Pathophysiology: Concepts of Altered Health States

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arly peoples were considered long-lived if they reached 30 years of age—that is, if they survived infancy. For many centuries, infant mortality was so great that large families became the tradition; many children in a family ensured that at least some would survive. Life expectancy has increased over the centuries, and today an individual in a developed country can expect to live about 71 to 79 years. Although life expectancy has increased radically since ancient times, human longevity has remained fundamentally unchanged. The quest to solve the mystery of human longevity, which appears to be genetically programmed, began with Gregor Mendel (1822–1884), an Augustinian monk. Mendel laid the foundation of modern genetics with the pea experiments he performed in a monastery garden. Today, geneticists search for the determinant, or determinants, of the human life span. Up to this time, scientists have failed to identify an aging gene that would account for a limited life span. However, they have found that cells have a finite reproductive capacity. As they age, genes are increasingly unable to perform their functions. The cells become poorer and poorer at making the substances they need for their own special tasks or even for their own maintenance. Free radicals, mutation in a cell’s DNA, and the process of programmed cell death are some of the factors that work together to affect a cell’s functioning.

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Concepts of Health and Disease Georgianne H. Heymann Carol M. Porth

HEALTH AND SOCIETY HEALTH AND DISEASE: A HISTORICAL PERSPECTIVE The Influence of Early Scholars The Nineteenth Century The Twentieth Century The Twenty-First Century PERSPECTIVES ON HEALTH AND DISEASE IN INDIVIDUALS Health Health and Disease as States of Adaptation Disease Etiology Pathogenesis Morphology Clinical Manifestations Diagnosis Clinical Course PERSPECTIVES ON HEALTH AND DISEASE IN POPULATIONS Epidemiology and Patterns of Disease Prevalence and Incidence Morbidity and Mortality Determination of Risk Factors The Framingham Study The Nurses’ Health Study Natural History Levels of Prevention Evidence-Based Practice and Practice Guidelines

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he concepts of what constituted health and disease at the beginning of the last century were far different from those of this century. In most of the industrialized nations of the world, people now are living longer and enjoying a healthier lifestyle. Much of this has been made possible by recent advances in science and technol-

ogy. There has been an increased knowledge of immune mechanisms; the discovery of antibiotics to cure infections; and the development of vaccines to prevent disease, chemotherapy to attack cancers, and drugs to control the manifestations of mental illness. The introduction of the birth control pill and improved prenatal care have led to decreased birth rates and declines in infant and child mortality. The benefits of science and technology also have increased the survival of infants born prematurely and of children with previously untreatable illnesses, such as immunodeficiency states and leukemia. There also has been an increase in the survival of very seriously ill and critically injured persons of all age groups. Consequently, there has been an increase in longevity, a shift in the age distribution of the population, and an increase in age-related diseases. Coronary heart disease, stroke, and cancer have now replaced pneumonia, tuberculosis, and diarrhea and enteritis—the leading causes of death in the 1900s. This chapter, which is intended to serve as an introduction to the book, is organized into four sections: health and society, historical perspectives on health and disease, perspectives on health and disease in individuals, and perspectives on health and disease in populations. The chapter is intended to provide the reader with the ability to view within a larger framework the historical aspects of health and disease and the relationship of health and disease to individuals and populations, and to introduce the reader to terms, such as etiology and pathogenesis, that are used throughout this text.

Health and Society Everyone who is born holds dual citizenship in the kingdom of the well and in the kingdom of the sick. Although we all prefer to use only the good passport, sooner or later each of us is obligated, at least for a spell, to identify ourselves as citizens of that other place.1 3

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After completing this section of the chapter, you should be able to meet the following objectives:

✦ Describe the concepts used to establish belief systems within a community and the effects on its health care practices ✦ Identify a disease believed to be generated by specific emotions and the characteristics ascribed to it ✦ Explain how mythologizing disease can be detrimental to individuals in a society

There is a long history that documents the concern of humans for their own health and well-being and that of their community. It is not always evident what particular beliefs were held by early humans concerning health and disease. Still, there is evidence that whenever humans have formed social groups, some individuals have taken the role of the healer, responsible for the health of the community by preventing disease and curing the sick. In prehistoric times, people believed that angry gods or evil spirits caused ill health and disease. To cure the sick, the gods had to be pacified or the evil spirits driven from the body. In time, this task became the job of the healers, or tribal priests. They tried to pacify the gods or drive out the evil spirits using magic charms, spells, and incantations. There also is evidence of surgical treatment. Trephining involved the use of a stone instrument to cut a hole in the skull of the sick person. It is believed that this was done to release spirits responsible for illness. Prehistoric healers probably also discovered that many plants can be used as drugs. The community as a whole also was involved in securing the health of its members. It was the community that often functioned to take care of those considered ill or disabled. The earliest evidence of this comes from an Old Stone Age cave site, Riparo del Romio, in southern Italy. There the remains of an adolescent dwarf were found. Despite his severe condition, which must have greatly limited his ability to contribute to either hunting or gathering, the young man survived to the age of 17 years. He must have been supported throughout his life by the rest of the community, which had incorporated compassion for its members into its belief system.2 Communities such as this probably existed throughout prehistory; separated from each other and without any formal routes of communication, they relied on herbal medicines and group activity to maintain health. Throughout history, peoples and cultures have developed their health practices based on their belief systems. Many traditions construed sickness and health primarily in the context of an understanding of the relations of human beings to the planets, stars, mountains, rivers, spirits, and ancestors, gods and demons, the heavens and underworld. Some traditions, such as those reflected in Chinese and Indian cultures, although concerned with a cosmic scope, do not pay great attention to the supernatural. Over time, modern Western thinking has shed its adherence to all such elements. Originating with the Greek tradition—which dismissed supernatural powers, although not environmental influences—and further shaped by the

Influences of zodiac signs on the human body. (Courtesy of the National Library of Medicine)

flourishing anatomic and physiologic programs of the Renaissance, the Western tradition was created based on the belief that everything that needed to be known essentially could be discovered by probing more deeply and ever more minutely into the flesh, its systems, tissues, cells, and DNA.3 Through Western political and economic domination, these health beliefs now have powerful influence worldwide. Every society has its own ideas and beliefs about life, death, and disease. It is these perceptions that shape the concept of health in a society. Although some customs and beliefs tend to safeguard human communities from disease, others invite and provoke disease outbreaks. The beliefs that people have concerning health and disease can change the destiny of nations. The conquering of the Aztec empire may be one example. Historians have speculated how Hernando Cortez, starting off with fewer than 600 men, could conquer the Aztec empire, whose subjects numbered millions. Historian William H. McNeill suggests a sequence of events that may explain how a tiny handful of men could subjugate a nation of millions. Although the Aztecs first thought the mounted, gunpowered Spaniards were gods, experience soon showed

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otherwise. Armed clashes revealed the limitations of horseflesh and of primitive guns, and the Aztecs were able to drive Cortez and his men from their city. Unbeknownst to the Aztecs, the Spaniards had a more devastating weapon than any firearm: smallpox. An epidemic of smallpox broke out among the Aztecs after their skirmishes with the Spaniards. Because the population lacked inherited or acquired immunity, the results were catastrophic. It is presumed that a quarter to a third of the population died from the initial onslaught. Even more devastating were the psychological implications of the disease: it killed only American Indians and left Spaniards unharmed. A way of life built around the old Indian gods could not survive such a demonstration of the superior power of the God the Spaniards worshipped. It is not hard to imagine then that the Indians accepted Christianity and submitted meekly to Spanish control.4 Although we live in an age of science, science has not eliminated fantasies about health; the stigmas of sickness and the moral meanings that they carry continue. Whereas people in previous centuries wove stories around leprosy, plague, and tuberculosis to create fear and guilt, the modern age has created similar taboos and mythologies about cancer and acquired immunodeficiency syndrome (AIDS). The myth of tuberculosis (TB) was that a person who suffered from it was of a melancholy, superior character— sensitive, creative, a being apart. Melancholy, or sadness, made one “interesting” or romantic. The general perception of TB as “romantic” was not just a literary device. It was a way of thinking that insinuated itself into the sensibilities and made it possible to ignore the social conditions, such as overcrowding and poor sanitation and nutrition, that helped breed tuberculosis. The infusion of beliefs into public awareness often is surreptitious. Just as tuberculosis often had been regarded sentimentally, as an enhancement of identity, cancer was regarded with irrational revulsion, as a diminution of the self.1 Current accounts of the psychological aspects of cancer often cite old authorities, starting with the Greek physician Galen, who observed that “melancholy women” are more likely to get breast cancer than “sanguine women.” Grief and anxiety were cited as causes of cancer, as well as personal losses. Public figures such as Napoleon, Ulysses S. Grant, Robert A. Taft, and Hubert Humphrey have all had their cancers diagnosed as the reaction to political defeat and the end to their political ambitions. Although distress can affect immunologic responsiveness, there is no scientific evidence to support the view that specific emotions, or emotions in general, can produce specific diseases—or that cancer is the result of a “cancer personality,” described as emotionally withdrawn, lacking self-confidence, and depressive. These disease mythologies contribute to the stigmatizing of certain illnesses and, by extension, of those who are ill. The beliefs about health and disease have the power to trap or empower people. They may inhibit people from seeking early treatment, diminish personal responsibility for practicing healthful behaviors, or encourage fear and social isolation. Conversely, they also can be the impetus for compassion to those who are ill, for commitment to

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improving one’s own health, and for support of efforts to improve the health status of others. In summary, what constitutes health and disease changes over time. Prehistoric times were marked by beliefs that angry gods or evil spirits caused ill health and disease. To cure the sick, the gods had to be pacified or the evil spirits driven from the body. Tribal healers, or priests, emerged to accomplish this task. Prehistoric healers used a myriad of treatments, including magic charms, spells, and incantations; surgical treatment; and plant medicines. Throughout history, the concept of health in a society has been shaped by its beliefs about life, death, and disease. Some beliefs and customs, such as exhibiting compassion for disabled community members, tend to safeguard human communities and increase the quality of life for all community members. Others invite and provoke disease outbreaks, such as myths about the causes of disease. Even though science and technology have advanced the understanding and treatment of disease, misconceptions and fantasies about disease still arise. In previous centuries, diseases such as leprosy, plague, and tuberculosis were fodder for taboos and mythologies; today, it is cancer and AIDS. The psychological effects of disease mythologies can be positive or negative. At their worst, they can stigmatize and isolate those who are ill; at their best, they can educate the community and improve the health of its members.

Health and Disease: A Historical Perspective After completing this section of the chapter, you should be able to meet the following objectives:

✦ Describe the contributions of the early Greek, Italian, and English scholars to the understanding of anatomy, physiology, and pathology ✦ State two important advances of the nineteenth century that helped to pave the way for prevention of disease ✦ State three significant advances of the twentieth century that have revolutionized diagnosis and treatment of disease ✦ Propose developments that will both hamper and contribute to the promotion of health and the elimination of disease in the twenty-first century

It has been said that those who do not know history are condemned to repeat it. There are many contributors to the understanding of how the body is constructed and how it works, and what disease is and how it can be treated, which in turn leads to an understanding of what health is and how can it be maintained. Much of what we take for granted in terms of treating the diseases that afflict humankind has had its origin in the past. Although they are seemingly small contributions in terms of today’s scientific advances, it is the knowledge

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produced by the great thinkers of the past that has made possible the many things we now take for granted.

THE INFLUENCE OF EARLY SCHOLARS Knowledge of anatomy, physiology, and pathology as we now know it began to emerge with the ancient Greeks. They were the first to recognize the distinction between internal and external causes of illness. To Hippocrates and his followers, we owe the foundations of the clinical principles and the ethics that grew into modern medical science. Hippocrates (460–377 BC) was a blend of scientist and artist. He believed that disease occurred when the four humors—blood from the heart, yellow bile from the liver, black bile from the spleen, and phlegm from the brain—became out of balance. These humors were said to govern character as well as health, producing phlegmatic, sanguine, choleric, and melancholic personalities. This belief paralleled the even older Chinese tradition, which was founded on the complementary principles of yin (female principle) and yang (male), whose correct proportions were essential for health. Hippocrates is identified with an approach to health that dictated plenty of healthy exercise, rest in illness, and a moderate, sober diet. It was Aristotle (384–322 BC) who, through his dissection of small animals and description of their internal

Hippocrates: A blend of scientist and scholar. (Courtesy of the National Library of Medicine)

anatomy, laid the foundations for the later scrutiny of the human body. For Aristotle, the heart was the most important organ. He believed it to be the center of the blood system as well as the center of the emotions. However, Aristotle’s main contributions were made to science in general. The person who took the next major step was Galen (AD 129–199), a physician to the emperors and gladiators of ancient Rome. Galen expanded on the Hippocratic doctrines and introduced experimentation into the study of healing. His work came to be regarded as the encyclopedia of anatomy and physiology. He demoted the heart—in his view, the liver was primary for venous blood, whereas the seat of all thought was the brain. He described the arteries and veins and even revealed the working of the nervous system by severing a pig’s spinal cord at different points and demonstrating that corresponding parts of the body became paralyzed. According to Galen, the body carried three kinds of blood that contained spirits charged by various organs: the veins carried “natural spirit” from the liver; the arteries, “vital spirit” from the lungs; the nerves, “animal spirit” from the brain. The heart merely warmed the blood. After Galen’s death, however, anatomic research ceased, and his work was considered infallible for almost 1400 years. As the great medical schools of universities reformed the teaching of anatomy in the early 1500s and integrated it into medical studies, it became apparent to anatomists that Galen’s data—taken from dogs, pigs, and apes—often were riddled with error. It was only with the work of Andreas Vesalius (1514–1564) that Galen’s ideas truly were challenged. Vesalius, professor of anatomy and surgery at Padua, Italy, dedicated a lifetime to the study of the human body. Vesalius carried out some unprecedentedly scrupulous dissections and used the latest in artistic techniques and printing for the more than 200 woodcuts in his De Humani Corporis Fabrica (“On the Fabric [Structure] of the Human Body”). He showed not only what bodily parts looked like but also how they worked. The book, published in 1543, set a new standard for the understanding of human anatomy. With this work, Vesalius became a leading figure in the revolt against Galen’s teachings. One of the most historically significant discoveries was made by William Harvey (1578–1657), an English physician and physiologist. He established that the blood circulates in a closed system impelled mechanically by a “pumplike” heart. He also measured the amount of blood in the circulatory system in any given unit of time—one of the first applications of quantitative methods in biology. Harvey’s work, published in On the Motion of the Heart and Blood in Animals (1628), provided a foundation of physiologic principles that led to an understanding of blood pressure and set the stage for innovative techniques such as cardiac catheterization. With the refinement of the microscope by the Dutch lens maker Anton van Leeuwenhoek (1632–1723), the stage was set for the era of cellular biology. Another early user of the microscope, English scientist Robert Hooke (1635–1703), published his Micrographia in 1665 in which

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William Harvey’s most eminent patient, King Charles I, and the future King Charles II look on as Harvey displays a dissected deer heart. (Courtesy of the National Library of Medicine)

he formally described the plant cells in cork and presented his theories of light and combustion and his studies of insect anatomy. His book presented the great potential of the microscope for biologic investigation. In it, he inaugurated the modern biologic usage of the word cell. A century later, German-born botanist Mathias Schleiden (1804–1881) and physiologist Theodor Schwann (1810–1882) observed that animal tissues also were composed of cells. Although Harvey contributed greatly to the understanding of anatomy and physiology, he was not interested in the chemistry of life. It was not until French chemist Antoine Lavoisier (1743–1794), who was schooled as a lawyer but devoted to scientific pursuits, overturned 100year-old theories of chemistry and established the basis of modern chemistry that new paths to examine body processes, such as metabolism, opened up. His restructured chemistry also gave scientists, including Louis Pasteur, the tools to develop organic chemistry. In 1796, Edward Jenner (1749–1823) conducted the first vaccination by injecting the fluid from a dairymaid’s cowpox lesion into a young boy’s arm. The vaccination by this English country doctor successfully protected the child from smallpox. Jenner’s discovery led to the development of vaccines to prevent many other diseases as well. Jenner’s classic experiment was the first officially recorded vaccination.

THE NINETEENTH CENTURY The nineteenth century was a time of spectacular leaps forward in the understanding of infectious diseases. For many centuries, rival epidemiologic theories associated disease and epidemics like cholera with poisonous fumes

Painting by Georges-Gaston Mélingue (1894). The first vaccination. Here Dr. Jenner introduces cowpox taken from dairymaid Sarah Nelmes (right) and introduces it into two incisions on the arm of James Phipps, a healthy 8-year-old boy. The boy developed cowpox, but not smallpox, when Jenner introduced the organism into his arm 48 days later. (Courtesy of the National Library of Medicine)

given off from dung heaps and decaying matter (poisons in the air, exuded from rotting animal and vegetable material, the soil, and standing water) or with contagion (person-to-person contact). In 1865, English surgeon Joseph Lister (1827–1912) concluded that microbes caused wound infections. He began to use carbolic acid on wounds to kill microbes and reduce infection after surgery. However, Lister was not alone in identifying hazards in the immediate environment as detrimental to health. English nurse Florence Nightingale (1820–1910) was a leading proponent of sanitation and hygiene as weapons against disease. It was at the English base at Scutari during the Crimean War (1854–1856) that Nightingale waged her battle. Arriving at the army hospital with a party of 38 nurses, Nightingale found nearly 2000 wounded and sick inhabiting foul, rat-infested wards. The war raged on, deluging the hospital with wounded as Nightingale not only organized the nursing care of the wounded but also provided meals, supplied bedding, and saw to the laundry. Within 6 months, she had brought about a transformation and slashed the death rate from approximately 40% to 2%.3

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Florence Nightingale caring for wounded at Scutari, Turkey, during the Crimean War. (Courtesy of the National Library of Medicine)

From the 1860s, the rise of bacteriology, associated especially with chemist and microbiologist Louis Pasteur in France and bacteriologist Robert Koch in Germany, established the role of microorganismal pathogens. Almost for the first time in medicine, bacteriology led directly to dramatic new cures. The technique of pasteurization is named after Louis Pasteur (1822–1895). He introduced the method in 1865 to prevent the souring of wine. Pasteur’s studies of fermentation convinced him that it depended on the presence of microscopic forms of life, with each fermenting medium serving as a unique food for a specific microorganism. He developed techniques for culturing microbes in liquid broths. Through his work, he was able to dispel the disease theory that predominated in the mid-nineteenth century, attributing fevers to “miasmas,” or fumes, and laid the foundation for the germ theory of disease. The anthrax bacillus, discovered by Robert Koch (1843–1910), was the first microorganism identified as a cause of illness. Koch’s trailblazing work also included identifying the organism responsible for tuberculosis and the discovery of a tuberculosis skin-testing material. In 1895, German physicist Wilhelm Röntgen (1845– 1923) discovered X rays. For the first time without a catastrophic event, the most hidden parts of a human body were revealed. Even though he understood that it was a significant discovery, Röntgen did not initially recognize the amazing diagnostic potential of the process he had discovered.

THE TWENTIETH CENTURY The twentieth century was a period of revolutionary industry in the science and politics of health. Concerns about the care of infants and children and the spread of infectious disease became prevailing themes in public and political arenas alike. It was during this time that private duty and public health nursing emerged as the means of delivering health care to people in their homes and in their communities. Social service agencies like the Henry Street Settlement in New York, founded by Lillian Wald, sent nurses into tenements to care for the sick.5 The placement of nurses in schools began in New York City in 1902 at the urging of Wald, who offered to supply a Henry Street nurse for 1 month without charge.5 Efforts to broaden the delivery of health care from the city to rural areas also were initiated during the early 1900s. The American Red Cross, which was reorganized and granted a new charter by Congress in 1905, established a nursing service for the rural poor that eventually expanded to serve the small town poor as well.5 Scientific discoveries and innovations abounded in the twentieth century. In the early 1900s, German bacteriologist Paul Ehrlich (1854–1915) theorized that certain substances could act as “magic bullets,” attacking disease-causing microbes but leaving the rest of the body undamaged. In 1910, he introduced his discovery: using the arsenic compound Salvarsan, he had found an effective weapon against syphilis. Through his work, Ehrlich launched the science of chemotherapy.

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The operating room. With the advent of anesthesia, knowledge of how microbes cause disease, and availability of incandescent lighting in the operating room, surgery became an option for treating disease. Rubber gloves had not yet been invented and the surgical team worked with bare hands to perform surgery. (Hahnemann Hospital, Chicago, IL. Courtesy Bette Clemons, Phoenix, AZ)

The first antibiotic was discovered in 1928 by English bacteriologist Sir Alexander Fleming (1881–1955). As he studied the relationship between bacteria and the mold Penicillium, he discovered its ability to kill staphylococci. However, it was not until the 1940s that later researchers, who were searching for substances produced by one microorganism that might kill other microorganisms, produced penicillin as a clinically useful antibiotic.

At the turn of the century, social service agencies like Henry Street Settlement in New York sent nurses into tenements to care for the sick. (Schorr T.M., Kennedy S.M. [1999]. 100 years of American nursing [p. 12]. Philadelphia: Lippincott Williams & Wilkins)

By the 1930s, innovative researchers had produced a cornucopia of new drugs that could be used to treat many of the most common illnesses that left their victims either severely disabled or dead. The medical community now had at its disposal medications such as digoxin to treat heart failure; sulfa drugs, which produced near-miraculous cures for infections such as scarlet fever; and insulin to treat diabetes.

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With the discovery of insulin, a once-fatal disease known from antiquity no longer carried a death sentence. Working together, Canadian physician Sir Frederick Banting (1891–1941) and physiologist Charles Best (1899–1978) isolated insulin from the pancreas of a dog in 1921. The extract, when given to diabetic dogs, restored their health. In January 1922, they successfully treated a young boy dying of diabetes with their pancreatic extracts. Although still incurable, it became possible to live with diabetes. One disease that remained not only incurable but untreatable through much of the twentieth century was tuberculosis. With no cure or preventive vaccine forthcoming, efforts at the turn of the century were dedicated to controlling the spread of tuberculosis. It was then that an alliance between organized medicine and the public resulted in the formation of voluntary local organizations to battle the disease. These organizations focused on education to counteract the fear of tuberculosis; at the same time, they warned against the disease. In 1904, the local organizations joined together to form a national organization, the National Association for the Study and Prevention of Tuberculosis. In 1918, the name was changed to the National Tuberculosis Association, which was renamed the American Lung Association in 1973.6 The national and local tuberculosis associations played a vital role in educating the public by running campaigns urging people to have skin tests and chest x-rays as a means of diagnosing tuberculosis. Once tuberculosis was diagnosed, an individual was likely to be sent to a sanatorium or tuberculosis hospital. There, good nourishment,

fresh air, and bed rest were prescribed in the belief that if the body’s natural defenses were strengthened, they would be able to overcome the tuberculosis bacillus. For almost half a century, this would be the prevailing treatment. It was not until 1945, with the introduction of chemotherapy, that streptomycin was used to treat tuberculosis. Outbreaks of poliomyelitis, which had increased in the early decades of the 1900s, served as the impetus for the work of American microbiologist Jonas Salk (1914–1995). At its peak, the virus was claiming 50,000 victims annually in the United States.3 Test trials of Salk’s vaccine with inactivated virus began in 1953, and it proved to prevent the development of polio. By 1955, the massive testing was complete, and the vaccine was quickly put into wide use. Surgical techniques also flourished during this time. A single technical innovation was responsible for opening up the last surgical frontier—the heart. Up to this time, the heart had been out of bounds; surgeons did not have the means to take over the function of the heart for long enough to get inside and operate.7 American surgeon John Gibbon (1903–1973) addressed this problem when he developed the heart-lung machine. Dramatic advances followed its successful use in 1953—probably none more so than the first successful heart transplantation performed in 1967 by South African surgeon Christiaan Barnard (1922–2001). For centuries, the inheritance of traits had been explained in religious or philosophical terms. Although English naturalist Charles Darwin’s (1809–1882) work dispelled long-held beliefs about inherited traits, it was Austrian bo-

A tuberculosis skin testing clinic. (Schorr T.M., Kennedy S.M. [1999]. 100 years of American nursing [p. 49]. Philadelphia: Lippincott Williams & Wilkins)

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The “iron lung,” which used negative pressure to draw air into the lungs, was used to provide ventilatory support for persons with “bulbar polio.” (Schorr T.M., Kennedy S.M. [1999]. 100 years of American nursing [p. 91]. Philadelphia: Lippincott Williams & Wilkins)

tanist Gregor Mendel’s (1822–1884) revolutionary theories on the segregation of traits, largely ignored until 1902, that laid the groundwork for establishing the chromosome as the structural unit of heredity. Many other scientists and researchers contributed to the storehouse of genetic knowledge. With the work by American geneticist James Watson (1928–) and British biophysicists Francis Crick (1916–) and Maurice Wilkins (1916–) in the early 1950s, which established the double-helical structure of DNA, the way to investigating and understanding our genetic heritage was opened. It is difficult, if not impossible, to single out all the landmark events of the twentieth century that contributed to the health of humankind. Among the other notable achievements are the development of kidney dialysis, oral contraceptives, transplant surgery, the computed axial tomography (CAT) scanner, and coronary angioplasty. Not all of the important advances in modern medicine are as dramatic as open-heart surgery. Often, they are the result of dogged work by many people and yield results only after a number of years, and then they frequently go unheralded. For example, vaccination programs, control of infectious diseases through improvements in sanitation of water and waste disposal, safer and healthier foods free from microbial contamination, identification of health risks from behaviors such as smoking, and improved prenatal care all have saved many lives in the twentieth century.

THE TWENTY-FIRST CENTURY The twenty-first century reveals new horizons, but also new problems. In greater numbers than ever, goods and people travel the world. There is unprecedented physical mobility—travel and migration from villages to cities and country to country—and interconnectedness. However, the benefits of physical mobility and interconnectedness

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are accompanied by risks. Diseases such as AIDS remind us that nothing is regional, local, or limited in its reach: contagious illness has a worldwide arena. The challenges of maintaining health and well-being in this global community are increasingly apparent. The inadvertent introduction of pathogens poses an unrelenting threat to public health, as does the deliberate use of microorganisms as weapons (see Chapter 18 for a discussion of bioterrorism and emerging global infectious diseases). In February 2003, the viral respiratory illness named severe acute respiratory syndrome (SARS) by the World Health Organization was first recognized in China.8 In the next few months, the illness swept through parts of Asia and spread to more than two dozen countries in North America, South America, and Europe. The disease was characterized by rapid onset and variable severity, ranging from mild illness to death. The prevention of SARS was a particular challenge because preventive interventions (e.g., vaccines and antibiotics) were unavailable. Containment became a global collaboration, with public health authorities utilizing isolation and quarantine to focus delivery of health care to people who were ill and to protect healthy people from getting sick. During the February to July outbreak, more than 8000 people worldwide became infected, and more than 900 died. Commerce also is an integral part of the growing world community, bringing goods and services once unobtainable into the global marketplace. Expanded international trade also provides the vehicle for the unwitting introduction or transmission of disease. One such instance occurred in the spring of 2003 in the United States.9 A multistate outbreak of human monkeypox, first identified in the Democratic Republic of the Congo in 1970, was traced by investigators to pet prairie dogs. The prairie dogs became infected when they were housed or transported along with infected Gambian giant rats, dormice, and rope squirrels that were part of a shipment of small mammals from Ghana. Spread of nonindigenous zoonotic pathogens to indigenous susceptible animal populations can be rapid and deadly. With such outbreaks lurks an additional danger—the potential for interspecies exchange, including between humans and animals such as pets. The widespread distribution of infected and potentially infected animals allowed epizootic spread of monkeypox through several states before effective interventions could be put into place. One of the challenges to the world health community will be to study the role of international travel and commerce in the emergence of infectious diseases through the dissemination of pathogens and their vectors throughout the world and then to develop long-term strategies of surveillance and intervention with the ultimate goal of curtailing their occurrence. In 1976, the World Health Organization (WHO) actually succeeded in eliminating smallpox from the face of the earth.10 This triumph gave substance to the idea that other infections, like measles, also might disappear if sufficient efforts were directed at worldwide campaigns to isolate and cure them. However, new infectious diseases, such as Lyme disease and Legionnaire’s disease, and new forms of old diseases, such as resistant strains of tuberculosis and malaria, have emerged and are readily spread

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worldwide. The powerful interventions used to fight these infections have had the unexpected effect of accelerating their biologic evolution and making them impervious to one after another form of chemical attack. Pathogens also can be introduced into the food chain and travel worldwide. The discovery that beef from cattle infected with bovine spongiform encephalopathy (BSE) may be the source of Creutzfeldt-Jakob disease led many countries to ban beef products from the United Kingdom when BSE was found to be prevalent in English herds. The introduction of such pathogens can be the result of ignorance, carelessness, or greed. Tobacco is a product that serves as a pathogen. In a quest for ever-increasing profits, the tobacco industry created a demand for its product by artificially raising the nicotine content of cigarettes so as to increase their addictive potential. This was done with the knowledge of the health risks of tobacco products, thanks to experiments conducted by the tobacco companies’ own medical scientists, but kept secret. If there is a blueprint for future advances, it is in the genes. The twenty-first century is destined to be dominated by advances in genetics. With the mapping of the human genome comes hope of cure for some of the most dreaded crippling and fatal diseases. The mapping of the human genome also has posed new ethical dilemmas, for with it comes the potential to predict the future health of persons based on their genes. It soon may be possible to differentiate between persons who will develop certain debilitating diseases and those who will not. Although advances in science and technology will continue to provide new treatments for many diseases, it has become apparent that there are more impressive rewards to be had by preventing diseases from becoming established in the first place. Ultimately, maintaining health is more resource conservative and cost effective than relying on the treatment of disease. Many decades ago, we learned that even though the “magic bullets” such as antibiotics had the ability to cure what was once considered incurable, much of our freedom from communicable disease is due to clean water, efficient sanitation, and good nutrition. We have become increasingly aware of the importance of preventive measures against noninfectious conditions, especially cancer and coronary heart disease. There is no better way to prevent disease and maintain health than by leading a healthy life, and increasingly, it will be the individual who is responsible for ensuring a healthy passage through life. In summary, Greek scholars were responsible for establishing the fundamentals of anatomy, physiology, and pathology that served as the earliest knowledge base for understanding health and disease. It was Hippocrates (460–377 BC) and his followers who laid the foundations of the clinical principles and ethics that grew into modern science. Although his belief that disease occurred when the four humors—blood, yellow and black bile, and phlegm—became out of balance was disproved, his approach to health that dictated plenty of healthy exercise, rest in illness, and a moderate, sober diet remains valid. Galen (AD 129–199) took the next major step, expand-

ing on Hippocratic doctrines and introducing experimentation into the study of healing. His work, gleaned through his role as physician to the emperors and gladiators of Rome and animal dissections, came to be regarded as the encyclopedia of anatomy and physiology and was considered infallible for almost 1400 years. Significant challenges to long-held beliefs began with the work of Andreas Vesalius (1514–1564), professor of anatomy and surgery at Padua, Italy. His published work, On the Fabric [Structure] of the Human Body, showing how the parts of the body looked and worked, set a new standard for the understanding of human anatomy. Other significant early contributions were made by scholars such as William Harvey (1578–1657), the English physician and physiologist, who in his book, On the Motion of the Heart and Blood in Animals, provided a physiologic framework for the circulation of blood; Anton van Leeuwenhoek (1632–1723), the Dutch lens maker who refined the microscope and set the stage for the era of cellular biology; and Edward Jenner (1749–1823), the English country physician who conducted the first successful vaccination. The nineteenth century was a time of major discoveries that paved the way for understanding infectious diseases. Significant contributions were made by such scientists as Joseph Lister, the English surgeon who concluded that microbes caused wound infections; German bacteriologist Robert Koch, who discovered the anthrax bacillus, thus identifying for the first time a microorganism and the illness it caused; and French chemist and microbiologist Louis Pasteur, who developed the technique of pasteurization. Perhaps the most notable technical innovation of the century was the discovery of X rays by German physicist Wilhelm Röntgen. The scientific undertakings and discoveries of the twentieth century were revolutionary. In 1910, Paul Ehrlich introduced chemotherapy, and in 1928, Sir Alexander Fleming discovered the first antibiotic as he studied the relationship between bacteria and the mold Penicillium. Diseases that had once been fatal or crippling were managed or prevented by new advances, such as the discovery of insulin by Sir Frederick Banting and Charles Best in 1922 and the development of the polio vaccine by Jonas Salk in 1953. Technical innovations set the stage for new surgical techniques. The creation of the heartlung machine by American surgeon John Gibbon paved the way for coronary bypass surgery and the first successful heart transplantation in 1967, which was performed by Christiaan Barnard, a South African surgeon. Other important advances included kidney dialysis, oral contraceptives, the CAT scanner, and coronary angioplasty. Public health programs also were responsible for greatly affecting the health of populations, such as those dedicated to increasing vaccination, improving sanitation of water and waste disposal, and identifying health risks. Knowledge about the influence of heredity on health and disease originated with Charles Darwin’s (1809–1882) evolutionary theories about inherited traits and with Gregor Mendel’s (1822–1884) theories on the segregation of traits, which laid the groundwork for establishing the chromosome as the structural unit of heredity. In the early 1950s, geneticist James Watson of the United States and British biophysicists Francis Crick and Maurice Wilkins presented their findings on the double-helical structure of DNA.

CHAPTER 1 The twenty-first century is predicted to be a time of great advances in the field of genetics, already evidenced by the substantial mapping of the human genome that has taken place. Scientists look to genetic research to provide advances that not only will predict who may develop disease but also will provide new treatments for those diseases. However promising future advances may appear, it is readily apparent that prevention is an equally important tool in maintaining health.

Perspectives on Health and Disease in Individuals After completing this section of the chapter, you should be able to meet the following objectives:

✦ State the World Health Organization definition of health ✦ Describe the function of adaptation as it relates to health and disease

✦ State a definition of pathophysiology ✦ Characterize the disease process in terms of etiology, pathogenesis, morphology, clinical manifestations, and prognosis ✦ Explain the meanings of reliability, validity, sensitivity, specificity, and predictive value as they relate to observations and tests used in the diagnosis of disease

What constitutes health and disease often is difficult to determine because of the way different people view the topic. What is defined as health is determined by many factors, including heredity, age and sex, cultural and ethnic differences, as well as individual, group, and governmental expectations.

HEALTH The World Health Organization (WHO) in 1948 defined health as a “state of complete physical, mental, and social well-being and not merely the absence of disease and infirmity.”10 Although ideal for many people, this was an unrealistic goal. At the World Health Assembly in 1977, representatives of the member governments of WHO agreed that their goal was to have all citizens of the world reach a level of health by the year 2000 that allows them to live a socially and economically productive life.10 The U.S. Department of Health and Human Services in Healthy People 2010 described the determinants of health as an interaction between an individual’s biology and behavior, physical and social environments, government policies and interventions, and access to quality health care.11

HEALTH AND DISEASE AS STATES OF ADAPTATION The ability of the body to adapt both physically and psychologically to the many stresses that occur in both health and disease is affected by a number of factors, including age, health status, psychosocial resources, and the rapidity

Concepts of Health and Disease

13

with which the need to adapt occurs (see Chapter 9). Generally speaking, adaptation affects the whole person. When adapting to stresses that are threats to health, the body uses those behaviors that are the most efficient and effective. It does not use long-term mechanisms when short-term adaptation is sufficient. The increase in heart rate that accompanies a febrile illness is a temporary response designed to deliver additional oxygen to tissues during the short period that the elevated temperature increases metabolic needs. On the other hand, hypertrophy of the left ventricle is a long-term adaptive response that occurs in persons with chronic hypertension. Adaptation is further affected by the availability of adaptive responses and the ability of the body to select the most appropriate response. The ability to adapt is dependent on the availability of adaptive responses—the greater number of available responses, the more effective the capacity to adapt. Adaptive capacity is decreased with extremes of age and with disease conditions that limit the availability of adaptive responses. The immaturity of the infant impairs the ability to adapt, as does the decline in functional reserve that occurs in the elderly. For example, infants have difficulty concentrating urine because of the immaturity of their renal tubular structures and therefore are less able than an older child or adult to cope with decreased water intake or exaggerated water losses. Similarly, persons with preexisting heart disease are less able to adapt to health problems that require recruitment of cardiovascular responses. Adaptation also is less effective when changes in health status occur suddenly rather than gradually. For instance, it is possible to lose a liter of blood through chronic gastrointestinal bleeding without developing signs of shock. On the other hand, a sudden hemorrhage that causes the loss of an equal amount of blood is apt to produce hypotension and circulatory shock. Even in advanced disease states, the body retains much of its adaptive capacity and is able to maintain the internal environment within relatively normal limits.

DISEASE The term pathophysiology, which is the focus of this book, may be defined as the physiology of altered health. The term combines the words pathology and physiology. Pathology (from the Greek pathos, meaning “disease”) deals with the study of the structural and functional changes in cells, tissues, and organs of the body that cause or are caused by disease. Physiology deals with the functions of the human body. Thus, pathophysiology deals not only with the cellular and organ changes that occur with disease but also with the effects that these changes have on total body function. Pathophysiology also focuses on the mechanisms of the underlying disease and provides the background for preventive as well as therapeutic health care measures and practices. A disease has been defined as any deviation from or interruption of the normal structure or function of a part, organ, or system of the body that is manifested by a characteristic set of symptoms or signs; the etiology, pathology, and prognosis may be known or unknown.12 The aspects

14

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Concepts of Health and Disease

of the disease process include the etiology, pathogenesis, morphologic changes, clinical manifestations, diagnosis, and clinical course.

ity, the progression from fatty streak to the occlusive vessel lesion seen in persons with coronary heart disease represents the pathogenesis of the disorder. The true etiology of atherosclerosis remains largely uncertain.

Etiology The causes of disease are known as etiologic factors. Among the recognized etiologic agents are biologic agents (e.g., bacteria, viruses), physical forces (e.g., trauma, burns, radiation), chemical agents (e.g., poisons, alcohol), and nutritional excesses or deficits. At the molecular level, it is important to distinguish between sick molecules and molecules that cause disease.13 This is true of diseases such as cystic fibrosis, sickle cell anemia, and familial hypercholesterolemia, in which genetic abnormality of a single amino acid, transporter molecule, or receptor protein produces widespread effects on health. Most disease-causing agents are nonspecific, and many different agents can cause disease of a single organ. For example, lung disease can result from trauma, infection, exposure to physical and chemical agents, or neoplasia. With severe lung involvement, each of these agents has the potential to cause respiratory failure. On the other hand, a single agent or traumatic event can lead to disease of a number of organs or systems. For example, severe circulatory shock can cause multiorgan failure. Although a disease agent can affect more than a single organ, and a number of disease agents can affect the same organ, most disease states do not have a single cause. Instead, most diseases are multifactorial in origin. This is particularly true of diseases such as cancer, heart disease, and diabetes. The multiple factors that predispose to a particular disease often are referred to as risk factors. One way to view the factors that cause disease is to group them into categories according to whether they were present at birth or acquired later in life. Congenital conditions are defects that are present at birth, although they may not be evident until later in life. Congenital malformation may be caused by genetic influences, environmental factors (e.g., viral infections in the mother, maternal drug use, irradiation, or intrauterine crowding), or a combination of genetic and environmental factors. Not all genetic disorders are evident at birth. Many genetic disorders, such as familial hypercholesterolemia and polycystic kidney disease, take years to develop. Acquired defects are those that are caused by events that occur after birth. These include injury, exposure to infectious agents, inadequate nutrition, lack of oxygen, inappropriate immune responses, and neoplasia. Many diseases are thought to be the result of a genetic predisposition and an environmental event or events that serve as a trigger to initiate disease development.

Pathogenesis Pathogenesis is the sequence of cellular and tissue events that take place from the time of initial contact with an etiologic agent until the ultimate expression of a disease. Etiology describes what sets the disease process in motion, and pathogenesis, how the disease process evolves. Although the two terms often are used interchangeably, their meanings are quite different. For example, atherosclerosis often is cited as the cause or etiology of coronary heart disease. In real-

Morphology Morphology refers to the fundamental structure or form of cells or tissues. Morphologic changes are concerned with both the gross anatomic and microscopic changes that are characteristic of a disease. Histology deals with the study of the cells and extracellular matrix of body tissues. The most common method used in the study of tissues is the preparation of histologic sections that can be studied with the aid of a microscope. Because tissues and organs usually are too thick to be examined under a microscope, they must be sectioned to obtain thin, translucent sections. Histologic sections play an important role in the diagnosis of many types of cancer. A lesion represents a pathologic or traumatic discontinuity of a body organ or tissue. Descriptions of lesion size and characteristics often can be obtained through the use of radiographs, ultrasonography, and other imaging methods. Lesions also may be sampled by biopsy and the tissue samples subjected to histologic study.

Clinical Manifestations Disease can be manifest in a number of ways. Sometimes, the condition produces manifestations, such as fever, that make it evident that the person is sick. Other diseases are silent at the onset and are detected during examination for other purposes or after the disease is far advanced. Signs and symptoms are terms used to describe the structural and functional changes that accompany a disease. A symptom is a subjective complaint that is noted by the person with a disorder, whereas a sign is a manifestation that is noted by an observer. Pain, difficulty in breathing, and dizziness are symptoms of a disease. An elevated temperature, a swollen extremity, and changes in pupil size are objective signs that can be observed by someone other than the person with the disease. Signs and symptoms may be related to the primary disorder, or they may represent the body’s attempt to compensate for the altered function caused by the pathologic condition. Many pathologic states are not observed directly—one cannot see a sick heart or a failing kidney. Instead, what can be observed is the body’s attempt to compensate for changes in function brought about by the disease, such as the tachycardia that accompanies blood loss or the increased respiratory rate that occurs with pneumonia. It is important to recognize that a single sign or symptom may be associated with a number of different disease states. For example, an elevated temperature can indicate the presence of an infection, heat stroke, brain tumor, or any number of other disorders. A differential diagnosis that describes the origin of a disorder usually requires information regarding a number of signs and symptoms. For example, the presence of fever, a reddened sore throat, and positive throat culture describe a “strep throat” infection. A syndrome is a compilation of signs and symptoms (e.g., chronic fatigue syndrome) that are characteristic of a specific disease state. Complications are possible adverse ex-

CHAPTER 1

tensions of a disease or outcomes from treatment. Sequelae are lesions or impairments that follow or are caused by a disease.

Diagnosis A diagnosis is the designation as to the nature or cause of a health problem (e.g., bacterial pneumonia or hemorrhagic stroke). The diagnostic process usually requires a careful history and physical examination. The history is used to obtain a person’s account of his or her symptoms, their progression, and the factors that contribute to a diagnosis. The physical examination is done to observe for signs of altered body structure or function. The development of a diagnosis involves weighing competing possibilities and selecting the most likely one from among the conditions that might be responsible for the person’s clinical presentation. The clinical probability of a given disease in a person of a given age, sex, race, lifestyle, and locality often is influential in arriving at a presumptive diagnosis. Laboratory tests, radiologic studies, CT scans, and other tests often are used to confirm a diagnosis.

Normality. An important factor when interpreting diagnostic test results is the determination of whether they are normal or abnormal. Is a blood count above normal, within the normal range, or below normal? Normality usually determines whether further tests are needed or if interventions are necessary. What is termed a normal value for a laboratory test is established statistically from test results obtained from a selected sample of people. The normal values refer to the 95% distribution (mean plus or minus two standard deviations [mean ± 2 SD]) of test results for the reference population.14 Thus, the normal levels for serum sodium (135 to 145 mEq/L) represent the mean serum level for the reference population ± 2 SD. The normal values for some laboratory tests are adjusted for sex or age. For example, the normal hemoglobin range for women is 12.0 to 16.0 g/dL and for men, 14.0 to 17.4 g/dL.15 Serum creatinine level often is adjusted for age in the elderly (see Chapter 36), and normal values for serum phosphate differ between adults and children. Reliability, Validity, Sensitivity, Specificity, and Predictive Value. The quality of data on which a diagnosis is based may be judged for its reliability, validity, sensitivity, specificity, and predictive value.16,17 Reliability refers to the extent to which an observation, if repeated, gives the same result. A poorly calibrated blood pressure machine may give inconsistent measurements of blood pressure, particularly of pressures in either the high or low range. Reliability also depends on the persons making the measurements. For example, blood pressure measurements may vary from one observer to another because of the technique that is used (e.g., different observers may deflate the cuff at a different rate, thus obtaining different values), the way the numbers on the manometer are read, or differences in hearing acuity. Validity refers to the extent to which a measurement tool measures what it is intended to measure. This often is assessed by comparing a measurement method with the best possible method of measure that is available. For example, the validity of blood pressure measurements ob-

Concepts of Health and Disease

15

tained by a sphygmomanometer might be compared with those obtained by intraarterial measurements. Measures of sensitivity and specificity are concerned with determining how well the test or observation identifies people with the disease and people without the disease. Sensitivity refers to the proportion of people with a disease who are positive for that disease on a given test or observation (called a true-positive result). Specificity refers to the proportion of people without the disease who are negative on a given test or observation (called a true-negative result). A test that is 95% specific correctly identifies 95 of 100 normal people. The other 5% are false-positive results. A false-positive test result, particularly for conditions such as human immunodeficiency virus (HIV) infection, can be unduly stressful for the person being tested (see Chapter 22). In the case of HIV testing, a positive result on the initial antibody test is followed up with a more sensitive test. On the other hand, false-negative test results in conditions such as cancer can delay diagnosis and jeopardize the outcome of treatment. Predictive value is the extent to which an observation or test result is able to predict the presence of a given disease or condition. A positive predictive value refers to the proportion of true-positive results that occurs in a given population. In a group of women found to have “suspect breast nodules” in a cancer-screening program, the proportion later determined to have breast cancer would constitute the positive predictive value. A negative predictive value refers to the true-negative observations in a population. In a screening test for breast cancer, the negative predictive value represents the proportion of women without suspect nodules who do not have breast cancer. Although predictive values rely in part on sensitivity and specificity, they depend more heavily on the prevalence of the condition in the population. Despite unchanging sensitivity and specificity, the positive predictive value of an observation rises with prevalence, whereas the negative predictive value falls.

Clinical Course The clinical course describes the evolution of a disease. A disease can have an acute, subacute, or chronic course. An acute disorder is one that is relatively severe, but selflimiting. Chronic disease implies a continuous, long-term process. A chronic disease can run a continuous course, or it can present with exacerbations (aggravation of symptoms and severity of the disease) and remissions (a period during which there is a lessening of severity and a decrease in symptoms). Subacute disease is intermediate or between acute and chronic: it is not as severe as an acute disease and not as prolonged as a chronic disease. The spectrum of disease severity for infectious diseases such as hepatitis B can range from preclinical to persistent chronic infection. During the preclinical stage, the disease is not clinically evident but is destined to progress to clinical disease. As with hepatitis B, it is possible to transmit the virus during the preclinical stage. Subclinical disease is not clinically apparent and is not destined to become clinically apparent. It is diagnosed with antibody or culture tests. Most cases of tuberculosis are not clinically apparent, and evidence of their presence is established by skin tests.

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Concepts of Health and Disease

Clinical disease is manifested by signs and symptoms. A persistent chronic infectious disease persists for years, sometimes for life. Carrier status refers to an individual who harbors an organism but is not infected, as evidenced by antibody response or clinical manifestations. This person still can infect others. Carrier status may be of limited duration, or it may be chronic, lasting for months or years. In summary, health is determined by many factors, including genetics, age and sex, and cultural and ethnic differences. The WHO defines health as a “state of complete physical, mental, and social well-being and not merely the absence of disease and infirmity.” The ability of the body to adapt to changes that occur in both health and disease is affected by such factors as age, health status, and psychosocial resources. Adaptation is further affected by the availability and number of adaptive responses. Extreme age and disease conditions, such as when changes occur suddenly rather than gradually, also affect the capacity to adapt. The term pathophysiology may be defined as the physiology of altered health. A disease has been defined as any deviation from or interruption of the normal structure or function of any part, organ, or system of the body that is manifested by a characteristic set of symptoms or signs and whose etiology, pathology, and prognosis may be known or unknown. The causes of disease are known as etiologic factors. Recognized etiologic agents include biologic agents (bacteria, viruses), physical forces (trauma, burns, radiation), chemical agents (poisons, alcohol), and nutritional excesses or deficits. Pathogenesis describes how the disease process evolves. Morphology refers to the structure or form of cells or tissues; morphologic changes are changes in structure or form that are characteristic of a disease. Disease can manifest itself through signs and symptoms. A symptom is a subjective complaint, such as pain or dizziness; a sign is an observable manifestation, such as an elevated temperature or a reddened sore throat. A syndrome is a compilation of signs and symptoms that are characteristic of a specific disease state. The clinical course of a disease describes its evolution. It can be acute (relatively severe, but self-limiting), chronic (continuous or episodic, but taking place over a long period), or subacute (not as severe as acute or as prolonged as chronic). Within the disease spectrum, a disease can be designated preclinical, or not clinically evident; subclinical, not clinically apparent and not destined to become clinically apparent; or clinical, characterized by signs and symptoms.

Perspectives on Health and Disease in Populations After completing this section of the chapter, you should be able to meet the following objectives:

✦ Define the term epidemiology ✦ Compare the meaning of the terms incidence and prevalence as they relate to measures of disease frequency

✦ Compare the sources of information and limitations of mortality and morbidity statistics

✦ Characterize the natural history of a disease ✦ Differentiate primary, secondary, and tertiary levels of prevention

✦ Propose ways in which practice guidelines can be used to improve health care

The health of individuals is closely linked to the health of the community and to the population it encompasses. The ability to traverse continents in a matter of hours has opened the world to issues of populations at a global level. Diseases that once were confined to local areas of the world now pose a threat to populations throughout the world. As we move through the twenty-first century, we are continually reminded that the health care system and the services it delivers are targeted to particular populations. Managed care systems are focused on a population-based approach to planning, delivering, providing, and evaluating health care. The focus of health care also has begun to emerge as a partnership in which individuals are asked to assume greater responsibility for their own health.

EPIDEMIOLOGY AND PATTERNS OF DISEASE Epidemiology is the study of disease in populations. It was initially developed to explain the spread of infectious diseases during epidemics and has emerged as a science to study risk factors for multifactorial diseases, such as heart disease and cancer. Epidemiology looks for patterns, such as age, race, dietary habits, lifestyle, or geographic location of persons affected with a particular disorder. In contrast to biomedical researchers, who seek to elucidate the mechanisms of disease production, epidemiologists are more concerned with whether something happens than how it happens.18 For example, the epidemiologist is more concerned with whether smoking itself is related to cardiovascular disease and whether the risk for heart disease decreases when smoking ceases. On the other hand, the biomedical researcher is more concerned about the causative agent in cigarette smoke and the pathway by which it contributes to heart disease. Much of our knowledge about disease comes from epidemiologic studies. Epidemiologic methods are used to determine how a disease is spread, how to control it, how to prevent it, and how to eliminate it. Epidemiologic methods also are used to study the natural history of disease, to evaluate new preventative and treatment strategies, to explore the impact of different patterns of health care delivery, and to predict future health care needs. As such, epidemiologic studies serve as a basis for clinical decision making, allocation of health care dollars, and development of policies related to public health issues.

Prevalence and Incidence Measures of disease frequency are an important aspect of epidemiology. They establish a means for predicting what diseases are present in a population and provide an indication of the rate at which they are increasing or decreas-

CHAPTER 1

ing. A disease case can be either an existing case or the number of new episodes of a particular illness that is diagnosed within a given period. Incidence is the number of new cases arising in a population during a specified time. It is determined by dividing the number of new cases of a disease by the population at risk for development of the disease during the same period. Prevalence is the number of people in a population who have a particular disease at a given point in time or period. It is determined by dividing the existing number of cases by the population at risk for development of the disorder during the same period. Incidence and prevalence rates always are reported as proportions (e.g., cases per 100 or cases per 100,000).

Morbidity and Mortality Morbidity and mortality statistics provide information about the functional effects (morbidity) and deathproducing (mortality) characteristics of a disease. These statistics are useful in terms of anticipating health care needs, planning of public education programs, directing health research efforts, and allocating health care dollars. Mortality or death statistics provide information about the trends in the health of a population. In most countries, people are legally required to record certain facts such as age, sex, and cause of death on a death certificate. Internationally agreed classification procedures (the International Classification of Diseases by the WHO) are used for coding the cause of death, and the data are expressed as death rates.10 Crude mortality rates (i.e., number of deaths in a given period) do not account for age, sex, race, socioeconomic status, and other factors. For this reason, mortality often is expressed as death rates for a specific population, such as the infant mortality rate. Mortality also can be described in terms of the leading causes of death according to age, sex,

17

Concepts of Health and Disease

race, and ethnicity. Among all persons 65 years of age and older, the five leading causes of death in the United States are heart disease, cancer, stroke, chronic obstructive lung disease, and pneumonia and influenza9 (Fig. 1-1). In 1997, for example, diabetes was the third leading cause of death among American Indians 65 years of age and older, the fourth leading cause of death among older Hispanic and black persons, and the sixth leading cause of death among older white persons and Asian Americans.11 Morbidity describes the effects an illness has on a person’s life. Many diseases, such as arthritis, have low death rates but have a significant impact on a person’s life. Morbidity is concerned not only with the occurrence or incidence of a disease but also with persistence and the long-term consequences of the disease.

DETERMINATION OF RISK FACTORS Conditions suspected of contributing to the development of a disease are called risk factors. They may be inherent to the person (high blood pressure or overweight) or external (smoking or drinking alcohol). There are different types of studies used to determine risk factors, including crosssectional studies, case-control studies, and cohort studies. Cross-sectional studies use the simultaneous collection of information necessary for classification of exposure and outcome status. They can be used to compare the prevalence of a disease in those with the factor (or exposure) with the prevalence of a disease in those who are unexposed to the factor, such as the prevalence of coronary heart disease in smokers and nonsmokers. Case-control studies are designed to compare persons known to have the outcome of interest (cases) and those known not to have

10 Leading Causes of Death, 1997 Heart Disease

10 Leading Causes of Death, 1900*

31.4%

Cancer

Pneumonia

23.3%

Stroke Chronic Obstructive Pulmonary Disease Unintentional Injuries

Tuberculosis

6.9%

5.2%

Injuries

2.7%

Suicide

1.3%

Cancer

Kidney Disease Chronic Liver Disease and Cirrhosis

1.1%

Senility

1.1%

Diphtheria

5

6.2%

Liver Disease

3.7%

0

8.3%

Heart Disease

4.1%

Diabetes

11.3%

Diarrhea and enteritis

4.7%

Pneumonia/Influenza

11.8%

10

15

20

25

Percent of all deaths

30

35

4.2% 3.7% 2.9% 2.3%

0

5

10

15

20

25

Percent of all deaths

* Not all States are represented. FIGURE 1-1 The 10 leading causes of death as a percentage of deaths in the United States, 1900 and 1997. (U.S. Department of Health and Human Services. [2000]. Healthy people 2010. Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System. [Unpublished data, 1997.] Accessible at http://web.health.gov/healthypeople/)

30

35

18

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Concepts of Health and Disease

the outcome of interest (control). Information on exposures or characteristics of interest is then collected from persons in both groups. For example, the characteristics of maternal alcohol consumption in infants born with fetal alcohol syndrome (cases) can be compared with those in infants born without the syndrome (control). A cohort is a group of persons who were born at approximately the same time or share some characteristics of interest. Persons enrolled in a cohort study (also called a longitudinal study) are followed over a period to observe some health outcome. A cohort may consist of a single group of persons chosen because they have or have not been exposed to suspected risk factors; two groups specifically selected because one has been exposed and the other has not; or a single exposed group in which the results are compared with the general population. The Framingham Study, which examined the characteristics of people who would later experience coronary heart disease, and the Nurses’ Health Study, which initially explored the relationship between oral contraceptives and breast cancer, are two well-known cohort studies.

CHART 1-1 Framingham Study: Significant Milestones

• 1960—Cigarette smoking found to increase risk of heart disease

• 1961—Cholesterol level, blood pressure, and • • • • • • •

The Framingham Study

•

One of the best-known examples of a cohort study is the Framingham Study, which was carried out in Framingham, Massachusetts.19 Framingham was selected because of the size of the population, the relative ease with which the people could be contacted, and the stability of the population in terms of moving into and out of the area. This longitudinal study, which began in 1950, was set up by the U.S. Public Health Service to study the characteristics of people who would later develop coronary heart disease. The study consisted of 5000 persons, aged 30 to 59 years, selected at random and followed for an initial period of 20 years, during which time it was predicted that 1500 of them would develop coronary heart disease. The advantage of such a study is that it can study a number of risk factors at the same time and determine the relative importance of each. Another advantage is that the risk factors can be related later to other diseases such as stroke. Chart 1-1 describes some of the significant milestones from the Framingham Study.

•

The Nurses’ Health Study A second well-known cohort study is the Nurses’ Health Study, which was developed by Harvard University and Brigham and Women’s Hospital. The study began in 1976 with a cohort of 121,700 female nurses, 30 to 55 years of age, living in the United States.20 Initially designed to explore the relationship between oral contraceptives and breast cancer, nurses in the study have provided answers to detailed questions about their menstrual cycle, smoking habits, diet, weight and waist measurements, activity patterns, health problems, and medication use. They have collected urine and blood samples and even provided researchers with their toenail clippings.21 In selecting the cohort, it was reasoned that nurses would be well organized, accurate, and observant in their responses and that physiologically they would be no different from other groups of women. It also was anticipated that their childbearing,

•

electrocardiogram abnormalities found to increase risk of heart disease 1967—Physical activity found to reduce risk of heart disease and obesity to increase risk of heart disease 1970—High blood pressure found to increase risk of stroke 1976—Menopause found to increase risk of heart disease 1977—Effects of triglycerides and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol noted 1978—Psychosocial factors found to affect heart disease 1986—First report on dementia 1988—High levels of HDL cholesterol found to reduce risk of death 1994—Enlarged left ventricle shown to increase risk of stroke 1996—Progression from hypertension to heart failure described 1997—Report of cumulative effects of smoking and high cholesterol on the risk of atherosclerosis

(Abstracted from Framingham Heart Study. [2001]. Research milestones. [On-line.] Available: http://rover.nhlbi.nih.gov/ about/framingham/timeline.htm.)

eating, and smoking patterns would be similar to those of other working women. The Nurses’ Health Study has yielded over 250 published papers on subjects as diverse as body mass index, weight change, and risk for adult-onset asthma in women22; smoking cessation and time course to decreased risk for coronary heart disease in middle-aged women23; electric blanket use and breast cancer24; waist circumference, waist⬊hip ratio, and risk for breast cancer25; and aspirin and risk for colorectal cancer.26 After 25 years, 90% of the nurses still respond promptly to the biennial questionnaire—a rate that far exceeds the average for other longitudinal studies.

NATURAL HISTORY The natural history of disease refers to the progression and projected outcome of a disease without medical intervention. By studying the patterns of a disease over time in populations, epidemiologists can better understand its natural history. A knowledge of the natural history can be used to determine disease outcome, establish priorities for health care services, determine the effects of screening and early detection programs on disease outcome, and compare the results of new treatments with the expected outcome without treatment.

CHAPTER 1

There are some diseases for which there are no effective treatment methods available, or the current treatment measures are effective only in certain people. In this case, the natural history of the disease can be used as a predictor of outcome. For example, the natural history of hepatitis C indicates that 80% of people who become infected with the virus fail to clear the virus and progress to chronic infection.27 Information about the natural history of a disease and the availability of effective treatment methods provides directions for preventive measures. In the case of hepatitis C, careful screening of blood donations and education of intravenous drug abusers can be used to prevent transfer of the virus. At the same time, scientists are striving to develop a vaccine that will prevent infection in persons exposed to the virus. The development of vaccines to prevent the spread of infectious diseases such as polio and hepatitis B undoubtedly has been motivated by knowledge about the natural history of these diseases and the lack of effective intervention measures. With other diseases, such as breast cancer, early detection through use of breast selfexamination and mammography increases the chances for a cure. Prognosis refers to the probable outcome and prospect of recovery from a disease. It can be designated as chances for full recovery, possibility of complications, or anticipated survival time. Prognosis often is presented in relation to treatment options—that is, the expected outcomes or chances for survival with or without a certain type of treatment. The prognosis associated with a given type of treatment usually is presented along with the risk associated with the treatment.

LEVELS OF PREVENTION Basically, leading a healthy life contributes to the prevention of disease. There are three fundamental types of prevention: primary prevention, secondary prevention, and tertiary prevention28 (Chart 1-2). Primary prevention is directed at keeping disease from occurring by removing all risk factors. Immunizations are examples of primary prevention. Secondary prevention detects disease early when it is still asymptomatic and treatment measures can affect a cure. The use of a Papanicolaou (Pap) smear for early detection of cervical cancer is an example of secondary prevention. Tertiary prevention is directed at clinical interventions that prevent further deterioration or reduce the complications of a

CHART 1-2 Levels of Prevention

• Primary prevention: Actions aimed at prevention of disease

• Secondary prevention: Actions aimed at early detection and prompt treatment of disease

• Tertiary prevention: Treatment and rehabilitation measures aimed at preventing further progress of the disease

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disease once it has been diagnosed. An example is the use of β-adrenergic drugs to reduce the risk for death in persons who have had a heart attack. Tertiary prevention measures also include measures to limit physical impairment and social consequences of an illness. Primary prevention often is accomplished outside the health care system. Chlorination and fluoridation of water supplies and laws that mandate seat belt use are examples of community-wide primary prevention. There are fewer community-wide efforts directed at secondary prevention, and those that are available usually do not involve the entire community. Examples include breast self-examination education programs and blood pressure screening programs. Nevertheless, many health care clinics are becoming increasingly devoted to primary and secondary prevention through such activities as prenatal and well-child care, immunizations, lifestyle counseling, and screening for early disease detection or risk factors. There are many fewer tertiary prevention efforts outside the health care system.

EVIDENCE-BASED PRACTICE AND PRACTICE GUIDELINES Evidence-based practice and evidence-based practice guidelines have recently gained popularity with clinicians, public health practitioners, health care organizations, and the public as a means of improving the quality and efficiency of health care.29,30 Their development has been prompted, at least in part, by the enormous amounts of published information about diagnostic and treatment measures for various disease conditions as well as demands for better and more cost-effective health care. Evidence-based practice has been defined as “the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients.”29 It is based on the integration of the individual expertise of the practitioner with the best external clinical evidence from systematic research.29 The term clinical expertise implies the proficiency and judgment that individual clinicians gain through clinical experience and clinical practice. The best external clinical evidence relies on the identification of clinically relevant research, often from the basic sciences, but especially from patient-centered clinical studies that focus on the accuracy and precision of diagnostic tests and methods, the power of prognostic indicators, and the effectiveness and safety of therapeutic, rehabilitative, and preventive regimens. Clinical practice guidelines are systematically developed statements intended to inform practitioners and clients in making decisions about health care for specific clinical circumstances.31,32 They not only should review various outcomes but also must weigh various outcomes, both positive and negative, and make recommendations. Guidelines are different from systematic reviews. They can take the form of algorithms, which are step-by-step methods for solving a problem, written directives for care, or a combination thereof. The development of evidence-based practice guidelines often uses methods such as meta-analysis to combine evidence from different studies to produce a more precise

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estimate of the accuracy of a diagnostic method or the effects of an intervention method.33 It also requires review: by practitioners with expertise in clinical content, who can verify the completeness of the literature review and ensure clinical sensibility; by experts in guideline development who can examine the method by which the guideline was developed; and by potential users of the guideline.31 Once developed, practice guidelines must be continually reviewed and changed to keep pace with new research findings and with new diagnostic and treatment methods. For example, the Guidelines for the Prevention, Evaluation, and Treatment of High Blood Pressure (see Chapter 25), first developed in 1972 by the Joint National Committee, have been revised seven times, and the Guidelines for the Diagnosis and Management of Asthma (see Chapter 31), first developed in 1991 by the Expert Panel, have undergone three revisions. Evidence-based practice guidelines, which are intended to direct client care, are also important in directing research into the best methods of diagnosing and treating specific health problems. This is because health care providers use the same criteria for diagnosing the extent and severity of a particular condition such as hypertension and because they use the same protocols for treatment. In summary, the health of individuals is closely linked to the health of the community and to the population it encompasses. Epidemiology is the study of disease in populations. It looks for patterns such as age, race, and dietary habits of persons who are affected with a particular disorder to determine under what circumstances the particular disorder will occur. Using epidemiologic methods, researchers determine how a disease is spread, how to control it, how to prevent it, and how to eliminate it. Epidemiologists use measures of disease frequency to predict what diseases are present in a population and as an indication of the rate at which they are increasing or decreasing. Incidence is the number of new cases arising in a population during a specified time. Prevalence is the number of people in a population who have a particular disease at a given point in time or period. Morbidity and mortality provide epidemiologists with information about the functional effects and death-producing characteristics of a disease. Mortality or death statistics provide information about the trends in the health of a population. Morbidity describes the effects an illness has on a person’s life. It is concerned with the incidence of disease as well as its persistence and long-term consequences. Conditions suspected of contributing to the development of a disease are called risk factors. They may be inherent to a person (high blood pressure) or external (smoking). Studies used to determine risk factors include cross-sectional studies, case-control studies, and cohort studies. Cross-sectional studies use the simultaneous collection of information necessary for classification of exposure and outcome status. Case-control studies are designed to compare subjects who are known to have the outcome of interest (cases) with those who are known not to have the outcome of interest (control). Cohort studies involve groups of persons who were born at approximately

the same time or share some characteristic of interest. The Framingham Study, which examined the characteristics of people in whom coronary heart disease would later develop, and the Nurses’ Health Study, which initially explored the relationship between oral contraceptives and breast cancer, are two well-known cohort studies. The natural history of disease refers to the progression and projected outcome of a disease without medical intervention. It can be used to determine disease outcome, establish priorities for health care services, provide direction for prevention and early detection programs, and compare treatment methods and their outcomes with untreated outcomes. Prognosis is the term used to designate the probable outcome and prospect of recovery from a disease. The three fundamental types of prevention are primary prevention, secondary prevention, and tertiary prevention. Primary prevention, such as immunizations, is directed at removing risk factors so that disease does not occur. Secondary prevention, such as a Pap smear, detects disease when it still is asymptomatic and curable with treatment. Tertiary prevention, such as β-adrenergic drugs to reduce the risk for death in persons who have had a heart attack, focuses on clinical interventions that prevent further deterioration or reduce the complications of a disease. Evidence-based practice and evidence-based practice guidelines are mechanisms that use the current best evidence to make decisions about the health care of individuals. They are based on the expertise of the individual practitioner integrated with the best clinical evidence from systematic review of credible research studies. Practice guidelines may take the form of algorithms, which are step-by-step methods for solving a problem, written directives, or a combination thereof.

References 1. Sontag S. (1990). Illness as metaphor. New York: Doubleday, Anchor Books. 2. James P., Thorpe N. (1995). Ancient inventions. New York: Random House, Ballantine Books. 3. Porter R. (1998). The greatest benefit to mankind: A medical history of humanity. New York: W.W. Norton & Company. 4. McNeill W.H. (1998). Plagues and peoples. New York: Doubleday, Anchor Books. 5. Schorr T.M., Kennedy M.S. (1999). 100 Years of American nursing. Philadelphia: Lippincott Williams & Wilkins. 6. American Lung Association. (1982, March). From Koch to today. American Lung Association Bulletin 68, 2–3. 7. Le Fanu J. (2000). The rise and fall of modern medicine. New York: Carroll & Graf. 8. CDC. (2003). Update: Severe acute respiratory syndrome– worldwide and United States, 2003. MMWR Morbidity and Mortality Weekly Report 52, 664–665. 9. CDC. (2003). Multistate outbreak of monkeypox: Illinois, Indiana, and Wisconsin, 2003. MMWR Morbidity and Mortality Weekly Report 52, 537–540. 10. World Health Organization. (2001). About WHO: Definition of health; disease eradication/elimination goals. [On-line.] Available: http://www.int/aboutwho/en/history/htm. Accessed February 19, 2004.

CHAPTER 1 11. U.S. Department of Health and Human Services. (2000). Healthy people 2010. National Health Information Center. [On-line.] Available: http://www.healthypeople./gov. 12. Dorland’s illustrated medical dictionary (29th ed., p. 511). (2000). Philadelphia: W.B. Saunders. 13. Waldenstrom J. (1989). Sick molecules and our concepts of illness. Journal of Internal Medicine 225, 221–227. 14. Brigden M.L., Heathcote J.C. (2000). Problems with interpreting laboratory tests. Postgraduate Medicine 107(7), 145–162. 15. Fischbach F. (2004). A manual of laboratory and diagnostic tests (6th ed., p. 74). Philadelphia: Lippincott Williams & Wilkins. 16. Bickley L. (2003). Bates’ guide to physical assessment and history taking (7th ed., pp. 783–802). Philadelphia: Lippincott Williams & Wilkins. 17. Dawson-Saunders B., Trapp R.G. (1990). Evaluating diagnostic procedures. In Dawson-Saunders B., Trapp R.G. (Eds.), Basic and clinical biostatistics (pp. 229–244). Norwalk, CT: Appleton & Lange. 18. Vetter N., Mathews I. (1999). Epidemiology and public health maintenance. Edinburgh: Churchill Livingstone. 19. Framingham Heart Study. (2001). Framingham Heart Study: Design, rationale, objectives, and research milestones. [On-line.] Available: http://www.nhlbi.nih.gov/about/framingham/ design.htm. Accessed February 19, 2004. 20. Channing Laboratory. (2004). Nurses health study. [On-line]. Available: http://www.channing.harvard.edu/nhs/hist.html. Accessed February 19, 2004. 21. Garland M., Morris J.S., Stamfer M.J., et al. (1995). Prospective study of toenail selenium levels and cancer among women. Journal of the National Cancer Institute 87, 497–505. 22. Carmago C.A., Weiss S.T., Zhang S., et al. (1999). Prospective study of body mass index, weight gain, and risk of adult-

23.

24.

25.

26.

27.

28. 29. 30. 31. 32.

33.

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onset asthma in women. Archives of Internal Medicine 159, 2582–2588. Kawachi I., Colditz G.A., Stamfer M.J., et al. (1994). Smoking cessation and time course of decreased risks of coronary heart disease in middle-aged women. Archives of Internal Medicine 154, 169–175. Laden F., Neas L.M., Tolbert P.E., et al. (2000). Electric blanket use and breast cancer in the Nurses’ Health Study. American Journal of Epidemiology 152, 41–49. Huang Z., Willett W.C., Colditz G.A., et al. (1999). Waist circumference, waist:hip ratio, and risk of breast cancer in the Nurses’ Health Study. American Journal of Epidemiology 150, 1316–1324. Giovannucci E., Egan K.M., Hunter D.J., et al. (1995). Aspirin and the risk of colorectal cancer in women. New England Journal of Medicine 333, 609–614. Liang J., Reherman B., Seeff L.B., et al. (2000). Pathogenesis, natural history, treatment, and prevention of hepatitis C. Annals of Internal Medicine 132, 296–305. Stanhope M., Lancaster J. (2000). Community and public health nursing (5th ed., p. 43). St. Louis: Mosby. Sackett D.L. (1996). Evidence based medicine: What it is and what it isn’t. British Medical Journal 312, 71–72. Youngblut J.M., Brooten D. (2001). Evidence-based practice: Why is it important. AACN Clinical Issues 12, 468–475. Shekelle P.G., Woolff S.H., Eccles M., et al. (1999). Developing guidelines. British Medical Journal 318, 593–596. Natsch S, van der Meer J.W.M. (2003). The role of clinical guidelines, policies, and stewardship. Journal of Hospital Infection 53, 172–176. Acton G.J. (2001). Meta-analysis: A tool for evidence-based practice. AACN Clinical Issues 12, 539–545.

CHAPTER

Concepts of Altered Health in Children

2

Judy Wright Lott

GROWTH AND DEVELOPMENT Prenatal Growth and Development Embryonic Development Fetal Development Birth Weight and Gestational Age Abnormal Intrauterine Growth Assessment Methods INFANCY Growth and Development Organ Systems Common Health Problems Health Problems of the Newborn Health Problems of the Premature Infant Health Problems of the Infant EARLY CHILDHOOD Growth and Development Common Health Problems EARLY SCHOOL YEARS TO LATE CHILDHOOD Growth and Development Common Health Problems ADOLESCENCE Growth and Development Common Health Problems

C

hildren are not miniature adults. Physical and psychological maturation and development strongly influence the type of illnesses children experience and their responses to these illnesses. Although many signs and symptoms are the same in persons of all ages, some diseases and complications are more likely to occur in the child. This chapter provides an overview of the developmental stages of childhood and the related health care needs of children. Specific diseases are presented throughout other sections of the book. At the beginning of the 20th century, a child in the United States had little chance of reaching adulthood: the infant mortality rate was 200 deaths per 1000 live births.1 Infectious diseases were rampant, and children, with their

immature and inexperienced immune systems and their frequent exposure to other infected children, were especially vulnerable. With the introduction of antimicrobial agents, infectious disease control, and nutritional and technologic advances, infant mortality decreased dramatically. Although infant mortality has declined over past decades, the record low of 6.9 infant deaths per 1000 live births in 2000 placed the United States only 28th in relation to other industrialized nations.2,3 Also of great concern is the difference in mortality rates for white and nonwhite infants. Infant death rates among African Americans, Native Americans, Alaska Natives, and Hispanics/Latinos in 2000 were all above the national average of 6.9 deaths per 1000 live births. The greatest disparity exists for African Americans, whose infant death rate (14.1 per 1000 in 2000) is nearly 2.5 times that of white infants (5.7 per 1000 in 2000). Recent data indicate that the racial disparities between white and African-American infant mortality rates are increasing.1–4 One of the more perplexing causes of infant mortality is the incidence of preterm birth among women of all races and classes. Despite continued, gradual declines in the overall infant mortality rate during the latter part of the 20th century, the incidence of premature births continues as a challenge to reducing the racial disparities as well as the overall incidence. Prematurity and consequent low birth weight is the leading cause of death in African-American infants. For white infants, the leading cause of death is congenital anomalies.1–3 Sudden infant death syndrome (SIDS) is the third leading cause of overall infant mortality among all races in the United States, accounting for approximately 9% of infant deaths.4 Congenital anomalies (birth defects) account for the most infant deaths, causing approximately one in five infant deaths overall. Efforts to decrease mortality rates are aimed at improving access to prenatal care and understanding the underlying causes of neonatal (i.e., infants younger than 28 days of age) mortality, congenital anomalies, and preterm delivery, which are still poorly understood despite continuing research. Many of the major causes of death during the post-neonatal period (i.e., age 28 days to 1 year)—SIDS, death from infectious diseases 23

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(e.g., pneumonia, influenza), and accidents—may be preventable through health promotion efforts such as routine infant care instruction, immunizations, and teaching of parenting skills.

Growth and Development After completing this section of the chapter, you should be able to meet the following objectives:

✦ Characterize the use of percentiles to describe growth and development during infancy and childhood

✦ Describe the major events that occur during prenatal development from fertilization to birth

✦ Define the terms low birth weight, small for gestational age, and large for gestational age

✦ Identify reasons for abnormal intrauterine growth ✦ Describe assessment methods for determination of gestational age

The phrase growth and development describes a process whereby a fertilized ovum becomes an adult person. Physical growth describes changes in the body as a whole or in its individual parts. Development, on the other hand, embraces other aspects of differentiation, such as changes in body function and psychosocial behaviors. Physical growth occurs in a cephalocaudal (head-totoe) direction. Relative body proportions change over the life span. In early fetal development, the head is the largest part of the body, but proportional size changes as the individual grows (Fig. 2-1). The average newborn weighs approximately 3000 to 4000 g and is 50 to 53 cm long. The first year is a period of rapid growth demonstrated by lengthening of the trunk and deposition of subcutaneous fat.5 After the first year until onset of puberty, the legs grow more rapidly than any other part of the body. The onset of puberty is marked by significant alterations in body proportions because of the effects of the pubertal growth spurt. The feet and hands are the first to grow. Because the trunk grows faster than the legs, at adolescence a large portion of the increase in height is a result of trunk growth. The brain also undergoes a period of

rapid growth. At birth, the brain is 25% of adult size; at 1 year, it is 50% of adult size; and at 5 years, it is 90% of adult size. The size of the head reflects brain growth.6 Linear growth is a result of skeletal growth. After maturation of the skeleton is complete, linear growth is complete. By 2 years of age, the length is 50% of the adult height. Beginning with the third year, the growth rate is 5 to 6 cm for the next 9 years. A growth spurt during adolescence is necessary for adult height to be reached. Males add approximately 20 cm and females 16 cm to height during this time. Weight is rapidly increased after birth. Generally by 6 months of age, the birth weight is doubled; by 1 year of age it is tripled. The average weight increase is 2 to 2.75 kg per year until the adolescent growth spurt begins.7 Growth and development encompass a complex interaction between genetic and environmental influences. The experience of each child is unique, and the patterns of growth and development may be profoundly different for individual children within the context of what is considered normal. Because of the wide variability, these norms often can be expressed only in statistical terms. Evaluation of growth and development requires comparison of an individual’s growth and development to a standard. Statistics are calculations derived from measurements that are used to describe the sample measured or to make predictions about the rest of the population represented by the sample. Because all individuals grow and develop at different rates, the standard must somehow take this individual variation into account. The standard typically is derived from measurements made on a sample of individuals deemed representative of the total population. When multiple measurements of biologic variables such as height, weight, head circumference, and blood pressure are made, most values fall around the center or middle of all the values. Plotting the data on a graph yields a bellshaped curve, which depicts the normal distribution of these continuously variable values (Fig. 2-2). The mean and standard deviation are common statistics used in describing the characteristics of a population. The mean represents the average of the measurements; it is the sum of the values divided by the number of values. A normal bell-shaped curve is symmetric, with the mean falling in the center of the curve and with one half of the values falling on either side of the mean. The standard de-

FIGURE 2-1 Changes in body proportions from the 2nd fetal month to adulthood. (Robbins W.J., Brody S., Hogan A.G., et al. [1928]. Growth. New Haven: Yale University Press. By permission of publisher)

CHAPTER 2 Fertilization

FIGURE 2-2 Relationship between percentile lines on the growth curve and frequency distributions of height at different ages. (Behrman R.E., Kliegman R.M., Jenson H.B. [2000]. Nelson textbook of pediatrics [16th ed., pp. 23–65]. Philadelphia: W.B. Saunders)

Gastrulation

25

Concepts of Altered Health in Children Cleavage

Implantation

Organogenesis

FIGURE 2-3 Milestones in development.

viation determines how far a value varies or deviates from the mean. The points 1 standard deviation above and below the mean include 68% of all values, 2 standard deviations 95% of all values, and 3 standard deviations 99.7% of all values.5 If a child’s height is within 1 standard deviation of the mean, he or she is as tall as 68% of children in the population. If a child’s height is greater than 3 standard deviations, he or she is taller than 99.7% of children in the population. The bell-shaped curve can also be marked by percentiles, which are useful for comparison of an individual’s values with other values. When quantitative data are arranged in ascending and descending order, a middle value, called the median, can be described with one half (50%) of the values falling on either side. The values can be further divided into percentiles. A percentile is a number that indicates the percentage of values for the population that are equal to or below the number. Percentiles are used most often to compare an individual’s value with a set of norms. They are used extensively to develop and interpret physical growth charts and measurements of ability and intelligence.

embryo (embryoblast). The structure is now called a blastocyst. By the sixth day, the blastocyst attaches to the endometrium. This is the beginning of implantation, and it is completed during the second week of development.8 Prenatal development is divided into two main periods. The first, or embryonic, period begins during the second week and continues through the eighth week after fertilization.6,8 During the embryonic period, the main organ systems are developed, and many function at a minimal level (see Chapter 7). The second, or fetal, period begins during the ninth week. During the fetal period, the growth and differentiation of the body and organ systems occur.

Embryonic Development Human development progresses through three phases.6 During the first stage of embryonic development, growth occurs through an increase in cell numbers and the elaboration of cell products. The second stage of development is one of morphogenesis (development of form), which

PRENATAL GROWTH AND DEVELOPMENT Human development is considered to begin with fertilization, the union of sperm and ovum resulting in a zygote (Fig. 2-3). The process begins with the intermingling of a haploid number of paternal (23,X or Y) and maternal (23,X) chromosomes in the ampulla of the oviduct that fuse to form a zygote. Within 24 hours, the unicellular organism becomes a two-cell organism and, within 72 hours, it is a 16-cell organism called a morula. This series of mitotic divisions is called cleavage. During cleavage, the rapidly developing cell mass travels down the oviduct to the uterus by a series of peristaltic movements. The morula enters the uterus approximately 3 days after fertilization. On the fourth day, the morula is separated into two parts by fluid from the uterus. The outer layer gives rise to the placenta (trophoblast), and the inner layer gives rise to the

PRENATAL DEVELOPMENT ➤ The prenatal period, which begins with implantation of the blastocyst, is divided into two periods: the embryonic period and the fetal period. ➤ The embryonic period spans the second through the eighth weeks of gestation. This period is marked by the formation of the germ layers, early tissue differentiation, and development of the major organs and systems of the body. ➤ The fetal period extends from the ninth week to birth. Development during the fetal period is largely concerned with rapid growth and differentiation of tissues, organs, and body systems.

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includes mass cell movement. During this stage, the movement of cells allows them to interact with each other in the formation of tissues and organs. The third stage is the stage of differentiation or maturation of physiologic processes. Completion of differentiation results in organs that are capable of performing specialized functions. With the onset of embryonic development, which begins during the second week of gestation, the trophoblast continues its rapid proliferation and differentiation, and the embryoblast evolves into a bilaminar embryonic disk. This flattened, circular plate of cells gives rise to all three germ layers of the embryo (i.e., ectoderm, mesoderm, endoderm). The third week is a period of rapid development, noted for the conversion of the bilaminar embryonic disk into a trilaminar embryonic disk through a process called gastrulation6,8 (see Fig. 2-3). The ectoderm differentiates into the epidermis and nervous system, and the endoderm gives rise to the epithelial linings of the respiratory passages, digestive tract, and glandular cells of organs such as the liver and pancreas. The mesoderm becomes smooth muscle tissue, connective tissue, blood vessels, blood cells, bone marrow, skeletal tissue, striated muscle tissue, and reproductive and excretory organs. The notochord, which is the primitive axis about which the axial skeleton forms, is also formed during the third week (see Chapter 49). The neurologic system begins its development during this period. Neurulation, a process that involves formation of the neural plate, neural folds, and their closure, is completed by the fourth week. Disturbances during this period can result in brain and spinal defects such as spina bifida. The cardiovascular system is the first functional organ system to develop. The primitive heart, which beats and circulates blood, develops during this period (see Chapter 26). By the fourth week, the neural tube is formed. The embryo begins to curve and fold into a characteristic C-shaped structure. The limb buds are visible, as are the otic pits (i.e., primordia of the internal ears) and the lens placodes (primordia of the lens of the eyes). The fifth week is notable for the rapid growth of the head secondary to brain growth. During the sixth week, the upper limbs are formed by fusion of the swellings around the branchial groove. In the seventh week, there is the beginning of the digits, and the intestines enter the umbilical cord (umbilical herniation). By the eighth week, the embryo is humanlike in appearance—eyes are open, and eyelids and ear auricles are easily identified.

Fetal Development The fetal period extends from the ninth week to birth.6,8 During the 9th to 12th weeks, fetal head growth slows, whereas body length growth is greatly accelerated. By the 11th week, the intestines in the proximal portion of the cord have returned to the abdomen. The primary ossification centers are present in the skull and long bones, and maturation of the fetal external genitalia is established by the 12th week. During the fetal period, the liver is the major site of red blood cell formation (i.e., erythropoiesis); at 12 weeks, this activity has decreased, and erythropoiesis

begins in the spleen. Urine begins to form during the 9th to 12th weeks and is excreted into the amniotic fluid.8 The 13th through 16th weeks are notable for ossification of the skeleton, scalp hair patterning, and differentiation of the ovaries in female fetuses. By the 17th through 20th week, growth has slowed. The fetal skin is covered with a fine hair called lanugo and a white, cheeselike material called vernix caseosa. Eyebrows and head hair are visible. In male fetuses, the testes begin to descend, and in female fetuses, the uterus is formed. Brown fat also forms during this period. Brown fat is a specialized type of adipose tissue that produces heat by oxidizing fatty acids. Brown fat is similar to white fat but has larger and more numerous mitochondria, which provide its brown color. Brown fat is found near the heart and blood vessels that supply the brain and kidneys and is thought to play a role in maintaining the temperature of these organs during exposure to environmental changes that occur after birth. During the 21st through 25th weeks, significant fetal weight gain occurs. The type II alveolar cells of the lung begin to secrete surfactant (see Chapter 29). The pulmonary system becomes more mature and able to support respiration during the 26th through 29th weeks. Breathing movements are present as a result of central nervous system (CNS) maturation. At this age, a fetus can survive if born prematurely and given intensive care. There also is an increasing amount of subcutaneous fat, with white fat making up 3.5% of body weight.6 The 30th through 34th weeks are significant for an increasing amount of white fat (8% of body weight), which gives the fetal limbs an almost chubby appearance.6 During the 35th week, grasp and the pupillary light reflex are present. If a normal-weight fetus is born during this period, it is premature by “date” as opposed to premature by “weight.”6 Expected time of birth is 266 days, or 38 weeks after fertilization, or 40 weeks after the last menstrual period (LMP).6 At this time, the neurologic, cardiovascular, and pulmonary systems are developed enough for the infant to make the transition to extrauterine life. The survival of the newborn depends on this adaptation after the placenta is removed.

Fetal Growth and Weight Gain. Development during the fetal period is primarily concerned with rapid growth and differentiation of tissues, organs, and systems. Fetal weight gain is linear from 20 weeks’ gestation through 38 weeks’ gestation. In the last half of pregnancy, the fetus gains 85% of birth weight. After 38 weeks’ gestation, the rate of growth declines, probably related to the constraint of uterine size and decreased placental function. After birth, weight gain again increases, similar to intrauterine rates. Birth weight can be affected by a variety of factors, including maternal nutrition, genetic factors, chronic maternal diseases, placental abnormalities, sex, socioeconomic factors, multiple births, chromosomal abnormalities, and infectious diseases.

BIRTH WEIGHT AND GESTATIONAL AGE At birth, the average weight of the full-term newborn is 3000 to 4000 g. Before 1961, infants weighing less than 2500 g were classified as premature. In 1961, owing to the

CHAPTER 2

recognition that factors other than gestational age affect birth weight, infants weighing less than 2500 g were classified as low birth weight (LBW). Lubchenco and Battaglia established standards for birth weight, gestational age, and intrauterine growth in the United States in the 1960s 9,10 (Fig. 2-4). With these standards, gestational age can be assessed, and normal and abnormal growth can be identified. The Colorado Growth Curve places newborns into percentiles.9 The 10th through 90th percentiles of intrauterine growth encompass 80% of births.11 Growth is considered abnormal when a newborn falls above or below the 90th and 10th percentiles, respectively. An infant is considered term when born between the beginning of the 38th week and completion of the 41st week. An infant is considered premature when born before the end of the 37th week and post-mature when born after the end of the 41st week. The lowest mortality rates occur among newborns with weights between 3000 and 4000 g with gestational ages of 38 to 42 weeks.12–14

Abnormal Intrauterine Growth Growth of the fetus in the uterus depends on a multitude of intrinsic and extrinsic factors. Optimal fetal growth depends on efficient placental function, adequate provision of energy and growth substrates, appropriate hormonal environment, and adequate room in the uterus. Birth weight variability in a population is primarily determined by maternal heredity, intrinsic fetal growth potential, and environmental factors. Abnormal growth, which can occur at

Concepts of Altered Health in Children

27

any time during fetal development, can have immediate and long-term consequences for the infant.

Small for Gestational Age. Small for gestational age (SGA) is a term that denotes fetal undergrowth. SGA is defined as birth weight less than 2 standard deviations below the mean for gestational age, or below the 10th percentile. It often is used interchangeably with intrauterine growth retardation (IUGR). Worldwide, between 30% and 40% of infants born at weights less than 2500 g are SGA. Mortality rates of severely affected SGA infants are five to six times those of normally grown infants of comparable gestational age. Fetal growth retardation can occur at any time during fetal development. Depending on the time of insult, the infant can have symmetric or proportional growth retardation or asymmetric or disproportional growth retardation. Impaired growth that occurs early in pregnancy during the hyperplastic phase of growth results in symmetric growth retardation. Because mitosis is affected, organs and tissues are smaller as a result of overall decreased cell number. Head circumference, length, and weight usually are represented within similar percentile grids, although the head may be smaller, as in microcephaly.15 This is irreversible postnatally. Causes of proportional IUGR include chromosomal abnormalities, congenital infections, and exposure to environmental toxins. Impaired growth that occurs later in pregnancy during the hypertrophic phase of growth results in asymmetric growth retardation.12–14 Infants with IUGR due to intrauterine malnutrition often have weight reduction out of proportion to length or head circumference but are spared impairment of head and brain growth.7 Tissues and organs are small because of decreased cell size, not decreased cell numbers. Postnatally, the impairment may be partially corrected with good nutrition. Maternal, placental, and environmental factors affect fetal growth. Because of the effects on the placenta (it also is undergrown), the risk for perinatal complications is higher. These include birth asphyxia, hyperglycemia, polycythemia, meconium (i.e., dark green, mucilaginous newborn stool) aspiration, and hypothermia. The long-term effects of growth retardation depend on the timing and severity of the insult. Many of these infants have developmental disabilities on follow-up examination, especially if the growth retardation is symmetric. They may remain small, especially if the insult occurred early. If the insult occurred later because of placental insufficiency or uterine restraint, with good nutrition catch-up growth can occur, and the infant may attain appropriate growth. Large for Gestational Age. Large for gestational age (LGA) is

FIGURE 2-4 Classification of newborns by birth weight and gestational age. (Redrawn from Battaglia F.C., Lubchenco L.O. [1967]. A practical classification of newborn infants by weight and gestational age. Journal of Pediatrics 71, 159)

a term that denotes fetal overgrowth. The definition of LGA is birth weight greater than 2 standard deviations above the mean for gestation, or above the 90th percentile. The excessive growth may result from a genetic predisposition or may be stimulated by abnormal conditions in utero. Infants of diabetic mothers may be LGA, especially if the diabetes was poorly controlled during pregnancy. Maternal hyperglycemia exposes the fetus to increased levels of glucose, which stimulates fetal secretion of insulin. Insulin increases fat deposition, and the result is a macrosomic (large body

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size) infant. Infants with macrosomia have enlarged viscera and are large and plump because of an increase in body fat. Complications when an infant is LGA include birth asphyxia and trauma due to mechanical difficulties during the birth process, hypoglycemia, and polycythemia.12

Assessment Methods Gestational age assessment can be divided into two categories: prenatal assessment and postnatal assessment. Prenatal assessment of gestational age most commonly includes careful menstrual history, physical milestones during pregnancy (e.g., uterine size, detection of fetal heart rate and movements), and prenatal tests for maturity (e.g., ultrasound, amniotic fluid studies). Nägele’s rule uses the first day of the LMP to calculate the day of labor by adding 7 days to the LMP and counting back 3 months.12 This method may be inaccurate if the mother is not a good historian or has a history of irregular menses, which interferes with identification of a normal cycle. Postnatal assessment of gestational age is done by examination of external physical and neuromuscular characteristics alone or in combination. Assessment of gestational age should be a part of every initial newborn examination.

Accurate assessment of gestational age facilitates risk assessment and identification of abnormalities and allows for earlier interventions. Dubowitz or Ballard developed the most common methods used in nurseries today. The Dubowitz method is comprehensive and includes 21 criteria using external physical (11) and neuromuscular (10) signs.16 The estimate of gestational age is best done within 12 hours of birth and is accurate within 1 week. The method is less accurate for infants born at less than 30 weeks’ gestational age. The Ballard method is an abbreviated Dubowitz method that includes 12 criteria, using 6 external physical and 6 neuromuscular signs (Fig. 2-5). The New Ballard Score (NBS) was updated and modified to include newborns at gestational ages of 20 to 44 weeks and is the most commonly used method. If performed within 12 hours post-birth by an experienced examiner, it is accurate to within 1 week.11 In summary, growth and development begin with union of ovum and sperm and are ongoing throughout a child’s life to adulthood. Abnormalities during this process can have profound effects on the infant. Prenatal development is com-

FIGURE 2-5 Ballard scoring system for determining gestational age in weeks. (Bickley L.S. [2003]. Bates’ guide to physical examination and history taking [p. 737]. Philadelphia: Lippincott Williams & Wilkins)

CHAPTER 2 posed of two periods—the embryonic period and the fetal period. During these periods, the zygote becomes the newborn with the organ maturity to make the adjustments necessary for extrauterine life. Infants born before this process is completed are called premature and can have major problems with extrauterine adjustments. Postnatal growth is rapid and ongoing and proceeds in an orderly and predictable manner.

Infancy After completing this section of the chapter, you should be able to meet the following objectives:

✦ Describe the use of the Apgar score in evaluating infant ✦ ✦ ✦ ✦

well-being at birth List three injuries that can occur during the birth process Describe physical growth and organ development during the first year of life Explain how the common health care needs of the premature infant differ from the health care needs of the term newborn or infant Differentiate between organic and nonorganic failure to thrive syndrome

Infancy is defined as that time from birth to approximately 18 months of age, the first 4 weeks of which are designated as the newborn or neonatal period. This is a period of rapid physical growth and maturation. The infant begins life as a relatively helpless organism and, through a process of progressive development, gains the skills to interact and cope with the environment. The infant begins life with a number of primitive reflexes and little body control. By 18 months, a child is able to run, grasp and manipulate objects, feed himself or herself, play with toys, and communicate with others.

GROWTH AND DEVELOPMENT Physical growth is rapid during infancy. After birth, there is a period of relative starvation as the infant adjusts to enteral feeding. Typically, infants lose approximately 5% to 10% of their birth weight, but within days, they begin to gain weight, and by 2 weeks, they are back to birth weight. Average birth weight for a term newborn is 3000 to 4000 g, and this weight usually is doubled by 6 months and tripled by approximately 1 year after birth. The median height at birth is 49.9 cm for girls and 50.5 cm for boys. During the first 6 months, height increases by 2.5 cm per month. By 1 year, the increase in length is 50% of the birth length. This increase is primarily in trunk growth. Median head circumference at birth is 34.5 cm for girls and 34.8 cm for boys. The skull bones of newborn infants are incomplete and are connected by bands of connective tissue called sutures. At the junction of the sutures are wider spaces of unossified membranous tissue called fontanels. The larger anterior fontanel is palpable until about 18 months to 2 years of age; the smaller

Concepts of Altered Health in Children

29

INFANCY ➤ Infancy, which is the time from birth to 18 months of age, is a period of rapid physical growth and maturation. ➤ From an average birth weight of 3000 to 4000 g in the fullterm infant and a median height of 49.9 cm for girls and 50.5 cm for boys, the infant manages to triple its weight and increase its length by 50% at 1 year of age. ➤ Developmentally, the infant begins life with a number of primitive reflexes and little body control. By 18 months, a child is able to run, grasp and manipulate objects, feed himself/herself, play with toys, and communicate with others. ➤ Basic trust, the first of Erikson’s psychosocial stages, develops as infants learn that basic needs are met regularly. ➤ At the age of 18 months or the end of the infancy period, the emergence of symbolic thought causes a reorganization of behaviors with implications for the many developmental domains that lie ahead as the child moves to the early childhood stage of development.

ones are replaced by bone by the end of the first year. The fontanels allow the infant’s head to be compressed slightly during birth and allow rapid brain growth. Premature closure of any suture in the skull is called craniostenosis or craniosynostosis. The clinical consequences of premature closure depends on which suture is affected. The closed suture prevents growth from occurring in the affected area, but growth continues in the unaffected sutures, resulting in an abnormally shaped head. The rapid increase in head circumference during the first year, is a good indicator of brain growth. Head circumference increases by 1.5 cm per month the first 6 months and 0.5 cm per month the second 6 months. Chest circumference at birth is smaller than head circumference. By 1 year, the head and chest are approximately equal in circumference; after 1 year, chest circumference exceeds head circumference.7 After birth, most organ systems continue to grow and mature in an orderly fashion. Variations in growth and development are responsible for the differences in body proportions. For example, during the fetal period, the head is the predominant part because of the rapidly growing brain, whereas during infancy, the trunk predominates, and in childhood, the legs predominate. The patterns of growth are cephalocaudal, proximodistal, and mass (size) to specific.

Organ Systems Organ systems must continue to grow and mature after delivery. Many are at a minimal level of functioning at birth. This often places the infant at risk for health problems.

Respiratory System. Onset of respiration must begin at birth for survival. By the late fetal period, the lungs are capable of respiration because the alveolar capillary membrane is sufficiently thin to allow for gas exchange.

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Characteristically, mature alveoli do not form until after birth. Before birth, the primordial alveoli appear as small ridges on the walls of the respiratory bronchioles and terminal saccules. After birth, the primordial alveoli enlarge as the lungs expand, but the most important increase in the size of the lungs results from an increase in the number of alveoli and growth of the airways. Infants are obligatory nose breathers until 3 to 4 months of age; any upper airway obstruction may cause respiratory distress.7 The trachea is small and close to the bronchi, and the bronchi’s branching structures enable infectious agents to be easily transmitted throughout the lungs. The softness of the supporting cartilage in the trachea, along with its small diameter, places the infant at risk for airway obstruction. The auditory (eustachian) tube is short and straight and closely communicates with the ear, putting the infant at risk for middle ear infections (see Chapter 55).

Cardiovascular System. Birth initiates major changes in the cardiovascular system when the circulation of fetal blood through the placenta ceases and the infant’s lungs expand and begin to function. The fetal shunts that allowed the blood to bypass the lungs (foramen ovale, ductus arteriosus) and the liver (ductus venous) close and cease to function. At birth, the size of the heart is large in relation to the chest cavity. The size and weight of the heart double the first year. Initially, the right ventricle is more muscular than the left ventricle, but this reverses in infancy. The heart rate gradually slows, and systolic blood pressure rises. Hematopoietic System. The hematopoietic system is responsible for the production of blood cells. The hematopoietic system is composed of pluripotent stem cells that differentiate to form the red blood cells (RBCs), white blood cells (WBCs), and platelets through a process called hematopoiesis. New blood cells are constantly being generated to replace older blood cells that are broken down. A balance between new blood cell production and blood cell breakdown is necessary for normal circulating volume. As red blood cells are broken down, one of the major byproducts of the breakdown of hemoglobin is bilirubin (see Chapter 16). The lipid-soluble form of bilirubin, which is called unconjugated bilirubin or indirect reacting bilirubin, combines with plasma proteins for transport in the blood and interstitial fluids. Unconjugated bilirubin is removed from the blood by the liver and conjugated to form a water-soluble form of bilirubin. Conjugated (direct-acting) bilirubin is excreted from the liver cells into the biliary system and then into the intestinal tract. Normally, about two thirds of the unconjugated bilirubin produced by a term newborn can be effectively cleared by the liver. However, the relative immaturity of the newborn liver and the shortened life span of the fetal red blood cells may predispose the term newborn to hyperbilirubinemia and yellowish pigmentation of the skin, known as jaundice (Fig. 2-6). With the establishment of sufficient enteral nutrition, regular bowel elimination, and normal fluid volume, the liver is usually able to clear the excess bilirubin. The presence of jaundice with elevation of either indirect or direct bilirubin that is present at birth, appears within the first 24 hours of life, or is persistent indicates a pathophysiologic cause and should be investigated.

FIGURE 2-6 Photo of a newborn infant with jaundice.

Gastrointestinal System. The infant’s gastrointestinal system is immature, and most digestive processes are poorly functioning until approximately 3 months of age. Solid food may pass incompletely digested and be evident in the stool. The newborn’s first stool is called meconium and is composed of amniotic fluid, intestinal secretions, shed mucosal cells, and sometimes blood from ingested maternal blood or minor bleeding of intestinal tract vessels. Passage of meconium should occur within the first 24 to 48 hours in healthy term newborns but may be delayed for up to 7 days in preterm newborns or in newborns who do not receive enteral nutrition owing to illness. At birth, sucking may be poor and require several days to become effective. The tongue thrust reflex is present and aids in sucking, but it disappears at approximately 6 months of age. Stomach capacity increases rapidly in the first months, but because of the limited capacity and rapid emptying, infants require frequent feeding.7 The infant’s genitourinary system is functionally immature at birth. There is difficulty in concentrating urine, and the ability to adjust to a restricted fluid intake is limited. The small bladder capacity causes frequent voiding.

Nervous System. The nervous system undergoes rapid maturation and growth during the infancy period. In contrast to other systems that grow rapidly after birth, the nervous system grows proportionately more rapidly before birth. The most rapid period of fetal brain growth is between 15 and 20 weeks of gestation, at which time there is a significant increase in neurons. A second increase occurs between 30 weeks’ gestation and 1 year of age. At birth, the average brain weighs approximately 325 g. By 1 year of age, the weight has tripled, and the brain weighs approximately 1000 g.7 Head circumference, one of the best indi-

CHAPTER 2

cators of brain growth, increases six times as much during the first year as it does during the second year of life. At birth, the nervous system is incompletely integrated but sufficiently developed to sustain extrauterine life. Most of the neurologic reflexes are primitive reflexes. Normal newborn reflexes, which include the Moro (startle), rooting (sucking), and stepping (placing) reflexes, can be used to evaluate the newborn and infant’s developing central nervous system. The maturation of the nervous system includes an increase in the size of neurons, size and number of glial cells, and number of interneuron connections and branching of axons and dendrites. As this maturation progresses, the level of infant functioning increases from simple to complex and from primitive reflexes to purposeful movement. Cortical control of motor functions is closely associated with myelination of nerve fibers. Myelination of the various nerve tracts progresses rapidly after birth and follows a cephalocaudal and proximodistal direction sequence, beginning with myelination of the spinal cord and cranial nerves and followed by the brain stem and corticospinal tracts.7 In general, sensory pathways become myelinated before motor pathways. The acquisition of fine and gross motor skills depends on this myelination and maturation. The first year of life also is filled with psychosocial developmental milestones for the infant. Basic needs must be met before the infant can accomplish these developmental tasks. Erikson described the development of a sense of trust as the task of the first stage.17 If trust is not acquired, the infant becomes mistrustful of others and frustrated with his or her inability to control the surrounding environment.

COMMON HEALTH PROBLEMS The birth process is a critical event. Prenatal influences, birth trauma, and prematurity have an immediate impact on survival and health. The common health problems in this section have been divided into three subsections:

Concepts of Altered Health in Children

31

health problems of the newborn, special needs of the premature infant, and health problems of the infant.

Health Problems of the Newborn The most profound physiologic change required of the newborn is the transition from intrauterine to extrauterine existence. Onset of respiration must begin at birth for survival. The first breath expands the alveoli and initiates gas exchange. The infant’s respiratory rate initially is rapid and primarily abdominal, but with maturation, the respiratory rate gradually slows. Birth also initiates major changes in the cardiovascular system. The fetal shunts, the foramen ovale and ductus arteriosus, begin to close, and the circulation of blood changes from a serial to a parallel circuit. (See Chapter 26 for further discussion.) In addition to establishing respiration, heat regulation is another response critical to the infant’s survival. At birth, the newborn’s temperature is about 0.5°C higher than the mother’s temperature. The temperature gradient causes vasodilation; thus, heat is lost rapidly, especially in a cold delivery room. The newborn’s large surface area and lack of subcutaneous fat predisposes to excessive heat loss. Marked heat loss and the consequent lowering of body temperature can cause an otherwise healthy newborn to develop respiratory distress.

Distress at Birth and the Apgar Score. The Apgar score, devised by Dr. Virginia Apgar, is a scoring system that evaluates infant well-being at birth.15 The system addresses five categories (i.e., heart rate, respiratory effort, muscle tone, reflex irritability, and color) with a total score ranging from 0 to 10, depending on the degree to which these functions are presented (Table 2-1). Evaluations are performed at 1 minute and 5 minutes after delivery. A score of 0 to 3 is indicative of severe distress, 4 to 6 of moderate distress, and 7 to 10 of mild to no distress. Most infants score 6 to 7 at 1 minute and 8 to 9 at 5 minutes. If the score is 7 or less, the evaluation should be repeated every 5 minutes until a score of 7 or greater is obtained. An abnormal score at 5 minutes is more predictive of problems with survival and neurologic outcome than at 1 minute.12 Birth Injuries. Injuries sustained during the birth process are responsible for a significant amount of neonatal mortality and morbidity. In 2000, birth injuries ranked as the eighth leading cause of infant death in the United States. Predisposing factors for birth injuries include macrosomia, prematurity, cephalopelvic disproportion, and dystocia (i.e., abnormal labor or childbirth).12,18 Cranial Injuries. The contour of the head of the newborn

often reflects the effects of the delivery presentation. In vertex (head-first) deliveries, the head is usually flattened at the forehead, with the apex rising and forming a plane at the end of the parietal bones and the posterior skull or occiput dropping abruptly. By 1 to 2 days of age, the head has taken on a more oval shape. Such head molding does not occur in babies born by breech presentation or by cesarian section. Caput succedaneum is a localized area of scalp edema caused by sustained pressure of the presenting part against

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TABLE 2-1

Apgar Score Assessment Score*

Criterion Heart rate Respiratory effort Muscle tone Reflex irritability Color Total

0

1

2

Absent Absent Limp No response Pale 0

100 Crying Well flexed Cry, gag Pink 10

* The Apgar score should be assigned at 1 minute and 5 minutes after birth, using a timer. Each criterion is assessed and assigned a 0, 1, or 2. The total score is the assigned Apgar score. If resuscitation is required beyond the 5 minutes, additional Apgar scores also may be assigned as a method to document the response of the newborn to the resuscitation.

the cervix. An accumulation of serum or blood forms above the periosteum from the high pressure caused by the obstruction. The caput succedaneum may extend across suture lines and have overlying petechiae, purpura, or ecchymosis. No treatment is needed, and it usually resolves over the first week of life.12,18 Cephalohematoma is a subperiosteal collection of blood from ruptured blood vessels. The margins are sharply delineated and do not cross suture lines. It usually is unilateral, but it may be bilateral, and it usually occurs over the parietal area. The swelling may not be apparent for 24 to 48 hours because subperiosteal bleeding is slow. The overlying skin is not discolored. An underlying skull fracture may be present. Treatment is not needed unless the cephalohematoma is large and results in severe blood loss or significant hyperbilirubinemia. Skull fracture and intracranial hemorrhage are associated complications. An uncomplicated cephalohematoma usually resolves within 2 weeks to 3 months.11,15 Fractures. Skull fractures are uncommon because the infant’s compressible skull is able to mold to fit the contours of the birth canal. However, fractures can occur and more often follow a forceps delivery or severe contraction of the pelvis associated with prolonged, difficult labor. Skull fractures may be linear or depressed. Uncomplicated linear fractures often are asymptomatic and do not require treatment. Depressed skull fractures are observable by the palpable indentation of the infant’s head. They require surgical intervention if there is compression of underlying brain tissue. A simple linear fracture usually heals within several months.12,18 The clavicle is the bone most frequently fractured during the birth process. It is more common in LGA infants and occurs when delivery of the shoulders is difficult in vertex (i.e., head) or breech presentations. The infant may or may not demonstrate restricted motion of the upper extremity, but passive motion elicits pain. There may be discoloration or deformity and, on palpation, crepitus (i.e., a crackling sound from bones rubbing together), and irregularity may be found. Treatment consists of immobilizing the affected arm and shoulder and providing pain relief.12,18

Peripheral Nerve Injuries. The brachial plexuses are situated above the clavicles in the anterolateral bases of the neck. They are composed of the ventral rami of the fifth cervical nerves through the first thoracic nerves. During vertex deliveries, excessive lateral traction of the head and neck away from the shoulders may cause a stretch injury to the brachial plexus on that side. In a breech presentation, excessive lateral traction on the trunk before delivery of the head may tear the lower roots of the cervical cord. If the breech presentation includes delivery with the arms overhead, an injury to the fifth and sixth cervical roots may result. When injury to the brachial plexus occurs, it causes paralysis of the upper extremity. The paralysis often is incomplete.12,18,19 Brachial plexus injuries include three types: ErbDuchenne paralysis (i.e., upper arm), Klumpke’s paralysis (i.e., lower arm), and paralysis of the entire arm. Risk factors include an LGA infant and a difficult, traumatic delivery. Erb-Duchenne paralysis occurs with injury to the fifth and sixth cervical roots. It is the most common type of brachial plexus injury and manifests with variable degrees of paralysis of the shoulder and arm. The position of the affected arm is adducted and internally rotated, with extension at the elbow, pronation of the forearm, and flexion of the wrist. When the infant is lifted, the affected extremity is limp. The Moro reflex is impaired or absent, but the grasp reflex is present. Klumpke’s paralysis results from injury to the seventh and eighth cervical and first thoracic nerve roots. It is rare and presents with paralysis of the hand. The infant has wrist drop, the fingers are relaxed, and the grasp reflex is absent. The Moro reflex is impaired, with the upper extremity extending and abducting normally while the wrist and fingers remain flaccid.12,18,19 Treatment of brachial plexus injuries includes immobilization, appropriate positioning, and an exercise program. Most infants recover in 3 to 6 months. If paralysis persists beyond this time, surgical repair (neuroplasty, end-to-end anastomosis, nerve grafting) may be done.19

Congenital Malformations. Congenital malformations are anatomic or structural abnormalities present at birth

CHAPTER 2

(see Chapter 7). They are a major cause of morbidity and mortality in children. In 2000, congenital anomalies accounted for 20.5% of infant deaths, including 22% of neonatal deaths and 17.3% of infant deaths beyond the neonatal period.3,4 Anomalies of the cardiovascular system and CNS account for most deaths due to congenital anomalies.3 Some stages of embryonic development are more at risk than others for development of congenital malformations after teratogen exposure. The causes of congenital malformations may be classified as genetic, environmental, or multifactorial.

Health Problems of the Premature Infant Infants born before 37 weeks’ gestation are considered premature. They often fall into the LBW category, defined as birth weight less than 2500 g. LBW and prematurity often go hand in hand. Most infants weighing less than 2500 g, and almost all weighing less than 1500 g, are premature. Mortality and morbidity are increased in the premature population and are inversely proportional to the length of gestation. The shorter the time of gestation, the greater is the risk for death or disability. The immaturity of the organ systems interferes with the successful transition to extrauterine life, predisposing this population to complications. Included in this group are those premature infants who have grown abnormally during their shortened gestation (i.e., LGA or SGA). Abnormal growth places an added stress on their transition to extrauterine life. Despite the advances in obstetric management since the late 1960s, the rate of premature delivery has not significantly changed. The incidence of preterm births (40). Body weight reflects both lean body mass and adipose tissue and cannot be used as a method for describing body composition or the percentage of fat tissue present. Statistically, the best percentage of body fat for men is between 12% and 20%, and for women, it is between 20% and 30%.10 During physical training, body fat usually decreases, and lean body mass increases.

Among the methods used to estimate body fat are skinfold thickness, body circumferences, hydrodensitometry, bioelectrical impedance, dual photon absorptiometry, computed tomography (CT), and magnetic resonance imaging (MRI). Measurements of skinfold thickness can provide a reasonable assessment of body fat, particularly if taken at multiple sites. They can provide information about the location of the fat and can be used, together with equations and tables, to estimate the percentage of lean body mass and fat tissue.11,12 However, these measurements often are difficult to perform and subject to considerable variation

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TABLE 11-7

Integrative Body Functions

Sources and Functions of Minerals

Mineral

Major Sources

Functions

Calcium

Milk and milk products, fish with bones, greens Table salt, meats, milk, eggs

Bone formation and maintenance; tooth formation, vitamin B absorption, blood clotting, nerve and muscle function Regulates pH of stomach, acid-base balance, osmotic pressure of extracellular fluids Aids in maturation of red blood cells (as part of B12 molecule) Catalyst for hemoglobin formation, formation of elastin and collagen, energy release (cytochrome oxidase and catalase), formation of melanin, formation of phospholipids for myelin sheath of nerves Strengthens bones and teeth Thyroid hormone synthesis and its function in maintenance of metabolic rate Hemoglobin synthesis, cellular energy release (cytochrome pathway), killing bacteria (myeloperoxidase)

Chloride Cobalt Copper

Organ meats, meats Cereals, nuts, legumes, liver, shellfish, grapes, meats

Fluoride Iodine

Fluorinated water Iodized salt, fish (saltwater and anadromous) Meats, heart, liver, clams, oysters, lima beans, spinach, dates, dried nuts, enriched and whole-grain cereals Milk, green vegetables, nuts, bread, cereals

Iron

Magnesium

Phosphorus

Meats, poultry, fish, milk and cheese, cereals, legumes, nuts

Potassium

Oranges, dried fruits, bananas, meats, potatoes, peanut butter, coffee

Sodium

Table salt, cured meats, meats, milk, olives

Zinc

Whole-wheat cereals, eggs, legumes

TABLE 11-8

Catalyst of many intracellular nerve impulses, retention of reactions, particularly those related to intracellular enzyme reactions; low magnesium levels produce an increase in irritability of the nervous system, vasodilatation, and cardiac dysrhythmias Bone formation and maintenance; essential component of nucleic acids and energy exchange forms such as adenosine triphosphate (ATP) Maintenance of intracellular osmolality, acid-base balance, transmission of nerve impulses, catalyst in energy metabolism, formation of proteins, formation of glycogen Maintenance of osmotic pressure of extracellular fluids, acidbase balance, neuromuscular function; absorption of glucose Integral part of many enzymes, including carbonic anhydrase, which facilitates combination of carbon dioxide with water in red blood cells; component of lactate dehydrogenase, which is important in cellular metabolism; component of many peptidases; important in digestion of proteins in gastrointestinal tract

Classification of Overweight and Obesity by BMI, Waist Circumference, and Associated Disease Risk* Disease Risk* Relative to Normal Weight and Waist Circumference BMI (kg/m2)

Underweight Normal† Overweight Obesity Extreme obesity

102 cm (>40 in) Women >88 cm (>35 in)

I II III

— — Increased High Very high Extremely high

— — High Very high Very high Extremely high

BMI, body mass index. *Disease risk for type 2 diabetes, hypertension, and cardiovascular disease. † Increased waist circumference also can be a marker for increased risk, even in persons of normal weight. (Expert Panel. [1998]. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. National Institutes of Health. [On-line.] Available: http://nhlbi.nih.gov/guidelines/ob_gdlns.htm.

CHAPTER 11

between observers, and they do not provide information about abdominal and intramuscular fat. The measurement of body circumferences has received attention because excess visceral or intraabdominal fat is associated with increased risk for diabetes and cardiovascular disease.13 Studies have also indicated that the subcutaneous fat at the abdomen is highly correlated with insulin resistance. A waist circumference greater than 40 inches in men and greater than 35 inches in women is considered high risk.13 The remaining methods of determining body fat except for bioimpedance are expensive and not portable and are usually done in research settings. Bioimpedance is performed by attaching electrodes at the wrist and ankle that send a harmless current through the body. The flow of the current is affected by the amount of water in the body. Because fat-free tissue contains virtually all the water and the conducting electrolytes, measurements of the resistance (i.e., impedance) to current flow can be used to estimate the percentage of body fat present.

Laboratory Studies Various laboratory tests can aid in evaluating nutritional status. Some of the most commonly performed tests are serum albumin and prealbumin to assess the protein status, total lymphocyte count and delayed hypersensitivity reaction to assess cellular immunity, and creatinine–height index to assess skeletal muscle protein. Vitamin and mineral deficiencies can be determined by measurements of their levels in blood, saliva, and other body tissues or by measuring nutrient-specific chemical reactions. All of these tests are limited by confounding factors and therefore need to be evaluated along with other clinical data. In summary, nutritional status describes the condition of the body related to the availability and use of nutrients. Nutrients provide the energy and materials necessary for performing the activities of daily living and for the growth and repair of body tissues. Metabolism is the organized process whereby nutrients such as carbohydrates, fats, and proteins are broken down, transformed, or otherwise converted to cellular energy. Glucose, fats, and amino acids from proteins serve as fuel sources for cellular metabolism. These fuel sources are ingested during meals and stored for future use. Glucose is stored as glycogen or converted to triglycerides in fat cells for storage. Fats are stored in adipose tissue as triglycerides. Amino acids are the building blocks of proteins, and most of the stored amino acids are contained in body proteins and as fuel sources for cellular metabolism. Energy is measured in heat units called kilocalories. The expenditure of body energy results from heat production (i.e., thermogenesis) associated with the BMR or basal energy equivalent, diet-induced thermogenesis, exercise-induced thermogenesis, and thermogenesis in response to changes in environmental conditions. The body requires more than 40 nutrients on a daily basis. Nutritional status reflects the continued daily intake of nutrients over time and the deposition and use of these nutrients in the body. The DRI is the Daily Recommended Intake of essential nutrients considered to be adequate to meet the known

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229

nutritional needs of healthy persons. The DRI has 22 age and sex classifications and includes recommendations for calories, protein, fat, carbohydrates, vitamins, and minerals. The nutritional status of a person can be assessed by evaluation of dietary intake, anthropometric measurements, health assessment, and laboratory tests. Health assessment includes a health history and physical examination to determine weight changes, muscle wasting, fat stores, functional status, and nutritional status. Anthropometric measurements are used for assessing body composition; they include height and weight measurements and measurements to determine the composition of the body in relation to lean body mass and fat tissue (e.g., skinfold thickness, body circumferences, hydrodensitometry, bioelectrical impedance, and CT scans).

Overnutrition and Obesity After completing this section of the chapter, you should be able to meet the following objectives:

✦ Define and discuss the causes of obesity and health risks associated with obesity

✦ Differentiate upper and lower body obesity and their implications in terms of health risk

✦ Discuss the treatment of obesity in terms of diet, behavior modification, exercise, social support, and surgical methods

Obesity is defined as a condition characterized by excess body fat. Clinically, obesity and overweight have been defined in terms of the BMI. Historically, various world bodies have used different BMI cutoff points to define obesity. In 1997, the World Health Organization defined the various classifications of overweight (BMI ≥25) and obesity (BMI ≥30). This classification was subsequently adopted by the National Institutes of Health (NIH).13 The use of a BMI cutoff of 25 as a measure of overweight raised some concern that the BMI in some men might be due to muscle rather than fat weight. However, it has been shown that a BMI cutoff of 25 can sensitively detect most overweight people and does not erroneously detect overlean people.14 Overweight and obesity have become national health problems, increasing the risk for hypertension, hyperlipidemia, type 2 diabetes, coronary heart disease, and other health problems. Sixty-four and one-half percent of the U.S. population is estimated to be overweight (BMI ≥25), and 30.5% of the population is obese (BMI ≥30).15 There was no difference in prevalence among men of different racial and ethnic groups. However, black women had a significantly higher rate of overweight and obesity than did white women. Hispanic women fell between the two groups. The prevalence in overweight and obesity is alarming not only because of the number of people affected but also because the prevalence continues to increase from previous surveys. The prevalence of severe obesity is increasing at an even faster rate, with persons who self-reported a BMI of at least 40 having increased from 1 in 200 to 1 in 50; those with a

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BMI of at least 50 from 1 in 2000 to 1 in 400; and those with a BMI of at least 30 from 1 in 10 to 1 in 5.16

CAUSES OF OBESITY The excess body fat of obesity often significantly impairs health, and as a result, obesity is the second leading cause of preventable death in the United States.17 This excess body fat is generated when the calories consumed exceed those expended through exercise and activity.18 Although factors that lead to the development of obesity are not well understood, they are thought to involve the interaction of genotype and environmental factors, which include social, behavioral, and cultural, with the physiology, metabolism, and genetics of the individual.19 In studies of persons who were overweight, the metabolic factors contributing to overweight were a low energy expenditure rate; a high respiratory quotient (RQ), which indicates the carbohydrate-to-fat oxidation ratio; and a low level of spontaneous physical activity.20 The average adjusted energy expenditure of overweight persons was 36.3 kcal/kg fat-free mass (FFM) but could range from 28 to 42 kcal/kg FFM. The RQ was likely to be high in those who gained weight, suggesting that the person was oxidizing more carbohydrate than fat. Epidemiologic surveys indicate that the prevalence of overweight may also be related to social and economic conditions. The second (1976 through 1980) National Health and Nutrition Examination Survey (NHANES II) has shown that if American women are divided into two groups according to economic status, the prevalence of obesity is much higher among those in the poverty group.21 In contrast, men above the poverty level had a higher prevalence of overweight than men below the poverty level. Obesity is known to run in families, suggesting a hereditary component. The question that surrounds this observation is whether the disorder arises because of genetic endowment or environmental influences. Studies of twins and adopted children have provided evidence that heredity contributes to the disorder.22 It is now believed that the heritability of the BMI is between 30% and 40%.20

Although genetic factors may explain some of the individual variations in terms of excess weight, environmental influences also must be taken into account. These influences include family dietary patterns, decreased level of activity because of labor-saving devices and time spent on the computer, reliance on the automobile for transportation, easy access to food, energy density of food, and super sizing of portions. The obese may be greatly influenced by the availability of food, the flavor of food, time of day, and other cues. The composition of the diet also may be a causal factor, and the percentage of dietary fat independent of total calorie intake may play a part in the development of obesity. Psychological factors include using food as a reward, comfort, or means of getting attention. Eating may be a way to cope with tension, anxiety, and mental fatigue. Some persons may overeat and use obesity as a means of avoiding emotionally threatening situations. It has been suggested that the increased prevalence of obesity in the United States has resulted from increased caloric intake together with a sedentary lifestyle and energy-saving conveniences.23 Even when a reasonable number of calories are consumed, fewer are expended because of inactivity. A low rate of energy expenditure may contribute to the prevalence of obesity in some families.

UPPER AND LOWER BODY OBESITY Two types of obesity based on distribution of fat have been described: upper body and lower body obesity. Upper body obesity is also referred to as central, abdominal, or male obesity. Lower body obesity is known as peripheral, glutealfemoral, or female obesity. The obesity type is determined by dividing the waist by the hip circumference. A waist-tohip ratio greater than 1.0 in men and 0.8 in women indicates upper body obesity (Fig. 11-4). Research suggests that fat distribution may be a more important factor for morbidity and mortality than overweight or obesity. The presence of excess fat in the abdomen out of proportion to total body fat is an independent predictor of risk factors and mortality. Waist circumference is positively correlated with abdominal fat content. Waist circumference of

OBESITY ➤ Obesity results from an imbalance between energy intake and energy consumption. Because fat is the main storage form of energy, obesity represents an excess of body fat. ➤ Overweight and obesity are determined by measurements of body mass index (BMI; weight [kg]/height [m2]) and waist circumference. A BMI of 25 to 29.9 is considered overweight; a BMI of 30 or greater as obese; and a BMI greater than 40 as very or morbidly obese. ➤ Waist circumference is used to determine the distribution of body fat. Central, or abdominal, obesity is an independent predictor of morbidity and mortality associated with obesity.

Fat biopsy

FIGURE 11-4 Distribution of body fat and size of fat cells in persons with upper and lower body obesity. (Courtesy of Ahmed Kissebah, M.D., Ph.D., Medical College of Wisconsin, Milwaukee)

CHAPTER 11

35 inches or greater in women and 40 inches or greater in men has been associated with increased health risk13 (see Table 11-8). Central obesity can be further differentiated into intraabdominal (viscera) fat and subcutaneous fat by the use of CT or MRI scans. However, intraabdominal fat usually is synonymous with central fat distribution. One of the characteristics of abdominal fat is that fatty acids released from the viscera go directly to the liver before entering the systemic circulation, having a potentially greater impact on hepatic function. Higher levels of circulating free fatty acids in obese persons, particularly those with upper body obesity, are thought to be associated with many of the adverse effects of obesity.18 In general, men have more intraabdominal fat and women more subcutaneous fat. As men age, the proportion of intraabdominal fat to subcutaneous fat increases. After menopause, women tend to acquire more central fat distribution. Increasing weight gain, alcohol, and low levels of activity are associated with upper body obesity. These changes place persons with upper body obesity at greater risk for ischemic heart disease, stroke, and death independent of total body fat. They also tend to exhibit hypertension, elevated levels of triglycerides and decreased levels of high-density lipoproteins, hyperinsulinemia and diabetes mellitus, breast and endometrial cancer, gallbladder disease, menstrual irregularities, and infertility. Visceral fat also is associated with abnormalities of metabolic and sex hormone levels.24 Weight loss causes a loss of visceral fat and has resulted in improvements in metabolic and hormonal abnormalities.25,26 Although peripheral obesity is associated with varicose veins in the legs and mechanical problems, it does not increase the risk for heart disease.27 In terms of weight reduction, some studies have shown that persons with upper body obesity are easier to treat than those with lower body obesity. Other studies have shown no difference in terms of success with weight reduction programs between the two types of obesity. Weight cycling (the losing and gaining of weight) has been found to have little or no effect on metabolic variables, central obesity, or cardiovascular risk factors or future amount of weight loss.28 More research is needed to determine its effect on dietary preference for fat, psychological adjustment, disordered eating, and mortality.29,30 It is postulated that perhaps it is the underlying obesity and not the weight fluctuation that affects life expectancy.31

HEALTH RISKS ASSOCIATED WITH OBESITY Obesity affects both psychosocial and physical well-being. In the United States as well as other countries, there are many negative stereotypes associated with obesity. People, especially women, are expected to be thin, and obesity may be seen as a sign of a lack of self-control. Obesity may negatively affect employment and educational opportunities as well as marital status. Obesity also may play a role in a person’s treatment by health professionals.32 Although nurses, physicians, and other health professionals are aware of the low success rate and difficulty in treating weight problems, they still may place the blame on the obese patient.32

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In terms of health problems, obese persons are more likely to have high blood pressure, hyperlipidemia, cardiovascular disease, stroke, glucose intolerance, insulin resistance, type II diabetes, stroke, gallbladder disease, infertility, and cancer of the endometrium, prostate, colon, uterine, ovaries, kidney, gallbladder, and in postmenopausal women, breast.20 The increased weight associated with obesity stresses the bones and joints, increasing the likelihood of arthritis. Other conditions associated with obesity include sleep apnea and pulmonary dysfunction, asthma, complications of pregnancy, menstrual irregularities, hirsutism, psychological distress, nonalcoholic steatohepatitis, carpal tunnel syndrome, venous insufficiency and deep vein thrombosis, and poor wound healing.20 Because some drugs are lipophilic and exhibit increased distribution in fat tissue, the administration of these drugs, including some anesthetic agents, can be more dangerous in obese persons. If surgery is required, the obese person heals slower than a nonobese person of the same age. Massive obesity, because of its close association with so many health problems, can be regarded as a disease in its own right.33 It is the second leading cause of preventable death. In men who have never smoked, the risk for death increases from 1.06 at a BMI of 24.5 to 1.67 at a BMI higher than 26.34 The waist-to-hip ratio is a less reliable predictor of mortality in women than BMI.

PREVENTION OF OBESITY Emphasis is being placed on the prevention of obesity. It has been theorized that obesity is largely preventable because hereditary factors exert only a moderate effect. Some experts indicate that prevention should focus on young children, adolescents, and young adults,35 while others would target the high-risk period from 25 to 35 years, menopause, and the year after successful weight loss.36 A more active lifestyle together with a low-fat diet (38°C or 90 beats per minute Respiratory rate >20 breaths per minute or PaCO2 50 breaths per minute).74

Diagnosis and Treatment Diagnosis of congestive failure in infants and children is based on symptomatology, chest radiographic films, electrocardiographic findings, echocardiographic techniques to assess cardiac structures and ventricular function (i.e., endsystolic and end-diastolic diameters), arterial blood gases to determine intracardiac shunting and ventilation-perfusion inequalities, and other laboratory studies to determine anemia and electrolyte imbalances. Treatment of congestive failure in infants and children includes measures aimed at improving cardiac function and eliminating excess intravascular fluid. Oxygen delivery must be supported and oxygen demands controlled or minimized. Whenever possible, the cause of the disorder is corrected (e.g., medical treatment of sepsis and anemia, surgical correction of congenital heart defects). With congenital anomalies that are amenable to surgery, medical treatment often is needed for a time before surgery and usually is continued in the immediate postoperative period. For many children, only medical management can be provided. Medical management of heart failure in infants and children is similar to that in adults, although it is tailored to

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the special developmental needs of the child. Inotropic agents such as digitalis often are used to increase cardiac contractility. Diuretics may be given to reduce preload, and vasodilating drugs may be used to manipulate the afterload. Drug doses must be carefully tailored to control for the child’s weight and conditions such as reduced renal function. Daily weighing and accurate measurement of intake and output are imperative during acute episodes of failure. Most children feel better in the semiupright position. An infant seat is useful for infants with chronic CHF. Activity restrictions usually are designed to allow children to be as active as possible within the limitations of their heart disease. Infants with congestive failure often have problems feeding. Small, frequent feedings usually are more successful than larger, less frequent feedings. Severely ill infants may lack sufficient strength to suck and may need to be tube fed. The treatment of heart failure in children should be designed to allow optimal physical and psychosocial development. It requires the full involvement of the parents, who often are the primary care providers; therefore, parent education and support is essential.

HEART FAILURE IN THE ELDERLY Congestive heart failure is one of the most common causes of disability in the elderly and is the most frequent hospital discharge diagnosis for the elderly. More than 75% of patients with CHF are older than 65 years of age. CHF also is a major cause of chronic disability, and annual expenditures exceed $10 billion.75 Among the factors that have contributed to the increased numbers of older people with CHF are the improved therapies for ischemic and hypertensive heart disease.75 Thus, persons who would have died from acute myocardial disease 20 years ago are now surviving, but with residual left ventricular dysfunction. Similarly, improved blood pressure control has led to a 60% decline in stroke mortality rates, yet these same people remain at risk for CHF as a complication of hypertension. Also, advances in treatment of other diseases have contributed indirectly to the rising prevalence of CHF in the older population. Coronary heart disease, hypertension, and valvular heart disease (particularly aortic stenosis and mitral regurgitation) are common causes of CHF in older adults.75,76 Although the pathophysiology of CHF is similar in younger and older persons, elderly persons tend to develop cardiac failure when confronted with stresses that would not produce failure in younger persons. There are four principal changes associated with cardiovascular aging that impair the ability to respond to stress.75 First, reduced responsiveness to β-adrenergic stimulation limits the heart’s capacity maximally to increase heart rate and contractility. A second major effect of aging is increased vascular stiffness, which results in an increased resistance to left ventricular ejection (afterload) and contributes to the development of systolic hypertension in the elderly. Third, in addition to increased vascular stiffness, the heart itself becomes stiffer and less compliant with age. The changes in diastolic

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stiffness result in important alterations in diastolic filling and atrial function. A reduction in ventricular filling not only affects cardiac output but also produces an elevation in diastolic pressure that is transmitted back to the left atrium, where it stretches the muscle wall and predisposes to atrial ectopic beats and atrial fibrillation. The fourth major effect of cardiovascular aging is altered myocardial metabolism at the level of the mitochondria. Although older mitochondria may be able to generate sufficient ATP to meet the normal energy needs of the heart, they may not be able to respond under stress.

Manifestations The manifestations of CHF in elderly persons often are masked by other disease conditions.77 Nocturia is an early symptom but may be caused by other conditions such as prostatic hypertrophy. Dyspnea on exertion may result from lung disease, lack of exercise, and deconditioning. Lower extremity edema commonly is caused by venous insufficiency. Among the acute manifestations of CHF in the elderly are increasing lethargy and confusion, probably the result of impaired cerebral perfusion. Activity intolerance is common. Instead of dyspnea, the prominent sign may be restlessness. Impaired perfusion of the gastrointestinal tract is a common cause of anorexia and profound loss of lean body mass. Loss of lean body mass may be masked by edema. The elderly also maintain a precarious balance between the managed symptom state and acute symptom exacerbation. During the managed symptom state, they are relatively symptom free while adhering to their treatment regimen. Acute symptom exacerbation, often requiring emergency medical treatment, can be precipitated by seemingly minor conditions such as poor compliance with sodium restriction, infection, or stress. Failure to seek medical care promptly is a common cause of progressive acceleration of symptoms.

Diagnosis and Treatment The diagnosis of heart failure in the elderly is based on the history, physical examination, chest radiograph, and electrocardiographic findings.77 However, the presenting symptoms of CHF often are difficult to evaluate. Symptoms of dyspnea on exertion are often attributed to a sign of “getting older” or deconditioning from other diseases. Ankle edema is not unusual in the elderly because the skin turgor decreases and the elderly tend to be more sedentary with the legs in a dependent position. Treatment of CHF in the elderly involves many of the same methods as in younger persons. Activities are restricted to a level that is commensurate with the cardiac reserve. Seldom is bed rest recommended or advised. Bed rest causes rapid deconditioning of skeletal muscles and increases the risk for complications such as orthostatic hypotension and thromboemboli. Instead, carefully prescribed exercise programs can help to maintain activity tolerance. Even walking around a room usually is preferable to continuous bed rest. Sodium restriction usually is indicated.

Age- and disease-related changes increase the likelihood of adverse drug reactions and drug–drug interactions. Drug dosages and the number of drugs prescribed should be kept to a minimum. Compliance with drug regimens often is difficult; the simpler the regimen, the more likely it is that the older person will comply. In general, the treatment plan for the elderly person with CHF must be put in the context of his or her overall needs. An improvement in the quality of life may take precedence over increasing the length of survival. In summary, the mechanisms of heart failure in children and the elderly are similar to those in adults. However, the causes and manifestations may differ because of age. In children, CHF is seen most commonly during infancy and immediately after heart surgery. It can be caused by congenital and acquired heart defects and is characterized by fatigue, effort intolerance, cough, anorexia, abdominal pain, and impaired growth. Treatment of CHF in children includes correction of the underlying cause whenever possible. For congenital anomalies that are amenable to surgery, medical treatment often is needed for a time before surgery and usually is continued in the immediate postoperative period. For many children, only medical management can be provided. In elderly people, age-related changes in cardiovascular functioning contribute to CHF but are not in themselves sufficient to cause heart failure. The manifestations of congestive failure often are different and superimposed on other disease conditions; therefore, CHF often is more difficult to diagnose in the elderly than in younger persons. Because the elderly are more susceptible to adverse drug reactions and have more problems with compliance, the number of drugs prescribed is kept to a minimum, and the drug regimen is kept as simple as possible.

REVIEW EXERCISES A 75-year-old woman with long-standing hypertension and angina due to coronary heart disease presents with ankle edema, nocturia, increased shortness of breath with activity, and a chronic nonproductive cough. Her blood pressure is 170/80 mm Hg, and her heart rate is 92 beats per minute. Electrocardiograph and chest x-ray reports indicate the presence of left ventricular hypertrophy. A. Relate the presence of uncontrolled hypertension and coronary artery disease to the development of heart failure in this woman. B. Explain the significance of left ventricular hypertrophy in terms of both a compensatory mechanism and a pathologic mechanism in the progression of heart failure. C. Use Figure 28-2 to explain this woman’s symptoms, including shortness of breath and nonproductive cough. A 26-year-old man is admitted to the emergency room with excessive blood loss following an automobile in-

CHAPTER 28

jury. He is alert and anxious, his skin is cool and moist, his heart rate is 135 beats per minute, and his blood pressure 100/85 mm Hg. He is receiving intravenous fluids, which were started at the scene of the accident by an emergency medical technician. He has been typed and cross-matched for blood transfusions, and a urinary catheter has been inserted to monitor his urine output. His urine output has been less than 10 mL since admission, and his blood pressure has dropped to 85/70 mm Hg. Efforts to control his bleeding have been unsuccessful, and he is being prepared for emergency surgery. A. Use information regarding the compensatory mechanisms in circulatory shock to explain this man’s presenting symptoms, including urine output. B. Use Figure 26-12 to hypothesize on this man’s blood loss and maintenance of blood pressure. C. The treatment of hypovolemic shock is usually directed at maintaining the circulatory volume through fluid resuscitation rather than maintaining the blood pressure through the use of vasoactive medications. Explain.

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U N I T

VII Respiratory Function

I

n the early studies of the body, there is almost no mention of the lungs or respiratory passages. Although the pneuma, or “vital spirits,” of the body were closely related to the air and vapors of the universe, the lungs and air passages were almost disregarded. It was not until the circulation of blood had been charted that real progress in understanding the respiratory system took place. A major step in the understanding of respiration began with the work of Robert Boyle (1627–1691), an Irish scholar. Using an air pump, Boyle proved that a candle would not burn and a small bird or mouse could not live inside a jar from which the air had been removed. Scientists at this time believed that when something burned, air lost a mysterious substance called phlogiston. It was the British clergyman Joseph Priestley (1733–1804) who discovered that a gas made by heating oxide of mercury supported combustion. He called this gas, which later became known as oxygen, dephlogisticated air. Priestley showed that a mouse lived longer in a given volume of dephlogisticated air than it did in ordinary air. Antoine Lavoisier (1743–1794), a French chemist, confirmed that oxygen was present in inspired air and carbon dioxide in expired air and gave oxygen its name. In 1791, just 16 years after Priestley’s discovery of oxygen, it was shown that blood contained both oxygen and carbon dioxide. From this point on, a detailed understanding of the respiratory system and its function proceeded rapidly.

CHAPTER

29

Control of Respiratory Function STRUCTURAL ORGANIZATION OF THE RESPIRATORY SYSTEM The Conducting Airways Nasopharyngeal Airways Laryngotracheal Airways Tracheobronchial Tree The Lungs and Respiratory Airways Respiratory Lobules Lung Circulation Pleura EXCHANGE OF GASES BETWEEN THE ATMOSPHERE AND THE LUNGS Basic Properties of Gases Ventilation and the Mechanics of Breathing Respiratory Pressures The Chest Cage and Respiratory Muscles Lung Compliance Airway Resistance Lung Volumes Pulmonary Function Studies Efficiency and the Work of Breathing EXCHANGE AND TRANSPORT OF GASES Ventilation Distribution of Ventilation Perfusion Distribution of Blood Flow and Body Position Hypoxia-induced Vasoconstriction Diffusion Matching of Ventilation and Perfusion Dead Air Space Shunt Mismatching of Ventilation and Perfusion Gas Transport Oxygen Transport Carbon Dioxide Transport CONTROL OF BREATHING Respiratory Center Chemoreceptors Lung Receptors Cough Reflex Dyspnea

R

espiration provides the body with a means of gas exchange. It is the process whereby oxygen from the air is transferred to the blood and carbon dioxide is eliminated from the body. Respiration can be divided into three parts: ventilation, or the movement of air between the atmosphere and the respiratory portion of the lungs; perfusion, or the flow of blood through the lungs; and diffusion, or the transfer of gases between the air-filled spaces in the lungs and the blood. The nervous system controls the movement of the respiratory muscles and adjusts the rate of breathing so that it matches the needs of the body during various levels of activity. The content in this chapter focuses on the structure and function of the respiratory system as it relates to these aspects of respiration. The function of the red blood cell in the transport of oxygen is discussed in Chapter 16.

Structural Organization of the Respiratory System After completing this section of the chapter, you should be able to meet the following objectives:

✦ State the difference between the conducting and the respiratory airways

✦ Trace the movement of air through the airways, ✦ ✦ ✦ ✦ ✦

beginning in the nose and oropharynx and moving into the respiratory tissues of the lung Describe the function of the mucociliary blanket Define the term water vapor pressure and cite the source of water for humidification of air as it moves through the airways Compare the supporting structures of the large and small airways in terms of cartilaginous and smooth muscle support Differentiate the function of the bronchial and pulmonary circulations that supply the lungs State the function of the two types of alveolar cells

The respiratory system consists of the air passages and the lungs. Functionally, the respiratory system can be divided into two parts: the conducting airways, through which 3

4

UNIT VII

Respiratory Function

CONDUCTING AND RESPIRATORY AIRWAYS ➤ Respiration requires ventilation, or movement of gases into and out of the lungs; perfusion, or movement of blood through the lungs; and diffusion of gases between the lungs and the blood. ➤ Ventilation depends on conducting airways, including the nasopharynx and oropharynx, larynx, and tracheobronchial tree, which move air into and out of the lungs but do not participate in gas exchange. ➤ Gas exchange takes place in the respiratory airways of the lungs, where gases diffuse across the alveolar-capillary membrane as they are exchanged between the lungs and the blood that flows through the pulmonary capillaries.

air moves as it passes between the atmosphere and the lungs, and the respiratory tissues of the lungs, where gas exchange takes place.

THE CONDUCTING AIRWAYS The conducting airways consist of the nasal passages, mouth and pharynx, larynx, trachea, bronchi, and bronchioles (Fig. 29-1). The air we breathe is warmed, filtered, and moistened as it moves through these structures. Heat is transferred to the air from the blood flowing through the walls of the respiratory passages; the mucociliary blanket removes foreign materials; and water from the mucous membranes is used to moisten the air. The conducting airways are lined with a pseudostratified columnar epithe-

Nasopharynx Oropharynx Epiglottis Trachea Intrapulmonary bronchus

Larynx Extrapulmonary bronchus Alveoli

Respiratory bronchiole

Parietal pleura Visceral pleura Diaphragm Pleural cavity

Esophagus FIGURE 29-1 Structures of the respiratory system.

lium that contains a mosaic of mucus-secreting goblet cells and cells that contain hairlike projections called cilia (Fig. 29-2). The epithelial layer gradually becomes thinner as it moves from the pseudostratified epithelium of the bronchi to the cuboidal epithelium of the bronchioles and then to the squamous epithelium of the alveoli. The mucus produced by the goblet cells in the conducting airways forms a layer, called the mucociliary blanket, that protects the respiratory system by entrapping dust and other foreign particles that enter the airways. The cilia, which constantly are in motion, move the mucociliary blanket with its entrapped particles toward the oropharynx, from which it is expectorated or swallowed. The function of the mucociliary blanket in clearing the lower airways and alveoli is optimal at normal oxygen levels and is impaired in situations of low and high oxygen levels. Clearance is facilitated by coughing. It is impaired by drying, such as breathing heated but unhumidified indoor air during winter. Cigarette smoking slows down or paralyzes the motility of the cilia. This slowing allows the residue from tobacco smoke, dust, and other particles to accumulate in the lungs, decreasing the efficiency of this pulmonary defense system. There also is evidence that smoking causes hyperplasia of the goblet cells, with a resultant increase in respiratory tract secretions and increased susceptibility to respiratory tract infections. As discussed in Chapter 31, these changes are thought to contribute to the development of chronic bronchitis and emphysema. The airways are kept moist by water contained in the mucous layer. Moisture is added to the air as it moves through the conducting airways. The capacity of the air to contain moisture or water vapor without condensation increases as the temperature rises. Thus, the air in the alveoli, which is maintained at body temperature, usually contains considerably more water vapor than the atmospherictemperature air that we breathe. The difference between the water vapor contained in the air we breathe and that found in the alveoli is drawn from the moist surface of the mucous membranes that line the conducting airways and is a source of insensible water loss. Under normal conditions, approximately 1 pint of water per day is lost in humidifying the air breathed. During fever, the water vapor in the lungs increases, causing more water to be lost from the respiratory mucosa. Also, fever usually is accompanied by an increase in respiratory rate so that more air passes through the airways, withdrawing moisture from its mucosal surface. As a result, respiratory secretions thicken, preventing free movement of the cilia and impairing the protective function of the mucociliary defense system. This is particularly true in persons whose water intake is inadequate.

Nasopharyngeal Airways The nose is the preferred route for the entrance of air into the respiratory tract during normal breathing. As air passes through the nasal passages, it is filtered, warmed, and humidified. The outer nasal passages are lined with coarse hairs, which filter and trap dust and other large particles from the air. The upper portion of the nasal cavity is lined with mucous membrane that contains a rich network

CHAPTER 29

Control of Respiratory Function

5

FIGURE 29-2 Airway wall structure: bronchus, bronchiole, and alveolus. The bronchial wall contains pseudostratified epithelium, smooth muscle cells, mucous glands, connective tissue, and cartilage. In smaller bronchioles, a simple epithelium is found, cartilage is absent, and the wall is thinner. The alveolar wall is designed for gas exchange, rather than structural support. (From Weibel E. R., Taylor R. C. [1988]. Design and structure of the human lung. In Fishman A. P. [Ed.]. Pulmonary diseases and disorders, Vol. 1. [p. 14] New York: McGraw-Hill)

Laryngotracheal Airways

of small blood vessels; this portion of the nasal cavity supplies warmth and moisture to the air we breathe. The mouth serves as an alternative airway when the nasal passages are plugged or when there is a need for the exchange of large amounts of air, as occurs during exercise. The oropharynx extends posteriorly from the soft palate to the epiglottis. The oropharynx is the only opening between the nose and mouth and the lungs. Both swallowed food on its way to the esophagus and air on its way to the larynx pass through it. Obstruction of the oropharynx leads to immediate cessation of ventilation. Neural control of the tongue and pharyngeal muscles may be impaired in coma and certain types of neurologic disease. In these conditions, the tongue falls back into the pharynx and obstructs the airway, particularly if the person is lying on his or her back. Swelling of the pharyngeal structures caused by injury, infection, or severe allergic reaction also predisposes a person to airway obstruction, as does the presence of a foreign body.

The larynx connects the oropharynx with the trachea. The walls of the larynx are supported by firm cartilaginous structures that prevent collapse during inspiration. The functions of the larynx can be divided into two categories: those associated with speech and those associated with protecting the lungs from substances other than air. The larynx is located in a strategic position between the upper airways and the lungs and sometimes is referred to as the “watchdog of the lungs.” The epiglottis, which is located above the larynx, is a large, leaf-shaped piece of cartilage that is covered with epithelium. During swallowing, the free edges of the epiglottis move downward to cover the larynx, thus routing liquids and foods into the esophagus. The cavity of the larynx is divided into two pairs of two-by-two folds of mucous membrane stretching from front to back with an opening in the midline (Fig. 29-3).

A Epiglottis

B Epiglottis Glottis

Vestibular folds (false vocal cords) Vocal folds (true vocal cords)

FIGURE 29-3 (A) Coronal section showing the position of the epiglottis, the vestibular folds (false vocal cords), the vocal folds (true vocal cords), and glottis. (B) Vocal cords viewed from above with the glottis closed and (C) with the glottis open.

Trachea

False vocal cord True vocal cord

Inner lining trachea

6

UNIT VII

Respiratory Function

The upper pair of folds, called the vestibular folds, has a protective function. The lower pair of folds has cordlike margins; they are termed the vocal folds because their vibrations are required for making vocal sounds. The vocal folds and the elongated opening between them are called the glottis. A complex set of muscles controls the opening and closing of the glottis. In addition to opening and closing the glottis for speech, the vocal folds of the larynx can perform a sphincter function in closing off the airways. When confronted with substances other than air, the laryngeal muscles contract and close off the airway. At the same time, the cough reflex is initiated as a means of removing a foreign substance from the airway. This protective mechanism prevents food and fluids from being pulled into the lungs where they can cause serious problems. During defecation and urination, inhaled air is temporarily held in the lungs by closing the glottis. The intraabdominal muscles then contract, causing both intraabdominal and intrathoracic pressures to rise. These collective actions are called the Valsalva maneuver. By producing an increase in intrathoracic pressure, the Valsalva maneuver decreases the return of blood to the heart, thereby inciting a series of circulatory reflexes. A tachycardia, or increase in heart rate, develops during the maneuver as the circulatory system compensates for the decrease in blood return to the heart. On termination of the maneuver, a short period of bradycardia, or decreased heart rate, occurs as blood that has been dammed back in the venous circulation returns to the heart.

Tracheobronchial Tree The tracheobronchial tree, which consists of the trachea, bronchi, and bronchioles, can be viewed as a system of branching tubes (Fig. 29-4). The trachea, or windpipe, is a

continuous tube that connects the larynx and the major bronchi of the lungs. The walls of the trachea are supported by horseshoe-shaped cartilages, which prevent it from collapsing when the pressure in the thorax becomes negative. The trachea is located anterior to the esophagus and extends to superior border of the fifth thoracic vertebra where it divides to form the right and the left primary bronchi. Each bronchus enters the lung through a slit called the hilus. The point at which the trachea divides is called the carina. The carina is heavily innervated with sensory neurons, and coughing and bronchospasm result when this area is stimulated, as during tracheal suctioning. The right primary bronchus is shorter and wider and continues at a more vertical angle with the trachea than the left primary bronchus, which is longer and narrower and forms a more acute angle with the trachea. The anatomic differences between the two bronchi also make it easier for foreign bodies to enter the right main bronchus than the left. On entering the lungs, the primary bronchi divide into secondary, or lobular, bronchi, which supply each of the lobes of the lungs (the right lung has three lobes; the left has two). The secondary bronchi continue to branch, forming the still smaller tertiary bronchi, which divide into the bronchioles. Bronchioles, in turn, branch repeatedly until they become the terminal bronchioles, the smallest of the conducting airways. This extensive branching is similar to a tree whose branches become smaller and more numerous as they divide. In all, there are approximately 23 levels of branching, beginning with the conducting airways and ending with the respiratory airways, where gas exchange takes place (Fig. 29-5). The right middle lobe bronchus is of relatively small diameter and length and sometimes bends sharply near its bifurcation. It is surrounded by a collar of lymph nodes that

Location of larynx Thyroid cartilage Cricoid cartilage Upper lobe

Tracheal cartilage Upper lobe

Right primary bronchus

Left primary bronchus Bronchioles

Middle lobe

Lower lobe

Lower lobe FIGURE 29-4 Larynx, trachea, and bronchial tree (anterior view).

CHAPTER 29

FIGURE 29-5 Idealization of the human airways. The first 16 generations of branching (Z) make up the conducting airways, and the last seven constitute the respiratory zone (or transitional and respiratory zone). BR, bronchus; BL, bronchiole; TBL, terminal bronchiole; RBL, respiratory bronchiole; AD, alveolar ducts; AS, alveolar sacs. (Weibel E. R. [1962]. Morphometry of the human lung [p. 111]. Berlin: Springer-Verlag)

drain the middle and the lower lobe and is particularly subject to obstruction. The secondary bronchi divide to form the tertiary segmental bronchi, which supply the bronchopulmonary segments of the lung. There are 10 segments in the right lung and 9 segments in the left lung (Fig. 29-6). These segments are identified according to their location in the lung (e.g., the apical segment of the right upper lobe) and are the smallest named units in the lung. Lung lesions such as atelectasis and pneumonia often are localized to a particular bronchopulmonary segment. The structure of the primary bronchi is similar to that of the trachea, in that these airways are supported by cartilaginous rings. As the bronchi move into the lungs, irregular plates of cartilage replace the horseshoe-shaped cartilage rings. These cartilaginous plates gradually become thinner and then disappear at the level of the respiratory bronchioles. Between the cartilaginous support and the mucosal surface are two crisscrossing layers of smooth muscle that wind in opposite directions (Fig. 29-7). Bronchospasm, or contraction of these muscles, causes narrowing of the bronchioles and impairs air flow.

7

Control of Respiratory Function

FIGURE 29-6 Bronchopulmonary segments of the human lung. Left and right upper lobes: (1) apical, (2) posterior, (3) anterior, (4) superior lingular, and (5) inferior lingular segments. Right middle lobe: (4) lateral and (5) medial segments. Lower lobes: (6) superior (apical), (7) medial-basal, (8) anterior-basal, (9) lateral-basal, and (10) posteriorbasal segments. The medial-basal segment (7) is absent in the left lung. (Fishman A. P. [1980]. Assessment of pulmonary function [p. 19]. New York: McGraw-Hill)

sels, lymph nodes, nerve fibers, thymus gland, and esophagus. The upper part of the lung, which lies against the top of the thoracic cavity, is called the apex, and the lower part, which lies against the diaphragm, is called the base. The lungs are divided into lobes: three in the right lung and two in the left (see Fig. 29-4).

Air

Lymphatics

Bronchiole

Pulmonary vein

Smooth muscle Pulmonary artery Pulmonary capillaries

THE LUNGS AND RESPIRATORY AIRWAYS The lungs are soft, spongy, cone-shaped organs located side by side in the chest cavity (see Fig. 29-1). They are separated from each other by the mediastinum (i.e., the space between the lungs) and its contents—the heart, blood ves-

Alveoli FIGURE 29-7 Lobule of the lung, showing the bronchial smooth muscle fibers, pulmonary blood vessels, and lymphatics.

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UNIT VII

Respiratory Function

The lungs are the functional structures of the respiratory system. In addition to their gas exchange function, they inactivate vasoactive substances such as bradykinin; they convert angiotensin I to angiotensin II; and they serve as a reservoir for blood storage. Heparin-producing cells are particularly abundant in the capillaries of the lung, where small clots may be trapped.

Respiratory Lobules The gas exchange function of the lung takes place in the lobules of the lungs. Each lobule, which is the smallest functional unit of the lung, is supplied by a branch of a terminal bronchiole, an arteriole, the pulmonary capillaries, and a venule (see Fig. 29-7). Gas exchange takes place in the terminal respiratory bronchioles and the alveolar ducts and sacs. Blood enters the lobules through a pulmonary artery and exits through a pulmonary vein. Lymphatic structures surround the lobule and aid in the removal of plasma proteins and other particles from the interstitial spaces. Unlike the larger bronchi, the respiratory bronchioles are lined with simple epithelium rather than ciliated pseudostratified epithelium (see Fig. 29-2). The respiratory bronchioles also lack the cartilaginous support of the larger airways. Instead, they are attached to the elastic spongework of tissue that contains the alveolar air spaces. When the air spaces become stretched during inspiration, the bronchioles are pulled open by expansion of the surrounding tissue. The alveolar sacs are cup-shaped, thin-walled structures that are separated from each other by thin alveolar septa. A single network of capillaries occupies most of the septa, so that blood is exposed to air on both sides. There are approximately 300 million alveoli in the adult lung, with a total surface area of approximately 50 to 100 m2. Unlike the bronchioles, which are tubes with their own separate walls, the alveoli are interconnecting spaces that have no separate walls (Fig. 29-8). As a result of this arrangement, there is a continual mixing of air in the alveolar structures. Small holes in the alveolar walls, the pores of Kohn, probably contribute to the mixing of air under certain conditions. The alveolar structures are composed of two types of cells: type I alveolar cells and type II alveolar cells (Fig. 29-9). The type I alveolar cells are flat squamous epithelial cells across which gas exchange takes place. The type II alveolar cells produce surfactant, a lipoprotein substance that decreases the surface tension in the alveoli. This action allows for greater ease of lung inflation and helps to prevent the collapse of smaller airways. The alveoli also contain alveolar macrophages, which are responsible for the removal of offending substances from the alveolar epithelium.

Lung Circulation The lungs are provided with a dual blood supply, the pulmonary and bronchial circulations. The pulmonary circulation arises from the pulmonary artery and provides for the gas exchange function of the lungs. Deoxygenated blood leaves the right heart through the pulmonary artery, which divides into a left pulmonary artery that enters the

FIGURE 29-8 Close-up of a cross section of a small bronchus and surrounding alveoli. (Courtesy of Janice A. Nowell, University of California, Santa Cruz)

left lung and a right pulmonary artery that enters the right lung. Return of oxygenated blood to the heart occurs by way of the pulmonary veins, which empty into the left atrium. The bronchial circulation distributes blood to the conducting airways and supporting structures of the lung. The bronchial circulation has a secondary function of warming and humidifying incoming air as it moves through the conducting airways. The bronchial arteries arise from the thoracic aorta and enter the lungs with the major bronchi, dividing and subdividing along with the bronchi as they move out into the lung, supplying them and other lung structures with oxygen. The capillaries of the bronchial circulation drain into the bronchial veins, the larger of which empties into the vena cava. The smaller of the bronchial veins empties into the pulmonary veins. This blood is unoxygenated because the bronchial circulation does not participate in gas exchange. As a result, this blood dilutes the oxygenated blood returning to the left side of the heart. The bronchial blood vessels are the only ones that undergo angiogenesis (formation of new vessels) and

CHAPTER 29

Alveolus

Alveolus

Nucleus Type II cell Type I cell

Microvili Lamellar inclusion body Mitochondria

Capillary

Endothelium

FIGURE 29-9 Schematic drawing of the two types of alveolar cells and their relation to alveoli and capillaries. Alveolar type I cells comprise most of the alveolar surface. Alveolar type II cells are located in the corner between two adjacent alveoli. Also shown are endothelial cells that line the pulmonary capillaries. (Rhoades R. A., Tanner G. A. [1996]. Medical physiology [p. 362]. Boston: Little, Brown)

Control of Respiratory Function

9

place. The conducting airways include the nasal passages, mouth and nasopharynx, larynx, and tracheobronchial tree. Air is warmed, filtered, and humidified as it passes through these structures. The lungs are the functional structures of the respiratory system. In addition to their gas exchange function, they inactivate vasoactive substances such as bradykinin; they convert angiotensin I to angiotensin II; and they serve as a reservoir for blood. The lobules, which are the functional units of the lung, consist of the respiratory bronchioles, alveoli, and pulmonary capillaries. It is here that gas exchange takes place. Oxygen from the alveoli diffuses across the alveolar capillary membrane into the blood, and carbon dioxide from the blood diffuses into the alveoli. The lungs are provided with a dual blood supply: the pulmonary circulation provides for the gas exchange function of the lungs and the bronchial circulation distributes blood to the conducting airways and supporting structures of the lung. The lungs are encased in a thin, transparent, double-layered serous membrane called the pleura.

Exchange of Gases Between the Atmosphere and the Lungs After completing this section of the chapter, you should be able to meet the following objectives:

develop collateral circulation when vessels in the pulmonary circulation are obstructed, as in pulmonary embolism. The development of new blood vessels helps to keep lung tissue alive until the pulmonary circulation can be restored.

✦ Describe the basic properties of gases in relation to their

PLEURA

✦ ✦

A thin, transparent, double-layered serous membrane, called the pleura, lines the thoracic cavity and encases the lungs. The outer parietal layer lies adjacent to the chest wall, and the inner visceral layer adheres to the outer surface of the lung (see Fig. 29-1). The parietal pleura forms part of the mediastinum and lines the inner wall of the thoracic or chest cavity. A thin film of serous fluid separates the two pleural layers, and this allows the two layers to glide over each other and yet hold together, so that there is no separation between the lungs and the chest wall. The pleural cavity is a potential space in which serous fluid or inflammatory exudate can accumulate. The term pleural effusion is used to describe an abnormal collection of fluid or exudate in the pleural cavity. In summary, the respiratory system consists of the air passages and the lungs, where gas exchange takes place. Functionally, the air passages of the respiratory system can be structurally divided into two parts: the conducting airways, through which air moves as it passes into and out of the lungs, and the respiratory tissues, where gas exchange actually takes

✦

✦ ✦ ✦ ✦

partial pressures and their pressures in relation to volume and temperature State the definitions of intrathoracic, intrapleural, and intra-alveolar pressures, and state how each of these pressures changes in relation to atmospheric pressure during inspiration and expiration State a definition of lung compliance Use Laplace’s law to explain the need for surfactant in maintaining the inflation of small alveoli State the major determinant of airway resistance Explain why increasing lung volume (e.g., taking deep breaths) reduces airway resistance Define inspiratory reserve, expiratory reserve, vital capacity, and residual volume Describe the method for measuring FEV1.0

BASIC PROPERTIES OF GASES The air we breathe is made up of a mixture of gases, mainly nitrogen and oxygen. These gases exert a combined pressure called the atmospheric pressure. The pressure at sea level, which is defined as one atmosphere, is 760 millimeters of mercury (mm Hg), or 14.7 pounds per square inch (PSI). When measuring respiratory pressures, atmospheric pressure is assigned a value of 0. A respiratory pressure of +15 mm Hg means that the pressure is 15 mm Hg above atmospheric pressure, and a respiratory pressure of −15 mm Hg is 15 mm Hg less than atmospheric pressure. Respiratory pressures often are expressed in centimeters of

10

UNIT VII

Respiratory Function

water (cm H2O) because of the small pressures involved (1 mm Hg = 1.35 cm H2O pressure). The pressure exerted by a single gas in a mixture is called the partial pressure. The capital letter “P” followed by the chemical symbol of the gas (PO2) is used to denote its partial pressure. The law of partial pressures states that the total pressure of a mixture of gases, as in the atmosphere, is equal to the sum of the partial pressures of the different gases in the mixture. If the concentration of oxygen at 760 mm Hg (1 atmosphere) is 20%, its partial pressure is 152 mm Hg (760 × 0.20). Water vapor is different from other types of gases; its partial pressure is affected by temperature but not atmospheric pressure. The relative humidity refers to the percentage of moisture in the air compared with the amount that the air can hold without causing condensation (100% saturation). Warm air holds more moisture than cold air. This is the reason that precipitation in the form of rain or snow commonly occurs when the relative humidity is high and there is a sudden drop in atmospheric temperature. The air in the alveoli, which is 100% saturated at normal body temperature, has a water vapor pressure of 47 mm Hg. The water vapor pressure must be included in the sum of the total pressure of the gases in the alveoli (i.e., the total pressure of the other gases in the alveoli is 760 − 47 = 713 mm Hg). Air moves between the atmosphere and the lungs because of a pressure difference. According to the laws of physics, the pressure of a gas varies inversely with the volume of its container, provided the temperature remains constant. If equal amounts of a gas are placed in two different-sized containers, the pressure of the gas in the smaller container is greater than the pressure in the larger container. The movement of gases is always from the container with the greater pressure to the one with the lesser pressure. The chest cavity can be viewed as a volume container. During inspiration, the size of the chest cavity increases, and air moves into the lungs; during expiration, air moves out as the size of the chest cavity decreases.

VENTILATION AND GAS EXCHANGE ➤ Ventilation refers to the movement of gases into and out of the lungs through a system of open airways and along a pressure gradient resulting from a change in chest volume. ➤ During inspiration, air is drawn into the lungs as the respiratory muscles expand the chest cavity; during expiration, air moves out of the lungs as the chest muscles recoil and the chest cavity becomes smaller. ➤ The ease with which air is moved into and out of the lung depends on the resistance of the airways, which is inversely related to the fourth power of the airway radius, and lung compliance, or the ease with which the lungs can be inflated. ➤ The minute volume, which is determined by the metabolic needs of the body, is the amount of air that is exchanged each minute. It is the product of the tidal volume or amount of air exchanged with each breath multiplied by the respiratory rate.

and air is not moving into or out of the lungs, as occurs just before inspiration or expiration, the intrapulmonary pressure is zero or equal to atmospheric pressure. The pressure in the pleural cavity is called the intrapleural pressure. The intrapleural pressure is always negative in relation to alveolar pressure, approximately −4 mm Hg between breaths when the glottis is open and the alveolar spaces are open to the atmosphere. The lungs and the chest wall have elastic properties, each pulling in the opposite direction. If removed from the chest, the lungs would contract to a smaller size, and the chest wall, if freed from the lungs, would expand. The opposing forces of the chest wall

VENTILATION AND THE MECHANICS OF BREATHING Ventilation is concerned with the movement of gases into and out of the lungs. There is nothing mystical about ventilation. It is purely a mechanical event that obeys the laws of physics as they relate to the behavior of gases. It relies on a system of open airways and the respiratory pressures created as the movements of the respiratory muscles change the size of the chest cage. The degree to which the lungs inflate and deflate depends on the respiratory pressures inflating the lung, compliance of the lungs, and airway resistance.

Intrapleural pressure Airway pressure

Intraalveolar pressure

Intrathoracic pressure

Respiratory Pressures The pressure inside the airways and alveoli of the lungs is called the intrapulmonary pressure or alveolar pressure. The gases in this area of the lungs are in communication with atmospheric pressure (Fig. 29-10). When the glottis is open

FIGURE 29-10 Partitioning of respiratory pressures.

CHAPTER 29

and lungs create a pull against the visceral and parietal layers of the pleura, causing the pressure in the pleural cavity to become negative. During inspiration, the elastic recoil of the lungs increases, causing intrapleural pressure to become more negative than during expiration. Without the negative intrapleural pressure holding the lungs against the chest wall, their elastic recoil properties would cause them to collapse. Although intrapleural pressure is negative in relation to alveolar pressure, it may become positive in relation to atmospheric pressure (e.g., during forced expiration and coughing). The intrathoracic pressure is the pressure in the thoracic cavity. It is essentially equal to intrapleural pressure and is the pressure to which the lungs, heart, and great vessels are exposed. Forced expiration against a closed glottis compresses the air in the thoracic cavity and produces marked increases in intrathoracic pressure and intrapleural pressure.

The Chest Cage and Respiratory Muscles The lungs and major airways share the chest cavity with the heart, great vessels, and esophagus. The chest cavity is a closed compartment bounded on the top by the neck muscles and at the bottom by the diaphragm. The outer walls of the chest cavity are formed by 12 pairs of ribs, the sternum, the thoracic vertebrae, and the intercostal muscles that lie between the ribs. Mechanically, the act of breathing depends on the fact that the chest cavity is a closed compartment whose only opening to the external atmosphere is through the trachea. Ventilation consists of inspiration and expiration. During inspiration, the size of the chest cavity increases, the intrathoracic pressure becomes more negative, and air

Control of Respiratory Function

is drawn into the lungs. Expiration occurs as the elastic components of the chest wall and lung structures that were stretched during inspiration recoil, causing the size of the chest cavity to decrease and the pressure in the chest cavity to increase. The diaphragm is the principal muscle of inspiration. When the diaphragm contracts, the abdominal contents are forced downward, and the chest expands from top to bottom (Fig. 29-11). During normal levels of inspiration, the diaphragm moves approximately 1 cm, but this can be increased to 10 cm on forced inspiration. The diaphragm is innervated by the phrenic nerve roots, which arise from the cervical level of the spinal cord, mainly from C4 but also from C3 and C5. Paralysis of one side of the diaphragm causes the chest to move up on that side rather than down during inspiration because of the negative pressure in the chest. This is called paradoxical movement. The external intercostal muscles, which also aid in inspiration, connect to the adjacent ribs and slope downward and forward (Fig. 29-12). When they contract, they raise the ribs and rotate them slightly so that the sternum is pushed forward; this enlarges the chest from side to side and from front to back. The intercostal muscles receive their innervation from nerves that exit the central nervous system at the thoracic level of the spinal cord. Paralysis of these muscles usually does not have a serious effect on respiration because of the effectiveness of the diaphragm. The accessory muscles of inspiration include the scalene muscles and the sternocleidomastoid muscles. The scalene muscles elevate the first two ribs, and the sternocleidomastoid muscles raise the sternum to increase the size of the chest cavity. These muscles contribute little to

Movement of the diaphragm in inspiration

A Air flow in

FIGURE 29-11 Movement of the diaphragm and changes in chest volume and pressure during inspiration and expiration. (A) Movement of diaphragm and expansion of the chest cavity during inspiration. (B) During inspiration, contraction of the diaphragm and expansion of the chest cavity produce a decrease in intrathoracic pressure, causing air to move into the lungs. (C) During expiration, relaxation of the diaphragm and chest cavity produce an increase in intrathoracic pressure, causing air to move out of the lungs.

11

Air flow out

Pressure

B

Pressure

C Inspiration

Expiration

12

UNIT VII

Respiratory Function

The normal compliance of both lungs in the average adult is approximately 200 mL/cm H2O. This means that every time the transpulmonary pressure increases by 1 cm/ H2O, the lung volume expands by 200 mL. It would take more pressure to move the same amount of air into a noncompliant lung.

Changes in Elastin and Collagen Composition of Lung Tissue. Lung tissue is made up of elastin and collagen

FIGURE 29-12 Expansion and contraction of the thoracic cage during expiration and inspiration, demonstrating especially diaphragmatic contraction, elevation of the rib cage, and function of the intercostals. (Guyton A. C., Hall J. E. [2000]. Textbook of medical physiology [10th ed., p. 433]. Philadelphia: W. B. Saunders)

quiet breathing but contract vigorously during exercise. For the accessory muscles to assist in ventilation, they must be stabilized in some way. For example, persons with bronchial asthma often brace their arms against a firm object during an attack as a means of stabilizing their shoulders so that the attached accessory muscles can exert their full effect on ventilation. The head commonly is bent backward so that the scalene and sternocleidomastoid muscles can elevate the ribs more effectively. Other muscles that play a minor role in inspiration are the alae nasi, which produce flaring of the nostrils during obstructed breathing. Expiration is largely passive. It occurs as the elastic components of the chest wall and lung structures that were stretched during inspiration recoil, causing air to leave the lungs as the intrathoracic pressure increases. When needed, the abdominal and the internal intercostal muscles can be used to increase expiratory effort (see Fig. 29-12). The increase in intra-abdominal pressure that accompanies the forceful contraction of the abdominal muscles pushes the diaphragm upward and results in an increase in intrathoracic pressure. The internal intercostal muscles move inward, which pulls the chest downward, increasing expiratory effort.

fibers. The elastin fibers are easily stretched and increase the ease of lung inflation, whereas the collagen fibers resist stretching and make lung inflation more difficult. In lung diseases such as interstitial lung disease and pulmonary fibrosis, the lungs become stiff and noncompliant as the elastin fibers are replaced with scar tissue. Pulmonary congestion and edema produce a reversible decrease in pulmonary compliance. Elastic recoil describes the ability of the elastic components of the lung to recoil to their original position after having been stretched. Overstretching the airways, as occurs with emphysema, causes the elastic components of the lung to lose their recoil, making the lung easier to inflate but more difficult to deflate because of its inability to recoil.

Surface Tension. An important factor in lung compliance is the surface tension in the alveoli. The alveoli are lined with a thin film of liquid, and it is at the interface between this liquid film and the alveolar air that surface tension develops. This is because the forces that hold the liquid film molecules together are stronger than those that hold the air molecules in the alveoli together. As an example, it is surface tension that holds the water molecules in a raindrop together. In the alveoli, excess surface tension causes the liquid film to contract, making lung inflation more difficult. The pressure in the alveoli (which are modeled as spheres with open airways projecting from them) can be predicted using Laplace’s law (pressure = 2 × surface tension/ radius). If the surface tension were equal throughout the lungs, the alveoli with the smallest radii would have the greatest pressure, and this would cause them to empty into the larger alveoli (Fig. 29-13). The reason this does not occur

Lung Compliance Lung compliance refers to the ease with which the lungs can be inflated. It is determined by the elastin and collagen fibers of the lung, its water content, and surface tension. Compliance can be appreciated by comparing the ease of blowing up a noncompliant new balloon that is stiff and resistant with a compliant one that has been previously blown up and stretched. Specifically, lung compliance (C) describes the change in lung volume (∆V) that can be accomplished with a given change in respiratory pressure (∆P). C = ∆V/∆P

P1

P2

FIGURE 29-13 Law of Laplace (P = 2 T/r, P = pressure, T = tension, r = radius). The effect of the radius on the pressure and movement of gases in the alveolar structures is depicted. Air moves from P1 with a small radius and higher pressure to P2 with its larger radius and lower pressure.

CHAPTER 29

is because of special surface tension–lowering molecules, called surfactant, that line the inner surface of the alveoli. Surfactant is a complex mixture of lipoproteins (largely phospholipids) and small amounts of carbohydrates that is synthesized in the type II alveolar cells. The surfactant molecule has two ends: a hydrophobic (water-insoluble) tail and a hydrophilic (water-soluble) head (Fig. 29-14). The hydrophilic head of the surfactant molecule attaches to the liquid molecules and the hydrophobic tail to the gas molecules, interrupting the intermolecular forces that are responsible for creating the surface tension. Surfactant exerts four important effects on lung inflation: it lowers the surface tension; it increases lung com-

Surfactant molecules in place

Alveolar wall

Air-liquid interface Liquid molecules Surfactant molecule

13

pliance and ease of inflation; it provides for stability and more even inflation of the alveoli; and it assists in preventing pulmonary edema by keeping the alveoli dry. Without surfactant, lung inflation would be extremely difficult, requiring intrapleural pressures of −20 to −30 mm Hg, compared with the pressures of −3 to −5 mm Hg that normally are needed. The surfactant molecules are more densely packed in the small alveoli than in larger alveoli, where the density of the molecules is less. Therefore, surfactant reduces the surface tension more effectively in the small alveoli, which have the greatest tendency to collapse, providing for stability and more even distribution of ventilation. Surfactant also helps to keep the alveoli dry and prevent pulmonary edema. This is because water is pulled out of the pulmonary capillaries into the alveoli when increased surface tension causes the alveoli to contract. The type II alveolar cells that produce surfactant do not begin to mature until the 26th to 28th week of gestation; consequently, many premature infants have difficulty producing sufficient amounts of surfactant. This can lead to alveolar collapse and severe respiratory distress. This condition, called infant respiratory distress syndrome, is the single most common cause of respiratory disease in premature infants. Surfactant dysfunction also is possible in the adult. This usually occurs as the result of severe injury or infection and can contribute to the development of a condition called adult respiratory distress syndrome (see Chapter 31).

Airway Resistance

Hydrophobic tail Hydrophilic head

Control of Respiratory Function

Intermolecular forces

High lung volume

Medium lung volume

Low lung volume

FIGURE 29-14 (Top) Alveolar wall depicting surface tension resulting from the intramolecular forces in the air–liquid film interface; the surfactant molecule with its hydrophobic tail and hydrophilic head; and its function in reducing surface tension by disrupting the intermolecular forces. (Bottom) The surface concentration of surfactant molecules at high, medium, and low lung volumes.

The volume of air that moves into and out of the air exchange portion of the lungs is directly related to the pressure difference between the lungs and the atmosphere and inversely related to the resistance that the air encounters as it moves through the airways. Airway resistance is the ratio of the pressure driving inspiration or expiration to airflow. The French physician Jean Léonard Marie Poiseuille first described the pressureflow characteristics of laminar flow in a straight circular tube, a correlation that has become known as Poiseuille’s law. According to Poiseuille’s law, the resistance to flow is inversely related to the fourth power of the radius (R = 1/r4). If the radius is reduced by one half, the resistance increases 16-fold (2 × 2 × 2 × 2 = 16). Airway resistance normally is so small that only small changes in pressure are needed to move large volumes of air into the lungs. For example, the average pressure change that is needed to move a normal breath of 500 mL of air into the lungs is approximately 1 to 2 cm H2O. Because the resistance of the airways is inversely proportional to the fourth power of the radius, small changes in airway caliber, such as those caused by pulmonary secretions or bronchospasm, can produce a marked increase in airway resistance. For persons with these conditions to maintain the same rate of airflow as before the onset of increased airway resistance, an increase in driving pressure (i.e., respiratory effort) is needed. Airway resistance is greatly affected by lung volumes, being less during inspiration than during expiration. This is because elastic-type fibers connect the outside of the

14

UNIT VII

Respiratory Function

airways to the surrounding lung tissues. As a result, these airways are pulled open as the lungs expand during inspiration, and they become narrower as the lungs deflate during expiration (Fig. 29-15). This is one of the reasons that persons with conditions that increase airway resistance, such as bronchial asthma, usually have less difficulty during inspiration than during expiration.

Laminar Versus Turbulent Flow. Airflow can be laminar or turbulent, depending on the velocity and pattern of flow. Laminar, or streamlined, airflow occurs at low flow rates in which the airstream is parallel to the sides of the airway. With laminar flow, the air at the periphery must overcome the resistance to flow, and as a result, the air in the center of the airway moves faster. Turbulent flow is disorganized flow in which the molecules of the gas move laterally, collide with one another, and change their velocities. Whether turbulence develops depends on the radius of the airways, the interaction of the gas molecules, and the velocity of airflow. It is most likely to occur when the radius of the airways is large and the velocity of flow is high. Turbulent flow occurs regularly in the trachea. Turbulence of airflow accounts for the respiratory sounds that are heard during chest auscultation (i.e., listening to chest sounds using a stethoscope). In the bronchial tree with its many branches, laminar airflow probably occurs only in the very small airways,

where the velocity of flow is low. Because the small airways contribute little resistance to airflow, they constitute a silent zone. In small airway disease (e.g., chronic obstructive pulmonary disease), it is probable that considerable abnormalities are present before the usual measurements of airway resistance can detect them.

Airway Compression. Airflow through the collapsible airways in the lungs depends on the distending airway (intrapulmonary) pressures that hold the airways open and the external (intrapleural or intrathoracic) pressures that surround and compress the airways. The difference between these two pressures (intrathoracic pressure minus airway pressure) is called the transpulmonary pressure. For airflow to occur, the distending pressure inside the airways must be greater than the compressing pressure outside the airways. During forced expiration, the transpulmonary pressure is decreased because of a disproportionate increase in the intrathoracic pressure compared with airway pressure. The resistance that air encounters as it moves out of the lungs causes a further drop in airway pressure. If this drop in airway pressure is sufficiently great, the surrounding intrathoracic pressure will compress the collapsible airways (i.e., those that lack cartilaginous support), causing airflow to be interrupted and air to be trapped in the terminal airways (Fig. 29-16). Although this type of airway compression usually is seen only during forced expiration in persons with normal respiratory function, it may occur during normal breathing in persons with lung diseases. For example, in conditions that increase airway resistance, such as emphysema, the pressure drop along the smaller airways is magnified, and an increase in intra-airway pressure is needed to maintain airway patency. Measures such as pursed-lip breathing increase airway pressure and improve expiratory flow rates in persons with chronic obstructive lung disease. This is also the basis for using positive end-expiratory pressure in persons who are on mechanical ventilators. Infants who are having trouble breathing often grunt to increase their expiratory airway pressures and keep their airways open.

Low lung volume

LUNG VOLUMES

High lung volume FIGURE 29-15 Interaction of tissue forces on airways during low and high lung volumes. At low lung volumes, the tissue forces tend to fold and place less tension on the airways and they become smaller; during high lung volumes, the tissue forces are stretched and pull the airways open.

Lung volumes, or the amount of air exchanged during ventilation, can be subdivided into three components: the tidal volume, the inspiratory reserve volume, and the expiratory reserve volume (Fig. 29-17). The tidal volume (TV), usually about 500 mL, is the amount of air that moves into and out of the lungs during a normal breath. The maximum amount of air that can be inspired in excess of the normal TV is called the inspiratory reserve volume (IRV), and the maximum amount that can be exhaled in excess of the normal TV is the expiratory reserve volume (ERV). Approximately 1200 mL of air always remains in the lungs after forced expiration; this air is the residual volume (RV). The RV increases with age because there is more trapping of air in the lungs at the end of expiration. These volumes can be measured using an instrument called a spirometer.

CHAPTER 29

15

Control of Respiratory Function

Oral airway pressure

Area of airway collapse Airway resistance

Forced expiration Intrapleural pressure

Nonrigid airways

B Airway pressure

A

Lung capacities include two or more lung volumes. The vital capacity equals the IRV plus the TV plus the ERV and is the amount of air that can be exhaled from the point of maximal inspiration. The inspiratory capacity equals the TV plus the IRV. It is the amount of air a person can breathe in beginning at the normal expiratory level and distending the lungs to the maximal amount. The functional residual capacity is the sum of the RV and ERV; it is the volume of air that remains in the lungs at the end of normal expiration. The total lung capacity is the sum of all the volumes in the lungs. The RV cannot be measured with the spirometer because this air cannot be expressed from the lungs. It is measured by indirect methods, such as the helium dilution method, the nitrogen washout techniques, or body plethysmography. Lung volumes and capacities are summarized in Table 29-1.

Pulmonary Function Studies The previously described lung volumes and capacities are anatomic or static measures, determined by lung volumes and measured without relation to time. The spirometer also is used to measure dynamic lung function (i.e., ventilation with respect to time); these tests often are used in assessing pulmonary function. Pulmonary function measures include maximum voluntary ventilation, forced vital capacity, forced expiratory volumes and flow rates, and forced inspiratory flow rates (Table 29-2). Pulmonary function is measured for various clinical purposes, including diagnosis of respiratory disease, preoperative surgical and anesthetic risk evaluation, and symptom and disability evaluation for legal or insurance purposes. The tests also are used for evaluating dyspnea, cough, wheezing, and abnormal radiologic or laboratory findings.

Total lung capacity

Inspiratory capacity Resting tidal volume

Functional residual capacity

Inspiratory reserve volume Vital capacity

FIGURE 29-16 Mechanism that limits maximal expiratory flow rate. (A) Airway patency and airflow in the nonrigid airways of the lungs rely on a transpulmonary pressure gradient in which airway pressure is greater than intrapleural pressure. (B) Airway resistance normally produces a drop in airway pressure as air moves out of the lungs. The increased airway pressure that occurs with forced expiration produces airway collapse in the nonrigid airways at the point where intrapleural pressure exceeds airway pressure.

Tidal volume (any level of activity)

Expiratory reserve volume

Residual volume

FIGURE 29-17 A tracing of respiratory volumes and capacities made with the use of a spirometer.

Special divisions for pulmonary function tests

Primary subdivisions of lung volume

0

16

UNIT VII

TABLE 29-1

Respiratory Function

Lung Volumes and Capacities

Volume

Symbol

Tidal volume (about 500 mL at rest) Inspiratory reserve volume (about 3000 mL) Expiratory reserve volume (about 1100 mL) Residual volume (about 1200 mL)

TV IRV

Functional residual capacity (about 2300 mL) Inspiratory capacity (about 3500 mL)

FRC

Vital capacity (about 4600 mL)

VC

Total lung capacity (about 5800 mL)

TLC

ERV RV

IC

Measurement Amount of air that moves into and out of the lungs with each breath Maximum amount of air that can be inhaled from the point of maximal expiration Maximum volume of air that can be exhaled from the resting endexpiratory level Volume of air remaining in the lungs after maximal expiration. This volume cannot be measured with the spirometer; it is measured indirectly using methods such as the helium dilution method, the nitrogen washout technique, or body plethysmography. Volume of air remaining in the lungs at end-expiration (sum of RV and ERV) Sum of IRV and TV Maximal amount of air that can be exhaled from the point of maximal inspiration Total amount of air that the lungs can hold; it is the sum of all the volume components after maximal inspiration. This value is about 20% to 25% less in females than in males.

The maximum voluntary ventilation measures the volume of air that a person can move into and out of the lungs during maximum effort lasting for 12 to 15 seconds. This measurement usually is converted to liters per minute. The forced expiratory vital capacity (FVC) involves full inspiration to total lung capacity followed by forceful maximal expiration. Obstruction of airways produces an FVC that is lower than that observed with more slowly performed vital capacity measurements. The forced expiratory volume (FEV) is the expiratory volume achieved in a given time period. The FEV1.0 is the forced expiratory

TABLE 29-2

volume that can be exhaled in 1 second. The FEV1.0 frequently is expressed as a percentage of the FVC. The FEV1.0 and FVC are used in the diagnosis of obstructive lung disorders. The forced inspiratory vital flow (FIF) measures the respiratory response during rapid maximal inspiration. Calculation of airflow during the middle half of inspiration (FIF25%–75%) relative to the forced midexpiratory flow rate (FEF25%–75%) is used as a measure of respiratory muscle dysfunction because inspiratory flow depends more on effort than does expiration.

Pulmonary Function Tests

Test

Symbol

Measurement*

Maximal voluntary ventilation Forced vital capacity

MVV FVC

Forced expiratory volume achieved in 1 second Percentage of forced vital capacity Forced midexpiratory flow rate

FEV1.0

Maximum amount of air that can be breathed in a given time Maximum amount of air that can be rapidly and forcefully exhaled from the lungs after full inspiration. The expired volume is plotted against time. Volume of air expired in the first second of FVC

Forced inspiratory flow rate

FEV1.0 /FVC% FEF25%–75%

FIF25%–75%

Volume of air expired in the first second, expressed as a percentage of FVC The forced midexpiratory flow rate determined by locating the points on the volume-time curve recording obtained during FVC corresponding to 25% and 75% of FVC and drawing a straight line through these points. The slope of this line represents the average midexpiratory flow rate. FIF is the volume inspired from RV at the point of measurement. FIF25%–75% is the slope of a line between the points on the volume pressure tracing corresponding to 25% and 75% of the inspired volume.

*By convention, all the lung volumes and rates of flow are expressed in terms of body temperature and pressure and saturated with water vapor (BTPS), which allows for a comparison of the pulmonary function data from laboratories with different ambient temperatures and altitudes.

CHAPTER 29

EFFICIENCY AND THE WORK OF BREATHING The minute volume, or total ventilation, is the amount of air that is exchanged in 1 minute. It is determined by the metabolic needs of the body. The minute volume is equal to the TV multiplied by the respiratory rate, which is normally about 6000 mL (500 mL TV × respiratory rate of 12 breaths/minute) during normal activity. The efficiency of breathing is determined by matching the TV and respiratory rate in a manner that provides an optimal minute volume while minimizing the work of breathing. The work of breathing is determined by the amount of effort required to move air through the conducting airways and by the ease of lung expansion, or compliance. Expansion of the lungs is difficult for persons with stiff and noncompliant lungs; they usually find it easier to breathe if they keep their TV low and breathe at a more rapid rate (e.g., 300 × 20 = 6000 mL) to achieve their minute volume and meet their oxygen needs. In contrast, persons with obstructive airway disease usually find it less difficult to inflate their lungs but expend more energy in moving air through the airways. As a result, these persons take deeper breaths and breathe at a slower rate (e.g., 600 × 10 = 6000 mL) to achieve their oxygen needs. In summary, the movement of air between the atmosphere and the lungs follows the laws of physics as they relate to gases. The air in the alveoli contains a mixture of gases, including nitrogen, oxygen, carbon dioxide, and water vapor. With the exception of water vapor, each gas exerts a pressure that is determined by the atmospheric pressure and the concentration of the gas in the mixture. Water vapor pressure is affected by temperature but not atmospheric pressure. Air moves into the lungs along a pressure gradient. The pressure inside the airways and alveoli of the lungs is called intrapulmonary (or alveolar) pressure; the pressure in the pleural cavity is called pleural pressure; and the pressure in the thoracic cavity is called intrathoracic pressure. Breathing is the movement of gases between the atmosphere and the lungs. It requires a system of open airways and pressure changes resulting from the action of the respiratory muscles in changing the volume of the chest cage. The diaphragm is the principal muscle of inspiration, assisted by the external intercostal muscles. The scalene and sternocleidomastoid muscles elevate the ribs and act as accessory muscles for inspiration. Expiration is largely passive, aided by the elastic recoil of the respiratory muscles that were stretched during inspiration. When needed, the abdominal and internal intercostal muscles can be used to increase expiratory effort. Lung compliance describes the ease with which the lungs can be inflated. It reflects the elasticity of the lung tissue and the surface tension in the alveoli. Surfactant molecules, produced by type II alveolar cells, reduce the surface tension in the lungs and thereby increase lung compliance. Airway resistance refers to the impediment to flow that the air encounters as it moves through the airways. Lung volumes and lung capacities reflect the amount of air that is exchanged during normal and forced breathing. The

Control of Respiratory Function

17

tidal volume (TV) is the amount of air that moves into and out of the lungs during normal breathing; the inspiratory reserve volume (IRV) is maximum amount of air that can be inspired in excess of the normal TV; and the expiratory reserve volume (ERV) is the maximum amount that can be exhaled in excess of the normal TV. The residual volume is the amount of air that remains in the lungs after forced expiration. Lung capacities include two or more lung volumes. The vital capacity equals the IRV plus the TV plus the ERV and is the amount of air that can be exhaled from the point of maximal inspiration. The minute volume, which is determined by the metabolic needs of the body, is the amount of air that is exchanged in 1 minute (i.e., respiratory rate and TV).

Exchange and Transport of Gases After completing this section of the chapter, you should be able to meet the following objectives:

✦ Trace the exchange of gases between the air in the alveoli and the blood in the pulmonary capillaries Differentiate between pulmonary and alveolar ventilation Explain why ventilation and perfusion must be matched Cite the difference between dead air space and shunt List four factors that affect the diffusion of gases in the alveoli ✦ Explain the difference between PO2 and hemoglobinbound oxygen and O2 saturation and content ✦ Explain the significance of a shift to the right and a shift to the left in the oxygen–hemoglobin dissociation curve

✦ ✦ ✦ ✦

The primary functions of the lungs are oxygenation of the blood and removal of carbon dioxide. Pulmonary gas exchange is conventionally divided into three processes: ventilation, or the flow of gases into and out of the alveoli of the lungs; perfusion, or flow of blood in the adjacent pulmonary capillaries; and diffusion, or transfer of gases between the alveoli and the pulmonary capillaries. The efficiency of gas exchange requires that alveolar ventilation occur adjacent to perfused pulmonary capillaries.

VENTILATION Ventilation refers to the exchange of gases in the respiratory system. There are two types of ventilation: pulmonary and alveolar. Pulmonary ventilation refers to the total exchange of gases between the atmosphere and the lungs. Alveolar ventilation is the exchange of gases within the gas exchange portion of the lungs. Ventilation requires a system of open airways and a pressure difference that moves air into and out of the lungs. It is affected by body position and lung volume as well as by disease conditions that affect the heart and respiratory systems.

Distribution of Ventilation The distribution of ventilation between the apex and base of the lung varies with body position and the weight of the

18

UNIT VII

Respiratory Function

lung and the effects of gravity on intrapleural pressure. Compliance reflects the change in volume that occurs with a change in pressure. It is less in fully expanded alveoli, which have difficulty accommodating more air, and greater in alveoli that are less inflated. In the seated or standing position, gravity exerts a downward pull on the lung, causing intrapleural pressure at the apex of the lung to become more negative than that at the base of the lung (Fig. 29-18). As a result, the alveoli at the apex of the lung are more fully expanded and less compliant than those at the base of the lung. The same holds true for lung compliance in the dependent portions of the lung in the supine or lateral position. In the supine position, ventilation in the lowermost (posterior) parts of the lung exceeds that in the uppermost (anterior) parts. In the lateral position (i.e., lying on the side), the dependent lung is better ventilated. The distribution of ventilation also is affected by lung volumes. During full inspiration in the seated or standing position, the airways are pulled open, and air moves into the more compliant portions of the lower lung. At low lung volumes, the opposite occurs. At functional residual capacity, the pleural pressure at the base of the lung exceeds airway pressure compressing the airways, so that ventilation is greatly reduced. In contrast, the airways in the apex of the lung remain open, and this area of the lung is well ventilated. Even at low lung volumes, some air remains in the alveoli of the lower portion of the lungs, preventing their

– 10 cm H 2 O

• • • • • • • • •

Intrapleural pressure

– 2.5 cm H 2 O 100%

50%

Volume

•

•

0 +10

– 20 –10 Intrapleural pressure (cm H 2 O) 0

– 30

FIGURE 29-18 Explanation of the regional differences in ventilation down the lung; the intrapleural pressure is less negative at the base than at the apex. As a consequence, the basal lung is relatively compressed in its resting state but expands more on inspiration than the apex. (West J. B. [2001]. Pulmonary physiology and pathophysiology [p. 43]. Lippincott Williams & Wilkins)

collapse. According to Laplace’s law (discussed previously), the pressure needed to overcome the tension in the wall of a sphere or an elastic tube is inversely related to its radius; therefore, the small airways close first, trapping some gas in the alveoli. There may be increased trapping of air in the alveoli of the lower part of the lungs in older persons and in those with lung disease (e.g., emphysema). This condition is thought to result from a loss in the elastic recoil properties of the lungs, so that the intrapleural pressure, created by the elastic recoil of the lung and chest wall, becomes less negative. In these persons, airway closure occurs at the end of normal instead of low lung volumes, trapping larger amounts of air.

PERFUSION The primary functions of the pulmonary circulation are to perfuse or provide blood flow to the gas exchange portion of the lung and to facilitate gas exchange. The pulmonary circulation serves several important functions in addition to gas exchange. It filters all the blood that moves from the right to the left side of the circulation; it removes most of the thromboemboli that might form; and it serves as a reservoir of blood for the left side of the heart. The gas exchange function of the lungs requires a continuous flow of blood through the respiratory portion of the lungs. Deoxygenated blood enters the lung through the pulmonary artery, which has its origin in the right side of the heart and enters the lung at the hilus, along with the primary bronchus. The pulmonary arteries branch in a manner similar to that of the airways. The small pulmonary arteries accompany the bronchi as they move down the lobules and branch to supply the capillary network that surrounds the alveoli (see Fig. 29-7). The meshwork of capillaries in the respiratory portion of the lungs is so dense that the flow in these vessels often is described as being similar to a sheet of blood. The oxygenated capillary blood is collected in the small pulmonary veins of the lobules; it then moves to the larger veins to be collected in the four large pulmonary veins that empty into the left atrium. The pulmonary blood vessels are thinner, more compliant, and offer less resistance to flow than those in the systemic circulation, and the pressures in the pulmonary system are much lower (e.g., 22/8 mm Hg versus 120/ 70 mm Hg). The low pressure and low resistance of the pulmonary circulation accommodate the delivery of varying amounts of blood from the systemic circulation without producing signs and symptoms of congestion. The volume in the pulmonary circulation is approximately 500 mL, with approximately 100 mL of this volume located in the pulmonary capillary bed. When the output of the right ventricle and input of the left ventricle are equal, pulmonary blood flow remains constant. Small differences between input and output can result in large changes in pulmonary volume if the differences continue for many heartbeats. The movement of blood through the pulmonary capillary bed requires that the mean pulmonary arterial pressure be greater than the mean pulmonary venous pressure. Pulmonary venous pressure increases in left-sided

CHAPTER 29

heart failure, allowing blood to accumulate in the pulmonary capillary bed and to cause pulmonary edema (see Chapter 28).

Control of Respiratory Function

19

tension and increased workload on the right heart. A low blood pH also produces vasoconstriction, especially when alveolar hypoxia is present (e.g., during circulatory shock).

Distribution of Blood Flow and Body Position As with ventilation, the distribution of pulmonary blood flow is affected by body position and gravity. In the upright position, the distance of the upper apices of the lung above the level of the heart may exceed the perfusion capabilities of the mean pulmonary arterial pressure (approximately 12 mm Hg); therefore, blood flow in the upper part of the lungs is less than that in the base or bottom part of the lungs (Fig. 29-19). In the supine position, the lungs and the heart are at the same level, and blood flow to the apices and base of the lungs becomes more uniform. In this position, blood flow to the posterior or dependent portions (e.g., bottom of the lung when lying on the side) exceeds flow in the anterior or nondependent portions of the lungs.

Hypoxia-induced Vasoconstriction The blood vessels in the pulmonary circulation undergo marked vasoconstriction when they are exposed to hypoxia. The precise mechanism for this response is unclear. When alveolar oxygen levels drop below 60 mm Hg, marked vasoconstriction may occur, and at very low oxygen levels, the local flow may be almost abolished. In regional hypoxia, as occurs with atelectasis, vasoconstriction is localized to a specific region of the lung. Vasoconstriction has the effect of directing blood flow away from the hypoxic regions of the lungs. When alveolar hypoxia no longer exists, blood flow is restored. Generalized hypoxia causes vasoconstriction throughout the lung. Generalized vasoconstriction occurs when the partial pressure of oxygen is decreased at high altitudes, or it can occur in persons with chronic hypoxia due to lung disease. Prolonged hypoxia can lead to pulmonary hyper-

Zone 1 PA > Pa > PV

Alveolar Pa

PA

Arterial

There are two types of air movement in the lung: bulk flow and diffusion. Bulk flow occurs in the conducting airways and is controlled by pressure differences between the mouth and the airways in the lung. Diffusion refers to the movement of gases in the alveoli and across the alveolar capillary membrane. Gas diffusion in the lung can be described by Fick’s law. Fick’s law states that the volume of a gas (V˙ gas) diffusing across the membrane per unit time is directly proportional to the partial pressure difference of the gas (P1 − P2), the surface area (SA) of the membrane, and the diffusion coefficient (D) and is inversely proportional to the thickness (T) of the membrane:

(P − P2 ) × SA × D ˙ Vgas = 1 T Several factors influence diffusion of gases in the lung. The administration of high concentrations of oxygen increases the difference in partial pressure between the two sides of the membrane and increases the diffusion of the gas. Diseases that destroy lung tissue (i.e., surface area for diffusion) or increase the thickness of the alveolar-capillary membrane adversely influence the diffusing capacity of the lungs. The removal of one lung, for example, reduces the diffusing capacity by one half. The thickness of the alveolar-capillary membrane and the distance for diffusion are increased in persons with pulmonary edema or pneumonia. The characteristics of the gas and its molecular weight and solubility constitute the diffusion coefficient and determine how rapidly the gas diffuses through the respiratory membranes. For example, carbon dioxide diffuses 20 times more rapidly than oxygen because of its greater solubility in the respiratory membranes. The factors that affect alveolar-capillary gas exchange are summarized in Table 29-3.

MATCHING OF VENTILATION AND PERFUSION

Zone 2 Pa > PA > PV PV

Venous

DIFFUSION

Distance

Zone 3 Pa > PV > PA Blood flow FIGURE 29-19 The uneven distribution of blood flow in the lung results from different pressures affecting the capillaries, which are affected by body position and gravity. (West J. B. [2000]. Respiratory physiology: The essentials [p. 29]. Philadelphia: Lippincott Williams & Wilkins)

The gas exchange properties of the lung depend on matching ventilation and perfusion, ensuring that equal amounts of air and blood are entering the respiratory portion of the lungs. Two factors may interfere with the matching of ventilation and perfusion: dead air space and shunt.

Dead Air Space Dead space refers to the volume of air that must be moved with each breath but does not participate in gas exchange. The movement of air through dead space contributes to the work of breathing but not to gas exchange. There are two types of dead air space: that contained in the conducting airways, called the anatomic dead space,

20

UNIT VII

TABLE 29-3

Respiratory Function

Factors Affecting Alveolar-Capillary Gas Exchange

Factors Affecting Gas Exchange

Examples

Surface area available for diffusion

Removal of a lung or diseases such as emphysema and chronic bronchitis, which destroy lung tissue or cause mismatching of ventilation and perfusion Conditions such as pneumonia, interstitial lung disease, and pulmonary edema, which increase membrane thickness Ascent to high altitudes where the partial pressure of oxygen is reduced. In the opposite direction, increasing the partial pressure of a gas in the inspired air (e.g., oxygen therapy) increases the gradient for diffusion Carbon dioxide, which is more soluble in the cell membranes, diffuses across the alveolar-capillary membrane more rapidly than oxygen.

Thickness of the alveolar-capillary membrane Partial pressure of alveolar gases

Solubility and molecular weight of the gas

and that contained in the respiratory portion of the lung, called the alveolar dead space. The volume of anatomic airway dead space is fixed at approximately 150 to 200 mL, depending on body size. It constitutes air contained in the nose, pharynx, trachea, and bronchi. The creation of a tracheostomy decreases anatomic dead space ventilation because air does not have to move through the nasal and oral airways. Alveolar dead space, normally about 5 to 10 mL, constitutes alveolar air that does not participate in gas exchange. When alveoli are ventilated but deprived of blood flow, they do not contribute to gas exchange and thereby constitute alveolar dead space. The physiologic dead space includes the anatomic dead space plus alveolar dead space. In persons with normal respiratory function, physiologic dead space is about the same as anatomic dead space. Only in lung disease does physio-

MATCHING OF VENTILATION AND PERFUSION ➤ Exchange of gases between the air in the alveoli and the blood in pulmonary capillaries requires a matching of ventilation and perfusion. ➤ Two factors interfere with matching of ventilation and perfusion: dead air space and shunt. ➤ Dead air space refers to the volume of air that is moved with each breath but does not participate in gas exchange. Anatomic dead space is that contained in the conducting airways that normally do not participate in gas exchange. Alveolar dead space results from alveoli that are ventilated but not perfused. ➤ Shunt refers to blood that moves from the right to the left side of the circulation without being oxygenated. With an anatomic shunt, blood moves from the venous to the arterial side of the circulation without going through the lungs. Physiologic shunting results from blood moving through unventilated parts of the lung. ➤ The blood oxygen level reflects the mixing of blood from alveolar dead space and physiologic shunting areas as it moves into the pulmonary veins.

logic dead space increase. Alveolar ventilation is equal to the minute ventilation minus the physiologic dead space ventilation.

Shunt Shunt refers to blood that moves from the right to the left side of the circulation without being oxygenated. As with dead air space, there are two types of shunts: physiologic and anatomic. In an anatomic shunt, blood moves from the venous to the arterial side of the circulation without moving through the lungs. Anatomic intracardiac shunting of blood due to congenital heart defects is discussed in Chapter 26. In a physiologic shunt, there is mismatching of ventilation and perfusion with the lung, resulting in insufficient ventilation to provide the oxygen needed to oxygenate the blood flowing through the alveolar capillaries. Physiologic shunting of blood usually results from destructive lung disease that impairs ventilation or from heart failure that interferes with movement of blood through sections of the lungs.

Mismatching of Ventilation and Perfusion Both dead air space and shunt produce a mismatching of ventilation and perfusion as depicted in Figure 29-20. With shunt (depicted on the left), there is perfusion without ventilation, resulting in a low ventilation–perfusion ratio. It occurs in conditions such as atelectasis in which there is airway obstruction (see Chapter 31). With dead air space (depicted on the right), there is ventilation without perfusion, resulting in a high ventilation–perfusion ratio. It occurs with conditions such as pulmonary embolism, which impairs blood flow to a part of the lung. The arterial blood leaving the pulmonary circulation reflects mixing of blood from normally ventilated and perfused areas of the lung as well as areas that are not ventilated (dead air space) or perfused (shunt). Many of the conditions that cause mismatching of ventilation and perfusion involve both dead air space and shunt. In chronic obstructive lung disease, for example, there may be impaired ventilation in one area of the lung and impaired perfusion in another area.

GAS TRANSPORT Although the lungs are responsible for the exchange of gases, it is the blood that transports these gases between the lungs and body tissues. The blood carries oxygen and

CHAPTER 29

Control of Respiratory Function

21

Airways Venous blood

Perfusion without ventilation FIGURE 29-20 Matching of ventilation and perfusion. (Center) Normal matching of ventilation and perfusion; (left) perfusion without ventilation (i.e., shunt); (right) ventilation without perfusion (i.e., dead air space).

carbon dioxide in the dissolved state and in combination with hemoglobin. Carbon dioxide also is converted to bicarbonate and transported in that form. The amount of a gas that can dissolve in plasma is determined by two factors: the solubility of the gas in the plasma and the partial pressure of the gas in the alveoli. In the clinical setting, blood gas measurements are used to determine the level of the partial pressure of oxygen (PO2) and carbon dioxide (PCO2) in the blood. Arterial blood commonly is used for measuring blood gases. Venous blood is not used because venous levels of oxygen and carbon dioxide reflect the metabolic demands of the tissues rather than the gas exchange function of the lungs. The PO2 of arterial blood normally is above 80 mm Hg, and the PCO2 is in the range of 35 to 45 mm Hg. Normally, the arterial blood gases are the same or nearly the same as the partial pressure of the gases in the alveoli. The arterial PO2 often

OXYGEN TRANSPORT ➤ Oxygen is transported in chemical combination with hemoglobin and as a gas dissolved in the plasma. ➤ Hemoglobin, which is the main transporter for oxygen, binds oxygen as it passes through the lungs and releases it as it moves through the tissues. ➤ The amount of oxygen that is carried as a dissolved gas is determined by the partial pressure of the gas in the lungs. ➤ The oxygen content of the blood, or the amount of oxygen that is available to the tissues, represents the total amount of oxygen carried by the hemoglobin (hemoglobin concentration [g/dL] multiplied by its saturation) plus the amount of oxygen that is carried in the dissolved state.

Arterial blood

Alveolus

Ventilation without perfusion

Normal

is written PaO2, and the alveolar PO2 as PAO2, with the same types of designations being used for PCO2. This text uses PO2 and PCO2 to designate both arterial and alveolar levels of the gases.

Oxygen Transport Oxygen is transported in two forms: in chemical combination with hemoglobin and in the dissolved state. The hemoglobin in red blood cells serves as a transport vehicle for oxygen. It binds oxygen in the pulmonary capillaries and releases it in the tissue capillaries. As oxygen moves into or out of the red blood cells, it dissolves in the plasma (Fig. 29-21). It is the dissolved form of oxygen that leaves the capillary, crosses cell membranes, and participates in cell metabolism.

Dissolved Oxygen. The partial pressure of oxygen (PO2) represents the level of dissolved oxygen in plasma. The amount of gas that can be dissolved in a liquid depends on the solubility of the gas and its pressure. The solubility of oxygen in plasma is fixed and very small. For every 1 mm Hg of PO2 present in the alveoli, 0.003 mL of oxygen becomes dissolved in 100 mL of plasma. This means that at a normal alveolar PO2 of 100 mm Hg, the blood carries only 0.3 mL of dissolved oxygen in each 100 mL of plasma. This amount (approximately 1%) is very small compared with the amount that can be carried in an equal amount of blood when oxygen is attached to hemoglobin. Although the amount of oxygen carried in plasma under normal conditions is small, it can become a lifesaving mode of transport in carbon monoxide poisoning, when most of the hemoglobin sites are occupied by carbon monoxide and are unavailable for transport of oxygen. The use of a hyperbaric chamber, in which 100% oxygen can be administered at high atmospheric pressures, increases the amount of oxygen that can be carried in the dissolved state.

22

UNIT VII

Respiratory Function

cell metabolism. As the oxygen moves out of the capillaries in response to the needs of the tissues, the hemoglobin saturation, which usually is approximately 95% to 97% as the blood leaves the left side of the heart, drops to approximately 75% as the mixed venous blood returns to the right side of the heart.

FIGURE 29-21 Transport of oxygen. (A) In the lung, oxygen (O2) moves across the alveolar membrane, becomes dissolved in the plasma (PO2), and then moves into the red blood cell (RBC) where it attaches to the hemoglobin molecule (HbO2) for transport to the tissues. (B) In the tissues, O2 dissociates from hemoglobin and leaves the RBC, becomes dissolved in the plasma (PO2), and then moves into tissue cells where it is used in the production of energy substrates.

Hemoglobin Transport. Hemoglobin is a highly efficient carrier of oxygen, and approximately 98% to 99% of the oxygen used by body tissues is carried in this manner. Hemoglobin with bound oxygen is called oxyhemoglobin, and when oxygen is removed, it is called deoxygenated or reduced hemoglobin. Each gram of hemoglobin carries approximately 1.34 mL of oxygen when it is fully saturated. This means that a person with a hemoglobin of 14 g/100 mL carries 18.8 mL of oxygen per 100 mL of blood. In the lungs, oxygen moves across the alveolar-capillary membrane, through the plasma, and into the red blood cell, where it forms a loose and reversible bond with the hemoglobin molecule. In normal lungs, this process is rapid, so that even with a fast heart rate, the hemoglobin is almost completely saturated with oxygen during the short time it spends in the pulmonary capillaries. The oxygenated hemoglobin is transported in the arterial blood to the peripheral capillaries, where the oxygen is released and made available to the tissues for use in

Binding Affinity of Hemoglobin for Oxygen. Oxygen that remains bound to hemoglobin cannot participate in tissue metabolism. The efficiency of the hemoglobin transport system depends on the ability of the hemoglobin molecule to bind oxygen in the lungs and release it as it is needed in the tissues. The affinity of hemoglobin refers to its capacity to bind oxygen. Hemoglobin binds oxygen more readily when its affinity is increased and releases it more readily when its affinity is decreased. As described in Chapter 16, the hemoglobin molecule is composed of four polypeptide chains with an ironcontaining heme group. Because oxygen binds to the iron atom, each hemoglobin molecule can bind four molecules of oxygen when it is fully saturated. Oxygen binds cooperatively with the heme groups on the hemoglobin molecule. After the first molecule of oxygen binds to hemoglobin, the molecule undergoes a change in shape. As a result, the second and third molecules bind more readily, and binding of the fourth molecule is even easier. In a like manner, the unloading of the first oxygen molecule enhances the unloading of the next molecule, and so on. Thus, the affinity of hemoglobin for oxygen changes with oxygen saturation. Hemoglobin’s affinity for oxygen is also influenced by pH, carbon dioxide concentration, and temperature. Hemoglobin binds oxygen more strongly under conditions of increased pH (alkalosis), decreased carbon dioxide concentration, and decreased body temperature and releases it more readily under conditions of decreased pH (acidosis), increased carbon dioxide concentration, and fever. Conditions that decrease affinity and favor unloading of oxygen reflect the level of tissue metabolism and need for oxygen. For example, increased tissue metabolism generates carbon dioxide and metabolic acids and thereby decreases the affinity of hemoglobin for oxygen. Heat also is a byproduct of tissue metabolism, explaining the effect of fever on oxygen binding. Red blood cells contain a metabolic intermediate called 2,3-diphosphoglycerate (2,3-DPG) that also affects the affinity of hemoglobin for oxygen. An increase in 2,3-DPG enhances unloading of oxygen from hemoglobin at the tissue level. An increase in 2,3-DPG occurs with exercise and the hypoxia that occurs with high altitude and chronic lung disease. Oxygen–Hemoglobin Dissociation Curve. The relation between the oxygen carried in combination with hemoglobin and the PO2 of the blood is described by the oxygen– hemoglobin dissociation curve, which is shown in Figure 29-22. The x axis of the graph depicts the PO2 or dissolved oxygen; the left y axis, hemoglobin saturation; and the right y axis, the oxygen content. The PO2 reflects the partial pressure of the gas in the lung (i.e., the PO2 is approximately 100 mm Hg when room air is being breathed, but can rise to 200 mm Hg or higher when oxygen enriched

CHAPTER 29

100

20

Plateau region

16

80 60

12 Steep region 8

20

A

0

O2 in physical solution 20

40

60

80

100

120

100

4

140 20

% Hemoglobin (Hb) saturation

Shift to left Shift to right

80 60

16 12

Normal P50

B

40

8

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4

0

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40

60

80

100

120

100

Oxygen content (mL/100 mL blood)

40

140 20

Normal Hb

16 12

Anemia 100

8 4

C

0

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60 80 100 PO2 (mm Hg)

120

140

FIGURE 29-22 Oxygen–hemoglobin dissociation curve. (A) Left boxed area represents the steep portion of the curve where oxygen is released from hemoglobin (Hb) to the tissues, and the top boxed area the plateau of the curve where oxygen is loaded onto hemoglobin in the lung. (B) The effect of body temperature, arterial PCO2, and pH on hemoglobin affinity for oxygen as indicated by a shift in the curve and position of the P50. A shift of the curve to the right due to an increase in temperature, PCO2, or decreased pH favors release of oxygen to the tissues. A decrease in temperature, PCO2, or increase in pH shifts the curve to the left and has the opposite effect. The P50 is the partial pressure of oxygen required to saturate 50% of hemoglobin with oxygen. (C) Effect of anemia on the oxygencarrying capacity of blood. The hemoglobin can be completely saturated, but the oxygen content of the blood is reduced.

Control of Respiratory Function

23

air is breathed). The hemoglobin saturation reflects the amount of oxygen that is carried by the hemoglobin. The S-shaped oxygen dissociation curve has a flat top portion representing binding of oxygen by the hemoglobin in the lungs and a steep portion representing its release into the tissue capillaries (see Fig. 29-22A). The S shape of the curve reflects the effect that oxygen saturation has on the conformation of the hemoglobin molecule and its affinity for oxygen. At approximately 100 mm Hg PO2, a plateau occurs, at which point the hemoglobin is approximately 98% saturated. Increasing the alveolar PO2 above this level does not increase the hemoglobin saturation. Even at high altitudes, when the partial pressure of oxygen is considerably decreased, the hemoglobin remains relatively well saturated. At 60 mm Hg PO2, for example, the hemoglobin is still approximately 89% saturated. The steep portion of the dissociation curve—between 60 and 40 mm Hg—represents the removal of oxygen from the hemoglobin as it moves through the tissue capillaries. This portion of the curve reflects the fact that there is considerable transfer of oxygen from hemoglobin to the tissues with only a small drop in PO2, thereby ensuring a gradient for oxygen to move into body cells. The tissues normally remove approximately 5 mL of oxygen per 100 mL of blood, and the hemoglobin of mixed venous blood is approximately 75% saturated as it returns to the right side of the heart. In this portion of the dissociation curve (saturation