After studying this chapter, the student is expected to: 1. Explain the role of pathophysiology in the diagnosis and treatment of disease. 2. Use the terminology appropriate for pathophysiology. 3. Explain the importance of a patient’s medical history. 4. Describe common cellular adaptations and possible reasons for the occurrence of each. 5. Identify precancerous cellular changes. 6. List the common causes of cell damage. 7. Describe the common types of cell necrosis and possible outcomes. anaerobic apoptosis autopsy biopsy endogenous exogenous gangrene homeostasis hypoxia iatrogenic idiopathic inflammation ischemia lysis lysosomal microorganisms microscopic morphologic probability Pathophysiology involves the study of functional or physiologic changes in the body that result from disease processes. This subject builds on knowledge of the normal structure and function of the human body. Disease development and the associated changes to normal anatomy and/or physiology may be obvious or may be hidden with its quiet beginning at the cellular level. As such, pathophysiology includes some aspects of pathology, the laboratory study of cell and tissue changes associated with disease. Disease may be defined as a deviation from the normal structure or function of any part, organ, system (or combination of these) or from a state of wellness. The World Health Organization includes physical, mental, and social well-being in its definition of health. A state of health is difficult to define because the genetic differences among individuals as well as the many variations in life experiences and environmental influences create a variable base. The context in which health is measured is also a consideration. A person who is blind can be in good general health. Injury or surgery may create a temporary impairment in a specific area, but the person’s overall health status is not altered. Homeostasis is the maintenance of a relatively stable internal environment regardless of external changes. Disease develops when significant changes occur in the body, leading to a state in which homeostasis cannot be maintained without intervention. Under normal conditions homeostasis is maintained within the body with regard to such factors as blood pressure, body temperature, and fluid balance. As frequent minor changes occur in the body, the compensation mechanisms respond, and homeostasis is quickly restored. Usually the individual is not aware of these changes or the compensations taking place. Steps to Heath (Box 1-1) are recommended to prevent disease. When one is defining “normal” limits for health indicators such as blood pressure or pulse, the values used usually represent an average or a small range. These values represent what is expected in a typical individual but are not an absolute criterion. Among normal healthy individuals, the actual values may be adjusted for factors such as age, gender, genetics, environment, and activity level. Well-trained athletes often have a slower pulse or heart rate than the average person. Blood pressure usually increases slightly with age, even in healthy individuals. Also, small daily fluctuations in blood pressure occur as the body responds to minor changes in activity, body position, and even emotions. Therefore it is impossible to state a single normal value for blood pressure or pulse rate. It is also important to remember that any one indicator or lab value must be considered within the total assessment for the individual client. Likewise, a discussion of a specific disease in a text presents a general description of the typical characteristics of that disease, but some differences in the clinical picture can be expected to occur in a specific individual, based on similar variables. Pathophysiology requires the use of knowledge of basic anatomy and physiology and is based on a loss of or a change in normal structure and function. This basis also saves relearning many facts! Many disorders affecting a particular system or organ, for example the liver, display a set of common signs and symptoms directly related to that organ’s normal structure and function. For example, when the liver is damaged, many clotting factors cannot be produced; therefore, excessive bleeding results. Jaundice, a yellow color in the skin, is another sign of liver disease, resulting from the liver’s inability to excrete bilirubin. Also, basic pathophysiologic concepts related to the causative factors of a disease, such as the processes of inflammation or infection are common to many diseases. Inflammation in the liver causes swelling of the tissue and stretching of the liver capsule, resulting in pain, as does inflammation of the kidneys. This cause and effect relationship, defined by signs and symptoms, facilitates the study of a specific disease. In this text, in order to provide a comprehensive overview of disease processes, the focus is on major diseases. Other disorders are included when appropriate to provide exposure to a broad range of diseases. The principles illustrated by these diseases can then be applied to other conditions encountered in practice. In addition, a general approach is used to describe diseases in which there may be several subtypes. For example, only one type of glomerulonephritis, a kidney disease, is described in the text, acute poststreptococcal glomerulonephritis, which represents the many forms of glomerulonephritis. Prevention of disease has become a primary focus in health care. The known causes of and factors predisposing to specific diseases are being used in the development of more effective preventive programs, and it is important to continue efforts to detect additional significant factors and gather data to further decrease the incidence of certain diseases. The Centers for Disease Control and Prevention in the United States have a significant role in collection of data about all types of disease and provide evidence based recommendations for prevention. Prevention includes such activities as maintaining routine vaccination programs and encouraging participation in screening programs such as blood pressure clinics and vision screening (Box 1-2). As more community health programs develop, and with the increase in information available on the internet, health care workers are becoming more involved in responding to questions from many sources, and have an opportunity to promote appropriate preventive measures in their communities. A sound knowledge of pathophysiology is the basis for preventive teaching in your profession. While studying pathophysiology, the student becomes aware of the complexity of many diseases, the difficulties encountered in diagnosis and treatment, and the possible implications arising from a list of signs and symptoms or a prognosis. Sophisticated and expensive diagnostic tests are now available. The availability of these tests, however, also depends on the geographic location of individuals, including their access to large, well-equipped medical facilities. More limited resources may restrict the number of diagnostic tests available to an individual, or a long waiting period may be necessary before testing and treatment are available. When a student understands the pathophysiology, comprehension of the manifestations and potential complications of a disease, and its treatment, usually follows. A solid knowledge base enables health care professionals to meet these increased demands with appropriate information. Individuals working in health care have found that many new scientific developments have raised ethical, legal, and social issues. For example, the recent explosion in genetic information and related technologies has raised many ethical concerns (see Chapter 21). In relatively new areas of research such as genetics, discussion and resolution of the legal and ethical issues lag far behind the scientific advances. Health research is most often funded by commercial sources (up to 80% according to some studies) and new breakthrough therapies are often announced before the start of any clinical trials. This causes increased hope and immediate demand for such treatments often as much as a decade before they become available. Understanding the research process and the time required for clinical trials of new therapies is crucial in answering questions about new therapies. The research process in the health sciences is a lengthy three-stage process that aims to demonstrate both the safety and effectiveness of a new therapy. The first stage in this process is often referred to as “basic science” in which researchers work to identify a technology that will work to limit or prevent the disease process. This stage is carried out in the laboratory and often requires the use of animals or cell cultures. The second stage involves a small number of human subjects to determine if the therapy is safe for humans. The third stage only takes place if the results of the previous research are positive; the majority of therapies do not make it to this point. In the third stage of research a large number of patients with the disease or at risk for the disease are enrolled in clinical trials. These are usually double blind studies in which the research subject and the person administering the treatment do not know if the subject is receiving a standard, proven therapy or the therapy being tested. The subject is identified by number only without the particular therapy administered. All results are recorded by the subject’s identification number. The principal investigator is responsible for tracking data collected in trials with many patients often in several different health centers. The data are then analyzed to determine if the new therapy is more effective than the traditional therapy. In studies of vaccines or other preventive measures, data are collected about the occurrence of disease in both the control and the experimental group to determine if the new measure reduces the incidence of the specific disease. Research findings that demonstrate merit after this three-stage process are often referred to as “evidence-based research findings.” The research data collected up to this point are then passed on to regulatory bodies such as the Food and Drug Administration for review. If the therapy is deemed safe and better than the standard therapy used in the past, the data will be approved for use for the specific disease identified in the research protocol. Evidence-based research does not take into account cost, availability, or social and cultural factors that may influence use and acceptance of a therapy. These factors may be quite significant and affect the physician’s or patient’s acceptance of a therapy. In some rare cases, stage three research trials will be stopped if there is a significant difference in the mortality rate for the experimental group versus the control group. Research on the first antiretroviral agent, AZT, was stopped 6 months early when the research showed a striking difference in survival rates. Those in the experimental group receiving AZT were outliving the control group in significant numbers. When the results were analyzed, trials stopped and all patients were given the option of receiving AZT. Once a therapy is approved for use, it may show additional potential to treat a different disease. Such use is termed “off-label” use. For the manufacturer to advertise the drug or therapy for use in different diseases, it must go through stage three clinical trials in patients having the new disease. An example of this is research using the drug thalidomide to treat malignancies such as multiple myeloma. Other issues may affect professional practice. Current technology provides an opportunity to prolong life through the use of various machines, many advances in surgery, and the use of organ transplants. Legal and ethical issues about fetal tissue transplants, stem cell therapies, experimental drugs or treatments, and genetic engineering continue to be difficult topics to address. In these developing areas, the primary goal is to reduce the incidence of disease and improve recovery rates. Concerns about new medical and health technologies include issues of access to therapy, costs, and relative risk versus benefits of new treatments. Questions have also been raised about the allocation of health care resources for new therapies such as heart transplants or in vitro fertilization (test-tube babies), which are very costly. A public health dilemma results because a choice must be made between a high-cost treatment for one person or a low-cost treatment for many people, given the limited resources available. In many cases evidence-based research is demonstrating little significant difference in outcomes for newer versus older technologies. A skilled and trained professional is essential in the use and interpretation of any technology. Clinical research funding is being directed to identifying treatments as well as preventive measures that are more effective on a cost-per-patient basis. Many options other than traditional therapies are now available. Treatment by acupuncture or naturopathy may be preferred (see Chapter 3). These options may replace traditional therapies or may be used in conjunction with them. A patient may seek an alternative or complementary mode of treatment to supplement traditional care; thus knowledge of these complementary therapies is often needed. It is also recognized that such therapies and practices should be part of a health history for any client seeking care. Many individuals in the health professions will be contributing to, completing, or updating a patient’s medical or health history (see Ready Reference 6 for an example). This information is essential to identify any impact health care activities might have on a patient’s condition, or how a patient’s illness might complicate care. The assessment includes questions on current and prior illnesses, allergies, hospitalizations, and treatment. Current health status is particularly important, and should include specific difficulties and any type of therapy or drugs, prescription, nonprescription, and herbal items, including food supplements. A basic form is usually provided for the patient to fill out, and then completed by the health professional asking appropriate follow-up questions to clarify the patient’s current condition and identify any potential problems. Knowledge of pathophysiology is essential to developing useful questions, understanding the implications of this information, and deciding on the necessary precautions or modifications required to prevent complications. For example, a patient with severe respiratory problems or congestive heart failure would have difficulty breathing in a supine position. Reducing stress may be important for a patient with high blood pressure. Prophylactic medication may be necessary for some patients to prevent infection or excessive bleeding. In some cases, additional problems or undesirable effects of medications may be detected. Constant updating of information and knowledge is required by both students and practitioners. Developments in all areas of health care are occurring at a very rapid rate primarily due to changes in technologies. New causes of disease and more detail regarding the pathophysiology of a disorder are uncovered, diagnostic tests are improved, and more effective drugs are formulated. Technology has greatly altered many aspects of health care. Extensive research projects continue in efforts to prevent, control, or cure many disorders. For example, research indicated that most cases of cervical cancer resulted from infection by human papillomavirus (HPV). The next step involved development of a vaccine effective against the most common strains of the virus. In clinical trials, use of the vaccine showed a reduction in the number of women developing cervical cancer. This vaccine is now available to young women to prevent cervical cancer in later years. It does not provide 100% prevention and other health prevention behaviors, such as routine screening, need to be maintained, but the number of actual cases of cervical cancer and the cost of treatment are expected to decline dramatically in the coming decades. It is essential for the student and practitioner to continually check for new information, employing reliable, accurate resources such as professional web sites, journals, or seminars. It is anticipated that many changes in health care will occur in the near future as electronic devices are more frequently used. For example, sensors implanted under the skin may measure blood glucose levels in diabetic patients or release the amount of insulin appropriate to the patient’s needs. The increased costs associated with technological advances then are balanced against the costs of hospitalization or chronic care. Reports from health professionals are gathered by the World Health Organization (WHO), United States Public Health Service, the Centers for Disease Control and Prevention (CDC), and state and local authorities, as well as agencies in countries around the world. These data are organized and published, leading to new research efforts, tracking new or deadly diseases or in some cases, signaling a warning about predisposing conditions or current treatments. Awareness of deviations from the expected outcomes is a responsibility of those working in health care. Keeping up with new discoveries may sometimes feel like “information overload,” but it is a critical part of professional practice. 1-1 Apply Your Knowledge Using the heart and the lungs, show how you can apply your prior knowledge of anatomy and physiology to your study of pathophysiology. (Hint: Change part of the normal structure and predict the resulting loss of function.)
Introduction to Pathophysiology
Learning Objectives
Key Terms
What Is Pathophysiology and Why Study It?
Understanding Health and Disease
Concept and Scope of Pathophysiology and Evidenced-Based Practice
Beginning the Process: A Medical History
New Developments and Trends
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