, drug therapy considerations in, 44, 44b, 44f Hepatic lipidosis anesthetic considerations in, 142-143, 143b nutritional management of, 260 pancreatitis with, 513 Hepatobiliary imaging, 528-529 Hepatobiliary neoplasia, 527-528, 527f-528f, 527t Hepatocellular adenoma, 527t Hepatocellular carcinoma, 527t Hepatoprotectants, 535t Heritability, 1271b-1272b Hermaphroditism, 1189 Hernia diaphragmatic, 907-909, 908f-909f peritoneopericardial, 324, 324f hiatal, 449, 449f Herpesvirus. See Feline herpesvirus-1 (FHV-1) Heska Second Generation E-Screen Test, 388-389, 389f Hetastarch, 68 Heterogeneity, genetic, 1281 Heterozygosity, 1271b-1272b Heterozygote, 1271b-1272b HEXB gene mutation, 1279 HHHHHM Quality of life scale, 802, 802t HHM. See Humoral hypercalcemia of malignancy (HHM) HHS. See Hyperglycemic hyperosmolar syndrome (HHS) Hiatal hernia, 449, 449f

Hiding as sign of stress, 1333f Hiding places for environmental enrichment, 229, 229f in veterinary hospitals, 16, 24f Hidrocystoma, apocrine, 416, 416f, 816, 817f High-definition oscillometric (HDO) system, 307-308 High-density lipoproteins (HDLs), 1105-1106 High-dose dexamethasone suppression test, 596-598, 596t High-efficiency particulate arresting (HEPA) filters, 422 High-fiber diet. See Fiber-enhanced diet High-grade intestinal lymphoma, 473-475, 474f Highly digestible diet for vomiting, 434 High-sodium isotonic crystalloids, 60-64, 62t combined with low-sodium crystalloids, 65-66 for hypovolemia, 74 Hind limb, musculoskeletal conditions of, 718-724 common calcaneal tendon rupture, 723-724, 723f-724f hip dysplasia, 718, 719f patellar luxation, 719-721 stifle ligamentous injury, 721-723, 722f Hindquarters, physical examination of, 36, 36f Hip dysplasia, 718, 719f patellar luxation and, 719 Hissing, 194 Histamine 2 (H2) blockers dosage adjustment in renal insufficiency, 42t for esophagitis and esophageal strictures, 445 Histamine in systemic anaphylaxis, 698 Histamine receptors in vomiting, 431, 434 Histoplasmosis, 1019-1020, 1019f History behavioral, 206-210 basic patient information in, 208-209 counseling skills in, 206-207 formulation of treatment plan and, 210 organization of consultation for, 207-208 “problem behavior” in, 210 questionnaire for, 208b of self-maintenance behaviors, 209 for senior cat, 1171b social environment in, 209 of cat, 4 diet, 262b medical, 26-31 in behavioral problem prevention, 160 in cardiovascular disease, 301-303 in diarrhea, 460-462, 461t initial information phase in, 26-27, 28b in nonregenerative anemia, 668 in ophthalmology, 807 in oral examination, 335-336 in population wellness program, 1321 prior and existing complaints in, 29-31, 31b in regenerative anemia, 656 routine, 28-29, 29f-30f in skin disease, 371-372 in vomiting, 428-429, 428t toxicology, 930, 930b HM. See Hypercalcemia of malignancy (HM) H5N1 avian influenza, 879, 1034-1036 zoonotic, 1093

1375

H1N1 influenza virus, 879, 1034-1036 zoonotic, 1093 Holding of community cats, 1292-1299, 1295b Holter monitoring, 303 Holtz-Celsus procedure, 814 Home blood glucose and insulin therapy monitoring at, 559-562, 560f-561f, 565b oral hygiene in, 168, 344 returning following hospitalization, 17-18 Homemade diets, 295-297 Homemade pet food, recipe for, 270b Home visit consultation, 207-208 Hookworms, 171, 499-500 control of in population wellness program, 1325 treatment of, 172t zoonotic, 1094 Horizontal leap as play behavior, 185, 186t Hormones in estrous and pregnancy, 1197-1198 male, 1184-1185 Horner’s syndrome, 762-763, 762f-763f Hospice, 1160 Hospitalization, 16-17, 17f returning home following, 17-18 Household products toxicity, 924-927 ant and roach baits, 924-925 ethylene glycol, 926-927 liquid potpourri and essential oils, 925-926, 926f pennies, 926 silica gel packets, 925 Housing cat-friendly, 23-24, 23f-24f group, 1336-1341, 1338b, 1338f-1342f long-term, 1336 in population wellness program, 1329-1341 feline communication and signs of stress and, 1331-1333, 1331b, 1332f-1333f feline social behavior and, 1330-1331 types of housing arrangements in, 1333-1334, 1334f-1336f short-term, 1334f Howell-Jolly bodies, 649f, 650 HPAI H5N1 avian influenza pandemic, 879, 1034-1036 Human albumin for albumin replacement, 67-68 Human chorionic gonadotropin (hCG) for control of estrus and reproduction, 1200, 1200t in cryptorchidism diagnosis, 1190b Humane capture of community cats, 1292-1299, 1292f Human neonatal incubator for oxygen delivery, 897f for pleural effusion, 897f Human recombinant regular insulin, transmucosal administration of, 49 Humans allergy to cats in, 419-424 contact of cats with, 1341-1343, 1342f raw food diet concerns in, 292 Humatin. See Paromomycin Humerus anatomy of, 704, 705f bone marrow collection from, 644-645, 645f osteosarcoma of, 724f Humidicribs for oxygen delivery, 897f for pleural effusion, 895 Humidity in population wellness program, 1352 Humoral hypercalcemia of malignancy (HHM), 631 Hunters, cats as, 4

1376

INDEX

Hunting environmental management of, 228-229, 229f as normal behavior, 195 Hybrid cat breeds genetic maps of, 1265-1266 genetic testing concerns in, 1284-1285 Hydralazine for hypertension, 309t with chronic kidney disease, 1122t stability of suspensions of, 47t Hydration in chronic kidney disease treatment, 969, 969b for constipation, 488 in palliative care, 1155-1156, 1155b-1156b Hydration deficits in diabetic ketoacidosis, 86 Hydration status, hypovolemia versus, 77-78 Hydrocephalus, 738, 738f Hydrochlorothiazide for cardiorenal syndrome, 1112 Hydrocortisone for hypoadrenocorticism, 609 for immunosuppression, 1135t Hydrogen peroxide for toxicosis, 916t, 931 Hydrometra, infertility due to, 1219, 1219f Hydromorphone for pain management, 99 dose ranges and route of administration for, 97t for sedation and premedication, 114t side effects of, 96-97 for urethral obstruction in feline idiopathic cystitis, 992t Hydronephrosis, 956-957, 957f Hydroxyethyl starch products, 68 Hydroxyurea as chemotherapy agent, 780 Hydroxyzine for pruritus in atopic cat, 390t for upper respiratory tract disease, 853t Hygiene, oral, at home, 168, 344 Hyperactivity, due to hyperthyroidism, 574-575 Hyperadrenocorticism, 592-602 acromegaly versus, 617 clinical features of, 592-594, 593f-594f, 593t diagnosis of, 594-598, 598f fragile skin with, 406, 406f insulin therapy resistance due to, 563t prognosis for, 602 screening tests for, 594-597, 596t treatment of, 598-602, 599t Hyperaldosteronism, 602-606 clinical features of, 603 diagnosis of, 604-605 diagnostic imaging in, 604, 604f etiology and pathophysiology of, 602-603 laboratory findings in, 603-604 treatment of, 601f, 605-606 Hyperbilirubinemia in liver disease, 522-524 Hypercalcemia approach to cat with, 626-627, 628b, 628t calcium oxalate uroliths and, 996 central nervous system signs of, 740 chronic renal disease with, 630 clinical signs of, 626, 626t fluid and electrolyte loss assessment for, 79t idiopathic, 632-633, 633f neoplasia-associated, 631 parathyroid hormone and decreased, 630-632 increased, 629-630

Hypercalcemia (Continued) normal, 632-633, 633f treatment of, 634-636, 634b-635b Hypercalcemia of malignancy (HM), 797-798 Hypereosinophilic syndrome, 678 Hyperesthesia syndrome, 763-764, 764t Hyperextension carpal, 717-718, 717f tarsal, 1236, 1236f Hyperglobulinemia, paraneoplastic, 795-796 Hyperglycemia with acromegaly, 613 in diabetes mellitus, 548 glucocorticoid-associated congestive heart failure and, 325 in hyperadrenocorticism, 594 stress, 3 diabetes mellitus versus, 548 Hyperglycemic hyperosmolar syndrome (HHS), 565-567 fluid therapy for, 87-88 Hyperkalemia fluid therapy for, 83 in urethral obstruction, 999-1000 anesthesia and, 141 Hyperkinesis in hyperthyroidism, 572t Hypernatremia central nervous system signs of, 740 fluid therapy for, 82 Hyperosmotic laxatives, 487t Hyperoxaluria, 761 genetics of, 1275t Hyperparathyroidism with chronic kidney disease, 974 nutritional secondary, 291-292 primary, 629 Hyperphosphatemia with chronic kidney disease, 973-974, 974t fluid therapy for, 83 with hyperthyroidism, 576 Hyperpigmentation, postinflammatory, 407 Hyperplasia cystic endometrial, 1219-1222, 1220f lymph node, 691 mammary, 791-792, 1203-1204, 1203f-1204f pancreatic nodular, 517, 517f splenic, 687 Hypersensitivity chemotherapy, 776 in feline infectious peritonitis, 1040 flea bite, 381, 383f dermatitis due to, 385, 385b food, 251-253, 252b, 252f skin disease due to, 386-387 in inflammatory bowel disease, 466 insect bite, 385-386, 386f eosinophilic lesion due to, 405 in Malassezia dermatitis, 384 mosquito bite, 405 in systemic anaphylaxis, 698 Hypertension, 307-309 with acromegaly, 614 in cardiorenal syndrome, 1112 causes of, 307 chronic kidney disease and, 970, 1120-1124, 1121t-1122t, 1123f clinical signs of, 307 definitions associated with, 307, 307t diagnosis of, 307-309, 308f-309f hyperthyroidism and, 573, 580 malignant, following renal transplantation, 961-962 portal, 526-527 treatment of, 309, 309t in palliative care, 1158-1159 “white coat”, 15 Hypertensive chorioretinopathy, 837-839, 838f

Hypertensive crisis, chronic kidney disease and, 1122-1123, 1122t Hyperthermia acepromazine-associated, 114 malignant, 728t opioid-associated, 96 Hyperthyroidism, 571-584 anesthetic considerations in, 139-141, 139b apathetic, 575 chronic kidney disease with, 1099-1101 clinical signs of, 572-575, 572t central nervous system, 740 diabetes mellitus with, 1101-1103 diagnosis of, 575-576 difficulties in, 576-579, 577f, 578t epidemiology of, 571 heart disease and, 325-326 hypercalcemia with, 633 insulin therapy resistance due to, 563t nutritional management of, 265-266 pathogenesis of, 571-572 as risk factor for cardiac disease, 301 treatment of, 579-584 client circumstances and, 581 concurrent conditions and, 579-581, 580f medical therapy for, 581-582 in palliative care, 1158-1159 radioactive iodine for, 583-584, 583f thyroidectomy for, 582-583, 582f-583f Hypertonic dehydration, low-sodium crystalloids for, 65 Hypertonicity, 56 Hypertonic saline solutions, 66 for hypovolemia, 74 Hypertrophic cardiomyopathy (HCM), 310-314 anesthetic considerations in, 143-145, 144b clinical signs of, 310-311, 310f-311f cranial cruciate ligament rupture and, 722-723 diagnosis of, 311-312, 311f-312f electrocardiography in, 303-304 genetics of, 1280-1281 genetic testing in, 166, 1274t, 1282 hyperthyroidism as cause of, 326 risk factors for, 301 treatment of, 312-314, 313f Hypervitaminosis A, 240, 248-249, 249t Hypervitaminosis D, 249, 249t with chronic kidney disease, 968 hypercalcemia associated with, 631-632 Hypoadrenocorticism, 606-609 clinical features of, 606, 607t diagnosis of, 607-608, 607t etiology and pathophysiology of, 606 fluid and electrolyte loss assessment in, 79t fluid loss associated with, 59t hypercalcemia with, 633-634 treatment of, 608-609 Hypoalbuminemia hypocalcemia with, 638 pleural effusion associated with, 905-906, 906f Hypoallergenic cat, 422 Hypocalcium, 636-640 clinical signs of, 636 in eclampsia, 1213 treatment of, 638-640 underlying causes of, 636-638, 637t Hypochromia, 648-649 Hypocobalaminemia diarrhea associated with, 435-436 in exocrine pancreatic insufficiency, 519-520 inflammatory bowel disease with, 468 Hypodipsia, fluid loss associated with, 59t

Hypoglycemia central nervous system signs of, 739 fluid therapy for, 64 home monitoring of in diabetes mellitus, 556-557 neonatal, 1238-1239 perioperative, 1248 in sepsis, 1243b paraneoplastic, 798 Hypokalemia with chronic kidney disease, 278-279 due to epinephrine release, 3 fluid therapy for, 83 muscle weakness due to, 729-730, 729f Hypokalemic myopathy, 728t Hypokalemic nephropathy, 83, 968-969, 975 Hypokalemic polymyopathy Burmese, 729-730 in hyperaldosteronism, 603 Hypoparathyroidism central nervous system signs of, 740 hypocalcemia due to, 636-638 Hypophosphatemia acute hemolyses secondary to, 666 fluid therapy for, 63-64 Hypophysectomy for acromegaly, 617 for hyperadrenocorticism, 598-599, 599t, 601-602 Hypophysis, 611 Hypoplasia cerebellar, 738-739, 739f testicular, 1188-1189 Hypospadias, 1187-1188 Hypotension during anesthesia, 134-135 Hypothalamic-pituitary-adrenal axis, feline idiopathic cystitis and, 987 Hypothermia acepromazine-associated, 114 neonatal, 1238 perioperative, 1248 Hypothyroidism, 584-588 adult-onset (spontaneous), 584-585 causes of, 584-585 clinical features of, 585-586, 586t congenital, 585 diagnosis of, 586-588 iatrogenic, 585 treatment of, 588 Hypotonicity, 56 Hypotonic low-sodium crystalloids, 64-65 combined with high-sodium crystalloids, 65-66 Hypotrichosis congenital, 401, 401f thymic atrophy with, 678, 1125t Hypovolemia, 58, 59t assessment of, 58, 73, 73b body response to, 59 crystalloid solutions for, 61 colloids versus, 66 hydration status versus, 77-78 monitoring response to therapy for, 74-77, 75b therapy options for, 73-74 Hypovolemic shock, 59, 73b hypertonic saline solutions for, 66 Hypoxemia, neonatal anesthesia and, 137 Hypoxia with erythrocytosis, 673-675 neonatal, 1238 I I131. See Radioactive iodine (I131) IAPP. See Islet amyloid polypeptide (IAPP) Iatrogenic hypoparathyroidism, 637 Iatrogenic hypothyroidism causes of, 585 clinical features of, 585, 586t

INDEX IBD. See Inflammatory bowel disease (IBD) Ibuprofen toxicity, 928-929 iCA. See Ionized calcium (iCA) ICF. See Intracellular fluid (ICF) ICP. See Intracranial pressure (ICP) Icterus, 525, 525b due to feline infectious peritonitis, 1040, 1041f Identification collar, 1317, 1317f, 1319b Identification of cat ear tipping for, 1300-1301, 1302f-1303f, 1304b microchipping for, 158-160 in population wellness program, 1316-1318, 1317f, 1319b, 1320f Idiopathic aggression, 224 Idiopathic chylothorax, 268-269 Idiopathic cystitis, 985-992 clinical signs of, 986 diagnosis of, 987-988, 988f management of, 281-282, 988-992, 989b-990b, 990f, 992t pathophysiology of, 986-987 prevalence of, 985 signalment and risk factors in, 985-986 Idiopathic epilepsy, 734-735 Idiopathic hepatic lipidosis, 530-533, 531b, 531f-532f, 532t anesthetic considerations in, 142-143, 143b Idiopathic polyarthritis, 712-713, 712b Idiopathic polyneuropathy, 761 Idiopathic pulmonary fibrosis, 875, 876f Idiopathic vestibular disease, 748 Idoxuridine, 821 for upper respiratory tract disease, 855 IgA. See Immunoglobulin A (IgA) IgE. See Immunoglobulin E (IgE) IGF-1. See Insulin-like growth factor-1 (IGF-1) IgM. See Immunoglobulin M (IgM) Iliac crest, bone marrow collection from, 644-645, 645f Illinois needle, 644 Imaging in acromegaly, 616, 616f in ascites, 539-541, 539f, 540t in dental and oral disease, 338-341 in diarrhea, 465 in heart disease, 304-305, 304f-305f hepatobiliary, 528-529 in hyperadrenocorticism, 598, 598f in hyperaldosteronism, 604, 604f of kidney and ureters, 944-945, 944f in lower urinary tract disease, 983-984, 983b, 984f, 985t in upper respiratory tract disease, 849-850, 849f-850f in vomiting, 430 Imatinib, 777t, 780 IMHA. See Immune-mediated hemolytic anemia (IMHA) Imidacloprid for flea control, 382t toxicity, 921 Imidacloprid/moxidectin, 172t Imidocarb, 1026 Imiquimod, 777t, 780 Immune-mediated adverse drug reactions, 1145 Immune-mediated blood transfusion reactions, 656 Immune-mediated hemolytic anemia (IMHA), 657-661, 659t Immune-mediated thrombocytopenia (IMTP), 685 Immune-related disorders anaphylaxis as, 698-700, 699t arthritis as, 711-713 therapy for, 715-716 inflammatory bowel disease as, 466

Immune-related disorders (Continued) systemic lupus erythematosus as, 696-697, 696b arthritis with, 712 ulcers and erosions associated with, 403 Immune system, impact of aging on, 1167 Immunity in kitten, 1240-1241 Immunization. See Vaccination Immunocompromised cat, management of, 1127-1128 Immunocompromised persons, cat ownership for, 1095 Immunodeficiency, 1124-1128, 1125f, 1125t stress and, 1126-1127 Immunodeficiency virus. See Feline immunodeficiency virus (FIV) Immunodiffusion test, agar-gel, 1023 Immunoglobulin intravenous, for immunosuppression, 1137 rabies, 1093 Immunoglobulin A (IgA) in food hypersensitivity, 251 Immunoglobulin E (IgE) in food hypersensitivity, 251-252 in human allergies to cats, 420 Immunoglobulin G (IgG) in colostrum and milk, 1240 in immune-mediated hemolysis, 657-658 in infectious myopathies, 758-759 in systemic anaphylaxis, 698 in Toxoplasmosis gondii infection, 509-510, 743-744 Immunoglobulin M (IgM) in immune-mediated hemolysis, 657-658 in Toxoplasmosis gondii infection, 509-510 Immunosuppression, due to feline leukemia virus, 1051-1053 Immunosuppressive therapy, 1134-1138 Aminophyllin ligands for, 1136 antibodies for, 1137 for chronic rhinosinusitis, 857-858 cytostatic drugs for, 1137 for diarrhea, 438-439, 438t following renal transplantation, 962 glucocorticoids for, 1135-1136, 1135t for immune-mediated hemolysis, 659-660, 659t for inflammatory bowel disease, 438-439, 438t, 468-469 for lymphocytic plasmacytic gastritis, 455 Immunotherapy for asthma and bronchitis, 874 for pruritus in atopic cat, 390-391 Impaction, anal sac, 409-410, 490 Imperforate anus, 1233f Impermeant solutes, 56 Implant, melatonin, for control of estrus and reproduction, 1201 IMTP. See Immune-mediated thrombocytopenia (IMTP) Inbreeding defined, 1271b-1272b infertility due to, 1218 Inbreeding depression, 1271b-1272b Incision for catheter placement, 71 Incisors, 329, 330t, 332f Incomplete dominance, 1271b-1272b Incontinence, urinary, 1008-1009, 1008b, 1008f Incubator for oxygen delivery, 897f for pleural effusion, 897f Inderal. See Propanolol Indirect ophthalmoscopy, 810f Indolent ulcer, 403-404, 403f

Indoor lifestyle feline idiopathic cystitis and, 986, 988-990 outdoor lifestyle versus, 161, 161f Induction of anesthesia, 118-127 alphaxalone in, 125-126 esophagitis due to, 443-444 etomidate in, 123-125 in geriatric patients, 139 in hyperthyroid patient, 140 inhalant anesthetics in, 126-127, 126f intravenous doses for, 118t ketamine in, 119-121 in neonates, 137, 1248-1249 propofol in, 122-123 telazol in, 121-122 thiopental in, 118-119 for upper respiratory disease diagnostics, 849 Indwelling catheters for urethral obstruction, 1001-1002 for urethral trauma, 1008 Ineffective osmoles, 56 Infarction intracranial, 746, 746f myocardial, 319 spinal cord, 756-757, 757f Infection anal sac, 490 following renal transplantation, 962 in immunocompromised cat, 1127 insulin resistance associated with, 551, 563t lower respiratory tract, 877-885 bacterial, 879-881, 880f fungal, 881 parasitic, 881-885 viral, 878-879 lymphadenopathy due to, 690b mammary gland, 1213-1214 nasal, 852-857, 853t, 854f, 856f pregnancy loss due to, 1223-1224, 1223b propofol-associated, 122 pruritus due to, 381-385 dermatophytosis, 385 Malassezia overgrowth, 383-384 pyoderma, 381-383, 383f, 384t quarantine for control of, 1349-1350 splenomegaly due to, 687, 688b stress and, 1126-1127 in struvite urolith formation, 280 Infectious disease, 1016-1089 associated with hepatopathy or hepatic inflammation, 534b bacterial, 1070-1082, 1071t bartonellosis as, 1070-1073 mycobacterial, 1073-1080, 1074t, 1075f-1076f, 1078t nocardiosis as, 1080, 1080f cytokines and, 696 fungal, 1016-1025 antifungal therapy for, 1024-1025, 1024t blastomycosis as, 1022-1023, 1022f coccidioidomycosis as, 1020-1022 cryptococcosis as, 1016-1019, 1017f-1018f, 1018b histoplasmosis as, 1019-1020, 1019f sporotrichosis as, 1023-1024, 1023f in kitten, 1241-1244, 1241b, 1241f-1242f molecular assays for detection of, 1082-1089, 1083f, 1085f population wellness programs and transmission and control of, 1316 rickettsial, 1025-1027 anaplasmosis as, 1027 ehrlichiosis as, 1026-1027 Rickettsia felis in, 1027 viral, 1029-1070 Bornavirus as, 1061-1062 coronavirus in, 1038-1047, 1041f-1043f, 1041t, 1044t, 1046b, 1046t

1377

Infectious disease (Continued) enteritis agents in, 1061 feline calicivirus in, 1031-1034, 1032f feline herpesvirus-1 in, 1029-1031, 1030f feline panleukopenia in, 1036-1038, 1037f influenza virus in, 1034-1036 papillomavirus in, 1062-1063, 1062f poxvirus in, 1063 rabies as, 1047-1048 retroviruses in, 1048-1061, 1048t Infectious enteritis, 477-480, 477t Infectious myelopathies, 752-753 Infectious myopathies, 758-759 Infectious orbital disease, 813 Infectious peritonitis. See Feline infectious peritonitis (FIP) Infectious polymyositis, 729 Inferior alveolar nerve block, 341-342, 342f Infertility with abnormal estrus, 1217-1218, 1218f cystic endometrial hyperplasiapyometra complex in, 1219-1222, 1220f-1221f female, 1215-1224, 1215b-1216b male, 1191-1193, 1191b-1192b with normal estrus, 1218-1219, 1219f vaginal cytology in, 1216-1217, 1216b, 1216f Infestation flea, 381 control products for, 382t tick, 381 Infiltrates in intestinal adenocarcinoma, 475, 475f in intestinal small cell lymphoma, 472, 472f in Mycobacterium avium complex, 1075-1076, 1075f splenic, 687 Inflammation anal sac, 490 cytokines in regulation of, 692 granulomatous hypercalcemia due to, 631-632 intestinal obstruction secondary to, 484 hyperpigmentation following, 407 of systemic lupus erythematosus, 696 Inflammatory bowel disease (IBD), 466-469 clinical presentation of, 466 concurrent with pancreatitis, 1114-1120, 1118t cytokines and, 695-696 diagnosis of, 467-468, 467f dietary therapy for, 259, 260b, 468 drug therapy for, 468-469 immunosuppressive therapy for, 438-439, 438t intestinal small cell lymphoma and, 470 organs concurrently affected in, 468 pancreatitis with, 513 pathophysiology of, 466 Inflammatory disease anemia of, 669-670 central nervous system, 742-744 cytokines and, 695-696 nasal, chronic, 857-858, 857f Inflammatory focal alopecia, 402 Inflammatory laryngitis, 858-859 Inflammatory leukogram, 676-677 Inflammatory myelopathies, 752-753 Inflammatory myopathies, 758-759, 758f Inflammatory tooth resorption, 344, 345f Influenza, 879, 1034-1036 Infraorbital nerve block, 341-342, 341f

1378

INDEX

Infusion analgesic constant-rate, 94, 95b wound, 104 drug therapy, fluid administration as vehicle for, 65 opioid, for balanced anesthesia, 130 Inhalant anesthetics for induction, 126-127, 126f for maintenance, 127-129 in balanced anesthesia, 131 in hyperthyroid patient, 140-141 for neonatal patient, 1248-1249 Inhaled corticosteroids for inflammatory airway disease, 871, 872b, 873f Injectable desmopressin for diabetes insipidus, 621-622 Injection-site sarcoma, 787-791, 788f-789f Injury. See Trauma Inner ear tumor, 749 InPouch TF system, 463, 507 Insect bite hypersensitivity, 385-386, 386f eosinophilic lesion due to, 405 Insecticide toxicity, 919-921 cholinesterase inhibitors, 919-920 pyrethrins and pyrethroids, 919, 920b Insensible fluid loss, 57 Insoluble calcium oxalate toxicity, 924 Inspiratory sounds in lower respiratory tract disease, 862 Instruments, dental, 337-338, 337f for tooth extraction, 350-351, 351f Insulin, 264 deficiency and resistance of in diabetes mellitus, 549-550 infection and, 551 obesity and, 551, 1104-1105, 1105t endocrine pancreas production of, 548t Insulin-dependent diabetes mellitus (IDDM). See Diabetes mellitus (DM) Insulin-like growth factor-1 (IGF-1) in growth hormone regulation, 612 testing of in acromegaly, 616 Insulinoma, 567-568 Insulin resistance, 1104 Insulin syringe, 23, 553 Insulin therapy, 552-562, 553t changing of insulin dosages by owners, 560 changing of insulins in, 558 for diabetic crisis, 565-567 for diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome, 87 intramuscular, 567 intravenous, 566-567, 566f dosing and monitoring protocols for, 555-557, 556b, 557f-558f, 558t glucometer choice in, 559 home monitoring of, 559-562, 560f-561f, 565b resistance to, 563-564, 563t transmucosal administration of, 49 for urethral obstruction, 1000 withholding of during fluid therapy for hyperglycemic hyperosmolar syndrome, 88 Insurance, pet, 158 Intercat aggression, 220-221, 221f Intercostal nerve block, 104 Interdental wiring for jaw fracture repair, 361-362, 362f Interestrus, length of, 1196b Interferons for feline herpesvirus-1, 1031 for feline immunodeficiency virus, 1060 for feline leukemia virus, 1053 for ocular herpesvirus infection, 822 Interferon-alpha, 693b for appetite stimulation in cardiovascular disease treatment, 257t

Interferon-alpha (Continued) for upper respiratory tract disease, 853t Interferon-gamma, feline infectious peritonitis and, 1040 Interferon-omega for feline infectious peritonitis, 1045 for feline panleukopenia virus, 1037-1038 for stomatitis, 350 Interleukin-1, 693b, 709-710 Interleukin-2, 694-695 Interleukin-4, 698 Interleukin-5, 698 Interleukin-6, 693b, 698, 966t Interleukin-8, 693b, 966t Interleukin-12, 693b, 694-695 Interleukin-13, 698 Interleukin-16, 698 Interleukin-18, 966t Interleukins, 694-695, 694f Intermediate-acting insulins, 553 stable glucose curve using, 558f International Renal Interest Society (IRIS) classification of renal disease, 963-964, 964b, 964t, 965f-966f prognosis and, 975-976 relationship of systemic arterial pressure to risk and, 1120-1121 Internet resources. See Resources Intersex cat, 1189, 1189f genetics of, 1264 Interspecies hybrids, genetic maps of, 1265 Interstitial cells, testicular, 1184 Interstitial cystitis, 985 Interstitial fluid compartment, 53-54 Interstitial radiographic patterns in lower respiratory tract disease, 862, 863t, 864f in airway disease, 867-868, 869f in idiopathic pulmonary fibrosis, 875, 876f Intervening sequence, 1271b-1272b Intervertebral disk disease (IVDD), 750-751, 750b, 750f-751f Interview questions, 27, 28b Intestinal disease, 466-496 constipation as, 484-489, 486t-487t infectious enteritis as, 477-480, 477t inflammatory bowel disease as, 466-469 clinical presentation of, 466 diagnosis of, 467-468, 467f dietary therapy for, 468 drug therapy for, 468-469 organs concurrently affected in, 468 pathophysiology of, 466 megacolon as, 488-489, 489f neoplasia as, 469-477 adenocarcinoma as, 475-476, 475f adenomatous polyps as, 476 eosinophilic sclerosing fibroplasia as, 476 hemangiosarcoma as, 477 high-grade lymphoma as, 473-475, 474f intestinal obstruction secondary to, 483-484 mast cell tumors as, 476 small cell lymphoma as, 469-473, 471f-472f, 472t stromal tumors as, 476-477, 477f obstruction as, 480-484 Intestinal length, 236-237 Intestinal obstruction, 480-484, 481f-484f Intestinal phosphate binders, 974 Intestinal wall thickening in intestinal small cell lymphoma, 471, 471f Intracavity administration of chemotherapeutic drugs, 774

Intracellular fluid (ICF) compartment, 53-55, 53f fluid movement between extracellular fluid compartment and, 54-55 Intracellular fluid (ICF) volume, depletion of, fluid therapy plan for, 78-80 Intracranial arachnoid cyst, 739 Intracranial disease, 734-747 anomalous and congenital, 738-739 degenerative, 737-738, 737f inflammatory, 742-744 metabolic and nutritional encephalopathies, 739-740 neoplasia, 740-742 lymphoma, 742 meningioma, 740-741, 741f pituitary tumor, 741-742, 742f seizure disorders, 734-737, 735f, 736t toxic, 744-746 vascular encephalopathies, 746-747 Intracranial pressure (ICP), thiopental for reduction of, 119b Intradermal skin testing in bronchial disease, 870 Intralesional administration of chemotherapeutic drugs, 774 Intramedullary spinal tumor, 753 Intramuscular administration of analgesic drugs, 94 of chemotherapeutic drugs, 774 of insulin, 567 Intraocular pressure (IOP) measurement, 808, 809f in glaucoma, 836, 836f Intraoral examination, 336-338, 337f Intraosseous catheter, 70, 71t neonatal, 1239, 1240f Intraperitoneal chemotherapy administration, 774 Intraspecies hybrids, genetic maps of, 1266 Intrathoracic chemotherapy administration, 774 Intravascular fluid compartment, 53 Intravenous administration of analgesic drugs, 94 of chemotherapeutic drugs, 773-774 of desmopressin for diabetes insipidus, 621-622 of fluids, 69-73, 71t for anaphylactic shock, 699 during anesthesia and surgery, 82 Intravenous anesthesia, total, 132 Intravenous catheter, 70, 71t neonatal, 1239-1240, 1239f placement of, 70-73, 72f Intravenous immunoglobulin (IV-Ig), 1137 Intravenous insulin therapy for diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome, 566-567, 566f Intravenous urography, 936t Intrinsic coagulation pathway, 680 Intron, 1271b-1272b Intussusception, 484, 484f postpartum, 1215 In utero transmission of feline immunodeficiency virus, 1056 Iodine deficiency of, 250t excess of, 249t radioactive for hyperthyroidism, 583-584, 583f reduced intake of for hyperthyroidism, 581-582 Iohexol clearance, 936t Ionized calcium (iCA), 625 in hypercalcemia, 626-627 in hypocalcemia, 637t IOP. See Intraocular pressure (IOP) measurement

IRIS. See International Renal Interest Society (IRIS) classification of renal disease Iris examination of, 33-34 melanoma of, 832-833, 832f Iron deficiency of, 250t excess of, 249t Iron-deficiency anemia, 668-669, 669t Irreversible inhibitors, 919 Ischemic damage due to acute renal failure, 957 Ischemic encephalopathy, 746-747, 747f Islet amyloid polypeptide (IAPP), 1105, 1105f Islets of Langerhans, 547 Isoerythrolysis, neonatal, 662-663, 1244-1245 Isoflurane for inhalant induction, 126-127 for maintenance of anesthesia, 128 Isolation in population wellness programs, 1351 Isoniazid (INH), 1078t toxicity of, 929 Isorhythmic dissociation, 321, 322f Isospora felis, 170t, 501-503, 501f Isospora rivolta, 170t, 501-503 Isothenuria, due to lily toxicosis, 922t Isotonic high-sodium crystalloids, 60-64, 62t combined with low-sodium crystalloids, 65-66 Itraconazole, 1024t, 1025 for dermatophytosis, 393-394 endemic, 395 for intestinal granulomatous inflammation, 484 for Malassezia dermatitis, 384 monitoring of long-term therapy with, 1139t for otitis media, 414 for skin disease, 384t for sporotrichosis, 1024 transdermal administration of, 48 for upper respiratory tract disease, 853t for yeast otitis, 413 IVDD. See Intervertebral disk disease (IVDD) Ivermectin, 172t, 499t for Aelurostrongylus abstrusus infection, 882 for demodicosis, 380-381 for fur mites and lice, 379-380 for Helicobacter gastritis, 454 IV-Ig. See Intravenous immunoglobulin (IV-Ig) Ixodes tick vector, 1027 J Jamshidi needle, 644, 644f Japanese show lily toxicity, 958t Jaw bones and joints of, 333, 334f fracture of, 359-362, 705-706, 706f mandibular, 359 maxillary, 360 repair of, 360-362, 360f-362f open-mouth locking of, 363-364, 364f tone of in anesthesia monitoring, 134 Jequirity bean toxicity, 924 Joints degenerative disease of, 709-710, 709b with acromegaly, 614 following cranial cruciate ligament rupture, 722 in senior cat, 1173-1174, 1173f, 1174b therapy for, 713-715, 715b of skull, 332-333, 334f Jones test, 811, 811f Jugular vein blood collection from, 15, 16f catheterization of, 70, 72f

INDEX Junior cat, behavioral needs of, 163 Juvenile period, behavioral development of kitten during, 185 K K+. See Potassium (K+) “Kangaroo cat”, 726 Kaolin, 916t Karyotype of domestic cat, 1263, 1264f KBr. See Potassium bromide (KBr) Keratin-derived chemokines as biomarker in human acute renal failure, 966t Keratitis in orbital disease, 812-813, 812f Keratoconjunctivitis, eosinophilic, 826, 826f Keratocytes, 649-650 Keratopathy, acute bullous, 827, 827f Ketamine for anesthesia in feral cats, 133 in balanced anesthetic technique, 129t, 131 epidural administration of, 105 for induction of anesthesia, 118t, 119-121, 120b neonatal, 1248 for upper respiratory disease diagnostics, 849 for pain management, 105, 1152 for sedation and premedication, 114t, 116-118 in urethral obstruction, 142, 1000 for total intravenous anesthesia, 132 Ketoacidosis, diabetic, 565-567 as diabetic crisis, 564-567 fluid therapy for, 86-87 low-carbohydrate diets and, 295 treatment and management protocol for, 565b Ketoconazole for hyperadrenocorticism, 599t, 600 for sporotrichosis, 1024 transdermal administration of, 48 Ketones, urinary, 941 Ketoprofen, 101 for degenerative joint disease, 714 dose ranges and route of administration for, 97t Key-Gaskell syndrome, 762 Kidney Crandell-Rees feline, 962-963 disease of (See Renal disease) imaging of, 944-945, 944f impact of aging on, 1167 palpation of during physical examination, 35 in salt balance, 55 Kidney biopsy, 945, 945f in urinary tract diagnosis, 936t KIM-1 as biomarker in human acute renal failure, 966t Kinavet. See Masitinib Kinavet CA-1. See Masitinib Kindling, 222 Kirschner wire, 705-706 Kitten, 1228-1251 analgesic use in, 106 anesthetic considerations for, 137-138, 137b behavioral development in, 182-190 after birth, 183-184 influence of parental factors on, 182-183 sensitive periods in, 184-185 behavioral development of, 184 behavioral needs of, 163, 163f behaviors of feeding as, 186-187 grooming as, 187-188 learning as, 188 play as, 185-186, 185f-186f, 186t social, 186, 188-189 toileting as, 187, 187f

Kitten (Continued) congenital defects in, 1232-1236, 1233b-1234b, 1233f-1236f developmental milestones for, 1231b diagnostics, 1236-1238, 1236t-1237t, 1237b diarrhea in, 1242 drug therapy in, 44-45 examination of, 1229-1232, 1231b-1232b, 1232f feline infectious peritonitis in, 1040, 1041f prevention of, 1046, 1046t feline leukemia virus testing in, 1054 feline panleukopenia virus in, 1037 feral capture of, 1305 taming of, 1306b flea infestation in, 381 immunity in, 1240-1241 infectious disease in, 1241-1244, 1241b, 1241f-1242f isoerythrolysis in, 662-663, 1244-1245 lymph node hyperplasia in, 691 morbidity and mortality of, 1228-1229, 1229t-1230t orphan, 1245-1246, 1245f-1246f parasitic prophylaxis in, 172 sepsis in, 1243-1244, 1243b, 1244f, 1244t socialization and, 188-189, 189f sensitive periods of, 9 socialization and training classes for, 198-205 equipment for, 200, 200f handling and, 201-202 litter training in, 201 location for, 200, 200f planning of, 199 punishment and, 201 recruitment and promotion of, 199 resources for, 202b rewards in, 201 sample curriculum for, 202-205, 202f-205f scratching and, 202 teaching kittens and, 200-201 value of, 199b spaying and neutering of, 1246-1249 tendon contracture in, 727 therapeutics for, 1238-1240, 1239f-1240f total dependence on queen, 183, 183f KPO4. See Potassium phosphate (KPO4) L LA. See Latex agglutination (LA) test Labial, oral anatomy and, 335 Labial mounting of dental radiographs, 340 Labor and delivery cesarean, 1212-1213, 1212b, 1213f normal, 1207-1209, 1209b postpartum problems following, 1213-1215 problems with, 1209-1213, 1210b Laboratories, domestic cat DNA, 1283t Laboratory testing/findings in acromegaly, 615 of fibrinogen and fibrinolysis, 684 in hemostasis disorders, 683-684 in hyperadrenocorticism, 594 in hyperaldosteronism, 603-604 in liver disease, 522-524, 523f oral, 338 sample collection for, 15-16 Laceration of common calcaneal tendon, 723 Lactase activity, 240 Lactated Ringer’s solution (LRS) composition of, 61t intraoperative administration of, 136 subcutaneous administration of, 65

Lactation in community cats, 1304-1305 energy requirements during, 245t nutrition during, 246 Lactobacillus acidophilus, 436 Lactoferrin, bovine for feline herpesvirus-1, 1031 for feline immunodeficiency virus, 1060 for stomatitis, 350 Lactulose for hepatoencephalopathy, 535t LAFB. See Left anterior fascicular block (LAFB) type pattern Lamina dura, 331-332 Lancet device for blood glucose monitoring, 561, 561f Language, body, 193-194, 193f Lanreotide for acromegaly, 617-618 Lanthanum carbonate, pharmacodynamic monitoring of, 1140t, 1142 Lantus insulin, 553t, 555, 558t changing of, 558 Lap, examination of cat on, 11-14, 12f Laparoscopy in gastrointestinal disease diagnosis, 430 in liver biopsy, 530 Laparotomy in gastrointestinal disease diagnosis, 430 LaPerm cat, phenotypic mutations in, 1276-1277, 1277f Largactil. See Chlorpromazine Large bowel, diarrhea involving, 461t Laryngitis, inflammatory, 858-859 Larynx disease of, 858-859 clinical signs of, 847 inflammatory laryngitis as, 858-859 neoplasia as, 859 paralysis as, 858 effects of endotracheal intubation on, 127 examination of, 34 Laser lithotripsy for urolith removal, 994-995, 994t Laser surgery for stomatitis, 350 L-asparaginase, 777t, 780 hypersensitivity to, 776 Lateral flank spay technique, 1300, 1301b Lateral saphenous vein for intravenous catheterization, 70 Latex agglutination (LA) test in cryptococcosis, 1018 in fungal central nervous system infection, 744 Latrodectus spp. bite, 927-928 Laundering for reduction of allergens, 422 Lavage bronchoalveolar, 864, 865b, 865f, 866t gastric, 931-932 nasal, 850, 850f thoracic, for pyothorax, 901-904 Laxatives, 487, 487t LD. See Linkage disequilibrium (LD) L-deprenyl, 1172 LDLs. See Low-density lipoproteins (LDLs) Lead toxicosis, 745 Lean body mass changes in different life stages, 1168t fluid losses and, 58 in senior cats, 1177f Leap, horizontal, 185, 186t Learning in cats, 8-9, 8f, 195 in kittens, 188 Leflunomide for immune-mediated hemolysis, 659t, 660-661 for immunosuppression, 1137 for rheumatoid arthritis, 716

1379

Left anterior fascicular block (LAFB) type pattern, 320-321 Left shift, regenerative, 676 Leg index measurement (LIM), 37f-38f Leiomyosarcoma gastrointestinal, 476-477, 477f hepatic, 527t Length, intestinal, 236-237 Lens-induced uveitis, 829t Lens luxation, 834 due to uveitis, 831-832 Lens of eye, 192 diseases of, 834-835, 834f-835f Lente insulin, 554-555 Lentigo, 407 Lentivirus, 1056-1061 Leprosy, 417, 1074t, 1077-1079 Leptin in progression of obesity to diabetes, 1105, 1105t Leptospira, 958 Lethargy due to dehydration, 58 in hypothyroidism, 586, 586t Leukemia, anemia due to, 672 Leukemia virus. See Feline leukemia virus (FeLV) Leukeran. See Chlorambucil Leukocytes disorders of, 675-679, 676b-677b evaluation of, 675 morphologic changes in, 649f urinary, 943 Leukocyte count elevated (See Neutrophilia) neonatal, 1236t peritoneal, 538b Leukocytosis, extreme neutrophilic, 676-677 Leukogram inflammatory, 676-677 physiologic, 675-676 stress, 676 Leukopenia in feline panleukopenia, 1037 Levemir insulin, 553t, 558t changing of, 558 Levetiracetam, 736t, 737 Levomethadone, 99-100 Leydig cells, testicular, 1184 LH. See Luteinizing hormone (LH) Liability, associated with care of community cats, 1309, 1309b Libido assessment in male infertility, 1192, 1192b Lice, 379-380 Lidocaine, 102 in balanced anesthetic technique, 129t, 131 in oral local and regional anesthesia, 341 for pain management, 1151 for ventricular arrhythmias, 321-322 Lidocaine cream for blood collection, 15 Lidocaine jelly for lubrication of feeding tube, 274 Lidocaine patch, 102 Life stage care, 153-178, 155f. See also Preventive health care Life stage nutrition, 244-247, 245t Lifestyle, indoor versus outdoor, 161, 161f Ligamentous injury to stifle, 721-723, 722f Lily-of-the-valley toxicity, 924 Lily toxicosis, 921-923, 922f-923f, 922t acute renal failure due to, 958, 958t LIM. See Leg index measurement (LIM) Lime sulfur rinse for demodicosis, 380-381 for dermatophytosis, 393 Lincomycin, 384t Linebreeding, infertility due to, 1218 Lingual, defined, 335 Lingual nerve, 335

1380

INDEX

Linkage disequilibrium (LD), 1267 Linoleic deficiency, 250t Lip(s) anatomy of, 333 avulsion of, 358, 358f congenital defects of, 355-357 physical examination of, 33 in assessment of skin diseases, 372 Lipemia in diabetes mellitus, 550 Lipid aspiration pneumonia, 876 Lipid complex amphotericin B, 1024-1025 Lipid emulsion in parenteral nutrition, 277, 277f Lipidosis, hepatic anesthetic considerations in, 142-143, 143b idiopathic, 530-533, 531b, 531f-532f, 532t nutritional management of, 260 pancreatitis with, 513 Lipocalin as biomarker in human acute renal failure, 966t Lipoprotein lipase (LPL) diabetes mellitus and, 550 genetics of deficiency of, 1275t Lipoproteins, 1105-1106 Liposomal amphotericin B, 853t Liposomal-encapsulated doxorubicin, 777t, 778 Liquid potpourri toxicity, 925-926, 926f Lissencephaly with microencephaly, 739 Listening, reflective, 206-207 Lithotripsy for urolith removal, 994-995, 994t Litter, sizes and numbers of, 1196b, 1198 Litter boxes, 162, 162f for kitten socialization classes, 200 management of in feline idiopathic cystitis, 989b, 990, 990f problems associated with, 217-218 Litter training, 201 Liver in glucose metabolism, 549 inflammation of, concurrent with inflammatory bowel disease, 468 involvement of in intestinal small cell lymphoma, 470 Liver disease, 522-537 amyloidosis as, 527-528 ascites as, 526-527, 538-546 aspirates and biopsies in, 529-530 cholestasis and icterus as, 525, 525b, 526f clinical signs of, 522 factor deficiency with, 680t feline cholangitis syndrome as, 533-534, 533f-534f, 534b fluid therapy for, 88-89 hepatobiliary imaging in, 528-529 hepatobiliary neoplasia as, 527-528, 527f-528f, 527t idiopathic hepatic lipidosis as, 530-533, 531b, 531f-532f, 532t liver function tests in, 524-525 nutritional management, 259-260 portal hypertension and hepatic encephalopathy, and acquired protosystemic shunting as, 526-527 routine laboratory testing in, 522-524, 523f therapy for, 530-535 Liver function tests, 524-525 L-lysine, 1031 Local anesthetic blocks brachial plexus, 103, 103f dental, 103, 341-342 distal paw, 103-104, 104f intercostal nerve, 104 for oral and dental disease treatment, 341-342 for pain, 102-104 wound infusion catheters, 104 Lochia, 1209

Locking of jaw, 363-364, 364f Locus, 1271b-1272b Lomustine as chemotherapy agent, 776-778, 777t for lymphoma, 784-785 for intestinal mast cell tumors, 476 Long-acting insulins, 553 stable glucose curve using, 557, 557f Long meow, 194 Long-term housing, 1336 Loratadine, 853t Lorazepam for behavior-modification therapy, 232t for cognitive dysfunction in senior cat, 1172t Lotensin. See Bonazepril Low-carbohydrate diet, 292-295 contraindications for, 295 for diabetes mellitus, 562-563 Low-density lipoproteins (LDLs), 1105-1106 Low-dose dexamethasone suppression test, 596-597, 596t Lower motor neuron disorders, 760-762 due to rabies, 1047-1048 Lower respiratory tract (LRT) disease, 861-891 aspiration pneumonia as, 875-876 asthma and chronic bronchitis as, 866-875 clinical signs of, 867 definitions of, 866 diagnosis of, 867-870, 869f-870f epidemiology of, 866 etiopathogenesis of, 866-867 treatment of, 870-875, 872b, 873f diagnosis of, 862-866 bronchoalveolar lavage in, 864, 865b, 865f, 866t bronchoscopy in, 864 computed tomography in, 864 fine needle aspiration in, 865 lung parenchymal biopsy in, 865-866 radiology in, 862-863, 863f-864f, 863t idiopathic pulmonary fibrosis as, 875, 876f infectious, 877-885 bacterial, 879-881, 880f fungal, 881 parasitic, 881-885, 883f, 884t viral, 878-879 neoplasia as, 877, 877f due to smoke inhalation, 876-877 traumatic, 876 Lower Sonoran life zone, 1020 Lower urinary tract disease, 980-1013, 981f diabetes mellitus concurrent with, 1106-1108 diagnosis of, 981-985, 982f cytoscopy in, 984-985 imaging in, 983-984, 983b, 984f, 985t physical exam and clinical signs in, 982, 982f urinalysis and urine collection in, 982-983, 983t early spay and neuter and, 1247 idiopathic cystitis as, 985-992 incontinence as, 1008-1009, 1008b, 1008f neoplasia as, 1005-1007, 1006f traumatic, 1007-1008 urethral obstruction as, 998-1004, 1000b, 1001f, 1003f urethral plugs as, 998 urinary tract infection as, 1004-1005 urolithiasis as, 992-998, 993f, 994t, 995f-998f Low-fat diet, 259 Low-grade intestinal lymphoma, 469-473, 471f-472f, 472t

Low-sodium hypotonic crystalloids, 64-65 combined with high-sodium crystalloids, 65-66 Loxosceles spp. bite, 928 LP gastritis. See Lymphocytic plasmacytic (LP) gastritis LPL. See Lipoprotein lipase (LPL) LRS. See Lactated Ringer’s solution (LRS) LRT. See Lower respiratory tract (LRT) disease LTCI. See Lymphocyte T-cell immunomodulator (LTCI) Lubricant laxatives, 487t Lufenuron for neonatal fleas, 1242-1243 Lung auscultation of in lower respiratory tract disease, 862 in physical examination, 34-35 disease of (See Pulmonary disease) Lung fluke, 882 Lung parenchymal biopsy, 865-866 Lungworm, 882 Lupus, 696-697, 696b arthritis with, 712 ulcers and erosion associated with, 403 Lutalyse. See Prostaglandin F2alpha Luteinizing hormone (LH) in male reproduction, 1184-1185 in ovulation, 1197 in reproductive status determination, 1204 Luxation dorsal scapular, 717 lens, 834, 834f due to uveitis, 831-832 patellar, 719-721 temporomandibular joint, 363, 363f Luxator, dental, 350-351, 351f Lymphadenopathy causes of, 690b clinical signs and physical findings in, 690-691 defined, 688 diagnostic plans for, 691 lymph node hyperplasia of young cats, 691 plexiform vascularization of lymph nodes in, 692 resembling lymphosarcoma, 691-692 therapy for, 691 Lymph nodes anatomy and function of, 688-690, 689f in head, 335 involvement of in intestinal small cell lymphoma, 470-471, 471f, 473 Lymphoblastic intestinal lymphoma, 473-475, 474f Lymphoblasts, spinal lymphoma and, 754, 754f Lymphocytes in lymph nodes, 690 neonatal values, 1236t Lymphocyte T-cell immunomodulator (LTCI) for feline immunodeficiency virus, 1060 for feline leukemia virus, 1053 Lymphocytic intestinal lymphosarcoma, 469-473 Lymphocytic plasmacytic (LP) gastritis, 455 Lymphoma, 782-786 associated with feline leukemia virus, 1050-1051, 1051f biologic behavior of, 784 of brain, 742 clinical features of, 783 cutaneous, 408f diagnosis and staging of, 783-784

Lymphoma (Continued) epitheliotropic, 398, 398f gastric, 457-458, 457f-458f hepatic, 527-528, 527f-528f incidence, etiology, and risk factors for, 782-783 intestinal high-grade, 473-475, 474f small cell, 469-473, 471f-472f, 472t laryngeal, 859 nasal cavity, 858 renal, 949-950 of spine, 753-754, 753f treatment and prognosis for, 784-785, 784t uveitis with, 829t Lymphosarcoma genetics of, 1272-1273 hepatic, 527t hypercalcemia associated with, 631 intestinal high-grade, 473-475 lymphocytic, 469-473 lymphadenopathy resembling, 691-692 mediastinal, pleural effusion due to, 900-901, 901f secondary intraocular, 833-834, 834f splenic, 687 Lynxacarus radovsky, 379 Lysine for herpesvirus infection, 268 for ocular herpesvirus infection, 822 for upper respiratory tract disease, 853t, 855 Lysosomal enzyme analysis, 737-738 Lysosomal storage disease, 737-738, 737f M MAC. See Mycobacterium avium complex (MAC) Macrophages bronchial lavage, 866t in bronchial disease, 868 Cytauxzoon schizont in, 663-664, 664f cytokines released from, 692, 693b, 694f in erythrocyte filtration, 686 feline coronavirus replication in, 1039 in lymph nodes, 690 Macrotumors, pituitary, 611 Magnesium addition of in fluid therapy, 63t, 64 in crystalloid solutions, 61t in dissolution of struvite uroliths, 280b excess of, 249t monitoring and correction of in diabetic ketoacidosis, 87 for plaque control, 256 Magnesium ammonium phosphate uroliths, 995 Magnesium sulfate for fecal flotation techniques, 170 Magnetic resonance imaging (MRI) in cerebrovascular accident, 746, 746f in feline infectious peritonitis, 743, 744f in feline ischemic encephalopathy, 746, 747f in hydrocephalus, 738, 738f in intervertebral disk disease, 750f-751f, 751 in meningioma, 741, 741f in peripheral vestibular disease, 749, 749f in pituitary tumors, 741, 742f in spinal cord infarction, 756-757, 757f Magnification in ophthalmic examination, 808-810, 809f Maine Coons cardiac mutations in, 311-312, 1256-1258 development of, 1256

INDEX Maintenance energy requirements (MERs) for senior cat, 1168 Maintenance fluids, 61, 80 hypotonic low-sodium crystalloids as, 64-65 Majoccchi’s granulomas, 392-393 Major allergen, 420 Major palatine nerve block, 341-342, 342f Malassezia overgrowth, 383-384 in atopic cat, 390 Male-male aggression, 220-221, 221f Male reproduction, 1184-1194 anatomy of, 1184-1185, 1185f-1186f control of, 1186-1187, 1187f infertility and, 1191-1193, 1191b-1192b mating behavior in, 1185-1186 penile conditions in, 1187-1188 testicular disease and conditions in, 1188-1191, 1189f, 1189t-1190t, 1190b Malignant hypertension, following renal transplantation, 961-962 Malignant hyperthermia, 728t Malignant lymphoma, 782-783. See also Lymphoma Malignant tumor. See also Neoplasia of middle and inner ear, 749 oral and maxillofacial, 365-366, 365f Mammary gland hyperplasia of, 791-792, 1203-1204, 1203f-1204f tumors of, 791-794, 791f, 792t Management oversight in population wellness program, 1320 Mandible bones and joints of, 333, 334f dentition in, 330t, 332f fracture of, 359, 705-706, 706f repair of, 360-362 squamous cell carcinoma of, 365-366, 365f Mandibular gland, 334-335 Mandibular lymph nodes, 335 Mandibular symphysis anatomy of, 333, 334f fracture of, 359 repair of, 360-361 Mandibulectomy, 367, 367f-368f Mannitol for cerebrovascular accident, 746 Mannosidosis, 1275t Manx cat phenotypic mutations in, 1277-1278, 1278f spinal anomalies in, 751-752, 752f MAOIs. See Monoamine oxidase inhibitors (MAOIs) Map, genetic, 1265-1266 Mapleson system, 133 Marbofloxacin for hemoplasmosis, 667-668 for mycobacterial infection, 1078t for otitis media, 414 for skin disease, 384t for upper respiratory tract infection, 853t Marine toad toxicity, 927 Maropitant, 105, 805t for appetite stimulation in cardiovascular disease treatment, 257t in chronic kidney disease therapy, 973t in hepatic lipidosis therapy, 532-533, 532t for vomiting, 432t, 433 in pancreatitis, 516 Marquis. See Ponazuril Masitinib, 777t, 780 Mask induction, 126-127 Massage examination and, 13, 13f for pain management, 1153 Mast cells in systemic anaphylaxis, 698

Mast cell tumor (MCT) hepatic, 527-528 intestinal, 476 splenic, 687 Master gland, 611 Masticatory muscles, 333 Mastitis, 1213-1214, 1214f Mastocytosis, hepatic, 527t Maternal aggression, 221 Maternal factors in behavioral development of kitten, 183, 183f in dystocia, 1210-1211, 1210b Maternally derived antibodies (MDAs), response to vaccination and, 173-174 Maternal transmission of feline immunodeficiency virus, 1056, 1058-1059 Mating behavior of male, 1185-1186 Matrix buprenorphine patch, 98 Matting of hair coat, 36-37, 37f Mattresses, pet allergens in, 421 Maxilla dentition in, 330t fracture of, 360, 705-706 repair of, 360-362 Maxillary artery, 335 Maxillary nerve block, 341-342, 341f Maxillectomy, 366-367 Maxillofacial tumors, 365-368 MCHC. See Mean corpuscular hemoglobin concentration (MCHC) MCV. See Mean corpuscular volume (MCV) MD. See Muscular dystrophy (MD) MDAs. See Maternally derived antibodies (MDAs) MDI. See Metered dose inhalers (MDI) MDS. See Myelodysplastic syndrome (MDS) MEA. See Mean electrical axis (MEA) Meal feeding in population wellness program, 1326 Mean arterial blood pressure monitoring during anesthesia, 134-135 during fluid therapy for hypovolemia, 75-76 Mean corpuscular hemoglobin concentration (MCHC), 648-649 Mean corpuscular volume (MCV), 656-657 Mean electrical axis (MEA), shifts in, 303-304 Median nerve, 704, 705f Mediastinal lymphosarcoma, pleural effusion due to, 900-901, 901f Medical care. See Health care Medical decision making in population wellness program, 1315 Medical history, 26-31 in anemia nonregenerative, 668 regenerative, 656 in behavioral problem prevention, 160 in diarrhea, 460-462, 461t initial information phase in, 26-27, 28b in ophthalmology, 807 in oral examination, 335-336 in population wellness program, 1321 prior and existing complaints in, 29-31, 31b routine, 28-29, 29f-30f in skin disease, 371-372 in vomiting, 428-429, 428t Medical record documentation of body weight in, 261 in population wellness program, 1316-1318 Medication. See Drug(s)/drug therapy Megace. See Megestrol acetate Megacolon, 488-489, 489f Megaesophagus, 447-448, 448f with myasthenia gravis, 757-758, 757f

Megestrol acetate for control of estrus and reproduction, 1200-1201, 1200t for termination of pregnancy, 1201 Melaleuca oil toxicity, 926 Melamine acute renal failure due to, 959 food contamination with, 251 Melanoma, iris, 832-833, 832f Melatonin for control of estrus and reproduction, 1200t, 1201 Melena in diarrhea, 461t in gastric ulceration, 455 Meloxicam, 101 chronic use of, 714 for degenerative joint disease, 713-715 dosage adjustment in renal insufficiency, 43-44 dose ranges and route of administration for, 97t doses for, 715b monitoring of long-term therapy with, 1139t for nasal neoplasia, 858 for pain management, 1151t, 1152 as “send home” medication, 105-106 for upper respiratory tract disease, 853t Melphalan, 777t, 778 Membranoproliferative glomerulonephritis, 951 Membranous glomerulonephritis, 951 MEMO. See Multimodal environmental modification (MEMO) Menace response in neuro-ophthalmic examination, 807, 808f, 808t Menghini technique for liver needle biopsy, 530 Meningioma, 740-741, 741f of spine, 754-755 Meningoencephalitis, 744 Meningoencephalocele, 739 Meningomyelitis, eosinophilic, 753 Meningomyelitis, infectious, 752 Mental nerve block, 341-342, 342f Mental stimulation in population wellness program, 1343-1345, 1343f Meow, 194 long, 194 trill/chirrup/greeting, 194 Meperidine, 99 dose ranges and route of administration for, 97t for pancreatitis, 516 Merosin-deficient myopathy, 728t MERs. See Maintenance energy requirements (MERs) Mesaticephalic cat, 332-333 Mesial, oral anatomy and, 335 Metabolic acidosis in chronic kidney disease, 969-970 in diabetic ketoacidosis, 87 fluid therapy and, 80 for hypovolemia, 77 in urethral obstruction, 999 Metabolic disease, neurologic signs of, 739-740 Metabolic myelopathies, 752 Metabolism of drugs, 40, 41t Metacam. See Meloxicam Metacentric chromosomes, 1263 Metaflumizone, 382t Metaldehyde toxicosis, 914-915, 931t Metastatic neoplasia hepatic, 527-528 mammary, 792 ocular, 833-834 Metered dose inhalers (MDI), 871, 872b, 873f Methadone for pain management, 99-100 dose ranges and route of administration for, 97t for sedation and premedication, 114t

1381

Methicillin-resistant Staphylococcus aureus (MRSA) in osteomyelitis, 725 zoonotic, 1092 Methimazole adverse effects of, 581 for hyperthyroidism, 575-576, 581-582 pharmacodynamic monitoring of, 1140t, 1141 transdermal administration of, 48 Methionine, nutritional requirements for, 238 Methocarbamol, 916t, 920b Methomyl toxicosis, 915 Methotrexate as chemotherapy agent, 777t, 779 for immunosuppression, 1137 for rheumatoid arthritis, 716 Methylene blue for Heinz body anemia, 665-666 Methylprednisolone for eosinophilic granuloma complex, 353 for immunosuppression, 1135 for insect bite hypersensitivity, 386 for pancreatitis with inflammatory bowel disease, 1118t, 1119 for stomatitis, 350 Methylprednisolone acetate for inflammatory airway disease, 871 for pruritus in atopic cat, 390t for upper respiratory tract disease, 853t Methylxanthines for inflammatory airway disease, 873-874 Metoclopramide in chronic kidney disease therapy, 973t dosage adjustment in renal insufficiency, 42t for esophagitis and esophageal strictures, 445 in hepatic lipidosis therapy, 532-533 for inadequate mild production, 1215 for nutritional care in cancer patients, 805t for vomiting, 431-433, 432t Metritis, 1214 Metronidazole for Clostridium diarrhea, 479 for diarrhea, 437, 437t for feline cholangitis syndrome, 534 for Giardia infection, 505 for Helicobacter gastritis, 454 for hepatoencephalopathy, 535t monitoring of long-term therapy with, 1139t for neonatal diarrhea, 1242 neurologic signs in toxicity with, 745 for nutritional care in cancer patients, 805t for pancreatitis with inflammatory bowel disease, 1118, 1118t for protozoal disease, 502t for small intestinal bacterial overgrowth, 480 stability of suspensions of, 47t for upper respiratory tract infection, 853t Metyrapone, 599t, 600 Metzenbaum scissors, 351, 351f MG. See Myasthenia gravis (MG) Mibolerone, 1201 Microagglutination of erythrocytes, 650 Microalbumineria, 944 Microbiome, 237 Microchipping, 28 in population wellness program, 1317-1318, 1318f, 1319b in preventive health care, 158-160 Microcytosis, 648-649 Microenema, 487

1382

INDEX

Microsporum canis dermatophytosis due to, 391 diagnosis of fungal culture for, 376f hair trichogram for, 376f molecular assays for, 1087 Wood’s lamp for, 375 zoonotic, 1094-1095 Micturition disorders, 1008-1009 Midazolam for permethrin toxicosis, 920b for sedation and premedication, 114-115, 114t administered with ketamine, 119-120 neonatal, 1248 Middle ear tumor, 749 Middle mental nerve block, 341-342, 342f Midstream urine collection, 938 in feline lower urinary tract disease, 983t Mik blood group, 650-651 Milbemycin, 172t, 499t for demodicosis, 380-381 otic, 412 for fur mites and lice, 379-380 for roundworms, 498 Milbemycin/praziquantel, 172t Miliary dermatitis, 404, 404f MILK. See Morphine, lidocaine, and ketamine (MILK) Milk drugs excreted in, 106 production of, 246 inadequate, 1215 Milk replacer for orphan kittens, 1245, 1245f Milk thistle for hepatoencephalopathy, 535, 536t Milkweed toxicity, 924 Mineral composition of uroliths, radiography in prediction of, 985t Mineralcorticoid function tests in hyperaldosteronism, 605 Mineralcorticoids for hypoadrenocorticism, 609 Mineralization extraneous skeletal, 726-727, 726f in stifle joint with cranial cruciate ligament rupture, 722, 722f Mineralization schedule for prediction of due date, 1206 Mineral oil ear swab cytology, 374 in otitis diagnosis, 411 Minerals deficiency of, 250t excess of, 249t Mineral salt uroliths, 997-998 “Minimal change disease”, 952 Minimum database in preventive health care, 165-166, 165t for senior cat, 1168-1169 for sick neonate, 1237b in weight loss in senior cats, 1180 Mink Tonkinese cat, 1273-1276, 1276f Minor allergen, 420 Mirtazapine for appetite stimulation in cardiovascular disease treatment, 257t in critical care setting, 272-273 in chronic kidney disease therapy, 973t monitoring of long-term therapy with, 1139t in palliative care, 1157 for cancer patients, 805t for pancreatitis with inflammatory bowel disease, 1118t, 1120 serotonin syndrome due to, 1152-1153 for vomiting, 431, 432t Misbehavior at veterinary visits, 3, 7b

Misoprostol, 916t, 929 Mites diagnosis of mineral oil ear swab for, 374 skin scrapings for, 374 ear, 377-379 otitis due to, 412 fur, 379-380 Mitotane, 598-600, 599t Mitoxantrone, 777t, 778 Mitral valve supravalvular stenosis of, 323 systolic anterior motion of, 301-302, 310f Mixed analgesics for pain management, 1152 Mobility in palliative medicine, 1158 questionnaire regarding for senior cat, 1174b Moderate-fat diet, 259 Modified Madison-Wisconsin protocol for chemotherapy treatment, 784t Modified transudates, peritoneal fluid, 542 Modified Ziehl-Neelsen stain, 508 Moist foods, 245 Molars, 330t Mole bait toxicity, 918-919 Molecular assays, 1082-1089, 1083f, 1085f bloodborne agents, 1086-1088 feline coronavirus, 1044-1045 gastrointestinal agents, 1086 ocular agents, 1088 respiratory agents, 1084-1086 in upper respiratory disease, 848 Monitoring during anesthesia, 133-136, 134f-135f of geriatric patients, 139 in hyperthyroid patient, 141 in hypertrophic cardiomyopathy, 144-145 of neonatal patient, 1249 in urethral obstruction, 142 of fluid therapy case example, 81-82 for diabetic ketoacidosis, 87 for hypovolemia, 74-77, 75b of insulin therapy, 555-557 at home, 559-562, 560f-561f, 565b Monoamine oxidase inhibitors (MAOIs), 1150 Monocytes feline coronavirus replication in, 1039 neonatal values, 1236t Monomeric foods, 259 Monorchid, 1189 “Monotomy effect”, 243 Montelukast for bronchial disease, 874 Morphine in balanced anesthetic technique, 130 epidural administration of, 100 for balanced anesthetic technique, 131 metabolism of, 41t for pain management, 100 dose ranges and route of administration for, 97t for sedation and premedication, 114t side effects of, 96-97 Morphine, lidocaine, and ketamine (MILK), 131 Mortality. See Death Mosaic, 1271b-1272b Mosquito bite hypersensitivity, 405 Motilin, 548t Motility, gastric, disorders of, 456-457 Motor neuron disease, 760-762 Mouth. See Oral entries Mowl, 194 Moxidectin, 382t MRI. See Magnetic resonance imaging (MRI)

MRSA. See Methicillin-resistant Staphylococcus aureus (MRSA) Mucinomimetic therapy, 823, 824f Mucolipidosis, 1275t Mucopolysaccharidosis, 1275t Mucosa, oral anatomy of, 332, 333f examination of, 336-337 Mucous membrane color of in cardiovascular disease, 302 in monitoring of fluid therapy for hypovolemia and, 76 pallor of due to anemia, 653 Mucus in feces, 461t Multimodal analgesia, 105 Multimodal environmental modification (MEMO), 162 for feline idiopathic cystitis, 990-991 Murmur, heart in hyperthyroidism, 572t, 573, 580 in hypertrophic cardiomyopathy, 310, 310f localization and characterization of, 302-303 in physical assessment of cardiovascular disease, 301-302 prevalence of, 300 Muscles masticatory, 333 neurologic, disorders of, 758-760 Muscle biopsy in muscular dystrophies, 759 in polymyositis, 758 Muscle condition scoring in obesity diagnosis, 261 in senior cat, 1169, 1170f, 1173f Muscle mass evaluation of in senior cat, 1169 loss of, assessment during physical examination, 37-39 Muscle tone, neonatal assessment of, 1231 Muscle wasting in senior cats, 1169, 1170f Muscle weakness due to hypokalemia, 729-730, 729f in neuromuscular disorders, 757, 757f Muscular dystrophy (MD), 759 Musculoskeletal disease, 704-733, 705f arthridities, 709-716 autoimmune, 711-713 degenerative joint disease, 709-710, 709b, 713-715, 715b infectious, 710-711 Scottish Fold arthropathy, 713 therapy for, 713-716 congenital, 1233b extraneous skeletal mineralization, 726-727, 726f fractures as, 704-709 capital femoral physeal, 707-708, 707f-708f mandibular and maxillary, 705-706, 706f nonunion, 709 patellar, 706-707, 707f pelvic, 708-709, 708f radial and ulnar, 707 of front limb, 717-718 carpal hyperextension injuries, 717-718, 717f dorsal scapular luxation, 717 of hind limb, 718-724 common calcaneal tendon rupture, 723-724, 723f-724f hip dysplasia, 718, 719f patellar luxation, 719-721 stifle ligamentous injury, 721-723, 722f myopathies, 728-731, 728t, 729b, 729f Burmese hypokalemic polymyopathy, 729-730 Devon Rex and Sphynx, 730, 730f

Musculoskeletal disease (Continued) glycogen storage disease type IV in Norwegian Forest cat, 730-731 infectious polymyositis, 729 myositis ossificans, 731 neoplasia, 724-725, 724f nutritional management of, 266 osteogenesis imperfecta, 727 osteomyelitis, 725 polydactyly, 725 radial hemimelia, 726, 726f tendon contracture, 727, 727f transitional vertebrae, 727-728 Musculoskeletal system, impact of aging on, 1167 weight loss and, 1179 Mutant allele, 1271b-1272b Mutation, genetic, 1271b-1272b point, 1271b-1272b silent, 1271b-1272b Mutation rate, 1271b-1272b Muzzle for examination, 14 for mandibular fracture, 360, 360f, 706 Myasthenia gravis (MG), 728t, 757-758, 757f paraneoplastic, 799 Mycetoma, 392-393 Mycobacterial infection, 1073-1080, 1074t feline leprosy as, 1077-1079 nonhealing wounds due to, 417 rapidly growing, 1079-1080 Mycobacterium avium complex (MAC), 1074t, 1075-1077, 1075f-1076f diagnosis of, 1076 therapy for, 1076-1077, 1078t Mycobacterium bovis, 1073-1075, 1074t, 1078t Mycobacterium fortuitum, 1079-1080 Mycobacterium lepraemurium, 417, 1074t Mycobacterium microti, 1073-1075, 1074t, 1078t Mycobacterium tuberculosis complex, 1073-1075, 1074t diagnosis of, 1076 therapy for, 1076-1077, 1078t Mycobacterium visibilis, 417 Mycoplasma arthritis associated with, 710-711 corneal ulcers due to, 825 in lower respiratory tract infection, 880, 880f molecular assays in diagnosis of, 1086 in upper respiratory tract infection, 852-853 zoonotic, 1091t Mycoplasma haemofelis in hemoplasmosis, 666-668, 667f in immune-mediated hemolysis, 658-659 molecular assays for diagnosis of, 1086-1087 Mycotic enteritis, 480 Mydriatics for glaucoma, 837 Myelodysplastic syndrome (MDS), 672 Myelofibrosis, 672 Myelography in spinal cord infarction, 756 in spinal trauma, 755, 755f Myelopathies, 749-757 congenital and developmental anomalies, 751-752, 752f degenerative, 750-751 inflammatory and infectious, 752-753 intervertebral disk disease as, 750-751, 750b, 750f-751f metabolic and nutritional, 752 neoplasia, 753-755, 753f-754f spinal cord infarction, 756-757, 757f traumatic, 755-756, 755f-756f vascular, 756-757 Myelophthisis, 672

INDEX Myocardial disease hypertrophic cardiomyopathy as (See Hypertrophic cardiomyopathy (HCM)) nutritional management of, 255-256 prevalence of, 300 Myocardial failure, hyperthyroidism and, 326 Myocardial infarction, 319 Myofibroblasts in glomerulonephritis, 952 Myoglobin, urinary, 941-942, 942t Myopathies, 728-731, 728t, 729b, 729f, 758-760 Burmese hypokalemic polymyopathy, 729-730 Devon Rex and Sphynx, 730, 730f glycogen storage disease type IV in Norwegian Forest cat, 730-731 infectious, 758-759 infectious polymyositis, 729 inflammatory, 758-759, 758f myositis ossificans, 731 primary noninflammatory, 759, 759f Myosin-binding protein C 3 gene mutation, 1280 Myosin-binding protein C mutation, 166, 311-312 Myositis ossificans, 731 Myotonia congenita, 728t, 759 N Na+. See Sodium (Na+) NAC. See N-acetylcysteine (NAC) N-acetyl-beta-D-glucosaminidase (NAG), 966-967 N-acetylcysteine (NAC) for acetaminophen toxicity, 928 for hepatoencephalopathy, 535, 536t NAG. See N-acetyl-beta-Dglucosaminidase (NAG) Nail bed cytology, 374-375, 375f examination of in assessment of skin diseases, 373 Nalbuphine, 98 Naloxone for neonate, 1213 for opioid-related hyperthermia, 96 Nandrolone decanoate, 257t Nasal catheter oxygen delivery, 896b-897b, 897f for pleural effusion, 895 Nasal desmopressin spray for diabetes insipidus, 620t, 621 Nasal discharge, 846-847 assessment of, 33 in chronic rhinosinusitis, 857, 857f differential diagnosis for, 847b in herpesvirus infection, 818f Nasal disease, 851-858 anatomical and functional, 851-852 brachycephalic syndrome as, 851 nasopharyngeal polyps as, 851, 851f nasopharyngeal stenosis as, 852 chronic inflammatory, 857-858, 857f clinical signs of, 846-847, 847b foreign bodies as, 858 infectious, 852-857 bacterial, 852-854, 853t fungal, 856-857, 856f viral, 854-856, 854f neoplasia as, 858 traumatic, 858 Nasal flush, 850, 850f Nasoesophageal feeding tube in critical care setting, 273-274, 273f-274f for idiopathic hepatic lipidosis, 531-532 Nasolacrimal system disease of, 817, 818f examination of, 811, 811f

Nasopharynx examination of, 849, 849f imaging of, 850, 850f polyp of, 748, 851, 851f stenosis of, 852 Natriuretic peptide, amino-terminal probrain, 1110 Natural killer (NK) cells, 694-695 Natural selection, 182 Naturevet. See Pentosan polysulfate Navelbine. See Vinorelbine Neck, physical examination of, 34, 34f in senior cat, 1179 Neckband for identification, 1317f Neck ventroflexion of Devon Rex and Sphynx myopathy, 730, 730f Necropsy, neonatal, 1238 Necrosis, digital, paraneoplastic, 795 Necrotizing otitis externa, proliferative, 416 Needle for biopsy bone marrow, 644, 644f in cancer diagnosis, 769-770 liver, 529-530 renal, 945, 945f, 953-954 for cerebrospinal fluid collection, 735 Needle thoracocentesis, 904 Negative contrast cystography, 983, 984f Negative predictive value (NPV), 1082 Neisseria animaloris, 880 Nemaline myopathy, 728t Nematodes, 496-500 hookworms, 499-500 Ollulanus tricuspis, 496-497 Physaloptera, 497 roundworms, 497-499, 498f, 499t Strongyloides, 497 whipworms, 497 Neonate. See also Kitten analgesic use in, 106 anesthetic considerations for, 137-138, 137b behavioral development of, 184 body temperature of, 1212-1213 congenital defects in, 1232-1236, 1233b-1234b, 1233f-1236f diagnostics, 1236-1238, 1236t-1237t, 1237b drug therapy in, 44-45 examination of, 1229-1232, 1231b-1232b, 1232f isoerythrolysis in, 662-663, 1244-1245 orphan, 1245-1246, 1245f-1246f resuscitation of, 1212-1213, 1212b sepsis in, 1243-1244, 1243b, 1244f, 1244t tendon contracture in, 727 Neoplasia, 768-806 adrenal catecholamine secreting, 602 hyperadrenocorticism due to, 592, 593f, 599t sex hormone secreting, 602 anal sac, 490-491 ascites secondary to, 544 biopsy techniques in, 769 brain, 740-742, 741f-742f catecholamine secreting adrenal, 602 chemotherapy for, 770-782 cytokines for treatment of, 692-694 esophageal, 448 eyelid, 816, 816f-817f feline immunodeficiency virusassociated, 1057-1058 feline leukemia virus-associated, 1050-1051 feline ocular sarcoma, 834-835, 835f gastric, 457-458, 457f-458f gastric ulceration due to, 455 hepatobiliary, 527-528, 527f-528f, 527t hypercalcemia associated with, 631 of individual toes, 409 injection-site sarcoma as, 787-791

Neoplasia (Continued) intestinal, 469-477 adenocarcinoma as, 475-476, 475f adenomatous polyps as, 476 eosinophilic sclerosing fibroplasia as, 476 hemangiosarcoma as, 477 high-grade lymphoma as, 473-475, 474f intestinal obstruction secondary to, 483-484 mast cell tumors as, 476 small cell lymphoma as, 469-473, 471f-472f, 472t stromal tumors as, 476-477, 477f intracranial, 740-742 lymphoma, 742 meningioma, 740-741, 741f pituitary tumor, 741-742, 742f laryngeal, 859 lower urinary tract, 1005-1007, 1006f lymphoma as, 782-786 mammary, 791-794 of middle and inner ear, 749 musculoskeletal, 724-725, 724f nasal, 858 oral and maxillofacial, 365-368, 365f, 367f-368f orbital, 813 ovarian, 1218 palliative care in, 802-806 pancreatic, 517-518, 518f paraneoplastic syndromes in, 794-802 pituitary, 611, 741-742, 742f adenoma as, 611 growth hormone-secreting, 611-618 macro-, 611 pulmonary, 877, 877f pleural effusion due to, 900-901, 901f renal, 949-950 rib, 910 screening diagnostics for, 768 secondary intraocular, 833-834, 834f in senior cat, 1173, 1173b signs of, 768 spinal, 753-755, 753f-754f splenic, 687-688, 688b staging of, 769 stromal gastrointestinal, 476-477, 477f ten common signs of, 1173b testicular, 1188 uveal, 832 Nephritis, tubulointerstitial, 962-963 Nephropathy, hypokalemic, 83, 968-969, 975 Nerium oleander toxicity, 923-924 Nerve blocks brachial plexus, 103, 103f dental, 103, 341-342 distal paw, 103-104, 104f inferior alveolar, 341-342, 342f infraorbital, 341-342, 341f intercostal nerve, 104 major palatine, 341-342, 342f maxillary, 341-342, 341f middle mental, 341-342, 342f for oral and dental disease treatment, 341-342 for pain, 102-104 wound infusion catheters, 104 Netraceutical therapy, 535 Netrin-1 as biomarker in human acute renal failure, 966t Nets for community cat capture, 1296-1297, 1297f improper use of, 1298f Neuroendocrine hepatic tumor, 527t Neurologic assessment, 39 in constipation, 485 Neurologic disease, 734-767, 735b congenital, 1233b feline hyperesthesia syndrome, 763-764, 764t

1383

Neurologic disease (Continued) feline infectious peritonitis, 1044 due to feline leukemia virus, 1051, 1052f Horner’s syndrome, 762-763, 762f-763f intracranial, 734-747 anomalous and congenital, 738-739 degenerative, 737-738, 737f inflammatory, 742-744 metabolic and nutritional encephalopathies, 739-740 neoplasia, 740-742 seizure disorders, 734-737, 735f, 736t toxic, 744-746 vascular encephalopathies, 746-747 lower motor neuron, 760-762 myelopathies, 749-757 congenital and developmental anomalies, 751-752, 752f degenerative, 750-751 inflammatory and infectious, 752-753 intervertebral disk disease as, 750-751, 750b, 750f-751f metabolic and nutritional, 752 neoplasia, 753-755, 753f-754f spinal cord infarction, 756-757, 757f traumatic, 755-756, 755f-756f vascular, 756-757 neuromuscular, 757-762, 757f fibrodysplasia ossificans progressiva, 759, 760f muscle disorders, 758-760, 758f-759f muscular dystrophies, 759 myasthenia gravis, 757-758, 757f myotonia congenita, 759 of neuromuscular junction, 757-758 peripheral vestibular, 747-749, 747f, 748t, 749f tetanus, 764-765, 764f Neurologic examination resources, 735b Neurologic system signs of acromegaly, 614 Neuromuscular disease, 757-762, 757f constipation due to, 486t fibrodysplasia ossificans progressiva, 759 muscle disorders, 758-760, 758f-759f muscular dystrophies, 759 myasthenia gravis, 757-758, 757f myotonia congenita, 759 of neuromuscular junction, 757-758 paraneoplastic, 798-799 Neuromyopathy, feline ischemic, 761 Neuron disease, 760-762 Neuro-ophthalmic assessment, 807, 808f, 808t Neuropathy diabetic, 564, 761, 761f pain of, 1150 paraneoplastic peripheral, 798-799 Neurotoxicity of ronidazole, 507 Neurotoxins for pain management, 1154 Neurotrophic agents for pain management, 1153-1154 Neurovascular structures of head, 335 Neuter. See Spay and neuter Neutropenia, 677-678, 677b due to chemotherapy, 775 cyclophosphamide therapy and, 716 Neutrophils Birman granulation anomaly of, 678 bronchial lavage, 866t in bronchial disease, 868 inflammation and, 676-677 Neutrophil count in chemotherapy, 775 in cyclophosphamide therapy, 716 neonatal, 1236t Neutrophil granule anomaly, 1125t Neutrophilia, 675-677, 676b Neutrophilic leukocytosis, extreme, 676-677

1384

INDEX

NGAL as biomarker in human acute renal failure, 966t Niacin, nutritional requirements, 240-241 NIBP. See Non-invasive blood pressure (NIBP) monitoring Nicergoline, 1172t Niemann-Pick disease, 737, 737f Nighttime yowling in senior cats, 1170-1171, 1171b Nipple examination in assessment of skin diseases, 373 Nitazoxanide for Cryptospordium felis, 508 for protozoal disease, 502t Nitenpyram, 381, 382t, 1242-1243 Nitrite, urinary, 943 Nitrogen, dietary protein and, 238 Nitroglycerin, transdermal administration of, 48 Nitrous oxide in balanced anesthesia, 129-130 Nits, 379 NK. See Natural killer (NK) cells NMDA. See N-methyl-D-aspartate receptor antagonist (NMDA) N-methyl-D-aspartate receptor antagonist (NMDA) for analgesia, 105 for pain management, 1151-1152, 1151t Nocardiosis, 1080, 1080f Nodular pancreatic hyperplasia, 517, 517f Nodule, cutaneous Cryptococcus, 1017-1018, 1018f Noise control for environmental health in population wellness programs, 1352-1353 Noncore vaccine in population wellness programs, 1325 Nonhealing wounds, 416-417, 416b Noninflammatory focal alopecia associated with treatments, 402 Non-invasive blood pressure (NIBP) monitoring, 307-308 Nonketotic hyperosmolar diabetes, 565 Nonregenerative anemia, 668-673 due to blood loss or hemolysis, 672 due to bone marrow disease, 672-673 of chronic renal disease, 670-671 defined, 668 diagnostic plans in, 668 due to feline leukemia virus infection, 671-672 history and physical examination in, 668 of inflammatory disease, 669-670 iron deficiency, 668-669, 669t in pure red cell aplasia, 672 Nonsteroidal antiinflammatory drugs (NSAIDs) adverse reactions to, 713-714 for analgesia, 100-105 for degenerative joint disease, 713-715 dosage adjustment in hepatic insufficiency, 44 in renal insufficiency, 42t, 43-44 dose ranges and route of administration for, 97t excretion of in milk, 106 gastric ulceration due to, 455 for long-term pain management, 1152 nephrotoxic effects of, 959 in palliative care, 1159 side effects of, 100-101 toxicity of, 916t, 928-929 for upper respiratory tract disease, 853t for uveitis, 831 Nonunion fracture, 709 Normochromia, 648-649 Normocytosis, 648-649 Normosol-R, 61t

Norsworthy technique for thyroid palpation, 574, 574f Norvasc. See Amlodipine Norwegian Forest cat, 728t, 730-731 Nose, physical examination of, 33 in assessment of skin diseases, 372 Notoedres cati, 379 diagnosis of, 379-380 paronychia due to, 408 skin scrapings for identification of, 373-374 Novartis. See Polysulfated glycosaminoglycan Novel protein, 259 Novel protein/carbohydrate diet, 434 Novelty in environmental management of behavior problems, 230 NPV. See Negative predictive value (NPV) NSAIDs. See Nonsteroidal antiinflammatory drugs (NSAIDs) N terminal-proBNP in congestive heart failure diagnosis, 306 as screening test for cardiac disease, 306 NT-proBNP. See Amino-terminal probrain natriuretic peptide (Nt-proBNP) Nubain. See Nalbuphine Nuclear scintigraphy for gastric emptying assessment, 456-457 in hyperthyroidism, 577-578, 577f in hypothyroidism, 588 Nucleated cells bronchial lavage, 866t pleural effusion fluid, 899t in idiopathic chylothorax, 904-905 Nucleoside analogs for feline herpesvirus-1, 1031 Nucleotide, defined, 1271b-1272b Numbering of teeth, 329-330, 330f-331f Numorphan, 99 Nursing, 186-187 Nursing care in enteral nutrition, 272 Nutrients, 238-241 deficiencies of, 238 excesses of, 248-249, 249t imbalances, 248 requirements of, 168 Nutrition in adult cat, 244-246, 245t anatomy and physiology associated with, 236-237 carbohydrates in, 239-240 carnivorous adaptations in, 243-244 in critical care, 270-278, 271f current controversies in, 289-298 carbohydrates as, 292-295, 293t homemade diets as, 295-297 raw food diets as, 289-292, 290b, 291t energy needs in, 244, 245t enteral, 272-277 appetite stimulants in, 272-273 enterostomy feeding tube in, 277 esophagostomy feeding tube in, 274-276, 275f-276f forced feeding in, 273, 273f gastrostomy feeding tube in, 276, 276f nasoesophageal feeding tube in, 273-274, 273f-274f nursing care and coaxing in, 272 orogastric feeding tube in, 273, 273f tube feeding in, 273 fats and fatty acids in, 239 “Golden Rules” of, 271-272 growth and, 246 inadequacy of in raw food diets, 291 life stage, 244-247, 245t in medical history, 29 normal feeding behavior and, 237, 243

Nutrition (Continued) in palliative care, 1156-1157, 1156f-1158f, 1157t oncologic, 803-804, 805t parenteral, 277-278, 277f centrally administered, 277-278 peripherally administered, 278 in population wellness program, 1326-1327, 1327f during pregnancy and lactation, 246 in preventive health care, 156t, 168-169, 177t protein and amino acids in, 238-239 for senior and geriatric cats, 246-247, 1168, 1168t vitamins in, 240-241 Nutritional disorders, 248-254 food components, 248-250 deficiencies, 249-250, 250t excesses, 248-249, 249t inappropriate, 250 food contaminants, 251 food hypersensitivity, 251-253, 252b, 252f food intolerance, 253 Nutritional encephalopathy, 739-740 Nutritional management of cancer, 266-268, 267f of cardiorenal syndrome, 1113 of cardiovascular disease, 255-256, 256b, 256f, 257t of chronic kidney disease, 278-279, 279b, 279f, 971-973, 972t-973t, 973b of chylothorax, 268-269, 268f in critical care, 270-278, 271f of dental and oral disease, 256-257 of diabetes mellitus with feline lower urinary tract disease, 1107-1108 of endocrinologic disease diabetes mellitus, 264-265, 265b hyperthyroidism, 265-266 obesity, 260-264, 262b-263b, 263f-264f of food-related illness, 269-270 of gastrointestinal disease, 258-259, 260b of hepatic disease, 259-260 of idiopathic cystitis, 991 of ophthalmologic disease, 268 of osteoarthritis, 266 of pancreatitis concurrent with inflammatory bowel disease, 1116-1117 of skin disorders, 257-258 of urinary tract disorders idiopathic cystitis, 281-282 urolithiasis, 279-281, 280b-281b Nutritional myelopathies, 752 Nutritional secondary hyperparathyroidism, hypocalcemia due to, 637-638 Nutritional support for hepatoencephalopathy, 535t for idiopathic hepatic lipidosis, 530-531 for pancreatitis, 516 Nylon muzzle for mandibular fracture, 360 Nystagmus in vestibular disease, 747 O OA. See Osteoarthritis (OA) Obesity, 169 carbohydrates and, 240, 294 defined, 261, 1103-1104 diabetes mellitus concurrent with, 1103-1106, 1105f, 1105t diagnosis of, 261 early spay and neuter and, 1247 energy requirements and, 245t flea allergy dermatitis and, 385 in hypothyroidism, 586t insulin resistance and, 551

Obesity (Continued) myocardial disease associated with, 255 nutritional management of, 260-264, 262b-263b, 263f-264f pathogenesis of, 261 prevention of, 264 senior cats and, 247, 1176, 1177f Object-directed play, 185-186, 186f, 186t O’Brien rule-of-thumb guidelines, 489 Observation, kitten learning by, 188 Obsessive-compulsive disorder (OCD), 213-214 Obstipation, 484-485, 488 Obstruction extrahepatic bile duct, 525 due to hydronephrosis, 956 intestinal, 480-484, 481f-484f renal, diuresis following, 83-84 ureteral, fluid therapy for, 83 urethral, 998-1004, 1000b, 1001f, 1003f anesthetic considerations in, 141-142, 141b fluid and electrolyte loss assessment for, 79t fluid therapy for, 83 urethral patency establishment in, 1000-1002 Obstructive otitis, 412-413, 413f Occlusal, oral anatomy and, 335 Occlusion of vein for vascular access, 71 Occult blood, urinary, 941-942 OCD. See Obsessive-compulsive disorder (OCD) Octreotide for acromegaly, 617-618 for idiopathic chylothorax, 905 Ocular proptosis, 813 Odontoblasts, 331 Odor, urinary, 939-940 Odor signals, 194-195 Odynophagia in esophageal disease, 442 OE. See Otitis externa (OE) OGTT. See Oral glucose tolerance test (OGTT) OI. See Otitis interna (OI) Oleander toxicity, 924 Olfaction, 192 Olfactory communication, 6 Olfactory stimulation in population wellness program, 1344, 1344f Oliguria, overhydration due to, 58 Oliguric renal disease, fluid therapy for, 84 Ollulanus tricuspis, 454, 496-497 OM. See Otitis media (OM) Omega-3 polyunsaturated fatty acids for asthma and bronchitis, 874 of cardiorenal syndrome, 1113 for degenerative joint disease, 715 for diabetes mellitus, 265 for skin disease, 258 Omeprazole in chronic kidney disease therapy, 973 for gastrointestinal ulcers, 434t, 435 for hepatoencephalopathy, 535t for nutritional care in cancer patients, 805t Oncology, 768-806. See also Neoplasia biopsy techniques in, 769-770 chemotherapy in, 770-782 injection-site sarcoma in, 787-791 lymphoma in, 782-786 mammary tumors in, 791-794 nutritional management in, 266-268, 267f palliative care in, 802-806 paraneoplastic syndromes in, 794-802 screening diagnostics in, 768 staging techniques in, 769 Ondansetron in chronic kidney disease therapy, 973t in hepatic lipidosis therapy, 532t

INDEX Ondansetron (Continued) for nutritional care in cancer patients, 805t for vomiting, 432t, 433 in pancreatitis, 516 Onion-containing foods, Heinz bodies due to, 665, 665b Onion toxicity, 250 Onsior. See Robenacoxib Onychectomy, 164 behavior and, 224-225 Oocyst of Toxoplasmosis gondii, 509, 510f Open-closing mouth vocalization, 194 Open-mouth jaw locking, 363-364, 364f Open-mouth vocalization, 194 Open pneumothorax, 906-907 Open tooth extraction, 351-353, 352f-354f Operant conditioning in behavior modification, 227 Ophthalmia neonatorum, 1241-1242, 1241f Ophthalmologic disease, 807-845 ancillary testing in, 811-812, 811f-812f chorioretinal, 837-841 due to enrofloxacin toxicity, 839-840, 839f hypertensive chorioretinopathy, 837-839, 838f progressive retinal atrophy, 841 taurine-deficient retinopathy, 840, 840f corneal and conjunctival, 817-827 acute bullous keratopathy, 827, 827f Chlamydophila felis, 819-823, 820t, 821b conjunctivitis, 823, 823f-824f corneal sequestration, 825-826, 825f-826f corneal ulceration, 824-825, 825f eosinophilic keratoconjunctivitis, 826, 826f feline herpesvirus, 818-819, 818f-819f, 820b symblepharon, 823-824, 824f examination techniques in, 807-811, 808f-811f, 808t eyelid and adnexal, 813-817 entropion, 814-815, 815f eyelid agenesis, 813-814, 814f herpetic dermatitis, 815-816, 815f nasolacrimal system disease, 817, 818f neoplasia, 816, 816f-817f third eyelid disease, 817, 817f glaucoma as, 836-837, 836f-837f history in, 807 of lens, 834-835, 834f-835f nutritional management of, 268 orbital, 812-813, 812f polymerase chain reaction for detection of agents in, 1088 uveal tract, 827-834 iris melanoma, 832-833, 832f secondary intraocular neoplasia, 833-834, 834f spastic pupil syndrome, 832, 832f uveal neoplasia, 832 uveitis, 827-832, 827f-828f, 829b, 829t, 830f-831f Opioids for analgesia, 96-100 for anesthesia premedication, 116-117, 117b in urethral obstruction, 142 in balanced anesthesia epidural/spinal, 130-131 infusion, 130 transdermal, 131 combinations of, 100 epidural administration of, 100 for long-term pain management, 1152 potential drug interactions with, 97 side effects of, 96-97 OP3 opioid agonists, 98-100

Opportunistic infection in immunocompromised cat, 1127 Optivisor, 809f Oral absorption of drugs in neonates and kittens, 45 Oral administration of analgesic drugs, 94 of chemotherapeutic drugs, 773 Oral anatomy, 329-335 bones and joints in, 332-333, 334f common terminology in, 335, 336f lymph nodes and tonsils in, 335 muscles, cheeks, and lips in, 333 neurovascular structures in, 335 oral mucosa in, 332, 333f palate in, 333-334, 334f periodontium in, 331-332 salivary glands in, 334-335 teeth in, 330-331, 332f eruption of, 329, 330t formulas of, 329-330, 330f-331f, 330t tongue in, 334, 335f Oral cavity, impact of aging on, 1167 weight loss and, 1179 Oral disease dentoalveolar trauma as, 348-349 diagnostic imaging in, 338-341 computed tomography in, 340-341, 340f radiography in, 338-340, 338f-339f eosinophilic granuloma complex as, 353, 355f feline calicivirus in, 1032-1033, 1032f feline orofacial pain syndrome as, 355 jaw fractures as, 359-362, 360f-362f local and regional anesthesia in treatment of, 341-342, 341f-342f nutritional management of, 256-257 orofacial soft tissue injury as, 358-359, 358f-359f palate defects as, 355-357, 357f periodontal, 342-344, 343f stomatitis as, 349-350 temporomandibular joint disorders as, 362-365, 363f-364f tooth resorption as, 344-348 tumors as, 365-368, 365f, 367f-368f Oral examination, 33, 335-338 diagnostic imaging in, 338-341 extraoral, 336 intraoral, 336-338, 337f laboratory, 338 patient history and clinical signs in, 335-336 Oral glucose tolerance test (OGTT), 1103 Oral health. See Dental care Oral hygiene, home, 168, 344 Oral hypoglycemic agents, 562 Oral mucosa anatomy of, 332, 333f examination of, 336-337 Oral transmucosal administration of analgesic drugs, 94-95 Orange trait, 1277-1278 Orbifloxacin, 853t Orbital disease, 812-813, 812f Orchitis, 1188 Organomegaly, abdominal distention due to, 540t Organophosphate pesticide toxicity, 919-920, 931t neurologic signs of, 745 treatment of, 916t Orofacial pain syndrome, 355 Orofacial soft tissue injury, 358-359, 358f-359f Orogastric feeding tube, 273, 273f Oronasal fistula, 356 Orphan neonate, 1245-1246, 1245f-1246f ORS. See Ovarian remnant syndrome (ORS) OSA. See Osteosarcoma (OSA) Oscillometric monitoring during anesthesia, 134-135

Oseltamivir, 1038 Osmolality, 56 of crystalloid solutions, 61t in hyperglycemic hyperosmolar syndrome, 88 Osmoles, ineffective, 56 Osmometer, 940 Osmoregulation, 56-57 Osteoarthritis (OA), 709 nutritional management of, 266 regenerative medicine for, 1153 in senior cats, 1173-1174 Osteochondrodysplasia, 713 Osteochondromatosis, 726 Osteodystrophy, due to nutritional deficiencies, 291-292 Osteogenesis imperfecta, 727 Osteomyelitis, 725 cryptococcal, 1017f Osteosarcoma (OSA), 724-725 hepatic, 527t of spine, 754-755 Osteotomy, bulla, for nasopharyngeal polyps, 851 Otitis, 410-416 allergic, 413 apocrine hidrocystoma as, 416, 416f due to demodicosis, 412 obstructive, 412-413, 413f due to Otodectes infestations, 412, 412f ototoxicity concerns in, 415-416 suppurative, 411 yeast, 413 Otitis externa (OE), proliferative necrotizing, 410-416 Otitis interna (OI), 410-416 intracranial complications of, 748-749, 748f vestibular signs of, 747-748, 747f Otitis media (OM), 413-415, 414f vestibular disease and, 415 Otodectes mites, 377-379, 379f otitis due to, 412, 412f skin scrapings for identification of, 373-374 Ototoxicity, 415-416 Outdoor access in population wellness program, 1345, 1345f-1346f Outdoor versus indoor lifestyle, 161, 161f Ovaban. See Megestrol acetate Ovarian cysts, 1218, 1218f Ovarian remnant syndrome (ORS), 1202-1203 Ovarian tumors, 1218 Ovariohysterectomy, 1221 Overgrooming, 188, 214 in feline symmetrical alopecia, 399 Overgrowth, small intestinal bacterial, 480 Overhydration, 58 Overlapping flap for cleft lip and/or palate, 356 Oversight in population wellness program, 1320 Overweight. See Obesity Ovulation hormonal induction of, 1219 hormones in, 1197 spontaneous, 1198, 1217 Owner(s) aggression directed toward, 222-223 caring for after death of cat, 1162-1163 contribution of to obesity in pet, 261 prevention of toxoplasmosis in, 511b Oxazepam for appetite stimulation in cardiovascular disease treatment, 257t for behavior-modification therapy, 232t for cognitive dysfunction in senior cat, 1172t

1385

Oxidative damage in chronic kidney disease, 973 to erythrocytes, 664-666, 665b in progression of obesity to diabetes, 1106 Oxidizing agents for disinfection, 1348b Oxygen central venous partial pressure of, 77 partial pressure of, 136 Oxygen cage, 896b-897b, 897f for pleural effusion, 895 Oxygen delivery monitoring during anesthesia, 134 during perfusion, 55 Oxygen-hemoglobin dissociation curve, 894, 894f Oxygen therapy, 896b-897b for pleural effusion, 895, 896f-897f Oxyglobin administration, 68 for anemia, 654-656 Oxymorphone for pain management, 99 dose ranges and route of administration for, 97t for sedation and premedication, 114t Oxytocin for dystocia, 1211 for inadequate mild production, 1215 for retained placenta, 1214-1215 for uterine evacuation in metritis, 1214 P Pacemaker implantation, 321 Packed cell volume (PCV) in anemia, 653 blood transfusion and, 655 of inflammatory disease, 669-670 regenerative, 657 in erythrocytosis, 673, 675 in immune-mediated hemolysis, 658 neonatal, 1236t Packed red blood cells for anemia, 654-655 hepatic insufficiency and, 44, 44f Pain aggression and misbehavior due to, 7-8, 223-224 of arterial thromboembolism, 316-317 assessment of, 90-94, 92f-93f during physical examination, 33 defined, 90-91 long-term causes of, 1149 clinical signs and diagnosis of, 1149-1150 overlooked causes of, 7b pathophysiology of, 1149 signs suggestive of, 1178t weight loss in senior cats and, 1178-1179, 1178t Pain management in arterial thromboembolism, 318 complementary therapies for, 1153 drug therapy for, 1150-1153, 1151t adverse drug reactions in, 1152-1153 antiepileptics, 1150-1151 mixed analgesics, 1152 N-methyl-D-aspartate, 1151-1152 nonsteroidal antiinflammatory drugs, 1152 opioids, 1152 psychoactive drugs, 1150 sodium channel blockers, 1151 environmental enrichment for, 1153 in feline cholangitis syndrome therapy, 534 in feline idiopathic cystitis, 991 future directions in, 1153-1154 in otitis media, 415 in palliative care, 1150-1153 of cancer, 802-803 in pancreatitis, 516 physical therapies for, 1153 for uveitis, 831

1386

INDEX

Pain syndrome, feline orofacial, 355 Palatal, defined, 335 Palate anatomy of, 333-334, 334f defects of, 355-357, 357f midsagittal split of, 705-706 Palatine nerve block, 341-342, 342f Palatine rugae, 333-334, 334f Palladia. See Toceranib Palliative medicine alleviating discomfort and optimizing comfort in, 1158-1159, 1159f caring for caregivers in, 1162-1163 dying with dignity in, 1159-1162 hydration in, 1155-1156, 1156b mobility in, 1158 nutrition in, 1156-1157, 1156f-1158f, 1157t oncologic, 802-806 pain assessment and management in, 1149-1155 quality of life and euthanasia decisions in, 1155-1163 Pallor, due to anemia, 653 Palpation abdominal of feces in constipation, 485 in high-grade intestinal lymphoma, 474 during physical examination, 35 of fetus, 1205 lymph node, 690-691 response to for pain assessment, 91 thyroid gland in hyperthyroidism, 573-574, 573f-574f during physical examination, 34f Palpebral reflex in anesthesia monitoring, 134 Pamidronate for cholecalciferol toxicity, 916t for hypercalcemia, 634 for vitamin D nephrotoxicosis, 968 Pancarpal arthrodesis, 717-718, 717f Pancreas, involvement of in intestinal small cell lymphoma, 470 Pancreatic bladder, 516-517 Pancreatic disease endocrine, 547-571 diabetes mellitus as, 547-567 gastrinoma as, 567 insulinoma as, 567-568 overview of, 547, 548t exocrine, 513-522 cysts, pseudocysts, and bladders as, 516-517 exocrine pancreatic insufficiency as, 518-520 neoplasia as, 517-518, 518f nodular hyperplasia as, 517, 517f pancreatitis as, 513-516, 514f-515f Pancreatic ducts, 523f Pancreatic enzymes for exocrine pancreatic insufficiency, 519-520 Pancreatic lipase immunoreactivity (PLI), 514 in diarrhea assessment, 464-465, 464t in inflammatory bowel disease with pancreatitis, 1116 Pancreatitis, 513-516, 514f-515f bile duct obstruction with, 525 concurrent with inflammatory bowel disease, 468, 1114-1120, 1118t in diabetic cat, 564 Pancur. See Fenbendazole Panleukopenia, 1036-1038, 1037f diarrhea due to, 477t, 478 pregnancy loss due to, 1224 vaccination against, 174t, 175 Panniculitis, mycobacterial, 1079 Panoptic, 808-810, 810f Panting in hyperthyroidism, 572t PaO2. See Partial pressure of oxygen (PaO2)

Papillae on tongue, 334, 335f Papillomavirus, 1062-1063, 1062f Paracetamol. See Acetaminophen Paragonimus kellicotti, 882 Parallel dental radiography, 338-339, 339f Paralysis associated with arterial thromboembolism, 316-317 facial, 761-762 laryngeal, 858 Paraneoplastic alopecia, 402, 402f Paraneoplastic exfoliative dermatitis, 398, 795, 795f Paraneoplastic syndrome (PNS), 794-802 cachexia and anorexia in, 799 dermatologic manifestations, 795, 795f endocrine manifestations, 797-798 hematologic alterations, 795-797 neuromuscular manifestations, 798-799 Parasites associated with hepatopathy or hepatic inflammation, 534b control of in community cats, 1303-1304 internet resources for, 159b, 177t in population wellness program, 1325 in preventive health care, 156t, 169-172 external, in kitten, 1242-1243 fecal assessment of feces for, 462-463 gastrointestinal, 496-512 cestodes, 500-501 nematodes, 496-500 protozoa, 501-511 testing for in population wellness programs, 1323, 1323b trematodes, 501 identified by skin scrapings, 373-374 lower respiratory tract, 881-885 heartworm, 883-885, 884t lung fluke as, 882 lungworm as, 882 Toxoplasmosis gondii in, 883, 883f prevalence of, 170t prophylaxis, 172, 172t for kittens, 172 skin disease due to, 377-381 demodicosis, 380-381, 380f fur mites and lice, 379-380 Otodectes, 377-379, 379f tick and flea infestations and flea bite hypersensitivity, 381 Parasitic zoonotic disease, 1093-1094, 1094f Parathyroid gland preservation in thyroidectomy, 582-583, 583f Parathyroid hormone (PTH) in calcium regulation, 625 hypercalcemia and, 627, 629-633, 633f in hypocalcemia, 637t Parathyroid hormone-related protein (PTHrP) in hypercalcemia, 627 in hypocalcemia, 637t Parental factors in behavioral development of kitten, 182-183 Parenteral administration of analgesic drugs, 94 Parenteral fluid therapy for diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome, 566 effects on urine, 938b Parenteral nutrition, 277-278, 277f centrally administered, 277-278 peripherally administered, 278 Paresis, associated with arterial thromboembolism, 316-317, 317f Paromomycin for Cryptospordium felis, 508 for protozoal disease, 502t

Paronychia, 408-409, 409f Parotid gland, 334-335 Parotid lymph node, 335 Paroxetine, 232t Pars distalis, 611 Pars nervosa, 611 Partial pressure of carbon dioxide (PCO2) monitoring during anesthesia, 136 Partial pressure of oxygen (PaO2) monitoring during anesthesia, 136 in monitoring of fluid therapy for hypovolemia, 77 Partial seizure, 734-735 complex, 734-735 simple, 734-735 Partial thromboplastin time (PTT), 524-525 Parturition, normal, 1207-1209, 1208f, 1209b Parvovirus, 1036-1038 diarrhea due to, 477t, 478 Passive immunity, neonatal, 1240 failure of, 1240-1241 Pasteurella spp., 880-881 Patella fracture of, 706-707, 707f luxation of, 719-721 Patent ductus arteriosus (PDA), 324-325 Paternal factors in behavioral development of kitten, 183 Pathogens contamination in raw food diets, 291, 291t of kittens, 1241b Patient history. See History Patient positioning for renal biopsy, 954 Paw anesthetic block distal, 103-104, 104f Paw examination, 34 in assessment of skin diseases, 373 Paw pads diseases of, 407-408, 408f for home blood glucose monitoring, 561 “Pawspice”, 1160 PB. See Phenobarbital (PB) PCO2. See Partial pressure of carbon dioxide (PCO2) PCR. See Polymerase chain reaction (PCR) PCV. See Packed cell volume (PCV) PDA. See Patent ductus arteriosus (PDA) PDH. See Pituitary cobalt radiation treatment (PDH) Peace lily toxicity, 924 Pectin, 916t Pectus excavatum, 910, 1235-1236, 1235f Pediatrics. See Kitten Pedigree, 1271b-1272b PEG. See Percutaneous endoscopic gastrostomy (PEG) feeding tube Pegvisomant, 618 Pelger-Huët anomaly, 679, 1125t Pelvic canal narrowing, 708-709 Pelvic fracture, 708-709, 708f Pemphigus foliaceus, 397-398, 397f Pemphigus vulgaris, 403 Penciclovir, 821-822 Penetrance, genetic, 1271b-1272b age-related, 1281 incomplete, 1280-1281 Penetrating wounds of oral cavity, 358 Penis anatomy of, 1184, 1185f-1186f conditions of, 1187-1188 Penny toxicity, 926 Pentastarch, 68 Pentazocine, 98 Pentosan. See Pentosan polysulfate Pentosan polysulfate for degenerative joint disease, 715 Pepcid AC. See Famotidine Perching places, 229, 229f

Percutaneous endoscopic gastrostomy (PEG) feeding tube, 531-532 Perforation corneal, examination of, 811 esophageal, due to foreign body, 447 Perfusion, 55 Periactin. See Cyproheptadine Perianal pruritus, 409 Perineal dermatitis, 492, 492f Perineal urethrostomy, 1003-1004, 1003f Perinephric pseudocysts (PNPs), 947-948, 948f Periodontal disease, 342-344, 343f prevention of in population wellness program, 1328 Periodontal ligament, 331 Periodontal probe, 337-338, 337f Periodontal therapy, 343-344, 344f Periodontitis, 342-343, 343f Periodontium, anatomy of, 331-332 Perioperative care, 112-150 anesthetic maintenance in, 127-132 balanced anesthetic techniques for, 129-132 inhalant anesthetics for, 127-129 equipment, monitoring and fluid therapy in, 133-136, 133f-135f of feral cats, 133 of geriatric patients, 138-139, 138b hepatic lipidosis and, 142-143 hyperthyroidism and, 139-141, 139b hypertrophic cardiomyopathy and, 143-145, 144b induction agents in, 118-127 alphaxalone as, 125-126 etomidate as, 123-125 inhalant anesthetics as, 126-127 intravenous doses for, 118t ketamine as, 119-121 propofol as, 122-123 telazol as, 121-122 thiopental as, 118-119 intubation in, 127 of neonatal patients, 137-138, 137b risk assessment in, 112, 113b, 113t sedation and premedication in, 112-127, 114t anticholinergics for, 117-118 opioids for, 116-117, 117b tranquilizers and sedatives for, 113-118 for surgical procedures for community cats, 1299-1300 total intravenous anesthesia in, 132 urethral obstruction and, 141-142, 141b Periosteal elevator, 351f-353f Periosteal proliferative polyarthritis (PPP), 711, 711b, 716 Peripherally administered parenteral nutrition, 278 Peripherally inserted central catheter (PICC), 70, 71t Peripheral neuropathy, paraneoplastic, 798-799 Peripheral pulses assessment in cardiovascular disease, 302 Peripheral sensory receptors in vomiting, 426 Peripheral venous catheter, 70, 71t, 72, 72f Peripheral vestibular disease (PVD), 747-749, 747f, 748t, 749f otitis and, 415 Peritoneal cavity, diseases affecting, 538-546 ascites as, 538-541 feline infectious peritonitis as, 1041t fluid analysis and classification in, 541-543 Peritoneal dialysis, 960-961, 960f Peritoneal fluid analysis and classification of, 541-543, 542t normal, 538, 538b

INDEX Peritoneopericardial diaphragmatic hernia (PPDH), 324, 324f, 907-908 Peritonitis bile, ascites due to, 545 feline infectious (See Feline infectious peritonitis (FIP)) septic ascites due to, 544-545, 544f hypocalcemia with, 638 Permanent teeth, eruption of, 329, 330t Permeant solutes, 56 Persian cat, 1256-1258 morphology of, 1256 Personality factors in group housing, 1337 Personal protective equipment (PPE), 771 Pest control for environmental health in population wellness programs, 1352-1353 Pesticide toxicity, 914-915, 915f, 916t, 931t neurologic signs of, 745 Pet dander, allergic reactions to, 419-424 Pethidine, 97t Petting aggression, 223 pH of crystalloid solutions, 61t gastric, oral absorption of drugs in neonates and kittens and, 45 urinary, 940-941 renal calculi prevention and, 956 struvite uroliths and, 280b, 995 Pharmacodynamic monitoring of long-term drug therapy, 1140-1142, 1140t Pharmacodynamics of alphaxalone, 125-126 of etomidate, 124 of ketamine, 120-121 of propofol, 123 of telazol, 121-122 of thiopental, 118-119 Pharmacokinetic monitoring of long-term drug therapy, 1142-1143, 1143t Pharmacokinetics of alphaxalone, 125-126 of etomidate, 125 of ketamine, 121 of propofol, 123 of telazol, 122 of thiopental, 119 Pharyngeal disease, nutritional management of, 259 Phenobarbital (PB) for feline hyperesthesia syndrome, 763, 764t for hepatoencephalopathy, 535t pharmacokinetic monitoring of, 1143t for seizures, 736, 736t stability of suspensions of, 47t for toxicosis, 916t Phenocopy, 1271b-1272b, 1273 Phenothiazines for sedation and premedication, 113-114 for vomiting, 432t, 433 Phenotype, 1270 defined, 1271b-1272b mutations of the domestic cat, 1273-1279, 1275f-1279f, 1275t Phenoxybenzamine for hypertension with chronic kidney disease, 1122t for urethral obstruction in feline idiopathic cystitis, 992t Pheromone, synthetic analogs of for behavior problems, 233 for feline idiopathic cystitis, 991 Philodendron spp. toxicity, 924, 925f Phimosis, 1188 Phlebostatic axis, 75 Phlebotomy for erythrocytosis, 675

Phobia, behavior problems associated with, 212 Phone call in client education, 9 Phosphate addition of in fluid therapy, 63-64, 63t in hypocalcemia, 637t low levels of fluid therapy for, 63-64 hemolytic anemia due to, 666 Phosphate binders hypercalcemia due to, 630 pharmacodynamic monitoring of, 1140t, 1142 Phosphate enema toxicity, 638 Phosphatidylserine, 1172 Phospholipase A2 in systemic anaphylaxis, 698 Phosphorodiamidate morpholino oligomers (PMOs), 878-879 Phosphorus deficiency of, 250t in dissolution of struvite uroliths, 280b excess of, 249t intake in chronic kidney disease, 279b, 973-974 monitoring and correction of in diabetic ketoacidosis, 86-87 neonatal values, 1237t for plaque control, 256 therapeutic renal diets and, 972t Physaloptera, 497 Physeal closure, early spay and neuter and, 1247 Physeal dysplasia, 707-708 Physeal fracture, capital femoral, 707-708, 707f-708f Physical examination, 31-39 of abdomen, 35-36 in anemia nonregenerative, 668 regenerative, 656 in cardiovascular disease, 301-303 in diarrhea, 462 final general assessment in, 36-39, 37b, 37f-38f frequency of in preventive health care, 155-158 handling during, 11-14, 12f-14f of head, 33-34, 33f of hindquarters and tail, 36 in hyperaldosteronism, 603 initial steps in, 31-33, 32f-33f in lower urinary tract disease, 982, 982f in male infertility, 1192 of neck and forelimbs, 34, 34f in nutritional planning, 244-245, 245t ophthalmic, 807-811, 808f-811f, 808t oral, 335-338 in population wellness program, 1321 in skin disease, 372-373 in thoracic cavity disease, 892 of thorax and trunk, 34-35, 35f in vomiting, 429 Physical features of cat-friendly practice, 21-24 equipment, 23, 23f examination rooms, 21-22, 22f housing, 23-24, 23f-24f public areas, 21, 21f-22f treatment areas, 22-23, 22f Physical stimulation in population wellness program, 1343-1345, 1345f Physical therapy for arterial thromboembolism, 318 in long-term pain management, 1153 Physiologic leukogram, 675-676 Pica, 214-215, 214f PICC. See Peripherally inserted central catheter (PICC) Pigmentary changes, 407 Pimobendan, 312

Pin for stifle ligamentous injury repair, 721 Pinnae, 192 deformed, otitis due to, 412, 412f for home blood glucose monitoring, 561, 561f Pinnal alopecia, 402, 402f Piperazine, 172t, 499t Piroxicam for nasal neoplasia, 858 for upper respiratory tract disease, 853t Pituitary-adrenal function tests in hyperadrenocorticism, 594-598 in hypoadrenocorticism, 608 Pituitary cobalt radiation treatment (PDH), 599t Pituitary dwarfism, 611 Pituitary gland, anatomy and physiology of, 611 Pituitary gland disorders, 610-625 acromegaly as, 611-618 causes of, 612 clinical features of, 612-615, 613b, 613f-614f diagnosis of, 615-616, 615b, 616f differential diagnosis for, 616-617 prognosis of, 618 treatment of, 617-618 Cushing’s disease as, 611 diabetes insipidus as, 618-622 dwarfism as, 611 tumors as, 611, 741-742, 742f Pituitary radiotherapy, 601 Pituitary tumors adenoma as, 611 growth hormone-secreting, 611-618 macro-, 611 Pit viper snake, 927 PIVKA. See Protein induced in vitamin K antagonism test (PIVKA) PK. See Pyruvate kinase (PK) PKD. See Polycystic kidney disease (PKD) Placenta premature separation of, 1223 retained, 1214-1215, 1214f Plague, 1071t Plantigrade stance, due to common calcaneal tendon rupture, 723, 723f Plants, poisonous, 921-924, 922f-924f, 922t central nervous system signs of, 745 Plaque(s) dental control of for stomatitis, 349-350 prevention of, 344 eosinophilic miliary dermatitis and, 404, 404f in pyoderma, 381-383, 383f Plasma for albumin replacement, 67 for anemia, 654-655 for hepatoencephalopathy, 535t Plasma cell pododermatitis, 408, 408f Plasma cells in lymph nodes, 690 Plasma osmolality, 56 Plasma resin activity (PRA), 605 Plasma volume, effective, 55-56 Platelets, 679 disorders of, 681b, 682 fresh whole blood transfusion for, 66-67 splenic storage of, 685-686 Platelet count, 683 in cyclophosphamide therapy, 716 Platelet-rich plasma for anemia, 654-655 Platelet-to-platelet adhesion, 679 Platinum chemotherapy agents, 779-780 Platynosomum spp., 501 Play aggression during, 221 as behavior in kitten, 163, 184-186, 185f-186f, 186t

1387

Pleiotropic effects, 1273 Pleiotropy, 1271b-1272b Pleocytosis in neurologic feline infectious peritonitis, 1044 Pleural access ports, 906 Pleural effusion, 892-895 analysis of, 895 categorization of, 899t causes of, 905f-906f chylothorax, 268, 268f, 904-905, 904f congestive heart failure, 310-311, 311f, 895-898, 900f feline infectious peritonitis, 898-900, 900f, 1040, 1041t neoplasia, 900-901, 901f overhydration, 58 pyothorax, 901-904, 902b-903b oxygen administration for, 895, 896b-897b, 896f-897f pleural access ports for, 906 radiography in, 893-894, 893f-894f stabilization in, 894-895, 894f thoracocentesis for, 895, 898b, 898f thoracostomy tubes for, 902b-903b, 902f-903f Pleural fluid, 892-893 in congestive heart failure, 895 in feline infectious peritonitis, 898-900, 1043, 1043b, 1043f in idiopathic chylothorax, 904-905 Pleurocentesis for congestive heart failure, 313, 313f for pleural effusion, 895 Plexiglass chamber induction, 126-127, 126f PLI. See Pancreatic lipase immunoreactivity (PLI) PLO. See Pluronic lecithin organogel (PLO) Pluronic lecithin organogel (PLO), 48 PMOs. See Phosphorodiamidate morpholino oligomers (PMOs) Pneumocystogram, 983 Pneumonia, 877-885 aspiration, 875-876 bacterial, 879-881, 880f fungal, 854f, 881 Histoplasma capsulatum, 1019 lipid aspiration, 876 parasitic, 881-885, 883f, 884t viral, 878-879 Pneumoperitoneum, abdominal distention due to, 540t Pneumothorax, 906-907, 907f PNPs. See Perinephric pseudocysts (PNPs) PNS. See Paraneoplastic syndrome (PNS) Poikilocytosis, 649-650 Point mutation, 1271b-1272b Poisoning. See Toxicology/toxicity Poisonous plants, 921-924 castor bean plant, 924 containing cardiac glycosides, 923-924 containing insoluble calcium oxalates, 924 cycad palms (cycas, zamia species), 924 lilies, 921-923, 922f-923f, 922t rhododendron species, 923, 923f-924f Poisonous snakes, 927 Poisonous spiders, 927-928 Policy development in population wellness program, 1314, 1314b Poliomyelitis, idiopathic, 753 Polyarteritis nodosa, 949 Polyarthritis idiopathic, 712-713, 712b periosteal proliferative, 711, 711b, 716 Polychromasia, 649-650 Polychromatophil, 649f Polycystic kidney disease (PKD), 946-947, 946f-947f DNA testing for, 1274t genetics of, 1267-1268, 1272, 1279

1388

INDEX

Polycythemia, 673-675, 674f paraneoplastic, 796 Polydactyly, 725 Polydipsia in acromegaly, 614-615 in diabetes insipidus, 618-619 in hyperadrenocorticism, 592-593, 593t in hypercalcemia, 626t in hyperthyroidism, 572t, 575 Polyethylene glycol for obstipation, 488 Polymerase chain reaction (PCR), 1083-1084, 1083f, 1085f in bartonellosis, 1072 for Cryptospordium felis diagnosis, 508 in detection of bloodborne agents, 1086-1088 in Escherichia coli diagnosis, 479 in feline calicivirus, 1033 in feline herpesvirus-1 infection, 1030 in feline immunodeficiency virus, 1059 in feline infectious peritonitis, 1045 for removal of chronic shedders, 1046 in feline leukemia virus, 1050, 1052 in gastrointestinal infection, 1086 in Giardia diagnosis, 504 in hemoplasmosis, 667 in ocular infection, 1088 in respiratory infection, 1084-1086 in rickettsial disease, 1026 in upper respiratory viral infections, 854 Polymorphism, genetic, 1271b-1272b Polymyopathy Burmese hypokalemic, 729-730 hypokalemic, in hyperaldosteronism, 603 Polymyositis, 758, 758f infectious, 729 Polyneuropathy, 760-762 congenital, 760-761 diabetic, 761 idiopathic, 761 Polypeptide islet amyloid, 1105 pancreatic, 548t Polyphagia with acromegaly, 613-614 in hyperthyroidism, 572t Polyps of ear, otitis due to, 412-413, 413f intestinal adenomatous, 476 nasopharyngeal, 748, 851, 851f Polysulfated glycosaminoglycan, 715 Polyunsaturated fatty acids excessive intake of, 249 omega-3 for asthma and bronchitis, 874 of cardiorenal syndrome, 1113 for degenerative joint disease, 715 for diabetes mellitus, 265 for skin disease, 258 Polyuria in acromegaly, 614-615 in diabetes insipidus, 618-619 fluid loss associated with, 59t in hyperadrenocorticism, 592-593, 593t in hypercalcemia, 626t in hyperthyroidism, 572t, 575 due to lily toxicosis, 922t Ponazuril for coccidia, 502-503, 1323b for protozoal disease, 502t Popular sire, 1271b-1272b Population density in population wellness program, 1347 Population medicine. See also Community cats care and control of community cats, 1290-1311 wellness, 1312-1356 Population wellness program, 1312-1356 behavioral care in, 1328-1346

Population wellness program (Continued) daily routine in, 1345-1346 at intake, 1328-1329, 1329f-1330f, 1330b mental and physical stimulation in, 1343-1345, 1343f-1345f monitoring in, 1346, 1346f proper housing and, 1329-1341 social companionship in, 1341-1343, 1342f breed-specific care in, 1328 components of wellness in, 1312-1313, 1313f disease testing in, 1321-1323 environmental health in, 1346-1353 cleaning and disinfection in, 1347-1349, 1348b general facility maintenance in, 1353 heating, ventilation, and air conditioning in, 1351-1352 noise and pest control in, 1352-1353 population density in, 1347 segregation of cats in, 1349-1351 staff training in, 1353 essential elements of, 1316 goals of, 1313 grooming in, 1327-1328 health surveillance (daily rounds) in, 1313 history in, 1321 infectious disease transmission and control in, 1316 management oversight in, 1320 medical decision making and euthanasia in, 1315 medical record keeping and cat identification in, 1316-1318, 1317f-1318f, 1319b, 1320f nutrition in, 1326-1327, 1327f parasite control and prevention in, 1325 periodontal disease prevention in, 1328 physical examination in, 1321 policy and protocol development in, 1314 problem prevention in, 1315 quality of life and the five freedoms in, 1314, 1314b spaying and neutering in, 1325-1326 stress and, 1315-1316 vaccination in, 1323-1325 Portal hypertension, 526-527 Portosystemic shunting (PSS), 526-527, 534-535 Positioning. See Patient positioning Positive contrast cystography, 984 Positive predictive value (PPV), 1082 Positive reinforcement-based training, 1344, 1345f Postinflammatory hyperpigmentation, 407 Postpartum problems, 1213-1215 Postrenal causes of acute renal failure, 958 Postsurgical osteomyelitis, 725 Posttraumatic intraocular sarcoma, 834-835 Posture(s) in communication, 5-6, 5f during estrus, 1196, 1196f pain scoring system based on, 91, 92f-93f Potassium bromide (KBr) for seizures, 736, 736t Potassium gluconate for hyperaldosteronism, 605 Potassium (K+) addition of in fluid therapy, 62-63 for hypercalcemia, 634 for appetite stimulation in cardiovascular disease treatment, 257t

Potassium (K+) (Continued) in crystalloid solutions, 61t for chronic kidney disease, 278-279 decreased in Burmese hypokalemic polymyopathy, 729-730 in secondary noninflammatory myopathies, 760 deficiency of, 250t (See also Hypokalemia) diabetes mellitus and metabolism of, 550 monitoring and correction of in diabetic ketoacidosis, 86 taurine deficiency and balance of, 256 therapeutic renal diets and, 972t Potassium phosphate (KPO4) for acute hemolysis due to severe hypophosphatemia, 666 as fluid additive, 63-64, 63t Potassium supplements, pharmacodynamic monitoring of, 1140t, 1142 Potpourri toxicity, 925-926, 926f Pounce as play behavior, 185, 186t Poxvirus, 879, 1063 PPDH. See Peritoneopericardial diaphragmatic hernia (PPDH) PPE. See Personal protective equipment (PPE) PPP. See Periosteal proliferative polyarthritis (PPP) PPV. See Positive predictive value (PPV) PRA. See Plasma resin activity (PRA) Practice, cat-friendly, 20-25 feline veterinarians and, 21 physical features of, 21-24 Pradofloxacin for hemoplasmosis, 667-668 for upper respiratory tract infection, 852-853, 853t for urinary tract infection, 1005 Pralidoxime chloride for toxicosis, 916t due to cholinesterase inhibitors, 920 Praziquantel, 172t, 499t for Paragonimus kellicotti, 882 for Platynosomum, 501 for roundworms, 498 Prazosin for hypertension with chronic kidney disease, 1122t for urethral obstruction in feline idiopathic cystitis, 992t PRCA. See Pure red cell aplasia (PRCA) Preauricular area alopecia in, 402 examination of in assessment of skin diseases, 372 Prebiotics for diarrhea, 436 Precordial thrill, 34-35 Predation, development of, 187 Predatory aggression, 224 Prednisolone adverse effects of, 473 as chemotherapy agent, 777t, 781 for lymphoma, 784-785 for chronic rhinosinusitis, 857-858 for feline cholangitis syndrome, 534 for heartworm prophylaxis, 885 for hemoplasmosis, 667-668 for hypoadrenocorticism, 609 for immune-mediated arthritis, 715-716 for immune-mediated hemolysis, 659-660, 659t for immunosuppression, 1135, 1135t for inflammatory airway disease, 871-872 for inflammatory bowel disease, 438-439, 468 for insect bite hypersensitivity, 386 for intestinal small cell lymphoma, 472-473, 472t

Prednisolone (Continued) for lymphocytic plasmacytic gastritis, 455 for otitis media, 414 for pancreatitis, 516 with inflammatory bowel disease, 1118t, 1119 for pemphigus foliaceus, 397-398 for plasma cell pododermatitis, 408 for pruritus in atopic cat, 390t for stomatitis, 350 for systemic lupus erythematosus, 697 for upper respiratory tract disease, 853t for uveitis, 831 Prednisone for appetite stimulation in cardiovascular disease treatment, 257t as chemotherapy agent, 781 for lymphoma, 784-785, 784t for hydrocephalus, 738 for hypercalcemia, 636 for immune-mediated arthritis, 715-716 for immune-mediated hemolysis, 659-660, 659t for immunosuppression, 1135, 1135t for inflammatory bowel disease, 438-439 Prednisone sodium succinate for anaphylaxis, 699t Pregabalin for pain management, 1150-1151 Pregnancy, 1204-1209 care of queen in, 1206-1207 in community cats, 1304-1305 diagnosis of, 1204-1206, 1205f-1206f energy requirements during, 245t hormonal events of, 1197-1198 labor and delivery in normal, 1207-1209, 1208f, 1209b problems with, 1209-1213, 1210b length of, 1196b loss of, 1222-1224, 1222b-1223b nonsurgical termination of, 1201 nutrition during, 246 postpartum problems following, 1213-1215 prediction of due date in, 1206, 1207b, 1207f, 1207t taurine deficiency during, 250 Preimplantation, 1233 Premature ventricular contraction, 319 Premedication before anesthesia, 112-127 anticholinergics for, 117-118 drugs commonly used for, 114t for geriatric patients, 139 in hyperthyroid patient, 140 in hypertrophic cardiomyopathy, 144 induction agents in, 118-127 alphaxalone as, 125-126 etomidate as, 123-125 inhalant anesthetics as, 126-127 intravenous doses for, 118t ketamine as, 119-121 propofol as, 122-123 telazol as, 121-122 thiopental as, 118-119 for neonates, 137, 1248 opioids for, 116-117 tranquilizers and sedatives for, 113-118 in urethral obstruction, 142 Premolars, 330t Prepubic urethrostomy, 1004 Prerenal acute renal failure, 958 Preventive health care, 151-180, 152f behavioral, 160-164 for adult and mature cat, 163 environmental enrichment in, 161-163, 162f for geriatric cat, 164

INDEX Preventive health care (Continued) indoor versus outdoor lifestyle and, 161, 161f for junior cat, 163 for kittens, 163, 163f for senior cat, 164 benefits of, 151-153 checklist for, 154f client communication in, 178 current barriers to, 151-152 dental care in, 167-168, 167f disaster preparedness and estate planning in, 160 discussion and action items in, 156t frequency of examination in, 155-158 genetic testing in, 166-167 grooming and claw care in, 164 internet resources for, 159b, 177t, 178 meeting costs of, 158, 159b microchipping in, 158-160 minimum database in, 165-166, 165t neutering in, 164-165 nutrition and weight management in, 168-169, 169f opportunities in, 152-153 parasite control in, 169-172, 170t, 172t retrovirus testing in, 166, 1053-1054, 1054b for senior cat, 1168-1169 vaccination in, 173-178, 174t Prey for cats, 237 Priapism, 1188 Prilocaine, 102 Prilocaine cream for blood collection, 15 Prilosec. See Omeprazole Primary noninflammatory myopathies, 759, 759f Probe, deoxyribonucleic acid, 1083 Probiotics for diarrhea, 436 for pancreatitis with inflammatory bowel disease, 1117-1119 Problem behaviors, behavior problems versus, 211 Prochlorperazine, 432t Prochlorpromazine, 973t Proestrus, vaginal cytology changes in, 1216b Progesterone in anestrus, 1196 in ovulation, 1197 in pseudopregnancy, 1198 Progestins adverse effects of, 1201 for control of estrus and reproduction, 1200-1201 Program. See Lufenuron Progressive retinal atrophy, 841 DNA testing for, 1274t genetics of, 1284 Prokinetics for constipation, 487t for esophagitis and esophageal strictures, 445 for vomiting, 431-433, 432t Prolactin in milk production, 1215 in pregnancy, 1197-1198 Prolapse rectal, 491-492 of third eyelid gland, 817 uterine, dystocia due to, 1211-1212 Proliferative glomerulonephritis, 951 Proliferative necrotizing otitis externa, 416 Proligesterone, 1200t, 1201 PromAce. See Acepromazine Promeris. See Metaflumizone Promotion of kitten classes, 199 Propanolol for heart rate control in hyperthyroidism, 326 for hypertension with chronic kidney disease, 1122t

Proparacaine hydrochloride for nasoesophageal tube placement, 273-274 Propentofylline, 1172, 1172t Prophylaxis heartworm, 885 parasitic, 172, 172t for kittens, 172 Propofol for induction of anesthesia, 118t, 122-123, 122b for upper respiratory disease diagnostics, 849 permethrin toxicosis-related seizures, 920b therapeutic considerations in senior and geriatric cats, 45-46 for total intravenous anesthesia, 132 Proptosis, 813 ProsaptideTX14 (A), 1153-1154 Prostaglandin F2alpha for control of estrus and reproduction, 1200t, 1201-1202 for cystic endometrial hyperplasiapyometra complex, 1221-1222 for retained placenta, 1214-1215 for uterine evacuation in metritis, 1214 Prostate, anatomy of, 1184 Protein deficiency of, 250t in skin disorders, 258 dietary, 238, 244 in cancer, 267b in cardiorenal syndrome, 1113 chronic kidney disease and, 279b, 971-973, 972t-973t in critical care, 272 for diabetes mellitus, 264-265, 265b digestibility of in different life stages, 1168t in dissolution of struvite uroliths, 280b excess of, 249t in hepatic disease, 260b in homemade diets, 296-297 hypersensitivity to, 253 for hyperthyroidism, 266b for idiopathic hepatic lipidosis, 532 in inflammatory bowel disease, 260b, 1117 obesity and, 262 in pancreatitis, 1117 restricted in queen, effects on kitten, 183 for senior cat, 247, 1168 effusion fluid in feline infectious peritonitis, 1043-1044, 1043b, 1044t peritoneal, 538b, 542t pleural, 899t neonatal values, 1237t novel, 259 for vomiting, 434 parathyroid hormone-related, in hypercalcemia, 627 urinary, 942-944, 942t in chronic kidney disease classification, 964 Protein-bound calcium, 625 Protein C in hemostasis, 680 Protein hydrolysate diet, 259 Protein induced in vitamin K antagonism test (PIVKA) in anticoagulant toxicity, 917 in liver disease, 524-525 Protein pump, 74 Protein S in hemostasis, 680 Proteinuria in glomerulonephritis, 951-952 due to lily toxicosis, 922t localization, causes, and findings in, 943t in renal disease

Proteinuria (Continued) chronic, 964, 964b, 965f, 970-971, 1121-1122, 1122t fluid therapy for, 84 in urinary tract diagnosis, 936t Prothrombin time (PT) in hemostasis evaluation, 683-684 in liver disease, 524-525 Protocol development in population wellness program, 1314, 1314b Proton pump inhibitors, 445 Protopam. See Pralidoxime chloride for toxicosis Protozoa, 501-511 associated with hepatopathy or hepatic inflammation, 534b coccidia, 501-503, 501f, 502t Cryptosporidium felis, 507-509, 508f Giardia duodenalis, 503-505, 504f, 504t pregnancy loss due to, 1223b, 1224 Toxoplasmosis gondii, 509-511, 510b-511b, 510f Tritrichomonas foetus, 505-507, 506f Proximal humerus, bone marrow collection from, 644-645, 645f ProZinc insulin, 553-554, 553t, 558t changing of, 558 Pruritus, 377-391 allergic causes of, 385-391 atopic dermatitis, 387-391, 388f-389f, 390t flea allergy dermatitis, 385, 385b food allergy, 252f, 386-387 insect bite hypersensitivity, 385-386, 386f flow chart for, 378f history in, 372 infectious causes of, 381-385 dermatophytosis, 385 Malassezia overgrowth, 383-384 pyoderma, 381-383, 383f, 384t parasitic causes of, 377-381 demodicosis, 380-381, 380f fur mites and lice, 379-380 Otodectes, 377-379, 379f tick and flea infestations and flea bite hypersensitivity, 381 perianal, 409, 409f Pseudocyst(s) pancreatic, 516-517 perinephric, 947-948, 948f Pseudohermaphroditism, 1189 Pseudomycetomas, 392-393 Pseudopregnancy, 1197 hormones in, 1198 length of, 1196b Pseudotumor, feline orbital, 813 PSS. See Portosystemic shunting (PSS) Psychoactive drugs for pain management, 1150 Psychological factors in constipation, 486t Psychotropic medication for behavioral problems, 230-233, 232b, 232t for excessive vocalization, 216-217 for fear aggression, 220 for intercat aggression, 221 for overgrooming, 214 for pica, 215 for redirected aggression, 222 for separation anxiety, 216 for urine spraying, 219 PT. See Prothrombin time (PT) PTH. See Parathyroid hormone (PTH) PTHrP. See Parathyroid hormone-related protein (PTHrP) PTT. See Partial thromboplastin time (PTT) Puberty female, 1195-1196, 1196b male, 1185, 1196b Public areas, cat-friendly practice and, 21, 21f-22f

1389

Public health considerations with zoonotic disease, 1095 Puerperal tetany. See Eclampsia Pulmonary disease, 861-891. See also Thoracic cavity disease aspiration pneumonia as, 875-876 asthma and chronic bronchitis as, 866-875 clinical signs of, 867 definitions of, 866 diagnosis of, 867-870, 869f-870f epidemiology of, 866 etiopathogenesis of, 866-867 treatment of, 870-875, 872b, 873f chylothorax as, nutritional management of, 268-269 diagnosis of, 862-866 bronchoalveolar lavage in, 864, 865b, 865f, 866t bronchoscopy in, 864 computed tomography in, 864 fine needle aspiration in, 865 lung parenchymal biopsy in, 865-866 radiology in, 862-863, 863f-864f, 863t idiopathic pulmonary fibrosis as, 875, 876f infectious, 877-885 bacterial, 879-881, 880f blastomycosis, 1022-1023, 1022f fungal, 881 parasitic, 881-885, 883f, 884t viral, 878-879 neoplasia as, 877, 877f pleural effusion due to, 900-901, 901f due to smoke inhalation, 876-877 traumatic, 876 Pulmonary edema, due to overhydration, 58 Pulmonary fibrosis, idiopathic, 875, 876f Pulmonary function testing, 870 Pulp, exposure of in tooth fracture, 348, 348f Pulp cavity, 331, 332f Pulp therapy, vital, 348 Pulse in cardiac disease diagnosis, 302 monitoring during anesthesia, 134 quality of for monitoring of fluid therapy for hypovolemia, 75 Pulse oximetry during anesthesia, 135-136, 135f Punch biopsy for cancer diagnosis, 769-770 Punctate reticulocyte, 648, 648f Punishment behavior modification and, 226 socialization and training classes for kittens and, 201 Pupils in communication, 5f dilation of for ophthalmic examination, 808-810 spastic pupil syndrome of, 832, 832f Pure red cell aplasia (PRCA), 672 Purina Fecal Scoring System, 1326, 1327f Purkinje neurons, disorganization of in cerebellar hypoplasia, 738-739, 739f Purring, 194 Puzzle, food, 263-264, 263f PVD. See Peripheral vestibular disease (PVD) Pyelonephritis, 950-951, 950f, 967-968 diabetes insipidus versus, 619 Pylorus anatomy, 451, 451f Pyoderma, 381-383, 383f, 384t Pyometra, 1219-1222, 1220f-1221f Pyothorax pleural effusion due to, 894f, 901 treatment of, 901-904, 902b-903b, 902f-903f

1390

INDEX

Pyrantel, 172t, 499t for roundworms, 498 in population wellness program, 1325 Pyrantel pamoate for diarrhea, 437, 437t neonatal, 1242 Pyrantel/praziquantel, 172t Pyrazinamide, 1078t Pyrethrins for flea control, 382t toxicity, 919, 920b, 931t Pyrethroids for flea control, 382t toxicity, 919, 920b Pyridostigmine bromide, 758 Pyridoxine, nutritional requirements, 241 Pyruvate kinase (PK) deficiency DNA testing for, 1274t hemolysis due to, 661-662 Pythium insidiosum, 484 Pyuria in urinary tract diagnosis, 936t PZI insulin, 554-555 changing of, 558 PZI-R insulin, 553-554 PZI-Vet insulin, 553 changing of, 558 Q Q fever, 1091t QT prolongation, 433 Quality of life palliative care and euthanasia and, 1155-1163 oncologic, 802 in population wellness, 1314 Quantitative polymerase chain reaction (PCR), 1084, 1085f Quarantine in population wellness programs, 1349-1350 Quarternary ammonium compounds for disinfection, 1348b Queen aggression in, 221 feline immunodeficiency virus infected, 1056, 1058-1059 licking of anogenital area by, 187, 187f reproduction in (See Female reproduction) role in predation of kitten, 187 social practices of, 196 taurine deficiency in, 250 total dependence of kitten on, 183, 183f Questioning, sensitive, 207 Questionnaire, behavioral, 207, 208b R RA. See Rheumatoid arthritis (RA) Rabies, 1047-1048 zoonotic, 1093 Rabies immunoglobulin (RIG), 1093 Rabies vaccine, 176 for community cats, 1301 in population wellness programs, 1324-1325 recommendations for, 174t Radiation hybrid (RH) genetic map, 1266 Radiation therapy for acromegaly, 617 for hyperadrenocorticism, 599t, 601 for injection-site sarcoma, 789 for lymphoma, 785 for mammary tumors, 793 for pituitary tumors, 742 Radioactive iodine (I131), 583-584, 583f Radiography in ascites, 539-541, 539f dental, 167, 338-340, 338f-339f tooth resorption, 167f, 346-347 in esophageal disease, 442-443 in esophagitis and esophageal strictures, 443

Radiography (Continued) in gastric foreign bodies, 453 in gastric neoplasia, 457, 457f in gastric ulceration, 456 in heart disease, 304-305, 304f-305f in hypertrophic cardiomyopathy, 311f-312f in peritoneopericardial diaphragmatic hernia, 324f in heartworm, 884t, 885 in hyperadrenocorticism, 598, 598f in hypoadrenocorticism, 608 in hypothyroidism, 588 in intestinal foreign body, 481-482, 481f-482f in liver disease, 528 in lower respiratory tract disease, 862-863, 863f-864f, 863t in asthma and chronic bronchitis, 867-868 in megacolon, 489, 489f neonatal, 1237 in pancreatitis, 514-515, 514f in pleural effusion, 893-894, 893f-894f due to feline infectious peritonitis, 1043, 1043f in pneumothorax, 906-907, 907f in prediction of mineral composition of uroliths, 985t for pregnancy diagnosis, 1205, 1205f in renal calculi, 955 in renal disease, 944, 944f in vomiting, 430 Radioimmunoassay in myasthenia gravis, 758 Radiotherapy, pituitary, 601 Radius fracture of, 707 hemimelia of, 726, 726f Raisins, nephrotoxic effects of, 959 Range-of-motion (ROM) exercise for pain management, 1153 Ranitidine in chronic kidney disease therapy, 973 for gastrointestinal ulcers, 434-435, 434t for nutritional care in cancer patients, 805t Rapidly growing mycobacteria (RGM), 1074t, 1079-1080 Rapid urease test in Helicobacter gastritis, 454 Raw foods diet, 289-292 RBBB. See Right bundle branch block (RBBB) RDW. See Red cell distribution width (RDW) Reactine. See Cetirizine Real-time polymerase chain reaction (PCR), 1084 Rearing as play behavior, 185, 186t Receptal. See Buserelin Recessive allele, 1271b-1272b Recipe for homemade dog and cat food, 270b Recombinant feline interferon (rFeIFN), 1060 Recombinant human erythropoietin (rhEPO) for anemia of chronic renal disease, 670-671, 974-975 pharmacodynamic monitoring of, 1140t, 1141 Recombinant human thyroid-stimulating hormone stimulation test, 587-588 Recombinant interferon-omega, 1037-1038 Recombination genetic map, 1265-1266 Recommendations for wellness services, 153, 154f Record keeping in population wellness program, 1316-1318 Recrudescent herpesvirus disease, 818-819, 820f

Recruitment for kitten classes, 199 Rectal disease. See Anorectal disease Rectal prolapse, 491-492 Rectal suppository for constipation, 487 Rectal temperature opioids associated with elevation of, 96 taking of, 32-33, 33f Red blood cells (RBCs). See Erythrocytes Red cell distribution width (RDW), 648-649, 649f Redirected aggression, 222 Red lily toxicity, 958t Red pulp, splenic, 685 Refeeding syndrome, 278 Reflective listening, 206-207 Reflexes in kitten, 184 Reflex uveitis, 829t Refractive index in urine specific gravity, 940 Refractometer, 940 Refrigeration of urine sample, 938 Regenerative anemia, 653, 656-668 acute blood loss in, 657 cytauxzoonosis in, 663-664, 664f defined, 656 diagnostic plans in, 656-657 due to feline hemoplasmosis, 666-668, 667f Heinz body, 664-666, 665b history and physical examination in, 656 due to hypophosphatemia, 666 immune-mediated hemolytic, 657-661, 659t inherited erythrocyte abnormalities in, 661-662 neonatal isoerythrolysis in, 662-663 Regenerative left shift, 676 Regenerative medicine, 1153 Regional anesthesia for oral and dental disease treatment, 341-342 Reglan. See Metoclopramide Regurgitation in esophageal disease, 441-442 due to megaesophagus, 447-448 due to vascular ring anomaly, 448 vomiting versus, 428-429, 441-442, 441t Rehydration. See Hydration Reiter’s disease, 711 Rejection, renal transplantation, 962 Relationship-centered care, 26, 27b, 27f Relative erythrocytosis, 673 Relaxin in pregnancy, 1197-1198, 1206 Relocation of community cats, 1308 Remeron. See Mirtazapine Remifentanil, 99 Remission of diabetes mellitus, 552 of systemic lupus erythematosus, 697 Remodeling, femoral neck, 152, 162f Renal agenesis, 946 Renal amyloidosis, 948-949 Renal biopsy, 945, 945f centers for full assessment of, 945, 952, 952b in glomerulonephritis, 952-953, 952b in urinary tract diagnosis, 936t Renal disease. See also Urinary tract disorders acute renal failure as, 957-960, 957f, 958t amyloidosis as, 948-949 associated with feline immunodeficiency virus, 1057-1058 chronic kidney disease as (See Chronic kidney disease (CKD)) diagnosis of, 936t, 937b creatinine ratio for, 944 imaging in, 944-945, 944f renal biopsy in, 945, 945f renal function tests in, 935-937 renal size assessment in, 935, 936b

Renal disease. See also Urinary tract disorders (Continued) urinalysis in, 937-943 urine culture and sensitivity for, 943-944, 944b dialysis for, 960-961, 960f feline infectious peritonitis as, 949 (See also Feline infectious peritonitis (FIP)) fluid therapy in, 82-84 concurrent with cardiac disease, 85-86 glomerulonephritis as, 951-954, 951b-952b, 953f hydronephrosis as, 956-957, 957f hyperparathyroidism secondary to hypocalcemia due to, 638 hypertension due to, 307 hyperthyroidism with, 575-576, 579-580, 580f idiopathic hypercalcemia and, 633 inherited, congenital, developmental, 946-948 neoplasia as, 949-950 nutritional management of, 278-279, 279b, 279f perinephric pseudocysts as, 947-948, 948f polyarteritis nodosa as, 949 polycystic kidney disease as, 946-947, 946f-947f genetics of, 1267-1268, 1272 pyelonephritis as, 950-951, 950f renal transplantation for, 961-962 ureteronephrolithiasis as, 955-956, 955f Renal failure, 957-960, 957f, 958t Renal function tests, 935-937 Renal hemodynamics, 937 Renal insufficiency, 962-963. See also Chronic kidney disease (CKD) drug dosage adjustments for, 40-45, 41t-42t, 42f in senior and geriatric cats, 45 insulin therapy resistance due to, 563t Renal size assessment, 935, 936b Renal system anesthesia in hyperthyroid patient and, 140 effects of acromegaly on, 614-615 impact of aging on, 1167 in salt balance, 55 Renal transplantation, 961-962 Renalzin, 974 Renomegaly, 936b Replacement fluids, 60-61 Replacement tooth resorption, 344, 345f “Report card”, 39 Reporting of adverse drug reaction, 1148, 1148t of food-related illness, 269, 269b Reproduction female, 1195-1227 clinical problems with, 1202-1204, 1205f control of, 1200-1202, 1200t determining status of, 1204 estrous cycle in, 1196-1197, 1196b, 1196f fertility and breeding management in, 1198-1200, 1199b hormonal events of estrous and pregnancy in, 1197-1198 infertility and, 1215-1224 normal gestation and parturition in, 1204-1209 puberty and, 1195-1196 seasonality in, 1195 spontaneous ovulation in, 1198 male, 1184-1194 anatomy of, 1184-1185, 1185f-1186f control of, 1186-1187, 1187f infertility and, 1191-1193, 1191b-1192b mating behavior in, 1185-1186 penile conditions in, 1187-1188

INDEX Reproduction (Continued) testicular disease and conditions in, 1188-1191, 1189f, 1189t-1190t, 1190b Reproductive status in group housing, 1337, 1338f RER. See Resting energy requirement (RER) Research on carbohydrates, 295 Resiniferatoxin, 1154 Resorption femoral neck, 152, 162f tooth, 167f, 344-348, 345f-347f, 347b classification of, 347b clinical signs of, 346, 346f-347f etiologic considerations in, 344-345 histologic features of, 347 nutritional implications in, 257 radiographic signs of, 346-347 replacement and inflammatory, 344, 345f treatment of, 347-348 Resources for care of community cats, 1309b for chemotherapy, 771b educational, 10b for environmental enrichment, 990b for kitten socialization and training classes, 202b for neurologic exam, 735b preventive health care, 159b for preventive health care, 153, 159b, 177t, 178 toxicology, 915b Respiratory depression due to anaphylaxis, 698-699 during anesthesia in geriatric patient, 138 due to telazol, 121 Respiratory rate monitoring during anesthesia, 134 neonatal, 1232b Respiratory rate assessment in physical examination, 35 Respiratory system effects of acromegaly on, 614 effects of intubation on, 127 Respiratory system disease, 846-913 aspiration pneumonia as, 875-876 asthma and chronic bronchitis as, 866-875 clinical signs of, 867 definitions of, 866 diagnosis of, 867-870, 869f-870f epidemiology of, 866 etiopathogenesis of, 866-867 treatment of, 870-875, 872b, 873f clinical signs of, 846-847, 847b, 862 diagnosis of, 847-851, 848b, 862-863 bronchoalveolar lavage in, 864, 865b, 865f, 866t bronchoscopy in, 864 exploratory rhinotomy in, 850-851 fine needle aspiration in, 865 imaging, biopsy, and deep cultures in, 849-850, 849f-850f, 862-863, 863f-864f, 863t lung parenchymal biopsy in, 865-866 noninvasive tests in, 847-849 idiopathic pulmonary fibrosis as, 875, 876f in kitten, 1241-1242, 1241f-1242f laryngeal, 858-859 nasal, 851-858 anatomical and functional, 851-852, 851f chronic inflammatory, 857-858, 857f foreign bodies as, 858 infectious, 852-857, 853t, 854f, 856f neoplasia as, 858 traumatic, 858 polymerase chain reaction for detection of agents in, 1084-1086

Respiratory system disease (Continued) pulmonary infection as, 877-885, 883f, 884t pulmonary neoplasia as, 877, 877f due to smoke inhalation, 876-877 of thoracic cavity, 892-913 clinical signs of, 892 general considerations in, 892 physical examination in, 892 pleural effusion as, 892-895 pneumothorax as, 906-907, 907f traumatic, 876 Response substitution in behavior modification, 227 Rest in feline idiopathic cystitis management, 989b Resting energy requirement (RER), 244, 245t in critical care, 272 daily fluid needs and, 58 in idiopathic hepatic lipidosis, 532 obesity and, 262 during pregnancy, 246 Resting places in environmental management of behavior problems, 229, 229f Restraint during examination, 13 for intravenous catheterization, 71 Restricted-fat diet, 259 Resuscitation endpoints, 75b Resuscitation of neonatal kittens, 1212-1213, 1212b Retained placenta, 1214-1215, 1214f Retching, 426 opioid-associated, 96-97 Reticulocytes, 648, 648f-649f Retina, 191-192 examination of, 33-34, 808-810, 810f Retinal detachment with hypertensive chorioretinopathy, 837-838, 838f with uveitis, 827-828, 828f Retinal disease, 837-841 due to enrofloxacin toxicity, 839-840, 839f hypertensive chorioretinopathy, 837-839, 838f progressive retinal atrophy, 841 DNA testing for, 1274t genetics of, 1284 taurine-deficient retinopathy, 840, 840f Retinopathy hypertensive, 837-839 taurine-deficient, 840, 840f Retroillumination in ophthalmic examination, 808-810, 809f Retropharyngeal lymph node, 335 Retrovirus(es), 1048-1061, 1048t, 1051b feline immunodeficiency virus as, 1056-1061 clinical signs of, 1057-1058, 1058f diagnosis of, 1058-1059 prevention and control of, 1061 transmission and pathogenesis of, 1056-1057 treatment of, 1059-1061 feline leukemia virus as, 1048-1056, 1049t clinical signs of, 1050-1051, 1051b, 1051f-1052f diagnosis of, 1052 prevention and control of, 1054-1056, 1054b-1055b transmission and pathogenesis of, 1049-1050, 1050t treatment of, 1052-1054, 1053b-1054b testing for, 29 in preventive health care, 166 Reverse transcriptase polymerase chain reaction (RT-PCR), 854, 1084 Reverse transcriptase (RTase) inhibitors, 1059-1060

Revolution. See Selamectin Rewards in socialization and training classes for kittens, 201 Rexing, 1276-1277 DNA testing for, 1274t rFeIFN. See Recombinant feline interferon (rFeIFN) RGM. See Rapidly growing mycobacteria (RGM) RH. See Radiation hybrid (RH) genetic map rhEPO. See Recombinant human erythropoietin (rhEPO) Rheumatoid arthritis (RA), 711-712, 712b treatment of, 715-716 Rhinitis, cryptococcal, 1017 Rhinoscopy, 850, 850f Rhinosinusitis, chronic, 857-858, 857f Rhinotomy, exploratory, 850-851 Rhipicephalus sanguineus tick vector, 1026 Rhododendron species toxicity, 923, 923f-924f Rib cage circumference measurement in feline body mass index, 37, 37f-38f Ribonucleic acid (RNA) feline immunodeficiency virus, 1057 feline leukemia virus, 1048, 1050, 1050t in molecular assays, 1082-1083 polymerase chain reaction, 1084 Rib(s) fracture of nontraumatic, 910 traumatic, 909-910 neoplasia of, 910 Ricinus communis toxicity, 924 Rickettsia felis, 1025-1027 molecular assays for diagnosis of, 1087 Rickettsial disease, 1025-1027 anaplasmosis as, 1027 ehrlichiosis as, 1026-1027 Rifampin, 1078t RIG. See Rabies immunoglobulin (RIG) Right axis deviation, 321 Right bundle branch block (RBBB), 321 Right-to-left shunting patent ductus arteriosus (PDA), 325 Right ventricular cardiomyopathy, arrhythmogenic, 315-316 Rimadyl. See Caprofen Ringer’s solution, 61t Ringworm. See Dermatophytosis Risk factors for cardiovascular disease, 301 for diabetes mellitus concurrent with feline lower urinary tract disease, 1106 genetic, 1280-1282 for hyperthyroidism concurrent with diabetes mellitus, 1101-1102 for idiopathic cystitis, 985-986 for intestinal foreign bodies, 480 for intestinal lymphoma high-grade, 473 small cell, 470 for lymphoma, 782-783 for pancreatitis, 513 for uroliths calcium oxalate, 996-997 struvite, 995, 995f Risus sardonicus, 764 Rivalta test, 900, 1043 RNA. See Ribonucleic acid (RNA) Roach bait toxicity, 924-925 Robenacoxib, 102, 1152 Robertsonian translocation, 1264 Rodenticide toxicity, 915-919 anticoagulant, 915-917, 916t bromethalin, 917 cholecalciferol, 917-918 strychnine, 918 zinc phosphide, 918-919 “Rodent ulcer”, 353

1391

ROM. See Range-of-motion (ROM) exercise Ronidazole for diarrhea, 437-438, 437t for protozoal disease, 502t for Tritrichomonas foetus, 507 Root, tooth, 330-331 Root canal therapy, 348-349, 349f Rooting reflex, 184 Rosary pea toxicity, 924 Rosebay toxicity, 923 Rosenthal needle, 644, 644f Rostral, oral anatomy and, 335 Rotating dome trochleoplasty, 720 Rouleaux formation of erythrocytes, 647, 647f, 650 Roundworms, 171, 497-499, 498f, 499t control of in population wellness program, 1325 Routes of administration for analgesic drugs, 94-96, 97t for fluid therapy, 69-73 transdermal, 47-48 transmucosal, 48-49 Routine, daily, in population wellness program, 1345-1346 Routine medical history, 28-29, 29f-30f RTase inhibitors. See Reverse transcriptase (RTase) inhibitors RT-PCA. See Reverse transcriptase polymerase chain reaction (RT-PCR) Rubrum lily toxicity, 958t Rugae, palatine, 333-334, 334f Runyon group IV, 1079 Rupture common calcaneal tendon, 723-724, 723f-724f cranial cruciate ligament, 721-722 lower urinary tract, 1007-1008 tracheal, due to endotracheal intubation, 127, 128f Rutin for chylothorax, 268-269 for idiopathic chylothorax, 905 S Sacrococcygeal separation, 756, 756f “Saddle thrombus”, 761 S-adenosylmethionone (SAMe) for cognitive dysfunction in senior cat, 1172 in feline cholangitis syndrome therapy, 534 in hepatic lipidosis therapy, 532-533, 532t for hepatoencephalopathy, 535, 536t for pancreatitis with inflammatory bowel disease, 1118t, 1120 Safety, homemade diets and, 296 Safety equipment for chemotherapy, 772b Saffan, 125-126 Salbutamol-albuterol for bronchial disease, 870-871, 872b Salbutamol for inflammatory airway disease, 873 Saline solutions hypertonic, 66 for hypovolemia, 74 for hypoadrenocorticism, 608 Salinomycin food contamination, 251 Salivary gland anatomy, 334-335 Salivation due to lily toxicosis, 922t opioid-associated, 96-97 Salmonella diarrhea due to, 477t, 479 food contamination with, 251 in raw food diet, 290-292 molecular assays for diagnosis of, 1086 pneumonia due to, 881 risk in veterinary facilities, 290b Salt. See Sodium

1392

INDEX

SAMe. See S-adenosylmethionone (SAMe) Sample collection, 15-16 of bone marrow, 643-646, 644b bronchoalveolar lavage for, 864 of cerebrospinal fluid, 735-736 corneal and conjunctival, 811-812, 811f in otitis media, 414 of semen, 1192-1193 of urine examination of, 939 handling of, 938-939 technique, 938 timing of, 937 for urine cortisol:creatinine ratio, 595 Sanofi Aventis. See Leflunomide Saphenous vein for intravenous catheterization, 70 Sarcoma feline ocular, 832, 834-835, 835f feline restrictive orbital, 813 hepatic, 527t injection-site, 787-791, 788f-789f Saturated salt for fecal flotation techniques, 170 Scabies, 379 Scale, examination of cat on, 22f Scaler, 343, 344f Scaling excessive, 391 in pyoderma, 381-383, 383f Scanning of patient during wellness visits, 158-160 Scapular luxation, 717 SCC. See Squamous cell carcinoma (SCC) Scent in communication, 6, 194-195 detection of, 192 Schiotz tonometer, 808 Schirmer tear test (STT), 808, 808f Schistocytes, 649-650, 649f School, cat allergens in, 421 SCI. See Spinal cord infarction (SCI) Scintigraphy for gastric emptying assessment, 456-457 thyroid in hyperthyroidism, 577-578, 577f in hypothyroidism, 588 Scissors, Metzenbaum, 351, 351f Sclera, examination of, 33-34 Sclerosing fibroplasia, gastrointestinal eosinophilic, 476 Scottish Fold cat, 1259 arthropathy in, 713, 713f phenotypic mutations in, 1277-1278, 1278f Scrapings corneal, 811-812, 811f skin, 373-374, 374f Scratching environmental management of, 229 as normal behavior, 164 in population wellness program, 1344, 1344f Scratching post, 164, 229 Screening for cancer, 768 for cardiovascular disease with electrocardiography, 303-304 with N terminal-proBNP, 306 of donor blood, 655 for hyperadrenocorticism, 594-597, 596t urine metabolic, 737-738 Scrotum anatomy of, 1184, 1185f involvement in feline infectious peritonitis, 1042, 1042f Scrubbing for intravenous catheterization, 70-71 Seasonality in female reproduction, 1195

Sebaceous glands adenitis of, 396 in communication, 6 Seborrhea syndromes, greasy, 396, 396f Secondary intraocular neoplasia, 833-834, 834f Second-order Horner’s syndrome, 763 Sedation, 112-127 drugs commonly used for, 113-118, 114t tranquilizers and sedatives for, 113-118 Segregation of cats for environmental health in population wellness program, 1349-1351 Seizures, 734-737 associated with hepatoencephalopathy, 535t cluster, 734-735 complex partial, 734-735 control of in toxicosis, 916t due to permethrin, 920b diagnosis of, 735-736, 735f focal, 734-735 generalized, 734-735 due to hypoglycemia, 739 partial, 734-735 secondary to hypocalcemia, 639 simple partial, 734-735 treatment of, 736-737, 736t Selamectin, 172t, 382t, 499t toxicity, 921 Selection, genetic, 1271b-1272b Selective serotonin reuptake inhibitors (SSRIs) for behavior problems, 232b, 233 for cognitive dysfunction in senior cat, 1172-1173 for feline hyperesthesia syndrome, 763-764, 764t monitoring of long-term therapy with, 1139t for pain management, 1150 adverse drug interactions in, 1152 Selegiline, 1172, 1172t Selenium deficiency of, 250t for plaque control, 256 Self-maintenance behaviors, 209 Selkirk Rex cat, 1276-1277, 1277f Semen collection, 1192-1193 Semen evaluation in male infertility, 1192-1193 Seminiferous tubules, 1184 “Send home” medications for analgesia, 105-106 Senior cat, 1166-1175 analgesic administration in, 106 anesthetic considerations for, 137b-138b behavior needs of, 164 cognitive dysfunction in, 1170-1173, 1171b, 1172t concurrent disease management for, 1174 degenerative joint disease in, 1173-1174, 1173f, 1174b dehydration in, 1169-1170 drug disposition in, 1167-1168, 1167t drug therapy considerations in, 45-46, 45f, 46b energy requirements for, 245t flea allergy dermatitis in, 385 impact of aging on, 1166-1168 neoplasia in, 1173, 1173b nutrition for, 246-247, 1168, 1168t urinary tract infection in, 1004 weight loss in, 1169-1170, 1170f, 1170t, 1176-1181 causes of, 1176-1178, 1177f diagnosis of, 1178-1180, 1178b, 1178t, 1179f management of, 1180, 1180b prevalence of, 1176, 1177f wellness care for, 1168-1169

Senses impact of aging on, 1167 normal behavior and, 191-193 understanding the cat and, 4-5 Sensible fluid loss, 57 Sensitive questioning, 207 Separation anxiety, 215-216 Sepsis fluid loss associated with, 59t neonatal, 1243-1244, 1243b, 1244f, 1244t Septal defect atrial, 323 ventricular, 322-323, 323f Septic bacterial arthritis, 710 Septicemic salmonellosis, 292 Septic exudates in pleural effusion, 899t, 901 Septic peritonitis ascites due to, 544-545, 544f hypocalcemia with, 638 Septic shock, fluid and electrolyte loss assessment for, 79t Sequestration, corneal, 825-826, 825f-826f Seroli cells, 1184 Serotonin, endocrine pancreas production of, 548t Serotonin receptors, vomiting and, 431 Serotonin syndrome, 1152 Serum bile acid concentration, 524 Serum chemistries in hypothyroidism, 587 in minimum database, 165t neonatal, 1237t Sesamoid bone, 704, 705f Sevelamer hydrochloride, pharmacodynamic monitoring of, 1142 7b protein, feline infectious peritonitis and, 1039, 1044-1045 Sevoflurane for inhalation induction, 126-127 for maintenance of anesthesia, 128-129 Sex chromosome, 1271b-1272b Sex linked, defined, 1271b-1272b Sex of kitten, assessment of, 1231 Sexual behaviors during play, 185 Sexual maturity, behavioral development and, 185 Shelves in colony-style housing, 1340-1341, 1341f “SHIRT” mnemonic, 627, 628b Shock anaphylactic, 698-700 fluid and electrolyte loss assessment for, 79t hypovolemic, 59, 73b hypertonic saline solutions for, 66 Short-term housing, 1334-1336, 1334f Shoulder anatomy, 704, 705f Shunting, portosystemic, 526-527, 534-535 Siamese cats, 1256-1258 fabric eating by, 214f, 215 morphology of, 1256 phenotypic mutations in, 1273-1276 SIBO. See Small intestinal bacterial overgrowth (SIBO) Side step as play behavior, 185, 186t Signalment in acromegaly, 612-615 in diabetes mellitus concurrent with feline lower urinary tract disease, 1106 in diarrhea, 460-462 in exocrine pancreatic insufficiency, 518 in hyperaldosteronism, 603 in hyperthyroidism concurrent with diabetes mellitus, 1101-1102 in idiopathic cystitis, 985-986 in intestinal foreign bodies, 480 in intestinal lymphoma

Signalment (Continued) high-grade, 473 small cell, 470 in medical history, 28 in pancreatitis, 513 in skin disease, 372 in systemic lupus erythematosus, 696 in vomiting, 428-429, 428t Silent heats, 1217 Silent mutation, 1271b-1272b Silica gel packet toxicity, 925 Silica uroliths, 985t Silymarin for hepatoencephalopathy, 535, 536t Simple partial seizure, 734-735 Singapura cat, 1273-1276, 1275f Single centrifugal feces flotation, 463b Single-nucleotide polymorphisms (SNPs), 1266-1267 Sinus arrhythmias, 302 Sire, popular, 1271b-1272b SIRS. See Systemic inflammatory response syndrome (SIRS) Sit, cats learning to, 8, 8f Skeletal mineralization, extraneous, 726-727, 726f Skeletal system signs of acromegaly, 614, 614f Skin examination of, 36-37 fragile, 406f in hyperadrenocorticism, 593-594, 594f hard, 406-407, 407f impact of aging on, 1167 Skin biopsy, 376-377, 377f equipment for, 373b Skin cytology, 374-375 Skin disease, 371-419 alopecia as, 399-402, 400f chin acne and chin furunculosis as, 398-399, 399f congenital, 1233b Cryptococcus nodule as, 1017-1018, 1018f dermatophytosis as, 391-396, 392f, 394f management in animal shelters, 395-396 diagnosis of, 371-377, 372f diagnostic tests for, 373-377, 373b medical history in, 371-372 physical examination in, 372-373 eosinophilic lesions as, 403-406 epitheliotropic lymphoma as, 398, 398f fragile skin as, 406, 406f greasy seborrhea syndromes as, 396, 396f hard skin as, 406-407, 407f nonhealing wounds as, 416-417, 416b nutritional management of, 257-258 otitis as, 410-416, 412f-414f paraneoplastic exfoliative dermatitis as, 398 paraneoplastic syndrome-associated, 795, 795f of paw pads, paronychia, and anal sacs, 407-410, 408f-410f pemphigus foliaceus as, 397-398, 397f pigmentary changes in, 407 pruritus as, 377-391 allergic causes of, 385-391 flow chart for, 378f infectious causes of, 381-385 parasitic causes of, 377-381 scaling, excessive as, 391 sebaceous adenitis as, 396 solar or actinic dermatitis as, 398 sporotrichosis as, 1023, 1023f ulcers and erosions as, 402-403, 403f Skin flap for eyelid agenesis, 814, 814f Skin scrapings, 373-374, 374f Skin tenting, 37-39

INDEX Skin testing in bronchial disease, 870 in feline atopic dermatitis, 388-389, 389f Skull, 334f SLE. See Systemic lupus erythematosus (SLE) Slide agglutination test, 647, 647f SLUDGE signs, 919 Slug bait toxicity, 914-915, 915f Small cell lymphoma gastric, 457, 458f hepatic, 527f-528f intestinal, 469-473, 471f-472f, 472t Small intestinal bacterial overgrowth (SIBO), 480 Small intestine diarrhea involving, 461t palpation of during physical examination, 35-36 Smell in dietary preferences, 237 sense of, 5, 192 Smoke inhalation, 876-877 Snail bait toxicity, 914-915, 915f Snakes, poisonous, 927 SNAP Giardia antigen test, 504 Snarling, 194 Sneezing, 847 SNPs. See Single-nucleotide polymorphisms (SNPs) SNS. See Sympathetic nervous system (SNS) SO. See Suppurative otitis (SO) “Soaker” catheter, 104 SOAP format, 38f, 39 Social environment in behavioral history, 209 Social interaction in environmental management of behavior problems, 230 Socialization kittens and, 186, 188-189, 189f in population wellness program, 1341-1343, 1342f housing and, 1330-1331 sensitive periods of, 9 Socialization and training classes, 198-205 equipment for, 200, 200f handling and, 201-202 litter training in, 201 location for, 200, 200f planning of, 199 punishment and, 201 recruitment and promotion of, 199 resources for, 202b rewards in, 201 sample curriculum for, 202-205, 202f-205f scratching and, 202 teaching kittens and, 200-201 value of, 198-205 Socialization period behavioral development of kitten during, 184-185 sensitive, 9 Social maturity, behavioral development and, 185 Social organization, 195-196, 196f Social play, 184-185 Social stress, 1332-1333 Sodium channel blockers, 1150-1151 Sodium (Na+) balance of, 52, 55-56 calcium oxalate uroliths, 280-281 in crystalloid solutions, 60-65, 61t for hypovolemia, 74 deficiency of, 250t disorders of concentration of, 56-57 in dissolution of struvite uroliths, 280b for plaque control, 256 restriction of

Sodium (Na+) (Continued) in cardiorenal syndrome, 1113 in chronic kidney disease, 279b, 970 in heart disease, 256, 256b therapeutic renal diets and, 972t Sodium profiling in dialysis, 960 Sodium sulfate for toxicosis, 916t Soft palate, 333-334 defects of, 356 Soft tissue injury, orofacial, 358-359, 358f-359f Soft tissue procedures for patellar luxation, 720 Solar dermatitis, 398 Solu-Delta-Cortef. See Prednisone sodium succinate Solutes in crystalloid solutions, 60 permeant and impermeant, 56 in sensible versus insensible fluid loss, 57 water balance and, 56 Somali cat erythrocyte membrane fragility in, 662 pyruvate deficiency in, 661-662 Somatic cell hybrid genetic map, 1265 Somatostatin, endocrine pancreas production of, 548t Somatostatin analogues for acromegaly, 617-618 Somogyi effect, 564 Sonic hedgehog gene mutation, 1277-1278 Sorbitol for toxicosis, 916t Sotalol for ventricular tachyarrythmias, 322 Sounds made by cats, 194 SPA. See Staphylococcus protein A (SPA) Spastic pupil syndrome (SPS), 832, 832f Spathiphyllum spp. toxicity, 924 Spatula, skin scraping, 373-374, 374f Spatula collection in skin disease diagnosis, 375 Spay and neuter of community cats patient selection and perioperative care, 1299-1300 surgical sterilization, 1300, 1300f, 1301b energy requirements and, 245t, 246 obesity due to, 169 pediatric, 1246-1249 physeal dysplasia with, 708 in population wellness program, 1325-1326 in preventive health care, 164-165 Special populations, analgesia for, 106 Specific gravity of effusion in feline infectious peritonitis, 1043b peritoneal, 538b, 542t urine in chronic kidney disease with hyperthyroidism, 1100 in diabetes insipidus, 619 in feline idiopathic cystitis, 987-988 in glomerulonephritis, 951 in hyperadrenocorticism, 594 in hypoadrenocorticism, 607t interpretation of, 940 neonatal, 1232b as renal function test, 935-936, 936t tooth resorption and, 344-345 values for, 940 Specimen collection. See Sample collection Spermatic cord, 1184 Spermatozoa, 1184 Spherocytes, 649-650, 649f Sphynx cat myopathy in, 730 phenotypic mutations in, 1276-1277, 1277f Spiders, poisonous, 927-928 Spill kit, chemotherapy, 771, 772b

Spina bifida, 751-752 Spinal administration of opioids, 130-131 Spinal column disorders of, 749-757 congenital and developmental, 751-752, 752f degenerative, 750-751 inflammatory and infectious, 752-753 intervertebral disk disease as, 750-751, 750b, 750f-751f metabolic and nutritional, 752 neoplasia, 753-755, 753f-754f spinal cord infarction, 756-757, 757f traumatic, 755-756, 755f-756f vascular, 756-757 involvement in myelopathies, 750 Spinal cord infarction (SCI), 756-757, 757f Spinal muscular atrophy, 1274t Spirometra spp., 500-501 Spironolactone for cardiorenal syndrome, 1112 for hyperaldosteronism, 605 for hypertension with chronic kidney disease, 1122t Spleen disorders of clinical signs and physical findings in, 686 diagnostic plans for, 686-687, 687f generalized splenomegaly as, 687, 688b localized lesions as, 687-688 therapy for, 688 function of, 685-686 microanatomy and circulation of, 685 palpation of during physical examination, 35 Splenectomy, 688 Splenomegaly, 687, 688b diagnosis of causes of, 686-687 Splinting for pectus excavatum, 1235-1236, 1236f Spontaneous hypothyroidism causes of, 584-585 clinical features of, 585, 586t Sporotrichosis, 1023-1024, 1023f in upper respiratory infection, 856f zoonotic, 1091t Spotting locus, 1277-1278 Spraying behavior, 194-195, 218-219 SPS. See Spastic pupil syndrome (SPS) Squamous cell carcinoma (SCC) esophageal, 448 eyelid, 816, 816f-817f hypercalcemia associated with, 631 oral and maxillofacial, 365-366, 365f orbital, 813 Squill toxicity, 924 SSRIs. See Selective serotonin reuptake inhibitors (SSRIs) “Stacked coins” arrangement associated with rouleaux formation, 647, 647f Staff for kitten socialization and training classes, 199 social contact with in population wellness program, 1341-1343, 1342f training of for environmental health in population wellness program, 1353 Staging of cancer, 769 injection-site sarcoma, 788 lower urinary tract, 1007 lymphoma, 783-784 mammary, 792, 792t oral and maxillofacial, 366 of chronic kidney disease, 278, 963-964, 964t, 965f-966f prognosis and, 975-976 Stain fecal smear, 463, 463b

1393

Stairs in colony-style housing, 1340-1341, 1341f Stand up as play behavior, 185, 186t Stanozolol, 257t Staphylococcus aureus methicillin-resistant in osteomyelitis, 725 zoonotic, 1092 in raw food diet-related illness, 291t Staphylococcus protein A (SPA), 1053 Staphylococcus spp. in osteomyelitis, 725 Stares, 193-194 Stargazer lily toxicosis, 921-923, 922f acute renal failure due to, 958t Starling forces, 54, 54b Status epilepticus (SE), 734-735 Steatitis, 249 Stem cells, cytokines in differentiation, proliferation, and maturation of, 695 Stenosis nasopharyngeal, 852 supravalvular mitral, 323 Stent, esophageal for strictures, 446 Sterilization of community cats, 1300, 1300f, 1301b. See also Spay and neuter Steroid anesthetics, 125-126 Stertor, 847 Stifle, ligamentous injury to, 721-723, 722f Stifle joint mineralization with cranial cruciate ligament rupture, 722, 722f Stimulant laxatives, 487, 487t Stimulation in population wellness program, 1343-1345, 1343f-1345f Stomach anatomy of, 451, 451f capacity of, 236 diseases of, 450-459 clinical presentation of, 451-452 gastric motility disorders and delayed gastric emptying as, 456-457 gastritis as, 452-455, 452f-453f, 455f neoplasia as, 457-458, 457f-458f ulceration as, 455-456 Stomatitis, 349-350, 349f feline herpesvirus-1 in, 1030 Stones. See Urolithiasis/uroliths Streptococci group A, zoonotic, 1092 in neonatal sepsis, 1243-1244 Stress behavioral signs of, 1331-1333, 1331b, 1332f disease and, 1126-1127 effects on urine pH, 940 feline idiopathic cystitis and, 986-988, 989b food aversion and, 237 grooming as sign of, 188 hyperglycemia associated with, 3 diabetes mellitus versus, 548 population wellness programs and, 1315-1316 housing and, 1331-1333, 1331b Stress leukogram, 676 Strictures, esophageal, 443-446, 444f, 445t String caught under tongue, vomiting or anorexia due to, 429 Stroke. See Cerebrovascular accident (CVA) Stroke volume in oxygen delivery, 55 Stromal tumor gastrointestinal, 476-477, 477f hepatic, 527t Stronghold. See Selamectin Strongyloides, 497 Struvite uroliths, 279-281, 280b, 995-996, 995f prevalence of, 993, 993f Strychnine toxicity, 918 STT. See Schirmer tear test (STT) “Stud tail”, 396

1394

INDEX

Subcutaneous administration of analgesic drugs, 94 of buprenorphine, 98 of chemotherapeutic drugs, 774 of desmopressin for diabetes insipidus, 621-622 of fluids, 65, 69 for hypercalcemia, 635, 635b in palliative care, 1155, 1156b of melatonin for control of estrus and reproduction, 1201 Subethmoid shelf, 192 Subgingival, defined, 335 Sublingual gland, 334-335 Substance P endocrine pancreas production of, 548t feline idiopathic cystitis and, 987 Substrate aversion, 218, 218f Subtelometric chromosomes, 1263 Subtotal colectomy for megacolon, 489 Sucking reflex, 184 Sucralfate for gastrointestinal ulcers, 434t, 435, 456 for hepatoencephalopathy, 535t stability of suspensions of, 47t for toxicosis, 916t Sulcoplasty for patellar luxation, 720 Sulfadimethoxine, 502t Sulfasalazine, 469 Sulfonamides dosage adjustment in renal insufficiency, 43 for nocardiosis, 1080 Summarizing, accurate, in behavior history taking, 207 Superb lily toxicity, 958t Supplements in fluid therapy, 62-64, 63f, 63t Supplies. See Equipment and supplies Suppository for constipation, 487 Suppurative otitis (SO), 411 Supracondylar foramen, 704, 705f Supragingival, defined, 335 Supravalvular mitral stenosis, 323 Supraventricular tachycardia, 319-320, 320f Suprelorin. See Deslorelin Surgery for acromegaly, 617 anesthesia during (See Anesthesia) for chylothorax, 905 for cleft lip and/or palate, 356 for common calcaneal tendon rupture, 723-724 for community cats ear tipping for identification, 1300-1301, 1302f-1303f, 1304b patient selection and perioperative care, 1299-1300 sterilization, 1300, 1300f, 1301b for gastric foreign body, 453 for gastrointestinal ulcers, 456 for hyperadrenocorticism, 598-599, 599t, 601-602 for injection-site sarcoma, 788-789 for intestinal foreign bodies, 483, 483f intravenous fluid therapy during, 82 for jaw fracture, 360 for mammary tumors, 793 neonatal, 137-138, 137b, 1248-1249 for oral maxillofacial tumors, 366-368, 367f-368f osteomyelitis following, 725 for pancreatitis, 516 for patellar luxation, 719-720 for spinal tumors, 755 for stifle ligamentous injury, 721-723 for urethral obstruction, 1003-1004, 1003f Surgical castration, 1186 Survival rates in hypertrophic cardiomyopathy, 310

Sustained-release formulations of analgesic drugs, 94 Sutures for pectus excavatum, 1235-1236, 1236f Swab conjunctival, 811-812, 811f ear, 374 mineral oil, 374 Swelling distal to intravenous catheter, 72, 72f of individual toes, 409 Swine flu, 879 Symblepharon, 823-824, 824f Symmetrical alopecia (FSA), 399, 401f Sympathetic nervous system (SNS), activation of in feline idiopathic cystitis, 987 Synctium-forming virus, 711 Synovial osteochondromatosis, 726-727, 726f Synthetic pheromone analogs, 233 Syringe(s), 23 for feeding of orphan kittens, 1245, 1245f insulin, 23, 553 Systemic arterial pressure, chronic kidney disease and, 1120-1121, 1121t Systemic hypertension. See Hypertension Systemic inflammatory response syndrome (SIRS), 79t Systemic lupus erythematosus (SLE), 696-697, 696b arthritis with, 712 ulcers and erosion associated with, 403 Systemic thromboembolism, 301 Systolic blood pressure in hypertension diagnosis and classification, 307-308, 307t chronic kidney disease and, 970 monitoring of during anesthesia, 134-135 during fluid therapy for hypovolemia, 75-76 Systolic clicks, 302 T T3. See Tri-iodothyronine (T3) T4. See Thyroxine (T4) Tablet, medication, esophageal damage due to, 444-445 Tabletop scale, 32f Tachyarrhythmias atrial, 322t ventricular, 319 treatment of, 322 Tachycardia atrial, 322t due to dehydration, 58 in hyperthyroidism, 572t supraventricular, 319-320, 320f ventricular, 319, 319f-320f Tachyzoites in Toxoplasmosis gondii infection, 509-510 Tacrolimus, 1136 Tactile communication, 6 Tactile stimulation, 1344 Taenia taeniaeformis, 171, 500-501 prevalence of, 170t Tail amputation of following spinal trauma, 756 blood pressure measurements from, 15, 15f in body language, 194 in communication, 6 examination of, 36, 36f in assessment of skin diseases, 373 greasy hair on, 396f Talwin. See Pentazocine Tame cat, reactive, feral cat versus, 1299 Tamiflu. See Oseltamivir

Taming of community kittens, 1305, 1306b Tape muzzle for mandibular fracture, 360, 360f Tapetum lucidum, 191-192 Tapeworms, 500-501 Target-organ damage (TOD) in chronic kidney disease, 1120 Tarsal hyperextension, 1236, 1236f TAS1R2 gene mutation, 1278-1279 Taste, 193 in dietary preferences, 237, 243 receptors for, 237, 243 Taste deterrents, 215 Tattoo for identification in population wellness program, 1318, 1320f Taurine deficiency of, 250, 250t dilated cardiomyopathy due to, 256, 256f, 301, 314 effects on pregnancy, 1223-1224 intake in hepatic disease, 260b nutritional requirements, 238-239 supplementation for diabetes mellitus, 265 Taurine-deficient retinopathy, 840, 840f Tavist. See Clemastine TCA. See Trichloroacetic acid (TCA) tCA. See Total calcium (tCA) TCAs. See Tricyclic antidepressants (TCAs) TCO2. See Total carbon dioxide concentration (TCO2) Teaching kittens, 200-201 Tear film break-up time (TFBUT), 811 Tea tree oil toxicity, 926 Teeth anatomy of, 236, 330-331, 332f eruption of, 329, 330t extraction of, 350-353, 351f-354f for stomatitis, 350 for tooth resorption, 347-348 formulas of, 329-330, 330f-331f, 330t numbering of, 329-330, 330f-331f physical examination of, 33 neonatal, 1231 resorption of, 167f, 344-348 classification of, 347b clinical signs of, 346, 346f-347f etiologic considerations in, 344-345 histologic features of, 347 nutritional implications in, 257 radiographic signs of, 346-347 replacement and inflammatory, 344, 345f treatment of, 347-348 Telazol for induction of anesthesia, 118t for sedation and premedication, 114t, 116-118, 121-122 Telazol, ketamine, and xylazine (TKX) technique, 133 Telogen effluvium, 399-401, 401f Temperature ambient in population wellness program, 1352 in veterinary hospital, 23-24 appendage, for monitoring of fluid therapy for hypovolemia, 77 body (See Body temperature) of food, 237 rectal opioids associated with elevation of, 96 taking of, 32-33, 33f Temporomandibular joint, 333, 334f disorders of, 362-365 ankylosis as, 364-365 luxation as, 363, 363f open-mouth jaw locking as, 363-364, 364f Tendon contracture, 727, 727f

Tenesmus in diarrhea assessment, 460-462, 461t Tenormin. See Atenolol Teratogen, 1233-1234 Terbinafine for dermatophytosis, 393-395, 396f for Malassezia dermatitis, 384 monitoring of long-term therapy with, 1139t for skin disease, 384t Terbutaline before bronchoscopy, 864 for emergency treatment of bronchial disease, 870-871 for inflammatory airway disease, 873 Territorial aggression, 223 Territorial boundaries, 196, 196f Testes anatomy of, 1184, 1185f disease and conditions of, 1188-1191, 1189f, 1189t-1190t, 1190b examination of, 36 involvement in feline infectious peritonitis, 1042, 1042f Testosterone, 1184-1185 Tetanospasmin, 764 Tetanus, 764-765, 764f, 1071t Tetany, secondary to hypocalcemia, 639 Tetracycline for anaplasmosis, 1027 for Bordetella pneumonia, 881 esophageal damage due to, 444 Texas A&M University for full assessment of renal biopsy, 945, 952b Texture, dietary dental disease prevention and, 257 in dietary preferences, 237 TFBUT. See Tear film break-up time (TFBUT) Theophylline for inflammatory airway disease, 873-874 pharmacokinetic monitoring of, 1143t Thiamine deficiency of, 249, 250t encephalopathy due to, 740 nutritional requirements, 241 Thiamin pyrophosphate (TPP), 241 Thiazide diuretics, 1112 Thiopental for induction of anesthesia, 118-119, 118t, 119b for total intravenous anesthesia, 132 Thiopurine methyltransferase, drug metabolism and, 40 Third eyelid disease, 817, 817f Third-order Horner’s syndrome, 763 Third spacing, 54 Thirst, 237 reduced sensitivity to in senior cat, 1169-1170, 1170f Thoracic cavity disease, 892-913 of chest wall, 909-910 chylothorax as, 904-905, 904f nutritional management of, 268-269 clinical signs of, 892 diaphragmatic hernia as, 907-909, 908f-909f general considerations in, 892 physical examination in, 892 pleural effusion as, 892-895 analysis of, 895 categorization of, 899t due to chylothorax, 904-905 due to congestive heart failure, 895-898, 900f due to feline infectious peritonitis, 898-900, 900f due to neoplasia, 900-901, 901f oxygen administration for, 895, 896b-897b, 896f-897f pleural access ports for, 906 due to pyothorax, 901-904, 902b-903b

INDEX Thoracic cavity disease (Continued) radiography in, 893-894, 893f-894f stabilization in, 894-895, 894f thoracocentesis for, 895, 898b, 898f pneumothorax as, 906-907, 907f Thoracic radiography in esophageal disease, 443 in heartworm, 884t in pancreatitis, 514-515 Thoracocentesis, 898b for pleural effusion, 895, 898b, 898f Thoracostomy tubes placement of, 902b-903b, 902f-903f for pyothorax, 901-904 Thorax, physical examination of, 34-35, 35f in senior cat, 1179 Thorazine. See Chlorpromazine 3c gene, 1039 Three-way connector, 72, 72f Thrombin, 679 Thrombin time, 684 Thrombocytopenia, 681b, 682, 684-685 paraneoplastic, 797 Thromboembolism arterial, 316-319, 316f-317f clinical signs of, 316-317, 317f recurrence and prevention of, 318-319 treatment of, 317-318 systemic, history in, 301 Thrombolytic therapy for arterial thromboembolism, 318 Thymic atrophy, Birman hypotrichosis and, 678 Thymoma-associated exfoliative dermatitis, 795 Thyroid dysgenesis, 585 Thyroid dyshormonogenesis, 585 Thyroidectomy for hyperthyroidism, 582-583, 582f-583f hypocalcemia following, 639 hypothyroidism following, 585 Thyroid function testing, 576 Thyroid gland enlarged in nonhyperthyroid cat, 579 examination of, 34, 34f palpation of, 573-574, 573f-574f Thyroid gland disorders adenocarcinoma as, 584 hyperthyroidism as, 571-584 anesthetic considerations in, 139-141, 139b clinical signs of, 572-575, 572t diagnosis of, 575-579, 577f, 578t epidemiology of, 571 heart disease and, 325-326 nutritional management of, 265-266 pathogenesis of, 571-572 treatment of, 579-584 hypothyroidism as, 584-588 causes of, 584-585 clinical features of, 585-586 diagnosis of, 586-588 treatment of, 588 Thyroid hormone in progression of obesity to diabetes, 1105, 1105t Thyroid releasing hormone (TRH) stimulation, 578-579, 578t Thyroid scintigraphy, 588 Thyroid-stimulating hormone (TSH) in hyperthyroidism, 578-579 in hypothyroidism, 587 Thyroid-stimulating hormone (TSH) stimulation test in hyperthyroidism, 579 in hypothyroidism, 587-588 Thyroxine (T4) assessment in minimum database, 165, 165t in hyperthyroidism, 571-572, 576 with chronic kidney disease, 1099 in hypothyroidism, 587

Thyroxine (T4) (Continued) in diabetic cat, 1102-1103 metabolism of, 41t normal levels in cat with hyperthyroidism, 576-579, 577f, 578t suppression of in chronic kidney disease, 964-966 TIBC. See Total iron-binding capacity (TIBC) Ticarcillin with clavulanic acid, 1244t Tick infestation, 381 Tick vector in cytauxzoonosis, 663 in rickettsial disease, 1025-1027 Tiger lily toxicosis, 921-923 acute renal failure due to, 958t Tiletamine, 1248 Tissue-core renal biopsy, 945 Tissue factors in hemostasis, 679 Tissue plasminogen activator (tPA), 680 TIVA. See Total intravenous anesthesia (TIVA) TKX. See Telazol, ketamine, and xylazine (TKX) technique TL1. See Trypsin-like immunoreactivity (TL1) T lymphocytes feline infectious peritonitis and, 1040 helper in airway inflammation, 866-867 cytokines in regulation of, 692, 695 feline immunodeficiency virus replication in, 1056-1057 feline infectious peritonitis and, 1039-1040 in intestinal small cell lymphoma, 438, 472f in lymph nodes, 690 TNR. See Trap-neuter-return (TNR) of community cats Toceranib, 777t, 780 TOD. See Target-organ damage (TOD) Toes, tumors and other swellings of individual, 409 Toileting, kittens and, 187, 187f Tolfenamic acid, 102, 714 Toltrazuril, 502-503 Tom cat effects of on kitten behavior, 183 male reproduction in, 1184-1194 anatomy of, 1184-1185, 1185f-1186f control of, 1186-1187, 1187f infertility and, 1191-1193, 1191b-1192b mating behavior in, 1185-1186 penile conditions in, 1187-1188 testicular disease and conditions in, 1188-1191, 1189f, 1189t-1190t, 1190b social practices of, 196 Tongs for community cat capture, 1297-1299, 1298f Tongue anatomy of, 334, 335f foreign body caught under, 429, 480 Tonicity in water balance, 56-57 Tonkinese cat, 1273-1276, 1276f Tonometer, 808, 809f TonoPen tonometer, 808, 809f TonoVet tonometer, 808, 809f Tonsils, 335 Tooth. See Teeth Toothbrush for sample collection for dermatophyte culture, 376 Toothbrushing, 168 for prevention of gingivitis, 342-343 Tooth extraction for tooth resorption, 347-348 Torbugesic. See Butorphanol Torbutol. See Butorphanol Torsemide, 1112 Torsion, uterine, 1211

Total calcium (tCA) in hypercalcemia, 626-627 in hypocalcemia, 637t Total carbon dioxide concentration (TCO2), 80 Total intravenous anesthesia (TIVA), 132 Total iron-binding capacity (TIBC), 669 Total thyroxine (TT4), 165 in hyperthyroidism in diabetic cat, 1102-1103 in minimum database, 165t Touch, 192-193 Towel-handling techniques, 14, 14f during physical examination, 32, 32f Towers in colony-style housing, 1340-1341, 1341f Toxascaris leonina, 171, 497-499, 498f diarrhea due to, 477t prevalence of, 170t Toxicology/toxicity, 914-933 acute renal failure due to, 958 associated with animals, 927-928 central nervous system, 744-746 of drugs, 928-929 acetaminophen, 928 aspirin, 929 enrofloxacin, 839-840, 839f 5-fluorouracil, 929 isoniazid, 929 nonsteroidal antiinflammatory drugs, 928-929 food-related, 269-270 of household products, 924-927 ant and roach baits, 924-925 ethylene glycol, 926-927 liquid potpourri and essential oils, 925-926, 926f pennies, 926 silica gel packets, 925 insecticides, 919-921, 920b onion, 250 online resources for, 915b pesticides, 745, 914-915, 915f, 916t phosphate enemas, hypocalcemia due to, 638 poisonous plants, 921-924, 922f-924f, 922t rodenticides, 915-919 anticoagulant, 915-917 bromethalin, 917 cholecalciferol, 917-918 strychnine, 918 zinc phosphide, 918-919 treatment of, 916t, 930-932, 930b, 931t vitamin A, 240, 248-249 vitamin D chronic kidney disease with, 968 hypercalcemia due to, 631-632 Toxocara cati, 171, 497-499, 498f diarrhea due to, 477t prevalence of, 170t Toxoplasmosis gondii, 509-511, 510b-511b, 510f in central nervous system, 743-744, 744f molecular assays in diagnosis of, 1088 in myopathies, 758-759 pneumonia due to, 883, 883f in polymyositis, 729 pregnancy loss due to, 1224 of spine, 752-753 zoonotic, 1093-1094 Toys for environmental enrichment, 228 in population wellness program, 1344-1345, 1345f for kitten socialization classes, 200, 200f tPA. See Tissue plasminogen activator (tPA) TPP. See Thiamin pyrophosphate (TPP) Trace elements deficiency of, 250t excess of, 249t

1395

Trachea, rupture of due to endotracheal intubation on, 127, 128f Traffic patterns in population wellness programs, 1351 Training, positive reinforcement-based, 1344, 1345f Training classes, 198-205 equipment for, 200, 200f handling and, 201-202 litter training in, 201 location for, 200, 200f planning of, 199 punishment and, 201 recruitment and promotion of, 199 resources for, 202b rewards in, 201 sample curriculum for, 202-205, 202f-205f scratching and, 202 teaching kittens and, 200-201 value of, 198-205 Tramadol, 100 for degenerative joint disease, 715 monitoring of long-term therapy with, 1139t for pain management, 1151t, 1152 Tranquilizers for sedation and premedication, 113-118 Tranquilizing of queen for breeding, 1199 Transdermal drug administration, 47-48 of analgesic drugs, 94 side effects of, 96 of fentanyl, 98-99, 131 for feline idiopathic cystitis, 991 for pain management, 1151t, 1152 of methimazole, 581 of opioids, in balanced anesthesia, 131 Transfusion, blood, 66-68 adverse reaction to, 656 for anemia, 654-656 cross-matching testing for, 646-647 for hemostatic disorders, 684 hepatic insufficiency and, 44, 44f neonatal, 1240 Transillumination in ophthalmic examination, 808-810, 809f Transitional cell lower urinary tract carcinoma, 1005-1006 Transitional period, behavioral development of kitten during, 184 Transitional vertebrae, 727-728 Transmucosal drug formulations/route, 48-49 Transplantation, renal, 961-962 Transportation to veterinary hospital, 9-10, 10f Transudates abdominal distention due to, 540t peritoneal fluid, 542 pleural fluid, 895, 899t Trap-neuter-return (TNR) of community cats, 1291, 1292t, 1294 anesthetic options for, 133 field capture for, 1292-1294, 1293f-1294f, 1295b large scale, 1308, 1308f surgical and medical procedures in, 1299-1300 Traps for capture of community cats, 1292-1293, 1292f-1293f Trauma carpal, 717-718 chest wall, 909-910 cleft palate due to, 356, 357f in community cat, 1305-1306, 1307f dentoalveolar, 348-349, 348f-349f fractures as (See Fracture(s)) intraocular sarcoma following, 834-835 lower urinary tract, 1007-1008 nasal, 858 orofacial soft tissue, 358-359, 358f-359f pleural effusion due to, 905-906, 905f

1396

INDEX

Trauma (Continued) pneumothorax due to, 906 pulmonary, 876 scapular, 717 spinal, 755-756, 755f-756f stifle ligamentous, 721-723, 722f Travel history in diarrhea assessment, 461t Treatment areas, cat-friendly, 22-23, 22f Treatment plan, behavioral history and, 210 Treats in socialization and training classes for kittens, 201 Trematodes, 501 TRH. See Thyroid releasing hormone (TRH) stimulation Triadan tooth-numbering system, modified, 329-330, 330f-331f Trial-and-error learning, 195 Triamcinolone, 1135t Trichiasis, 814, 814f Trichloroacetic acid (TCA), 816 Trichobezoar esophageal, 446, 447f gastric, 452-453, 453f Trichogram, hair, 375, 376f Trichomonas foetus diarrhea due to, 477t Giardia duodenalis versus, 504t Trichophyton mentagrophytes, zoonotic, 1094f Trichuris vulpis, 477t, 497 Tricks, learning of, 8, 8f Tricyclic antidepressants (TCAs) for behavior problems, 232b, 233 for cognitive dysfunction in senior cat, 1172-1173 for feline hyperesthesia syndrome, 763-764, 764t for feline idiopathic cystitis, 991-992 monitoring of long-term therapy with, 1139t for pain management, 1150 Trifluridine, 821 Trigeminal nerve anatomy of, 335 sensitization of in feline orofacial pain syndrome, 355 Triglycerides in pleural effusion fluid, 899t Tri-iodothyronine (T3) in hyperthyroidism, 571-572 suppression testing in, 578, 578t Trill/chirrup/greeting meow, 194 Trilostane, 599t, 600-601 Trimethoprim-sulfamethoxazole dosage adjustment in renal insufficiency, 42t, 43 for meningoencephalitis, 744 for neonatal sepsis, 1244t for nocardiosis, 1080 for protozoal disease, 502t for skin disease, 384t for upper respiratory tract infection, 853t Tripelennamine, 699t Triple phosphate uroliths, 995 Tritrichomonas foetus, 463, 505-507, 506f Cryptospordium felis with, 508 molecular assays for diagnosis of, 1086 in pyometra, 1220 Trochleoplasty for patellar luxation, 720 Tropicamide, 808 Tru-Cut biopsy, 530, 769-770 Trunk, physical examination of, 34-35, 35f Trypsin-like immunoreactivity (TL1) in exocrine pancreatic insufficiency, 519 testing of in diarrhea assessment, 464-465, 464t TSH. See Thyroid-stimulating hormone (TSH)

Tuberculin syringe, 23 Tube(s) feeding (See Feeding tube) thoracostomy placement of, 902b-903b, 902f-903f for pyothorax, 901-904 Tubulointerstitial nephritis, 962-963 Tularemia, 1071t zoonotic, 1091t Tumor necrosis factor, 693b Tumor necrosis factor-alpha, 709-710 Tumor(s). See Neoplasia Turbidity, urinary, 939 20-carbon long-chain fatty acids, 258 “Twisty cats”, 726 Two-handed technique for thyroid palpation, 574, 574f Tylosin for Clostridium perfringens diarrhea, 479 for pancreatitis with inflammatory bowel disease, 1118t Tympanic membrane examination in otitis media, 414, 414f Type A adverse drug reactions, 1144-1145 diagnosis of, 1146 management of, 1147 Type B adverse drug reactions, 1145 diagnosis of, 1147 management of, 1147-1148 Type B blood, neonatal isoerythrolysis and, 662-663 Type 1 diabetes mellitus. See also Diabetes mellitus (DM) nutritional management of, 264-265 pathophysiology of, 549-550, 550f Type 2 diabetes mellitus. See also Diabetes mellitus (DM) nutritional management of, 264-265 pathophysiology of, 549-550, 550f Type I collagen defects in osteogenesis imperfecta, 727 Type I hypersensitivity reaction, 698 Type II hypersensitivity reaction, 1040 Tyrosinase gene mutation, 1265 Tyrosine kinase inhibitors, 777t, 780 Tyrosine-related protein 1, 1273-1276 Tyzzer disease, 480 U UBA. See Urine bile acids (UBA) UDCA. See Ursodeoxycholic acid (UDCA) U40 insulin syringe, 553 Ulcerative dermatitis, 1030, 1030f Ulcer/ulcerations corneal, 824-825, 825f examination of, 811 feline herpesvirus-1 and, 818, 819f cutaneous, 402-403, 403f indolent, 403-404, 403f eosinophilic, 353 gastrointestinal, 455-456 vomiting associated with, 434-435, 434t oral, 1032-1033, 1032f of paw pads, 407, 408f Ulnar fracture, 707 Ultiva. See Remifentanil Ultram. See Tramadol Ultrasound in ascites, 539f, 541f in diarrhea assessment, 465 in feline lower urinary tract disease, 984, 984f for fetal assessment, 1205-1206 in gastric neoplasia, 457, 457f in gastric ulceration, 456 for gestational age prediction, 1206, 1207b in hyperadrenocorticism, 598, 598f in hyperaldosteronism, 604, 604f

Ultrasound (Continued) in inflammatory bowel disease, 467, 467f in intestinal foreign body, 482, 482f in intestinal lymphoma high-grade, 474, 474f small cell, 471, 471f in intussusception, 484, 484f in liver disease, 528-529 in lower urinary tract neoplasia, 1006, 1006f neonatal, 1238 ocular, 812, 812f in pancreatitis, 514-515, 515f in pleural effusion, 894 in polycystic kidney disease, 946-947, 947f for pregnancy diagnosis, 1205-1206 in renal biopsy, 953-954 in renal calculi, 955 in renal disease, 945 in splenic disorders, 686-687, 687f in urinary tract diagnosis, 936t in vomiting, 430 Umbilical cord assessment of, 1231, 1232f kittens entwined in, 1208-1209, 1208f UMN/GP ataxia. See Upper motor neuron/general proprioceptive (UMN/GP) ataxia Uncinaria spp., 171 Understanding the cat, 4-5 Underweight associated with hyperthyroidism, 265 in senior cat, 1176 Unfractioned heparin, 318 UPC. See Urine protein to creatinine (UPC) ratio Upper motor neuron/general proprioceptive (UMN/GP) ataxia, 750 Upper respiratory tract disease, 846-861 clinical signs of, 846-847, 847b diagnosis of, 847-851, 848b exploratory rhinotomy in, 850-851 imaging, biopsy, and deep cultures in, 849-850, 849f-850f noninvasive tests in, 847-849 feline herpesvirus-1 in, 1029 laryngeal, 858-859 nasal, 851-858 anatomical and functional, 851-852, 851f chronic inflammatory, 857-858, 857f foreign bodies as, 858 infectious, 852-857, 853t, 854f, 856f neoplasia as, 858 traumatic, 858 population wellness program and, 1315 Upper urinary tract disorders, 935-980 acute renal failure as, 957-960, 957f, 958t chronic kidney disease as (See Chronic kidney disease (CKD)) diagnosis of, 935-945, 936t, 937b creatinine ratio for, 944 imaging in, 944-945, 944f renal biopsy in, 945, 945f renal function tests in, 935-937 renal size assessment in, 935, 936b urinalysis in, 937-943 urine culture and sensitivity for, 943-944, 944b dialysis for, 960-961, 960f feline infectious peritonitis as, 949 glomerulonephritis as, 951-954, 951b-952b, 953f hydronephrosis as, 956-957, 957f inherited, congenital, developmental, 946-948 perinephric pseudocysts as, 947-948, 948f polyarteritis nodosa as, 949

Upper urinary tract disorders (Continued) polycystic kidney disease as, 946-947, 946f-947f pyelonephritis as, 950-951, 950f renal amyloidosis as, 948-949 renal neoplasia as, 949-950 renal transplantation for, 961-962 ureteronephrolithiasis as, 955-956, 955f Urate uroliths, 281, 281b radiographic appearance of, 985t Urea neonatal values, 1237t plasma osmolality and, 56 Urea cycle, 238 Urease testing in Helicobacter gastritis, 454 Ureteronephrolithiasis, 955-956, 955f Ureters calculi in, 955-956 imaging of, 944-945, 944f obstruction of, 83 Urethral obstruction, 1000b anesthetic considerations in, 141-142, 141b fluid and electrolyte loss assessment for, 79t fluid therapy for, 83 ongoing medical management of, 1002-1003 stabilization in, 999-1000 surgical management of, 1003-1004, 1003f urethral patency establishment in, 998-1004, 1001f Urethral plugs, 998 Urethral rupture, 1007-1008 Urethrostomy, 1003-1004, 1003f Urginea maritima toxicity, 923-924 Urinalysis, 937-943 in ascites, 539 collection technique for, 938 examination of sample, 939 in feline idiopathic cystitis, 987-988 in hyperadrenocorticism, 593t in hypoadrenocorticism, 607, 607t in hypothyroidism, 587 interpretation of, 939-943, 939f, 942t-943t in liver disease, 524 in lower urinary tract disease, 982-983 in minimum database, 165t timing of sample collection for, 937 Urinary casts due to lily toxicosis, 922t in urinary tract diagnosis, 936t Urinary incontinence, 1008-1009, 1008b, 1008f Urinary signs in hyperthyroidism, 575 Urinary tract disorders, 935-1013 acute renal failure as, 957-960, 957f, 958t chronic kidney disease as (See Chronic kidney disease (CKD)) congenital, 1233b diagnosis of, 935-945, 936t, 937b creatinine ratio for, 944 imaging in, 944-945, 944f renal biopsy in, 945, 945f renal function tests in, 935-937 renal size assessment in, 935, 936b urinalysis in, 937-943 urine culture and sensitivity for, 943-944, 944b dialysis for, 960-961, 960f feline infectious peritonitis as, 949 glomerulonephritis as, 951-954, 951b-952b, 953f hydronephrosis as, 956-957, 957f inherited, congenital, developmental, 946-948 lower, 980-1013, 981f diabetes mellitus concurrent with, 1106-1108

INDEX Urinary tract disorders (Continued) diagnosis of, 981-985, 982f, 983b, 983t, 984f, 985t idiopathic cystitis as, 281-282, 985-992 incontinence as, 1008-1009, 1008b, 1008f neoplasia as, 1005-1007, 1006f traumatic, 1007-1008 urethral obstruction as, 998-1004, 1000b, 1001f, 1003f urethral plugs as, 998 urinary tract infection as, 1004-1005 urolithiasis and urethral plugs as, 278-279, 279b, 279f urolithiasis as, 992-998, 993f, 994t, 995f-998f perinephric pseudocysts as, 947-948, 948f polyarteritis nodosa as, 949 polycystic kidney disease as, 946-947, 946f-947f pyelonephritis as, 950-951, 950f renal amyloidosis as, 948-949 renal neoplasia as, 949-950 renal transplantation for, 961-962 ureteronephrolithiasis as, 955-956, 955f Urinary tract infection (UTI), 1004-1005 in hyperthyroidism, 575 urine culture and sensitivity in, 943-944 Urination outside of litter box, 217-218 Urine acidic, 941 alkaline, 941 in odor signals, 194-195 in sensible fluid loss, 57 volume of in different life stages, 1168t Urine bile acids (UBA), 524 Urine collection for lower urinary tract disease diagnosis, 982-983, 983t for urine cortisol:creatinine ratio, 595 Urine cortisol:creatinine ratio, 595-598, 596t Urine creatinine assessment in liver disease, 524 Urine culture and sensitivity, 943-944, 944b in urinary tract infection, 1005 Urine dipsticks, 562 Urine metabolic screening, 737-738 Urine output for monitoring of fluid therapy for hypovolemia, 76-77 neonatal, 1232b Urine pH, 940-941 renal calculi prevention and, 956 struvite uroliths and, 280b, 996 Urine protein, 944 Urine protein to creatinine (UPC) ratio, 942-943 in systemic lupus erythematosus, 697 Urine samples, measuring of, 15-16, 16f Urine sediment examination, 939, 943 Urine specific gravity (USG) in chronic kidney disease with hyperthyroidism, 1100 in diabetes insipidus, 619 in feline idiopathic cystitis, 987-988 in glomerulonephritis, 951 in hyperadrenocorticism, 594 in hypoadrenocorticism, 607t interpretation of, 940 neonatal, 1232b as renal function test, 935-936, 936t tooth resorption and, 344-345 values for, 940 Urine spraying, 194-195, 218-219 Urine testing in diarrhea, 463-465 for home blood glucose monitoring, 561-562 neonatal, 1237 in vomiting, 429

Uroabdomen, ascites due to, 545 Urobilinogen, 941 Urography excretory, 944-945 intravenous, 936t Urohydropropulsion, voiding, 994, 994t Urolithiasis/uroliths, 992-998 calcium oxalate, 996-997, 996f-998f feline lower urinary tract disease due to, 981f, 984 mineral composition of based radiographic appearance of, 985t nutritional management of, 279-281, 280b-281b prevalence of, 992-993, 993f prevention of, 280, 280b removal of, 993-995, 994t renal, 955-956, 955f struvite, 995-996, 995f Ursodeoxycholic acid (UDCA) in feline cholangitis syndrome therapy, 534 for hepatoencephalopathy, 535, 536t for pancreatitis with inflammatory bowel disease, 1120 Ursodiol for pancreatitis with inflammatory bowel disease, 1118t USG. See Urine specific gravity (USG) Uterine horn anomalies, 1204, 1205f Uterus dystocia due to abnormalities of, 1211 evacuation for metritis, 1214 palpation of during physical examination, 35 Uterus unicornis, 1204, 1205f UTI. See Urinary tract infection (UTI) Utrecht University for full assessment of renal biopsy, 945, 952b Uveal tract disease, 827-834 iris melanoma, 832-833, 832f neoplasia, 832 secondary intraocular neoplasia, 833-834, 834f spastic pupil syndrome, 832, 832f uveitis, 827-832, 827f-828f, 829b, 829t, 830f-831f Uveitis, 827-832, 827f-828f, 829b, 829t, 830f-831f secondary intraocular neoplasia and, 833-834 V VAAE. See Vaccine-associated adverse events (VAAE) Vaccination, 173-178, 174t anaphylactic response to, 700 Bordetella bronchiseptica, 854 Chlamydophila felis, 854 of community cats, 1301-1302 feline calicivirus, 1034 feline immunodeficiency virus, 1059, 1061 feline leukemia virus, 1055-1056 feline panleukopenia virus, 1038 feline viral rhinotracheitis, calcivirus, panleukopenia in population wellness programs, 1323-1324 for upper respiratory infection prevention, 855-856 history of, 29 in diarrhea assessment, 461t internet resources for, 177t in population wellness program, 1323-1325 in preventive health care, 156t for senior cats, 1169 sarcoma associated with injection site, 787-791, 788f-789f Vaccine-associated adverse events (VAAE), 700 Vacuuming, cat allergies and, 422 Vaginal cytology in infertility, 1216-1217, 1216b, 1216f

Valacyclovir, 855 Vanadium supplementation for diabetes mellitus, 265 Variable expression, genetic, 1281 Vascular access. See Venous access Vascular encephalopathies, 746-747, 746f Vascular myelopathies, 756-757 Vascular radiographic patterns in lower respiratory tract disease, 862, 863t Vascular ring anomaly, 448 Vasculitis, of feline infectious peritonitis, 1040 Vasectomy, 1186-1187, 1187f Vasoactive intestinal peptide, 548t Vasoconstriction for monitoring of fluid therapy for hypovolemia, 76 Vasodilation, fluid loss associated with, 59t Vasomotor tone for monitoring of fluid therapy for hypovolemia, 76 Vasopressin response test, 936t VCP. See Veterinary cuttable plate (VCP) Vectra. See Dinotefuran Venipuncture, neonatal, 1236-1237 Venous access for fluid therapy, 69-70, 71t Ventilation for environmental health in population wellness programs, 1351-1352 Ventral in oral anatomy, 335 Ventricular arrhythmias, 319-322 Ventricular enlargement, 303-304 Ventricular extrasystoles, 302 Ventricular premature contraction (VPC), 319 Ventricular septal defect (VSDs), 322-323, 323f Ventricular tachycardia (VT), 319, 319f-320f Ventrum, examination of in assessment of skin diseases, 373 Veraflox. See Pradofloxacin Vertebrae, transitional, 727-728 Vertebral heart scale (VHS), 304, 304f-305f Very low-density lipoproteins (VLDLs), 1105-1106 Vestibular disease, 747-749, 747f, 748t, 749f otitis media and otitis interna and, 415 Veterinarian communication with client, 152, 178 feline, 21 handling of cat, perception of client regarding, 152-153 Veterinary cuttable plate (VCP), 718 Veterinary hospital, transportation of cat to, 9-10, 10f Veterinary Medicine Directorate: Suspected Adverse Reaction Surveillance Scheme, 1148t Veterinary Oral Health Council (VOHC), 168 Veterinary team, perspective of on feline-friendly handling, 3 Veterinary visit a better way, 3 cat’s perspective on, 3 client’s perspective on, 2 feline-friendly, 9-18 client education in, 9, 10b first veterinary visits and kitten classes in, 10 getting cat out of carrier in, 10-11, 11f handling during examination in, 11-14, 12f-14f handling for laboratory sample collection in, 15-16 hospitalization in, 16-17, 17f receiving cat and client in, 10 returning home in, 17-18 the situation today, 9 transportation of cat in, 9-10, 10f

1397

Veterinary visit (Continued) first, 10 misbehavior and aggression at, 7-8, 7b veterinary team’s perspective on, 3 Vetsulin/Caninsulin, 553t, 554, 558t VHS. See Vertebral heart scale (VHS) Vibrissae, tactile, 193 Vidarabine, 821 Video, feline, 1343f Videotaping of cat for behavioral history, 208 for medical history, 27 Viewing places in environmental management of behavior problems, 230 Vinblastine, 777t, 779 Vincristine, 777t, 779 for lymphoma, 784-785, 784t Vinorelbine, 777t, 779 Viral arthritis, 711 Viral enteritis, 477-478 Viral infection, 1029-1070 associated with hepatopathy or hepatic inflammation, 534b Bornavirus as, 1061-1062 coronavirus in, 1038-1047 clinical signs of, 1040-1042, 1041f-1042f, 1041t diagnosis of, 1042-1045, 1043b, 1043f, 1044t prevention and control of, 1046-1047, 1046b, 1046t transmission and pathogenesis of, 1039-1040 treatment of, 1045 enteritis agents in, 1061 feline calicivirus in, 1031-1034, 1032f feline herpesvirus-1 in, 1029-1031, 1030f (See also Feline herpesvirus-1 (FHV-1)) feline orbital pseudotumor associated with, 813 feline panleukopenia in, 1036-1038, 1037f influenza virus in, 1034-1036 lower respiratory tract, 878-879 nasal, 854-856, 854f papillomavirus in, 1062-1063, 1062f poxvirus in, 1063 pregnancy loss due to, 1223b, 1224 rabies as, 1047-1048 retroviruses in, 1048-1061, 1048t feline immunodeficiency virus as, 1056-1061 feline leukemia virus as, 1048-1056, 1049t zoonotic, 1093 Virulent systemic feline calicivirus (VS-FCV), 1032-1033 Virus detection assay, 1044-1045 Virus isolation of feline calicivirus, 1033 of feline herpesvirus-1, 1030 Vision, 4-5, 191-192 Visual communication, 5-6, 5f Visual stimulation in population wellness program, 1343, 1343f Vital pulp therapy, 348 Vitamins deficiency of, 250t excess of, 249t nutritional requirements, 240-241, 244 in parenteral nutrition, 277, 277f supplementation for diarrhea, 435-436 Vitamin A deficiency of, 250t skin disease associated with, 258 excess of, 240, 248-249, 249t nutritional requirements, 240 Vitamin B1 deficiency of, 249 nutritional requirements, 241

1398

INDEX

Vitamin B3, nutritional requirements, 240-241 Vitamin B6, nutritional requirements, 241 Vitamin B12 (cobalamin) for appetite stimulation in cardiovascular disease treatment, 257t diarrhea and, 435-436, 464-465, 464t in exocrine pancreatic insufficiency treatment, 520 in hepatic lipidosis therapy, 532-533, 532t in inflammatory bowel disease treatment, 468 monitoring of long-term therapy with, 1139t Vitamin B for appetite stimulation, 257t Vitamin C intake of in chronic kidney disease, 279b in hepatic disease, 260b for osteogenesis imperfecta, 727 for plaque control, 256 Vitamin D deficiency of, 250t excess of, 249, 249t hypercalcemia associated with, 631-632 nephrotoxic effects of, 959 treatment of, 968 nutritional requirements, 240 tooth resorption and, 257, 344-345 Vitamin D metabolites in hypercalcemia, 627 Vitamin D nephrotoxicosis, 968 Vitamin D3 toxicity, 917-918, 959 Vitamin E deficiency of, 250, 250t skin disease associated with, 258 for hepatoencephalopathy, 536t intake in chronic kidney disease, 279b intake in hepatic disease, 260b for plaque control, 256 Vitamin K1 antagonism or deficiency of, 680t, 682 for anticoagulant rodenticide toxicity, 916t in hepatic lipidosis therapy, 532-533, 532t Vitamin K deficiency in liver disease, 524-525 Vivitonin. See Propentofylline VLDLs. See Very low-density lipoproteins (VLDLs) VMO. See Vomeronasal organ (VMO) Vocal communication, 6 Vocalization in communication, 194 excessive, 216-217 Voided urine sample, 938 in feline lower urinary tract disease, 983t Voiding urohydropropulsion, 994, 994t Volume deficit, calculation of, 78 Vomeronasal organ (VMO), 192 Vomiting, 426-431, 427f biopsies in, 430 blood and urine testing in, 429 in chronic gastritis, 454-455 defined, 426 diagnosis of, 427f with diarrhea, 460-462 fluid and electrolyte loss assessment for, 79t

Vomiting (Continued) fluid loss due to, 57, 59t in gastric disease, 451-452 in gastric neoplasia, 457 with gastrointestinal ulcers, 434-435, 434t in hyperthyroidism, 572t imaging in, 430 due to lily toxicosis, 922t linear foreign body under tongue and, 480 opioid-associated, 96-97 in pancreatitis, 516 pathways in stimulation of, 426-427, 426f physical examination in, 429 regurgitation versus, 428-429, 441-442, 441t signalment and clinical history in, 428-429, 428t therapies for, 431-435, 432t Vomiting center, 426, 426f VPC. See Ventricular premature contraction (VPC) VSDs. See Ventricular septal defect (VSDs) VS-FCV. See Virulent systemic feline calicivirus (VS-FCV) VT. See Ventricular tachycardia (VT) W Walchia americana, 379 Walking, development of, 184 Walkways in colony-style housing, 1340-1341, 1341f Warfarin toxicity, 915-916 Water, mixing drugs with, 46 Water balance, 52, 56-57 body fluid compartments in, 53-55, 53f steady state and concept of maintenance in, 52-53 Water deprivation, fluid loss associated with, 59t Water deprivation test for diabetes insipidus, 619 in urinary tract diagnosis, 936t Water intake for dissolution of struvite uroliths, 280b increasing of for idiopathic cystitis, 991 neonatal, 1232b normal, 237 ways to increase, 281b Weakness in hyperthyroidism, 572t, 575 due to hypokalemia, 729-730, 729f due to lily toxicosis, 922t in neuromuscular disorders, 757, 757f Weaning of kitten, 184-185, 187 nutrition following, 246 Wedge biopsy for cancer diagnosis, 770 Wedge recession trochleoplasty, 720 Weighing of cat during physical examination, 32, 32f during weight loss for obesity, 264 Weight changes in different life stages, 1168t documentation of in medical record, 261 drug dosages and, 46 fluid losses and, 57-58 management of in preventive health care, 156t, 168-169, 169f

Weight (Continued) in medical history, 29 normal, 191 in obesity, 261 Weight gain in hypothyroidism, 586t neonatal, failure of, 1231 during pregnancy, 246 Weight loss assessment during physical examination, 37-39 for degenerative joint disease, 713 for diabetes mellitus, 264-265 diarrhea assessment and, 461t energy requirements for, 245t in hyperadrenocorticism, 594 in hyperthyroidism, 572t, 573 in inflammatory bowel disease, 466, 468 for obesity, 262-264 for osteoarthritis, 266 in senior cat, 1169-1170, 1170f, 1170t, 1176-1181 causes of, 1176-1178, 1177f diagnosis of, 1178-1180, 1178b, 1178t, 1179f management of, 1180, 1180b prevalence of, 1176, 1177f Well cat acute onset diarrhea in, 462 chronic diarrhea but no weight loss in, 464 diabetes mellitus treatment in, 552-564 neutropenia in, 677 Wellness. See also Preventive health care defined, 1312 population (See Population wellness program) Wet food, 168-169 for constipation, 487-488 Wheezing, 862 Whipworms, 497 Whiskers, 193 examination of in assessment of skin diseases, 372 White blood cells (WBCs). See Leukocytes “White coat” hypertension, 15 White pulp, splenic, 685 Whole blood transfusion, 66-67 for anemia, 654-655 for hemostatic disorders, 684 hepatic insufficiency and, 41t, 44, 44f Widow spider bite, 927-928 Winged infusion sets, 70 Wiring for jaw repair, 360-362, 361f-362f for mandibular fracture, 705, 706f for repair of traumatic split of hard palate, 705-706 Wolbachia pipientis, 883-884 Wood lily toxicity effects of, 958t Wood’s lamp examination, 375, 375f in dermatophytosis, 393 World, cat’s perception of, 4-5 World Health Organization (WHO) mammary tumor staging classification, 792t Wound, nonhealing, 416-417, 416b Wound infusion catheters, 104 Wrapping of intravenous catheter, 72, 72f

X Xanthine uroliths, 985t X chromosome, 1263, 1264f inactivation of, 1271b-1272b Xenobiotic glucuronidation capacity, 40, 41t Xylazine for anesthesia in feral cats, 133 for sedation and premedication, 114t, 115-116 for toxicosis, 916t Y Y chromosome, 1263, 1264f Yeast dermatitis, 383-384 in atopic cat, 390 Yeast otitis, 411, 413 Yersinia enterocolitica, 477t, 480 Yersinia pestis, zoonotic, 1092 Yersinia pseudotuberculosis, 480 Yowling, 194 nighttime, in senior cats, 1170-1171, 1171b Z Zafirlukast, 874 Zantac. See Ranitidine Zantedeschia spp. toxicity, 924, 925f Zeniquin. See Marbofloxacin Zidovudine (AZT) for feline immunodeficiency virus, 1059-1060 monitoring of long-term therapy with, 1139t Ziehl-Neelsen staining for Cryptospordium felis diagnosis, 508 in Mycobacterium infection, 1076 Zinc for appetite stimulation in cardiovascular disease treatment, 257t deficiency of, 250t skin disease associated with, 258 excess of, 249t toxicity, due to pennies, 926 Zinc phosphide toxicity, 918-919 Zinc sulfate fecal flotation techniques, 170 for Giardia diagnosis, 504 Zinecard. See Dexrazone Zithromax. See Azithromycin Zofran. See Ondansetron Zolazepam for sedation and premedication, 114-115 neonatal, 1248 Zonisamide, 736, 736t Zoonotic disease, 1090-1096, 1091b, 1091t bacterial, 1091-1093, 1092f cat bites, 1090-1091 cat ownership of by immunecompromised persons and, 1095 with Cryptospordium felis, 508-509 fungal, 1094-1095, 1094f with Giardia, 505 parasitic, 1093-1094, 1094f public health considerations in, 1095 with roundworms, 499 with salmonellosis, 290 with tapeworms, 501 with Toxoplasmosis gondii, 511 with Tritrichomonas foetus, 507 viral, 1093 Zygomatic gland, 334-335 Zyrtec. See Cetirizine

FREQUENTLY USED ABBREVIATIONS AAFP ACE ACT ADH ALP ALT ARF AST AVMA BAL BER BID BP BSA BSAVA BUN CAPC CBC CHF CK CKD cm CMI CNS CO2 COX CRI CRT CSF CT CVMA CVP DCM DDAVP DIC DJD DKA DNA DSH ECF ECG EDTA EEG EGC ELISA EPA EPO FA FCK FCoV FCV FECV FeLV FHV, FHV-1

American Association of Feline Practitioners Angiotensin-converting enzyme Activated clotting time Antidiuretic hormone Alkaline phosphatase Alanine aminotransferase Acute renal failure Aspartate aminotransferase American Veterinary Medical Association Bronchoalveolar lavage Basal energy requirement Every 12 hours Blood pressure Body surface area British Small Animal Veterinary Association Blood (serum) urea nitrogen Companion Animal Parasite Council Complete blood cell count Congestive heart failure Creatine kinase Chronic kidney disease Centimeter Cell-mediated immunity Central nervous system Carbon dioxide Cyclooxygenase Constant rate infusion Capillary refill time Cerebrospinal fluid Computed tomography Canadian Veterinary Medical Association Central venous pressure Dilated cardiomyopathy Desmopressin acetate Disseminated intravascular coagulation Degenerative joint disease Diabetic ketoacidosis Deoxyribonucleic acid Domestic short hair Extracellular fluid Electrocardiography Ethylenediaminetetraacetic acid Electroencephalogram Eosinophilic granuloma complex Enzyme-linked immunosorbent assay Eicosapentaenoic acid Erythropoietin Fluorescent antibody Flat chest kitten Feline coronavirus Feline calicivirus Feline enteric coronavirus Feline leukemia virus Feline herpesvirus

FIP FIV FNA fPLI FPV FSH fT4 fTLI FVR FVRCP

FUO GABA GAG GFR GGT GI GnRH H&E Hb HCG HCT HCM IBD iCa ICF ICP IFA

IFN Ig IHC IM IN IO IOP IU IV IVS Kcal KCl Kg LH LMN LRS LV m2 MCHC MCV MDI ME mg MIC

Feline infectious peritonitis Feline immunodeficiency virus Fine needle aspiration Feline pancreatic lipase immunoreactivity Feline panleukopenia virus Follicle-stimulating hormone Free thyroxine Feline trypsin-like immunoreactivity Feline viral rhinotracheitis Feline viral rhinotracheitis, calicivirus, panleukopenia virus (vaccine) Fever of unknown origin Gamma-aminobutyric acid Glycosaminoglycan Glomerular filtration rate Gamma-glutamyltransferase Gastrointestinal Gonadotropin-releasing hormone Hematoxylin and eosin (stain) Hemoglobin Human chorionic gonadotropin Hematocrit Hypertrophic cardiomyopathy Inflammatory bowel disease Ionized calcium Intracellular fluid Intracranial pressure Indirect fluorescent antibody or immunofluorescence assay Interferon Immunoglobulin Immunohistochemistry Intramuscular(ly) Intranasal(ly) Intraosseous Intraocular pressure International units Intravenous(ly) Intraventricular septum Kilocalorie Potassium chloride Kilogram Luteinizing hormone Lower motor neuron Lactated Ringer’s solution Left ventricle Square meters Mean corpuscular hemoglobin concentration Mean corpuscular volume Maternally derived immunity Metabolizable energy Milligram Minimal inhibitory concentration

mL MLV mm MRI NaCl NI NMDA NPO NSAIDs O.D. OP O.S. PCR PCV PD PDA PE PGF2α PKD PLR PO PP PRA PT PTT PU PZI RBC RDW RER RNA RV SAM SAMe SBA SC SG SID SIRS SPF SSRI T3 T4 TCA TID TP TSH UA UMN USDA USG UTI VD WBC WSAVA

Milliliter Modified live virus Millimeter Magnetic resonance imaging Sodium chloride Neonatal isoerythrolysis N-methyl-D-aspartate (receptor) Nothing per os (fasting) Nonsteroidal antiinflammatory drugs Oculus dexter (Latin), right eye Organophosphate Oculus sinister (Latin), left eye Polymerase chain reaction Packed cell volume Polydipsia Patent ductus arteriosus Pectus excavatum Prostaglandin F2α Polycystic kidney disease Pupillary light reflex Per os (by mouth) Polyphagia Progressive retinal atrophy Prothrombin time Partial thromboplastin time Polyuria Protamine zinc insulin Red blood cell Red cell distribution width Resting energy requirement Ribonucleic acid Right ventricle Systolic anterior motion s-Adenosylmethionine Serum bile acids Subcutaneous(ly) Specific gravity Every 24 hours; once daily Systemic inflammatory response syndrome Specific-pathogen free Selective serotonin reuptake inhibitor Triiodothyronine Thyroxine Tricyclic antidepressant Every 8 hours Total protein Thyroid stimulating hormone Urinalysis Upper motor neuron United States Department of Agriculture Urine specific gravity Urinary tract infection Ventrodorsal White blood cell World Small Animal Veterinary Association

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