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Patho Chap 1

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Chapter 1 Introduction to Pathophysiology
Lee-Ellen C. Copstead
Key Questions
• What is pathophysiology?
• How are etiology and pathogenesis used to predict clinical manifestations and response to therapy?
• How are normal and abnormal physiologic parameters defined?
• What general factors affect the expression of disease in a particular person?
• What kinds of information about disease can be gained through understanding concepts of epidemiology?

http://evolve.elsevier.com/Copstead/
• Review Questions and Answers
• Glossary (with audio pronunciations for selected terms)
• Animations
• Case Studies
• Key Points Review
Pathophysiology derives from the intersection of two older, related disciplines: pathology (from pathos, suffering) and physiology (from physis, nature). Pathology is the study and diagnosis of disease through examination of organs, tissues, cells, and bodily fluids. Physiology is the study of the mechanical, physical, and biochemical functions of living organisms. Together, as pathophysiology, the term refers to the study of abnormalities in physiologic functioning of living beings.
Pathophysiology seeks to reveal physiologic responses of an organism to disruptions in its internal or external environment. Because humans exhibit considerable diversity, healthy structure and function are not precisely the same in any two individuals. However, discovering the common and expected responses to abnormalities in physiologic functioning is useful, and it allows a general prediction of clinical progression, identification of possible causes, and selection of interventions that are most likely to be helpful. Thus, pathophysiology is studied in terms of common or “classic” presentations of disorders.
Historically, descriptions of diseases were based on observations of those individuals who attracted medical attention because they exhibited abnormal signs or complained of symptoms. Over time, cases with similar presentations were noted and treatments that had been successful before were used again. In some cases, similarities among individuals pointed to possible common causes. With the advent of more sophisticated measurements of physiologic and biochemical function, such as blood pressure measurements, blood chemistry values, x-ray images, and DNA analysis, the wide variability in the expression of diseases and disorders in the population became apparent, as did the opportunity to discover diseases at earlier stages, before they were clinically obvious. Screening programs that evaluated large segments of the population revealed the complexity and diversity of disease expression, even in persons with the same genetic defect. Thus, although the study of pathophysiology is necessarily a study of the usual and expected responses of the body to a given disruption, individuals often vary significantly from a classic presentation, making the diagnostic process complex and challenging.
Advances in genomic and epigenomic characterization, innovative technologies, and revolutionary approaches to the analysis of genetic variation and function have made studies and treatments possible that were not even imaginable just a few years ago. As a result, definitions of the living world have been virtually transformed and permeate every branch of biological science. Benefits of this new biology include a deeper understanding of evolution, greater insights into immune mechanisms, and nearly every advance against cancer and acquired immunodeficiency syndrome (AIDS).
Genetic manipulation also raises sensitive and complex ethical and moral questions that did not exist half a century ago. Scientists are able to experiment with genetic manifestations and their mechanisms of action, dramatically altering medical practice, especially the management of inherited diseases. New capabilities have led to experimental treatments such as gene therapy–molecular surgery powerful enough to cure and alter the next generation. The study of pathophysiology assumes even greater significance as genetic research shows fresh insights and hopeful new treatments for human diseases.
Pathophysiology examines disturbances of normal mechanical, physical, and biochemical functions, either caused by a disease or resulting from a disease or abnormal syndrome or condition. For example, the study of a toxin released by a bacterium has evolved from the science of infectious diseases, as well as the harmful effects of that toxin on the body, one possible result being sepsis. Another example is the study of the chemical changes that take place in body tissue as the result of inflammation.
Although individual study of specific diseases undertaken in medical pathology textbooks helps students identify subtle differences between similar diseases, the study of pathophysiology is dynamic and conceptual, seeking to explain processes and relationships common to a number of pathologies. For example, the pathophysiology of inflammation, hypotension, fluid volume deficit, hypoxia, and ischemia is important to the understanding of a large number of different pathologies, but each separate process is not necessarily a specific disease.
Pathophysiology includes four interrelated topics: etiology, pathogenesis, clinical manifestations, and treatment implications—the framework used throughout this textbook. Specific diseases will be used as illustrative examples of conditions in which particular pathophysiologic processes may occur.
Framework for Pathophysiology
Etiology
Etiology, in its most general definition, is the study of the causes or reasons for phenomena.1 A description of etiologic process includes the identification of those causal factors that, acting in concert, provoke a particular disease or injury. When the cause is unknown, a condition is said to be idiopathic. If the cause is the result of an unintended or unwanted medical treatment, the resulting condition is said to be iatrogenic. Most disorders are multifactorial, having several different etiologic factors that contribute to their development. For example, coronary heart disease is a result of the interaction of genetic predisposition, diet, exposure to cigarette smoke, elevated blood pressure, and perhaps numerous other lifestyle and hormonal factors acting in concert. None of these individual factors can be said to cause the disease. When the link between an etiologic factor and development of a disease is less than certain, but the probability is increased when the factor is present, it is termed a risk factor. The identification of risk factors is important for disease prevention and various levels of prevention provide focus for the epidemiology section at the end of this chapter.
BOX 1-1 ETIOLOGIC CLASSIFICATION OF DISEASES
Congenital (inborn) diseases or birth defects
Degenerative diseases
Iatrogenic diseases
Idiopathic diseases
Immunologic diseases
Infectious diseases
Inherited diseases
Metabolic diseases
Neoplastic diseases
Nutritional deficiency diseases
Physical agent–induced diseases
Psychogenic diseases
Some diseases are closely linked with etiologic factors, such that they are said to be the causative agents in the disease. For example, microbial pathogens are considered to be causative agents for infectious diseases: human immunodeficiency virus causes HIV disease, influenza viruses cause the flu, and Mycobacterium tuberculosis causes pulmonary tuberculosis. These diseases do not occur unless the pathogen is present in the body; however, this does not mean that the infection will have the same consequences in each case, because many host factors affect the clinical course. Even when the link between disease and etiologic agent is strong, only a portion of the population exposed to the factor may develop the disease. For example, in persons who consume large quantities of alcohol and develop liver cirrhosis, it is the alcohol consumption that is considered to be the cause, yet only a portion of persons who drink heavily will develop cirrhosis.2 Thus categorizing the probable etiologies for diseases is a long, difficult research process and, not surprisingly, the exact causes of most disorders remain incompletely understood. Several classification schemes have been proposed to categorize diseases according to etiology. Box 1-1 summarizes an example of an etiologic classification system. No classification system is truly comprehensive and some diseases fall into multiple categories. Some diseases may receive different designations in the future, as further research reveals new data.
Pathogenesis
Pathogenesis refers to the development or evolution of a disease, from the initial stimulus to the ultimate expression of the manifestations of the disease.3 The sequence of physiologic events that occurs in response to an etiologic agent is a dynamic interplay of changes in cell, tissue, organ, and systemic function. As the ways in which intricate intercellular communication networks control physiologic function are discovered, pathogenesis is being increasingly understood on the cellular level. One of the best examples of this communication network is the immune system and its interactions with essentially every other cell in the body. A disruption in the delicate system of checks and balances between immune tolerance of normal cells and immune surveillance for abnormal cells and foreign antigens is at the root of a large number of degenerative and inflammatory diseases.
Pathologic disruptions in cellular behavior lead, in turn, to changes in organ and system function that may be detected by clinical or laboratory examination. Most pathophysiology texts take a systems approach to presenting information. This approach builds on the way in which students learn anatomy and physiology and has its roots in medical specialization. Usually the clinical examination of a patient is also conceptualized by a systems approach. Although the division into systems is useful for dividing the content into conceptual pieces, it is important to remember that the organism functions as an integrated whole and the intercellular communication networks are not confined within single systems. In summary, pathogenesis is a description of how etiologic factors are thought to alter physiologic function and lead to the development of clinical manifestations that are observed in a particular disorder or disease.
Clinical Manifestations
Manifestations of disease that are observed are termed signs of disease. Such objective data may be gathered by clinical examination or by biochemical analysis, diagnostic imaging, and other laboratory tests. The subjective feelings of an abnormality in the body are termed symptoms. By definition, symptoms are subjective and can only be reported by the affected individual to an observer. For example, the feeling of nausea is a symptom, whereas vomiting is objectively observed and is a sign. Some signs and symptoms, such as fever and headache, are nonspecific and, although they designate that something is amiss, they do not indicate a specific cause. In this case further examination and, often, laboratory tests are needed to focus on the possible causes of the signs and symptoms. Many diseases and disorders are characterized by a particular constellation of signs and symptoms, the knowledge of which is essential for accurate detection and diagnosis. When the etiology of a particular set of signs and symptoms has not yet been determined, the disorder may be termed a syndrome. For example, AIDS was originally detected as a set of signs and symptoms related to a deficiency of helper T cells of unknown cause, now known to be a late stage of HIV infection.4
The clinical manifestations of some diseases may change significantly over time, resulting in a completely different clinical presentation at different stages. Knowledge of the possible stages of a disease is helpful in making an appropriate diagnosis and anticipating the clinical course.
Stages and Clinical Course
Early in the development of a disease, the etiologic agent or agents may provoke a number of changes in biological processes that can be detected by laboratory analysis, although no recognition of these changes by the patient has occurred. The interval between exposure of a tissue to an injurious agent and the first appearance of signs and symptoms may be called a latent period or, in the case of infectious diseases, an incubation period. The prodromal period, or prodrome, refers to the appearance of the first signs and symptoms indicating the onset of a disease. Prodromal symptoms often are nonspecific, such as headache, malaise, anorexia, and nausea. During the stage of manifest illness, or the acute phase, the disease reaches its full intensity, and signs and symptoms attain their greatest severity. Sometimes during the course of a disease, the signs and symptoms may become mild or even disappear for a time. This interval may be called a silent period or latent period. For example, in the total-body irradiation syndrome, a latent period may occur between the prodrome and the stage of manifest illness. Another example is syphilis, which may have two latent periods: one occurring between the primary and secondary clinical stages and another occurring between the secondary and tertiary stages.5
A number of diseases have a subclinical stage, during which the patient functions normally, although the disease processes are well established. It is important to understand that the structure and function of many organs provide a large reserve or safety margin, so that functional impairment may become evident only when organ damage has become advanced. For example, chronic renal disease can completely destroy one kidney and partly destroy the other before any symptoms related to a decrease in renal function are perceived.6
The clinical course of a disease is often classified as acute or chronic. An acute condition has relatively severe manifestations but runs a short course measured in hours, days, or a few weeks. A chronic condition lasts for months to years. Sometimes chronic disease processes begin with an acute phase and become prolonged when the body's defenses are insufficient to overcome the causative agent or stressor. In other cases, chronic conditions develop insidiously and never have an acute phase.
Some diseases (e.g., some types of autoimmune diseases) follow a course of alternating exacerbations and remissions. An exacerbation is a relatively sudden increase in the severity of a disease or any of its signs and symptoms. A remission is an abatement or decline in severity of the signs and symptoms of a disease. If a remission is permanent (sometimes defined as longer than 5 years), the person is said to be cured.
Convalescence is the stage of recovery after a disease, injury, or surgical operation. Occasionally a disease produces a subsequent pathologic condition called a sequela (plural: sequelae). For example, the sequela of an inflammatory process might be scarring. The sequelae of acute rheumatic inflammation of the heart might be scarring and deformation of cardiac valves. In contrast, a complication of a disease is a new or separate process that may arise secondarily because of some change produced by the original problem. For example, bacterial pneumonia may be a complication of viral infection of the respiratory tract.
Treatment Implications
An understanding of the etiology, pathogenesis, and clinical consequences of a particular disorder may suggest, or “imply,” that certain treatments could be helpful. For example, understanding that a person with septic shock has excessive dilation of blood vessels that contributes to hypotension implies that fluid administration would likely be helpful. In contrast, most patients with cardiogenic shock have fluid overload, and hypotension in this case is unlikely to improve with fluid administration. Care must be taken not to rely on theoretical implications when evidence-based treatment recommendations are available. When subjected to evaluation by rigorous randomized clinical trials, many treatments that seem as though they should help based on pathophysiology fail to pass the test of application.
The treatment implications discussed in pathophysiology texts usually are general statements rather than specific prescriptions. For example, the pathophysiology of heart failure is characterized by fluid overload, which implies that diuretic therapy would be useful; however, the exact selection of a drug and the dosing schedule would depend on a number of factors particular to the individual patient. Specific treatment recommendations are beyond the scope of a pathophysiology text and can be found in pharmacology and clinical practice textbooks.
KEY POINTS
• Pathophysiology includes four interrelated topics: etiology, pathogenesis, clinical manifestations, and treatment implications.
• Etiology refers to study of the proposed cause or causes of a particular disease process. Etiology is a complex notion because most diseases are multifactorial, resulting from interplay between genetic constitution and environmental influences.
• Pathogenesis refers to the proposed mechanisms whereby an etiologic stimulus leads to typically observed clinical manifestations. Pathogenesis describes the direct effects of the initiating event, as well as the usual physiologic responses and compensatory mechanisms.
• Clinical manifestations describe the signs and symptoms that typically accompany a particular pathophysiologic process. Manifestations may vary depending on the stage of the disorder, individual variation, and acuity or chronicity.
• An understanding of the etiology, pathogenesis, and clinical consequences of a particular disorder may imply that certain treatments could be helpful.
Concepts of Normality in Health and Disease
The ability to measure numerous structural, physiologic, biochemical, and genetic parameters in an individual allows the evaluation of information that is helpful in the diagnosis and monitoring of clinical diseases. Many of these same measures are commonly used to screen for disease or to evaluate the risks of a disease occurring in the future. To determine whether a certain finding is indicative of disease or “abnormal,” it must be compared with what is “normal.” The obviousness of this statement belies the difficulty in determining what is normal and the degree of deviation from normal that would be considered abnormal. Many clinical parameters are evaluated by direct observation by the examiner. Skin color and warmth, quality of pulses, briskness of pupil reactions to light, mental acuity, muscle strength, joint mobility, heart sounds, lung sounds, bowel sounds, balance, psychological affect, and level of consciousness are but a few examples of assessments that are subjectively interpreted based on the examiner's observations. Deciding whether a clinical finding is normal, a normal variation, or an abnormality indicative of a disorder is essential. Reliability of data obtained from observation is dependent upon the examiner's skill and experience. Often the clinical examination is not sufficient to determine definitively the underlying pathophysiologic processes, and diagnostic testing is undertaken to provide more information.
Statistical Normality
Some of the variables that are measured to diagnose disease are relatively easy to declare as normal or abnormal because they occur in only two states; for example, a bone is either broken or not broken on x-ray examination. However, most diagnostic variables occur in the population according to a “bell curve” or normal distribution.7 This means that a large enough sample taken from the population should give a good estimate of the range of values in the population. Statistics are often used to determine the standard deviation of the variable in question, and then a normal range is suggested as the mean ±2 standard deviations. This means that 95% of the values in the population are expected to fall in the normal range and 5% will be either higher or lower (Figure 1-1). The “population” chosen to serve as the normal reference population must be carefully selected to represent the individual to be tested for disease, because many variables are influenced by age and gender.
For example, bone density can be measured in the population by radiologic imaging and then a mean and standard deviation can be calculated. Women typically have lower bone density than men, and older women have lower bone density than younger women. If an elderly woman's bone density is compared to women of her own age group, it may fall within the normal range, but when compared to a group of younger women, it is more than 2 standard deviations below the mean. Which is the right comparison group to use to determine if she has osteoporosis? There is controversy on this point because, in this situation, it is difficult to determine the difference between disease and the effects of normal aging.
Often, when assessing a person's health status, a change in some value or factor is more significant than the actual value of the factor. A blood pressure of 90/70 mm Hg may not be significant if that is the usual value. However, if a person usually has a blood pressure of 120/80 mm Hg, a reading of 90/70 mm Hg could indicate a significant change. Individuals are typically evaluated more than once—generally two or three times—to establish deviation from their usual value.
FIGURE 1-1 Representative example of a normal bell curve for a physiologic variable. Many physiologic variables are normally distributed within the population, so the mean ±2 standard deviations include 95% of the normal values in the sample. Approximately 2.5% of values will be above the normal range and 2.5% will be below it. There may be overlap between the values in a normal sample and those in the population with a disease, making interpretation difficult in some cases.

Reliability, Validity, and Predictive Value
The accurate determination of whether a specific condition is present or absent depends on the quality and adequacy of the data collected, as well as the skill of interpretation. Decisions about the data needed are based on the initial clinical presentation and a working knowledge of pathophysiology, which guide hypothesis generation about probable etiologies. During the clinical examination, data are analyzed and a number of likely explanations for the clinical presentation may emerge. These possible explanations are “probabilities” based on knowledge and past experience with similar cases. The purpose of further data collection, particularly laboratory and diagnostic testing, is to refine the initial probability estimates and identify the most likely diagnosis. The success of this approach depends on the selection of appropriate tests based on the pretest probabilities, as well as on the validity, reliability, and predictive value of the tests.
Validity, or accuracy, is the degree to which a measurement reflects the true value of the object it is intended to measure. For example, a pulse oximeter is designed to measure arterial oxygen saturation, and the closeness of the reading to a direct measurement of oxygen saturation in an arterial blood sample reflects its accuracy. Reliability, or precision, is the ability of a test to give the same result in repeated measurements. An instrument or laboratory test can be reliable, yet inaccurate. Repeated measurements with the pulse oximeter could give the same result each time, but if those values are significantly different from the “gold standard” of an arterial blood sample, the oximeter data would have poor validity.
Some measurements vary according to the reagents and laboratory methods used. For example, prothrombin time (PT) is sensitive to the reagent used. In one method of determining PT, the reagent—a substance composed of thromboplastin and calcium—is added to decalcified plasma to create a reaction resulting in clot formation. The PT is then determined by measuring the length of time it takes for clotting to occur after this reagent is added and compared to the normative average. Portions of the same blood sample sent to several different laboratories could return significantly different PT results. In fact, this is such a problem that laboratories now use a correction procedure to normalize the PT values across labs. The corrected PT value is reported as the International Normalized Ratio (INR), which has higher reliability than the PT.8
The predictive value of a test is the extent to which the test can differentiate between the presence or absence of a condition in an individual. The positive predictive value is an estimate of the probability that disease is present if the test is positive. The negative predictive value is an estimate of the probability that disease is absent if the test is negative. The predictive value of a test depends in part upon the sensitivity and specificity of the test and in part upon the probability of the disease being present before the test is obtained. Most tests are not perfectly specific and sensitive so the results must be interpreted probabilistically in view of the diagnostic hypotheses being tested.
Sensitivity and specificity are measures of how well a given test can discriminate between persons with and without a given condition. Sensitivity is the probability that the test will be positive when applied to a person with the condition. For example, if a kit for testing a throat swab for the presence of streptococcal infection has a sensitivity of 80%, then 20% of a group of people with streptococcal throat infection would erroneously test negative for the condition (false negative rate). Another example is the blood test for HIV antibodies, which has a sensitivity of 99% and would fail to detect the condition in only 1% of a group of individuals who had HIV antibodies in their blood. Specificity is the probability that a test will be negative when applied to a person who does not have a given condition. If the streptococcal throat swab kit has a specificity of 95%, then 5% of those tested who do not actually have the condition would erroneously test positive (false positive rate). The importance of evaluating the accuracy and precision of data is paramount because inappropriate diagnoses and clinical management could occur if decisions are predicated on invalid or unreliable data.
The positive predictive value of a test is improved when sensitivity and specificity are high and the test is applied to individuals who have a high probability of having the condition being tested. If the likelihood of a condition in the population being tested is low (e.g., a 2% prevalence rate), then a positive result in a test with 99% specificity and 99% sensitivity would only have a 67% positive predictive value.9 This means that testing low-likelihood or low-risk individuals would produce a high percentage of false positive results (33% in the preceding example). Therefore deciding who to test for a given condition based on the probability of the condition being present is as important as the sensitivity and specificity of the test. A good working knowledge of pathophysiology is necessary to generate the hypotheses that guide collection of appropriate data and facilitate the diagnostic process.
Individual Factors Influencing Normality
Variations in physiologic processes may be a result of factors other than disease or illness. Age, gender, genetic and ethnic background, geographic area, and time of day may influence various physiologic parameters.10 Care must be taken to interpret “abnormal” findings with consideration of these possible confounding factors. In addition, the potential for spurious findings always exists. Thus, trends and changes in a particular individual are more reliable than single observations. Single measurements, observations, or laboratory results that seem to indicate abnormality must always be judged in the context of the entire health picture of the individual. One slightly elevated blood glucose level does not mean clinical diabetes, a single high blood pressure reading does not denote hypertension, and a temporary feeling of hopelessness does not indicate clinical depression.
Cultural Considerations
Each culture defines health and illness in a manner that reflects its experience. Cultural factors determine which signs, symptoms, or behaviors are perceived as abnormal. An infant from an impoverished culture with endemic chronic diarrhea and a degree of malnutrition would be viewed as abnormal in a progressive culture, such as a well-baby clinic in Sweden. Given cultural variations that affect definitions of normal and abnormal, the resulting pattern of behaviors or clinical manifestations affects what the culture labels as illness.11
Age Differences
Many biological factors vary with age, and the normal value for a person at one age may be abnormal at another. Physiologic changes, such as hair color, skin turgor (tension), and organ size, vary with age. In general, most organs shrink; exceptions are the male prostate and the heart, which enlarge with age.12 Special sensory changes, such as severely diminished near-sight, high-tone hearing loss, and loss of taste discriminations for sweet and salty, are normal in an elderly adult and abnormal in a middle-aged adult or child. There are fewer sweat glands and less thirst perception in an elderly person than in a young adult or child. Elderly persons have diminished temperature sensations and can therefore sustain burn injuries—from a heating pad or bath water—because they do not perceive heat with the same intensity as do middle-aged adults. A resting heart rate of 120 beats per minute is normal for an infant but not for an adult.
Gender Differences
Some laboratory values, such as levels of sex and growth hormones, show gender differences. The complete blood cell count shows differences by gender in hematocrit, hemoglobin, and red blood cell (RBC) count.13 For example, the normal range of hemoglobin concentration for adult women is lower than that for adult men—for adult women, the normal hemoglobin range is 12 to 16 g/100 ml of blood whereas for adult men the normal range is 13 to 18 g/100 ml of blood.13 There are also gender differences in the erythrocyte sedimentation rate (ESR). Normally, in males, the ESR is less than 13 mm/hr; it is slightly higher in females.13 There are differences by gender in creatinine values. For females, the normal serum creatinine level is 0.4 to 1.3 mg/dl; for males, the normal range is 0.6 to 1.5 mg/dl.13 Research into gender differences also suggests that, on average, males snore more; have longer vocal cords, better daylight vision, and higher metabolic rates; and are more likely to be left-handed than females.14 Research suggests, too, that females and males have different communication styles and respond differently to similar conditions.
Situational Differences
In some cases, a deviation from the usual value may occur as an adaptive mechanism, and whether the deviation is considered abnormal depends on the situation. For example, the RBC count increases when a person moves to a high altitude.15 The increase is a normal adaptive response to the decreased availability of oxygen at a high altitude and is termed acclimatization. A similar increase in the RBC count at sea level would be abnormal.
Time Variations
Some factors vary according to the time of day; that is, they exhibit a circadian rhythm or diurnal variation. In interpreting the result of a particular test, it may be necessary to know the time at which the value was determined. For example, body temperature and plasma concentrations of certain hormones (such as growth hormone and cortisol) exhibit diurnal variation. Reflecting fluctuation in plasma levels, the peak rate in urinary excretion for a particular steroid (17-ketosteroid) occurs between 8 am and 10 am for persons who customarily rise early in the morning and is about two to three times greater than the lowest rate in the same people, which occurs between midnight and 2 am, usually during sleep.16 The urinary excretion of ions (e.g., potassium) also exhibits diurnal variation. Figure 1-2 illustrates circadian rhythms of several physiologic variables for persons living on a standard day-active schedule.
KEY POINTS
• Determining whether clinical findings are normal, abnormal, or normal variation is an essential but often difficult process in evaluating for the presence or absence of disease.
• Normal ranges for laboratory tests are typically defined as the mean ±2 standard deviations; thus, 5% of the normal population may fall outside the normal range despite the absence of disease. Laboratory tests must be evaluated in concert with clinical information.
• The predictive value of a clinical test is the extent to which it can differentiate between the presence and absence of disease in an individual. Tests with high sensitivity and specificity generally have better predictive value.
• Variations in physiologic processes may be a result of factors other than disease or illness. Age, gender, genetic and ethnic background, geographic area, and time of day may influence various physiologic parameters.
• Trends and changes in a particular individual are more reliable than single observations.
Patterns of Disease in Populations
Concepts of Epidemiology
Differences among individuals are, of course, very important in determining the diseases to which they are susceptible and their reactions to
FIGURE 1-2 Circadian rhythms of several physiologic variables in a human subject depict the effect of light and dark. In an experiment with lights on (open bars at top) for 16 hours and off (black bars at top) for 8 hours, temperature readings and plasma growth hormone, plasma cortisol, and urinary potassium levels exhibit diurnal variation.

(Redrawn from Vander AJ et al: Human physiology, ed 7, New York, 1998, McGraw-Hill.) the diseases once contracted. But epidemiology, or the study of patterns of disease involving aggregates of people (Figure 1-3), provides yet another important dimension. Information may be gained by examining the occurrence, incidence, prevalence, transmission, and distribution of diseases in large groups of people or populations.
Endemic, Pandemic, and Epidemic Diseases
A disease that is native to a local region is called an endemic disease. If the disease is disseminated to many individuals at the same time, the situation is called an epidemic. Pandemics are epidemics that affect large geographic regions, perhaps spreading worldwide. Because of the speed and availability of human travel around the world, pandemics are more common than they once were. Almost every flu season, a new strain of influenza virus quickly spreads from one continent to another.
Aggregate Factors
Principal factors affecting patterns of disease in human populations include the following: (1) age (i.e., time in the life cycle), (2) ethnic group, (3) gender, (4) socioeconomic factors and lifestyle considerations, and (5) geographic location.
Age
In one sense, life is entirely different during the 9 months of gestation. The structures and functions of tissues are different: they are primarily dedicated to differentiation, development, and growth. Certainly the environment is different; the individual is protected from the light of day, provided with predigested food (even preoxygenated blood), suspended in a fluid buffer, and maintained at incubator temperature. This is fortunate because the developing embryo or fetus has
FIGURE 1-3 A, The aggregate focus in disease: influence of crowds upon disease transmission. Crowd gathered at a public market in Russia. B, Crowds gathered to purchase goods at a public market in Guangzhou, China.

(Photographed by L-E Copstead.) relatively few homeostatic mechanisms to protect it from environmental change. (The factors that produce disease in utero are discussed in Chapter 6.) Diseases that arise during the postuterine period of life and affect the neonate include immaturity, respiratory failure, birth injuries, congenital malformations, nutritional problems, metabolic errors, and infections. These conditions are discussed in separate chapters.
Accidents, including poisoning, take their toll in childhood. Infections in children reflect their increased susceptibility to agents of disease. Consideration of other childhood diseases is addressed in each chapter, as appropriate and given separate consideration throughout the text. The study of childhood processes and of changes that occur in this period of life is the domain of pediatrics; specific diseases that occur during maturity (ages 15 to 60) are emphasized in this text.
The changes in function that occur during the early years of life are termed developmental processes. Those that occur during maturity and postmaturity (age 60 and beyond) are called aging processes. The study of aging processes and other changes that occur during this period of life is called gerontology. The effects of aging on selected body systems are so important physiologically that they also receive separate consideration throughout the text. The immune, cardiac, respiratory, musculoskeletal, neurologic, special sensory, endocrine, gastrointestinal, and integumentary systems are among those affected by the process of aging.
Ethnic group
It is difficult to differentiate precisely between the effects of ethnicity on patterns of disease and the socioeconomic factors, religious practices, customs, and geographic considerations with which ethnicity is inseparably bound. For example, carcinoma of the penis is virtually unknown among Jews and Muslims who practice circumcision at an early age (avoiding the carcinogenic stimulus that arises from accumulation of smegma about the glans penis).
However, comparisons reveal significant differences in the occurrence of certain disease states in ethnic groups that seem to be more closely related to genetic predisposition than to environmental factors. For example, sickle cell anemia has a much higher rate of occurrence in African populations, whereas pernicious anemia occurs more frequently among Scandinavians and is rare among black populations worldwide.
The study of racial and ethnic group variation in disease states is the domain of medical anthropology. Volumes have been written about disease-specific differences that relate to racial or ethnic group differences. In clinical practice, recognition of diversity in disease risk by racial or ethnic group is useful in disease diagnosis, prevention, and management. Ethnic group–specific differences, where important, are presented in individual chapters.
Gender
Particular diseases of the genital system obviously show important differences between the sexes; men do not have endometriosis nor do women have hyperplasia of the prostate, and carcinoma of the breast is more common in women than in men. Pyelonephritis is more common in young women than in men of comparable age (before they develop prostatic hyperplasia) because the external urethral orifice of women is more readily contaminated, and bacteria can more easily travel up a short urethra than a long one. Less obviously related to the reproductive system, the onset of severe atherosclerosis in women is delayed nearly 20 years or more over that in men, presumably because of the protective action of estrogenic hormone.
There are also gender-specific factors that defy explanation.17 For example, systemic lupus erythematosus is much more common in women.18 Toxic goiter and hypothyroidism are also more common in women.19 Rheumatoid arthritis is more common in women, but osteoarthritis affects men and women with equal frequency.20 Thromboangiitis obliterans (a chronic, recurring, inflammatory peripheral vascular disease) occurs more commonly in men.21 Gender differences in predisposition to cancer and other diseases are presented throughout the text.
Socioeconomic factors and lifestyle considerations
The environment and the political climate of countries determine how people live and the health problems that are likely to ensue. The importance of poverty, malnutrition, overcrowding, and exposure to adverse environmental conditions, such as extremes of temperature, is obvious. Volumes have been written about the effects of socioeconomic status on disease. Sociologists study the influence of these factors. Social class influences education and occupational choices.
Disease is related to occupational exposure to such agents as coal dust, noise, or extreme stress.22 Lifestyle considerations are closely related to socioeconomic factors. People living in the United States, for example, consume too much food, alcohol, and tobacco and do not exercise enough. Childhood obesity is a problem in the United States. Arteriosclerosis; cancer; diseases of the kidney, liver, and lungs; and accidents cause most deaths in the United States. By contrast, people living in developing nations suffer and frequently die from undernutrition and infectious diseases.
However, infectious disease is not limited to developing countries.23 The Centers for Disease Control and Prevention (CDC) estimates that 2 million people annually acquire infections while hospitalized and 90,000 people die as a result of those infections. More than 70% of hospital-acquired infections have become resistant to at least one of the drugs commonly used to manage them, largely attributable to the overprescribing of antibiotics.24 Staphylococcus, the leading cause of hospital infections, is now resistant to 95% of first-choice antibiotics and 30% of second-choice antibiotics. Poor hygiene is considered the leading
FIGURE 1-4 Risk factors for schistosomiasis include the widespread use of irrigation ditches that harbor the intermediate snail host.

(Photographed in China by L-E Copstead.) source for infections acquired during hospitalizations. Unfortunately, efforts to convince health care personnel to reduce transmission of infection through practices as simple as more frequent and thorough hand washing have met with only modest success.
The incidence of many parasitic diseases is closely tied to socioeconomic factors and lifestyle considerations. Worm infections, for example, are related to the use of human feces as fertilizer. In some areas, such as parts of Asia, Africa, and tropical America, the frequency of schistosomiasis (a parasitic infestation by blood flukes) is directly related to the widespread use of irrigation ditches that harbor the intermediate snail host.25 There is adequate opportunity for transmission of schistosomiasis because children often play in these ditches and families wash their clothes in ditch water (Figure 1-4).
Trichinosis, a disease caused by the ingestion of Trichinella spiralis, occurs almost entirely from eating inadequately cooked, infected pork. People who are fond of raw meat and inadequately cooked sausage are at highest risk.
Education is often very effective in changing lifestyle patterns that contribute to disease. In Tokyo, for example, mass public education about minimizing the use of sodium—a common ingredient in most traditional Japanese cooking—has been effective in changing dietary practices.
Examples of educational efforts directed at lifestyle modification in the United States are numerous.26–28 Antidrug, antismoking, and pro-fitness messages fill the media and are prevalent on the Internet. Choosing healthy alternatives over unhealthy ones is made easier through positive peer pressure and support groups.
Geographic location
Patterns of disease vary greatly by geographic location. Certainly there is considerable overlap with ethnicity, socioeconomic factors, and lifestyle choices, but physical environment also is an important aspect. Obviously, frostbite in Antarctica and dehydration in the Sahara are examples of disorders that are more prevalent in specific geographic settings. However, important patterns of disease
FIGURE 1-5

Geographic distribution of malaria. (From Patton KT, Thibodeau GA: Anatomy & physiology, ed 8, St Louis, 2013, Mosby, p 113.) occur within individual countries. For example, the incidence and type of malnutrition vary tremendously by geographic region.
Many diseases have a geographic pattern for reasons that are clear. For example, malaria, an acute and sometimes chronic infectious disease resulting from the presence of protozoan parasites within red blood cells, is transmitted to humans by the bite of an infected female Anopheles mosquito. The Anopheles mosquito can live only in certain regions of the world29 (Figure 1-5).
FIGURE 1-6 Healthy aging: elders exercising in an aerobics class (A) and painting (B) illustrate the concept that aging and disease are not synonymous. The artist, a healthy woman in her mid-70s, is also a breast cancer survivor.

(Photographed by Therese A. Capal, Rockville, Md.)
Fungal diseases are both more common and more serious in hot, humid regions. But some infectious diseases are highly limited geographically for reasons that are not well understood. For example, bartonellosis, which is also called Carrión disease, is found only in Peru, Ecuador, Chile, and Colombia.30 This disease resembles malaria superficially in that the minute rickettsia-like organisms invade and destroy erythrocytes. Humans are infected by the bite of the sand fly. Although conditions in other parts of the world should be favorable for this disease, it remains limited geographically.
Taking a world view, there is widespread recognition of the importance of geographic factors in influencing human disease.31 The World Health Organization (WHO) and the National Institutes of Health (NIH) have been deeply concerned with geographic problems in disease. Consult WHO and NIH home pages on the World Wide Web for additional information. (Web locations are provided on the Evolve website.)
Levels of Prevention
The goal of health care should encompass much more than the prevention of illness. What is needed instead is some notion of positive health or physical “wholeness” that extends beyond the absence of ill health. WHO defines health as complete physical, mental, and social well-being and not merely the absence of disease or infirmity.31 For some individuals, health implies the ability to do what they regard as worthwhile and to conduct their lives as they want. Aging and ill health are not synonymous, and many elders enjoy excellent health, even in the face of chronic disease (Figure 1-6).
Epidemiologists suggest that treatment implications fall into categories called levels of prevention. There are three levels of prevention: primary, secondary, and tertiary. Primary prevention is prevention of disease by altering susceptibility or reducing exposure for susceptible individuals. Secondary prevention (applicable in early disease, i.e., preclinical and clinical stages) is the early detection, screening, and management of the disease. Tertiary prevention (appropriate in the stage of advanced disease or disability) includes rehabilitative and supportive care and attempts to alleviate disability and restore effective functioning.32
Primary prevention
Prolongation of life has resulted largely from decreased mortality from infectious disease. Primary prevention in terms of improved nutrition, economy, housing, and sanitation for those living in developed countries is also responsible for increased longevity. Certain childhood diseases—measles, poliomyelitis, pertussis (whooping cough), and neonatal tetanus—are decreasing in prevalence, owing to a rapid increase in coverage by immunization programs. More than 120 million children younger than age 5 in India were immunized against poliomyelitis in a single day in 1996.33 Globally, coverage of children immunized against six major childhood diseases increased from 5% in 1974 to 80% in 1995.33 In 1985 Rotary International launched the PolioPlus program to protect children worldwide from the cruel and fatal consequences of polio. In 1988 the World Health Assembly challenged the world to eradicate polio. Since that time, Rotary International's efforts and those of partner agencies, including the WHO, the United Nations Children's Fund, the CDC, and governments around the world, have achieved a 99% reduction in the number of polio cases worldwide.33
The prevalence of cardiovascular diseases in developed countries (except those in Eastern Europe) is diminishing, thanks to the spread of health education and promotion. Infant and child death rates and the overall death rate are continuing to decrease globally.
High school education programs about abstinence from sex and ways to “say no” to drugs, alcohol, and tobacco are other examples of primary prevention making a difference in the lives of people. Primary prevention also includes adherence to safety precautions, such as wearing seat belts, observing the posted speed limit on highways, and taking precautions in the use of chemicals and machinery. Violent crimes involving dangerous weapons must be stopped to achieve primary prevention of the traumatic or fatal injuries they cause.
Environmental pollutants poison the body's organs. Some experts fear the emergence of an epidemic of cancer attributable to the carcinogenic chemicals afflicting the environment.34 Public health measures to ensure clean food, air, and water prevent many diseases, including cancer. As air, water, and soil quality is improved, the risk of exposure to harmful carcinogens is minimized.
Secondary prevention
Yearly physical examinations and routine screening are examples of secondary prevention that lead to the early diagnosis of disease and, in some cases, cures. The routine use of Papanicolaou (Pap) smears has led to a decline in the incidence of invasive cancer of the uterine cervix. Also, more women are examining their own breasts monthly for cancer; thus, earlier diagnoses are achieved.
Prenatal diagnosis of certain genetic diseases is possible. New diagnostic laboratory techniques provide definitive information for the genetic counseling of parents. This information can aid in predicting chances of involvement or noninvolvement of offspring for a given genetic disorder (e.g., Down syndrome). One technique, amniocentesis, consists of removing a small amount of fluid from the amniotic sac that surrounds the fetus and analyzing the cells and chemicals in the fluid. Blood samples can also be obtained from the fetus by amniocentesis; the amniotic fluid and fetal blood are then studied to determine defects in enzymes, to ascertain gender, and to measure substances associated with defects in the spinal cord and brain.
Tertiary prevention
Once a disease becomes established, treatment—within the context of traditional Western medicine—generally falls into one of the following two major categories: medical (including such measures as physical therapy, pharmacotherapy, psychotherapy, radiation therapy, chemotherapy, immunotherapy, and experimental gene therapy) and surgical. Numerous other subspecialties of medicine and surgery also have evolved to focus on a given organ or technique. In a clinical setting, a large array of professional caregivers provides rehabilitative and supportive tertiary prevention to the diseased individual. Every professional brings the perspective of his or her discipline to the caregiving situation. Each makes clinical judgments about the patient's needs and problems and decides which goals and intervention strategies are most beneficial.
KEY POINTS
• Epidemiology is the study of patterns of disease in human populations.
• Diseases may be endemic, epidemic, or pandemic depending upon location and the number of people affected.
• Aggregate factors such as age, ethnicity, gender, lifestyle, socioeconomic status, and geographic location are epidemiologic variables that influence the occurrence and transmission of disease in populations.
• Understanding the epidemiologic aspects of a disease is essential for effective prevention and treatment.
Summary
Most people recognize what it is to be healthy and would define disease or illness as a change from or absence of that state. Under closer scrutiny, the concept of health is difficult to describe in simple, succinct terms. Correspondingly, the concepts of disease and illness also are complex. Environment, genetic constitution, socioeconomic status, lifestyle, and previous physical health all affect the timing and ultimate expression of disease in individuals.
Because humans exhibit considerable diversity, healthy structure and function are not precisely the same in any two individuals. By discovering common and expected patterns of responses to abnormalities, general prediction of etiology, pathogenesis, clinical manifestations, and targeted levels of prevention and intervention becomes possible.

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References
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...1984 By George Orwell Download free eBooks of classic literature, books and novels at Planet eBook. Subscribe to our free eBooks blog and email newsletter. Part One  1984 Chapter 1 I t was a bright cold day in April, and the clocks were striking thirteen. Winston Smith, his chin nuzzled into his breast in an effort to escape the vile wind, slipped quickly through the glass doors of Victory Mansions, though not quickly enough to prevent a swirl of gritty dust from entering along with him. The hallway smelt of boiled cabbage and old rag mats. At one end of it a coloured poster, too large for indoor display, had been tacked to the wall. It depicted simply an enormous face, more than a metre wide: the face of a man of about forty-five, with a heavy black moustache and ruggedly handsome features. Winston made for the stairs. It was no use trying the lift. Even at the best of times it was seldom working, and at present the electric current was cut off during daylight hours. It was part of the economy drive in preparation for Hate Week. The flat was seven flights up, and Winston, who was thirty-nine and had a varicose ulcer above his right ankle, went slowly, resting several times on the way. On each landing, opposite the lift-shaft, the poster with the enormous face gazed from the wall. It was one of those pictures which are so contrived that the eyes follow you about when you move. BIG BROTHER IS WATCHING YOU, the caption beneath it ran. Inside the flat a......

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Mammitas Garden Cove

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Sda Manual

...permission. Texts credited to NEB are from The New English Bible. © The Delegates of the Oxford University Press and the Syndics of the Cambridge University Press 1961, 1970. Reprinted by permission. Texts credited to NIV are from the Holy Bible, New International Version. Copyright © 1973, 1978, 1984, International Bible Society. Used by permission of Zondervan Bible Publishers. Bible texts credited to RSV are from the Revised Standard Version of the Bible, copyright © 1946, 1952, 1971, by the Division of Christian Education of the National Council of the Churches of Christ in the U.S.A. Used by permission. Texts credited to RV are from The Holy Bible, Revised Version, Oxford University Press, 1911. Printed in U.S.A. 09 08 07 06 5 4 3 2 1 ISBN 0-8280-1947-9 ISBN 0-8280-1948-7 hardcover paperback Printed and distributed by the Review and Herald® Publishing Association Hagerstown, Maryland 21740 Table of Contents Introduction ...................................................................................... xix Historical Development of the Seventh-day Adventist Church ... xix Historical Development of the Church Manual .......................... xix Content of the Church Manual...................................................... xxi Procedure for Changes in the Church Manual ............................. xxi Clarification of Meaning...

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