What is a disease?

Types of Disease

It is difficult to answer the question “What is disease?” To the patient, disease means discomfort and disharmony with the environment. To the treating physician or surgeon, it means a set of signs and symptoms. To the pathologist, it means one or more structural changes in body tissues, called lesions, which may be viewed with or without the aid of magnifying lenses.

The study of lesions, which are the essential expression of disease, forms part of the modern science of pathology. Pathology had its beginnings in the morgue and the autopsy room, where investigations into the cause of death led to the appreciation of “morbid anatomy”—at first by gross (naked-eye) examination and later microscopically. Much later, the investigation of disease moved from the cold autopsy room to the patient’s bedside, from the dead body to the living body, on which laboratory tests and biopsies are performed for the purpose of establishing a diagnosis and addressing proper treatment.

Diagnosis is the art of determining not only the character of the lesion but also its etiology, or cause. Because so much of this diagnostic work is done in laboratories, the term “laboratory medicine” has increased in popularity. The explosion in high technology has expanded the field of laboratory medicine tremendously. The diagnostic laboratory today is highly automated and sophisticated, containing a team of laboratory technologists and scientific researchers rather than a single pathologist.

The lesions laid bare by the pathologist usually bear an obvious relation to the symptoms, as in the gross lesions of acute appendicitis, the microscopic lesions in poliomyelitis, or even the chromosomal lesions in genetically inherited conditions such as Down syndrome. Yet there may be lesions without symptoms, as in early cancer or “silent” diseases such as tuberculosis. There may also be symptoms without obvious lesions, as in the so-called psychosomatic diseases, functional disorders, and psychiatric illnesses. It is likely that future research will reveal the presence of “biochemical lesions” in these cases. The presence of lesions distinguishes
organic disease, in which there are gross or microscopic pathologic changes in an organ, from functional disease, in which there is a disturbance of function without a corresponding obvious organic lesion. Although most diagnoses consist largely of naming the lesion (such as cancer of the lung or a tooth abscess), diseases should truly
be considered in the light of disordered function rather than altered structure. Scientists are searching beyond the presence of obvious lesions in tissues and cells to the submicroscopic, molecular, and biochemical alterations affecting the chemistry of cells.

Not every disease has a specific etiology. A syndrome is a complex of signs and symptoms with no specific etiology or constant lesion. It results from interference at some point with a chain of body processes, causing impairment of body function in one or more systems. A specific biochemical molecular derangement caused by yet undiscovered agents is usually found. An example is Acquired immunodeficiency syndrome (AIDS), for which a specific human immunodeficiency virus (HIV) agent is now accepted as the etiologic agent.

Some diseases have an acute (sudden) onset and run a relatively short course, as with acute tonsillitis or the common cold. Others run a long, protracted course, as with tuberculosis and rheumatoid arthritis; these are called chronic illnesses. The healthy body is in a natural state of readiness to combat disease, and thus there is a natural tendency to recover from disease. This is especially true in acute illness, in which inflammation tends to heal with full resolution of structure and function. Sometimes, however, healing does not occur, and the disease overwhelms the body and causes death. Therefore, a patient with acute pneumonia may have a full recovery, with complete healing and resolution of structure and function, or may die. The outcome of disease can vary between the extremes of full recovery and death and can run a chronic, protracted course eventually leading to severe loss of function. The accurate diagnosis of disease is essential for its treatment and prognosis, a forecast of what may be expected to happen.

There are four aspects to the study of disease. The first is etiology, or cause; for example, several viruses cause the common cold. The second is pathogenesis, or course, which refers to the sequence of events in the body that occurs in response to injury and the method of the lesion’s production and development. The relation of an etiologic agent to disease, of cause to effect, is not always as simple a matter as it is in most acute illnesses; for example, a herpesvirus causes the development of fever blisters. In many illnesses, indeed in most chronic illnesses, the concept of one agent causing one disease is an oversimplification. In tuberculosis, for example, the causative agent is a characteristic slender microbe called tubercle bacillus (Mycobacterium tuberculosis). Many people may be exposed to and inhale the tuberculosis bacteria, but only a few will get the disease; also, the bacteria may lurk in the body for years and become clinically active only as a result of an unrelated, stressful situation that alters the body’s immunity, such as prolonged strain, malnutrition, or another infection. In investigating the causation and pathogenesis of disease, several factors—such as heredity, sex, environment, nutrition, immunity, and age—must be considered. That is why there is no simple answer to questions such as “Does cigarette smoking cause cancer?” and “Does a cholesterol-rich diet cause hardening of the blood vessels (atherosclerosis)?” The third aspect to the study of disease relates to morphologic and structural changes associated with the functional alterations in cells and tissues that are characteristic of the disease. These are the gross and microscopic findings that allow the pathologist to establish a diagnosis. The fourth aspect to disease study is the evaluation of functional abnormalities and their clinical significance; the nature of the morphologic changes and their distribution in different organs or tissues influence normal function and determine the clinical features, signs and symptoms, and course and outcome (prognosis) of disease.

All forms of tissue injury start with molecular and structural changes in cells. Cells are the smallest living units of tissues and organs. Along with their substructural components, they are the seat of disease. Cellular pathology is the study of disease as it relates to the origins, molecular mechanisms, and structural changes of cell injury.

The normal cell is similar to a factory. It is confined to a fairly narrow range of function and structure dictated by its genetic code, the constraints of neighboring cells, the availability of and access to nutrition, and the disposal of its waste products. It is said to be in a “steady state,” able to handle normal physiologic demands and to respond by adapting to other excessive or strenuous demands (such as the muscle enlargement seen in bodybuilders) to achieve a new equilibrium with a sustained workload. This type of adaptive response is called hypertrophy. Conversely, atrophy is an adaptive response to decreased demand, with a resulting diminished size and function.

If the limits of these adaptive responses are exceeded, or if no adaptive response is possible, a sequence of events follows that results in cell injury. Cell injury is reversible up to a certain point, but if the stimulus persists or is severe, then the cell suffers irreversible injury and eventual death. For example, if the blood supply to the heart muscle is cut off for only a few minutes and then restored, the heart muscle cells will experience injury but can recover and function normally. If the blood flow is not restored until one hour later, however, the cells will die.

Whether specific types of stress induce an adaptive response, a reversible injury, or cell death depends on the nature and severity of the stress and on other inherent, variable qualities of the cell itself. The causes of cell injury are many and range from obvious physical trauma, as in automobile accidents, to a subtle, genetic lack of enzymes or hormones, as in diabetes mellitus. Broadly speaking, the causes of cell injury and death can be grouped into the following categories: hypoxia, or a decrease in the delivery of available oxygen; physical agents, as with mechanical and thermal injuries; chemical poisons, such as carbon monoxide and alcohol, tobacco, and other addictive drugs; infectious agents, such as viruses and bacteria; immunological and allergic reactions, as with certain sensitivities; genetic defects, as with sickle cell disease; and nutritional imbalances, such as severe malnutrition and vitamin deficiencies or nutritional excesses predisposing a patient to heart disease and atherosclerosis.

Causes of Disease

By far the most common cause of disease is infection, especially by bacteria. Certain forms of animal life known as animal parasites may also live in the body and produce disease; parasitic diseases are common in low-income societies and countries. Diseases can also be caused by viruses, forms of living matter so minute that they cannot be seen with the most powerful light microscope; they are visible, however, with the electron microscope. Viruses have attracted much attention for their role in many diseases, including cancer.

Bacteria, or germs, can be divided into three morphologic groups: cocci, which are round; bacilli, which are rod-shaped; and spirilla or spirochetes, which are spiral-shaped, like a corkscrew. Bacteria produce disease either by their presence in tissues or by their production of toxins (poisons). They cause inflammation and either act on surrounding tissues, as in an abscess, or are carried by the bloodstream to other distant organs.
Strep throat is an example of a local infection by cocci—in this case, streptococci. Some dysenteries and travelers’ diarrheas are caused by coliform bacilli.
Syphilis is an example of a disease caused by a spirochete. The great
epidemics of history, such as bubonic plague and cholera, have been caused by bacteria, as are tuberculosis, leprosy, typhoid, gas gangrene, and many others. Bacterial infections are treatable with antibiotics, such as penicillin.

Viruses, on the other hand, are not affected by antibiotics; they infect and live within the cell itself and are therefore protected. Viruses cause a wide variety of diseases. Some, such as many childhood diseases, the measles, and the common cold, run a few days’ course. Others, such as poliomyelitis and AIDS, can cause serious body impairment. Still others are probably involved in causing cancer and such diseases as multiple sclerosis.

Of the many physical agents causing injury,
trauma is the most obvious; others relate to external temperatures that are either too high or too low. A high temperature may produce local injury, such as a burn, or general disease, such as heatstroke. Heatstroke results from prolonged direct exposure to the sun (sunstroke) or from very high temperatures, so that the heat-regulating mechanism of the body becomes paralyzed. The internal body temperature shoots up to alarming heights, and collapse, coma, and even death may result. Low temperatures can cause local frostbite or general hypothermia, which can also lead to death.

Other forms of physical agents causing injury are
radiation and atmospheric pressure. Increased atmospheric pressure can cause the “bends,” a
decompression sickness that can affect deep-sea divers. The pressure of the water causes inert gases, such as nitrogen, to be dissolved in the blood plasma. If the diver passes too rapidly from a high to a normal atmospheric pressure, the excessive nitrogen is released, forming gas bubbles in the blood. These tiny bubbles can cause the blockage of small vessels of the brain and result in brain damage. The same problem can occur in high-altitude aviators unless the airplane is pressurized.

The study of chemical poisoning, or toxicology, as a cause of disease is a large and specialized field. Poisons may be introduced into the body by accident (especially in young children), in the course of suicide or homicide, and as industrial pollution. Lead poisoning is a danger because of the use of lead in paints and soldering. Acids and carbon monoxide are emitted into the atmosphere by industry, and various chemicals are dumped into the ground and water. Such environmental damage will eventually affect plants, livestock, and humans.

Hypoxia (lack of oxygen) is probably the most common cause of cell injury, and it may also be the ultimate mechanism of cell death by a wide variety of physical, biological, and chemical agents. Loss of adequate blood and oxygen supply to a body part, such as a leg, is called
ischemia. If the blood loss is very severe, the result is hypoxia or anoxia. This condition may also result from narrowing of the blood vessels, called atherosclerosis. If this narrowing occurs in the artery of the leg, as may be seen in patients with advanced diabetes, then the tissues of the foot will eventually die, a condition known as gangrene. An even more critical example of ischemia is blockage of the coronary arteries of the heart, resulting in a myocardial infarction
(heart attack), with damage to the heart muscle. Similarly, severe blockage of arteries to the brain can cause a stroke.

Nutritional diseases can be caused either by an excessive intake and storage of foodstuffs, as in extreme obesity, or by a deficiency. Obesity is a complex condition often associated with hereditary tendencies and hormonal imbalances. The deficiency conditions are many. Starvation and malnutrition can occur because of intestinal illnesses that prevent the delivery of food to the blood (malabsorption) or because of debilitating diseases such as advanced cancer. Even more important than general malnutrition as a cause of disease is a deficiency of essential nutrients such as
minerals, vitamins, and other trace elements. Iron deficiency causes
anemia, and calcium deficiency causes
osteoporosis (bone fragility). Vitamin deficiencies are also numerous, and deficiency of the trace element iodine causes a thyroid condition called
goiter.

Genetic defects as a cause of cellular injury and disease are of major interest to many researchers. The results of genetic disorders may be as visible as the physical characteristics seen in patients with Down syndrome or as subtle as molecular alterations in the coding of the hemoglobin
molecule that causes sickle cell disease.

Cellular injuries and diseases can be induced by immune mechanisms. The anaphylactic reaction to a foreign protein, such as a bee sting or drug, can actually cause death. In the autoimmune diseases, such as
lupus erythematosus, the
immune system turns against the cellular components of the very body that it is supposed to protect.

Finally, neoplastic diseases, or cancers, are presently of unknown etiology. Some are innocuous growths, while others are highly lethal. Diagnosing cancer and determining its precise nature can be an elaborate, and elusive, process. The methods involve clinical observations and laboratory tests; a biopsy of the involved organ may be taken and analyzed.

Perspective and Prospects

It is sometimes said that the nature of disease is changing and that more people are dying of heart failure and cancer than was once the case. This does not mean that these diseases have actually become more common, although more people do die from them. This increase is attributable to a longer life span and vastly improved diagnostic methods.

For primitive humans, there were no diseases, only patients stricken by evil; therefore, magic was the plausible recourse. Magic entails recognition of the principle of causality—that, given the same predisposing conditions, the same results will follow. In a profound sense, magic is early science. In ancient Egypt, priests assumed the role of healers. Unlike magic, religion springs from a different source. Here the system is based on the achievement of results against, or in spite of, a regular sequence of events. Religion heals with miracles and antinaturals that require the violation of causality. The purely religious concept of disease, as an expression of the wrath of gods, became embodied in many religious traditions.

The ancient Greeks are credited with attempts at introducing reason to the study of disease by asking questions about the nature of things and considering the notion of health as a harmony, as the adjustment of such opposites as high and low, hot and cold, and dry and moist. Disease, therefore, was a disharmony of the four elements that make up life: earth, air, fire, and water. This concept was refined by Galen in the second century and became dogma throughout the Dark Ages until the Renaissance, when the seat of disease was finally assigned to organs within the body itself through autopsy studies. Much later, in the nineteenth century, the principles espoused by French physiologist Claude Bernard were introduced, whereby disease was considered not a thing but a process that distorts normal physiologic and anatomic features. The nineteenth-century German pathologist Rudolf Virchow emphasized the same principle—that disease is an alteration of life’s processes—by championing the concept of cellular pathology, identifying the cell as the smallest unit of life and as the seat of disease.

As new diseases are discovered and old medical mysteries deciphered, as promising new medicinal drugs and vaccines are tested and public health programs implemented, the age-old goal of medicine as a healing art seems to be closer at hand.

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