Disease: signs and symptoms

Disease may be acute, chronic, malignant, or benign. Of these terms, chronic and acute have
to do with the duration of a disease, malignant and benign with its potentiality for causing
death.

An acute disease process usually begins abruptly and is over soon. Acute appendicitis, for
example, is characterized by the sudden onset of nausea, vomiting, and pain usually localized
in the lower right side of the abdomen. It usually requires immediate surgical treatment. The
term chronic refers to a process that often begins very gradually and then persists over a long
period. For example, ulcerative colitis—an inflammatory condition of unknown cause that is
limited to the colon—is a chronic disease. Its peak incidence is early in the second decade of
life. The disease is characterized by relapsing attacks of bloody diarrhea that persist for
weeks to months. These attacks alternate with asymptomatic periods that can last from weeks
to years.

The terms benign and malignant, most often used to describe tumours, can be used in a more
general sense. Benign diseases are generally without complications, and a good prognosis
(outcome) is usual. A wart on the skin is a benign tumour caused by a virus; it produces no
illness and usually disappears spontaneously if given enough time (often many years).
Malignancy implies a process that, if left alone, will result in fatal illness. Cancer is the
general term for all malignant tumours.

Diseases usually are indicated by signs and symptoms. A sign is defined as an objective
manifestation of disease that can be determined by a physician; a symptom is subjective
evidence of disease reported by the patient. Each disease entity has a constellation of signs
and symptoms more or less uniquely its own; individual signs such as fever, however, may be
found in a great number of diseases. Some of the common manifestations of disease—as they
relate to an imbalance of normal homeostasis—are taken up in this section. They are covered
more at length in the article diagnosis.

Fever is an abnormal rise in body temperature. It is most often a sign of infection but can be
present whenever there is tissue destruction, as, for example, from a severe burn or when
large amounts of tissue have died because of lack of blood supply. Body temperature is
controlled by the thermostatic centre in the hypothalamus. Certain protein and polysaccharide
substances called pyrogens, released either from bacteria or viruses or from destroyed cells of
the body, are capable of raising the thermostat and causing a rise in body temperature. Fever
is a highly significant indicator of disease.

An increase in the number of circulating phagocytic white blood cells (leukocytosis),

mentioned above (see Maintenance of health: Defense against biotic invasion: Phagocytic
cells of the body), is one of the more common manifestations of disease. The stimulus for
such an event may be any inflammatory process in the body, such as is caused by bacteria,
viruses, or any process that leads to the destruction of cells. Such leukocytosis is reflected in
the white blood cell count, which may be substantially elevated above the normal upper value
of 10,000 cells per cubic millimetre of blood.

The pulse rate is another easily obtainable and important piece of information. The heart rate
varies with the level of physical activity: the heart beats faster during exercise and more
slowly during rest. Persons who are physically active typically have a lower resting heart rate
than sedentary individuals. Research suggests that a slower resting rate (e.g., under 50 beats
per minute) is associated with reduced mortality. Moreover, an inappropriate heart rate (or
pulse) can be indicative of disease. The heart rate increases in the feverish patient. A weak,
rapid pulse rate may be a sign of severe blood loss or of disease within the heart itself.
Irregularity of the pulse (arrhythmia) is an important indicator of heart malfunction.

The respiratory rate (rate of breathing) is modified by disease. Persons with fever have an
increased respiratory rate (hyperventilation), which serves to lower body temperature (this
rapid breathing is analogous to the panting of a dog). Hyperventilation is a common response
to painful stress. Any condition leading to acidosis (lowering of body pH) similarly drives the
respiratory rate upward. Diseases of the lungs—with the accompanying inability to oxygenate
the blood adequately—have a similar effect.

Temperature, pulse, and respiratory rate—called the vital signs—may be important

manifestations of disease. A fourth vital sign, blood pressure, is equally significant. Among
other things, it indicates the amount of blood in circulation. A decrease in circulating blood
volume, as is seen with severe bleeding, lowers the blood pressure and deprives the tissues of
adequate blood flow. Reflexes are initiated that compensate for the reduced blood volume
and blood pressure. The heart rate increases and compensates to some extent for the sudden
reduction in blood volume and pressure; at the same time, peripheral blood vessels in such
areas as the abdomen constrict, tending to divert the reduced blood volume to the more vital
areas such as the brain and head. Unusual elevation of pressure (hypertension) is a disease by
itself.

Fluid and electrolyte imbalances may be further consequences of homeostatic failure and
additional significant manifestations of disease. The causes of these abnormalities are
complex. Edema, or swelling, results from shifts in fluid distribution within body tissues.
Edema may be localized, as when the leg veins are narrowed or obstructed by some disease
process. The pressure of the blood in the distended veins rises, and fluid is driven out of the
vessels into the tissues, causing swelling of the extremity. Generalized edema is seen in renal
(kidney) disease that causes abnormal retention of sodium and water. Heart failure is an
additional cause of generalized edema, usually most manifest as swollen feet and ankles.
Alterations such as dehydration, hyperventilation, and tissue destruction can all lead to
varying fluid and electrolyte derangements. The levels of the serum electrolytes (sodium,
potassium, bicarbonate, chloride), determined relatively easily in the laboratory, provide the
physician with valuable clues to deranged homeostasis induced by disease.

Finally, the determination of body pH and a number of blood tests designed to evaluate
adequate (or inadequate) metabolic regulation provide diagnostic clues of homeostatic
failure. These tests include determination of the levels of the blood glucose, blood urea
nitrogen, and serum protein.

The disease diabetes mellitus provides an excellent example of failure of the homeostatic
mechanisms. Diabetes is a common disease of metabolic-endocrine (ductless gland) origin
involving a relative or absolute deficiency of insulin, a hormone that plays a major role in
carbohydrate metabolism. Any or all of the homeostatic derangements can be found in this
disease. Patients with a severe form of diabetes may at one time be dehydrated because of
obligatory excretion of water (osmotic diuresis), be acidotic because of formation of
increased amounts of keto acids derived from the oxidation of free fatty acids, be
hyperventilating as a result of the acidosis, be comatose because of high levels of blood
glucose, have a weak pulse because of severe dehydration, have electrolyte abnormalities,
and so on. The signs and symptoms are numerous, all illustrating the interdependence of the
homeostatic mechanisms, which, when not functioning properly, provide the manifestations
of disease.

At the most elemental level, disease develops when any disruptive or adverse influence
overcomes the homeostatic and defensive controls of the body. As will be seen, there are
numerous influences that can tip the scales of health toward disease. Viruses and bacteria are
obvious threats to health. There are a great many others, some so subtle as to be poorly
understood. The following section focuses on the causes of disease rather than on a detailed
description of each entity. It represents one method of classification. There is considerable
overlap in categories; certain diseases grouped as metabolic-endocrine in origin could also be
classified as diseases of genetic origin. Indeed, the interdependence of the organ systems, the
metabolic pathways, and the defense systems renders finite classification in medicine
difficult. The human body acts as a unit—an individual—both in health and in disease.

The causes of disease

The search for the causes (etiologies) of human diseases goes back to antiquity. Hippocrates,
a Greek physician of the 4th and 5th centuries bce, is credited with being the first to adopt the
concept that disease is not a visitation of the gods but rather is caused by earthly influences.
Scientists have since continually searched for the causes of disease and, indeed, have
discovered the causes of many.

In the development of a disease (pathogenesis) more is involved than merely exposure to a

causative agent. A room full of people may be exposed to a sufferer from a common cold, but
only one or two may later develop a cold. Many host factors determine whether the agent will
induce disease or not. Thus, in the pathogenesis of disease, the resistance, immunity, age, and
nutritional state of the person exposed, as well as virulence or toxicity of the agent and the
level of exposure, all play a role in determining whether disease develops.

In the following sections the many types of human disease will be divided into categories,
and in each only a few examples will be given to establish the nature of the process. These
categories are divided on the basis of the presumed etiology of the disease. Many diseases are
still of unknown (idiopathic) origin. With others the cause may be suspected but not yet
definitively proved. In a few instances the discovery of the etiology of a disease represents
the individual achievement of a solitary investigator who may have worked many years on
the problem; the story of Louis Pasteur and the discovery of the cause of anthrax is a classic
example. More often the individual investigator who makes the final breakthrough stands on
the shoulders of hundreds of earlier workers who provided bits and pieces of knowledge vital
to the final understanding.

1. Diseases of genetic origin

Certain human diseases result from mutations in the genetic complement (genome)
contained in the deoxyribonucleic acid (DNA) of chromosomes. A gene is a discrete
linear sequence of nucleotide bases (molecular units) of the DNA that codes for, or
directs, the synthesis of a protein; there are an estimated 20,000 to 25,000 genes in the
 human genome. Proteins, many of which are enzymes, carry out all cellular functions.
Any alteration of the DNA may result in the defective synthesis and subsequent
malfunctioning of one or more proteins. If the mutated protein is a key enzyme in
normal metabolism, the error may have serious or fatal consequences. More than
5,000 distinct diseases have been ascribed to mutations that result in deficiencies of
critical enzymes.

2. Heredity and environment

Diseases can be spread across a wide spectrum, with predominantly genetic diseases
at one extreme of the spectrum and diseases of largely environmental origin at the
other. In the genetic part of the spectrum are diseases such as Turner’s syndrome; in
the environmental part are infectious diseases and chemical poisoning. Between these
two extremes lie most human diseases—those with both genetic and environmental
causative influences that are significant. Indeed, even at the very extreme ends of the
spectrum both factors play some role. The genetic constitution dictates in part the
host’s response to environmental challenges. Similarly, environmental factors play
significant roles in the manifestation of genetically induced disease. Sickle cell
anemia, for example, an inherited disease characterized by abnormal red blood cells
and hemoglobin, is seriously exacerbated by low levels of oxygen in the air.
3. Chemical injury: poisoning
A poison is any substance that can cause illness or death when ingested in small
quantities. This definition excludes the multitude of substances that cause damage if
ingested in large quantities. For example, even oxygen and glucose, so crucial to life,
are toxic to cells when administered at high concentrations.

4. Drugs
Drugs are another important cause of poisoning. It is a pharmacological principle that,
for any therapeutic gain derived from a drug, a price is paid. There are few drugs used
today that have no side effects (i.e., effects unintended when the drug is
administered). Although these side effects may be harmless and inconsequential,
certain drugs have side effects that are potent. Similarly, a drug may be useful in a
certain dose range but harmful when larger doses are taken. Morphine, for example, is
an excellent drug for the control of severe pain, but it can depress respiration, and too
much of it can cause death. All drugs are, therefore, potentially harmful.

Stanley L. Robbins Jonathan H. Robbins Dante G. Scarpelli