Introduction
Stress
is the rate of wear and tear, in particular the strain on the nervous system, in an organism. It is the sum of all adaptive reactions in the body and manifests itself by a specific syndrome that consists of all the nonspecifically induced changes within the individual.
Adaptive reactions, or adaptation, are the processes by which the organism adjusts itself to changed circumstances. A syndrome is a group of symptoms usually appearing together in a disease. Nonspecific changes are those that involve many organs of the body and can be induced by a variety of causal factors. Nevertheless, the form in which these changes appear is quite specific: It is the general adaptation syndrome (GAS), first described by Hans Selye in the 1950’s. The explanation of this seeming contradiction lies in the fact that stress produces two kinds of change: one that is nonspecifically caused and appears in a nonspecific form, called the primary change; and one that, although nonspecifically caused, is specific in form, the secondary change called general adaptation syndrome.
Stages
The general adaptation syndrome is composed of three stages. The first is the alarm reaction, in which the body arms itself for defense against an aggression (such as a bacterial or viral infection, physical damage, or a strong nervous stimulus) but has had no time to adjust itself to the new condition. The second is the stage of resistance, in which the body succeeds in adapting itself to the condition. The third is the stage of exhaustion, in which the body’s resistance breaks down with the loss of its adaptive response, a development that can lead to death.
There are three main signs of the first (alarm reaction) stage: an enlargement of the cortex (outer layer) of the adrenal glands; a degeneration of the thymus gland (located in the front of the chest, playing an important role in defense against infections) and the lymphatic system (the vessels that carry the lymph, or white blood, and the lymph nodes, including the spleen and tonsils); and the appearance of gastrointestinal (stomach and gut) ulcers.
In the second (resistance) stage, the body is at its highest level of adaptation, above the normal range, and the body organs return to their normal state. The adrenals, which in the first stage completely discharged their hormones, again accumulate large amounts of hormones. In the last (exhaustion) stage, the adrenals again lose their secretions and the other organs degenerate even more; the body’s resistance drops to below-normal levels. Although the third stage can lead to death, this is not necessarily the outcome. Often a person undergoes all three stages only to recuperate at the end. A marathon runner goes through all stages of the general adaptation syndrome and, although completely exhausted at the end of the race, regains strength after only a few hours of rest.
The adrenal glands have an important role in the general adaptation syndrome. These are two little glands, each sitting on top of one of the kidneys. The gland is composed of an outer part, or cortex, and a core, or medulla. The cortex is subdivided into layers, one of which manufactures the so-called mineralocorticoids, aldosterone and desoxycorticosterone (DOCA), which have a role in electrolyte (salt) metabolism and have a proinflammatory effect in the body; the second layer secretes the glucocorticoids, cortisol and cortisone, which play a role in sugar metabolism and have an anti-inflammatory effect. Inflammation is a local defense mechanism of the body; the anti-inflammatory hormones suppress this defensive weapon. They also promote the spread of infections and the formation of gastrointestinal ulcers. In spite of this apparent antagonism between the two types of cortical hormones, their effects are absolutely necessary for the body to resist aggression. If the adrenal glands are damaged to a degree that they can no longer produce these hormones, then, without treatment, death is inevitable. In contrast, the hormones secreted by the medullary part of the adrenal gland, epinephrine (also known as adrenaline) and norepinephrine, are not absolutely necessary for survival because they are also produced by nerve endings in other parts of the body.
Agents and Effects
Any agent that attacks the body will induce both specific and nonspecific effects. These are direct effects, such as a burn wound, and indirect effects, which are of two kinds: one that triggers the proinflammatory mechanism, inducing it to fight the damage, and one that triggers the anti-inflammatory mechanism, which limits the extent of the damage. The system is actually a bit more complex than this; another component, the so-called conditioning factors, must be taken into account.
Conditioning factors are agents or situations that themselves have no independent effects; however, they can modify the response to a particular stimulus. There are external and internal conditioning factors. The external ones comprise, for example, geographical, social, and nutritional factors, whereas the internal conditioning factors are those determined by genetics and previous experiences.
Based on this information, the sequence of events that occurs when a stressor (a stress inducer) acts on an individual may be summarized as follows: The brain senses the stimulus and sends messages to the adrenal medulla, inducing it to release epinephrine, and to the pituitary gland, inducing it to release adrenocorticotropic hormone (ACTH). Epinephrine has two effects: It acts on the pituitary gland, increasing the secretion of ACTH, and it acts on most of the body tissues, increasing their rate of activity. The heart rate, breathing rate, and blood pressure are increased, as well as the blood sugar level. All these changes prepare the organism for fight or flight. ACTH, in the meantime, reaches the adrenal cortex and induces the secretion of anti-inflammatory hormones. Simultaneously, proinflammatory hormones are released. Both types act on the tissues affected directly by the stressor and also have a systemic effect on the whole body, inducing the general adaptation syndrome. The particular type and degree of response are modulated by the conditioning factors.
Stress and Disease
Disease
could be defined as an alteration, as a result of a changed environment, of the structure and function of tissues that interferes with their ability to survive. To produce a disease, two types of factors are necessary: environmental, or external, factors; and the response of the organism, or internal factors. The discovery that stress elicits a specific response, the general adaptation syndrome, made it possible to apply exact measurements to the state of stress and its consequences (stress-induced diseases). Although the general adaptation syndrome has a defensive purpose in the body because it promotes adaptation to new conditions, an excess of adaptive hormones can induce untoward symptoms, that is, cause disease. This aspect of stress, that adaptive reactions can themselves become harmful, is one of the most important characteristics of the phenomenon. It made physicians realize that there are many diseases that are not caused by specific agents such as microorganisms, toxic chemicals, or injuries, but rather by the response of tissues to these aggressors (stressors). An example of this type of disease is an allergy such as hay fever or hives. It was found that the inflammation of the nasal passages, eyes, or skin is caused by the tissues reacting against chemicals contained in pollen or in some foods. The body fights these reactions with glucocorticoids (anti-inflammatory hormones) secreted by the adrenal cortex. This discovery, that adrenal glucocorticoids have anti-inflammatory and antiallergic effects, was immediately applied in clinical medicine to treat very grave diseases such as arthritis and asthma. The glucocorticoids proved to be lifesaving in these cases.
As the phenomenon of stress is primarily produced by a strain on the nervous system, it seemed reasonable to look into the role of the general adaptation syndrome in nervous and mental diseases. It became clear that what is called maladaptation can be the cause of a nervous breakdown or even outright mental disease. This realization led physicians to search for the connection between psychological maladjustments and bodily diseases. The result was the foundation of the medical specialty called psychosomatic medicine. It is known that what is called “executive disease”—that is, gastrointestinal ulcers and high blood pressure, sometimes accompanied by a nervous breakdown—is induced by the inability to adjust to a new situation, by an exceptionally heavy workload, or by fear of responsibility and an inability to make decisions. Psychosomatic medicine attempts to elucidate the way in which maladaptation causes disease as well as the way in which it influences aging and the degenerative diseases of old age, in particular, coronary heart disease and cancer. It is known that chronological age is not the same as physiological age. That is, a fifty-year-old person, from the point of view of tissue integrity and function, may be much older than a seventy-year-old person whose tissues are still in good functioning order. The underlying causes of these individual differences are based in an individual’s differential response to stressful situations.
As an outgrowth of the study of stress and the GAS, two subfields of research opened up: the psychology of stress and psychophysiology. The study of stress psychology implies that human behavior is affected by biological mechanisms that appear to be a common heritage of all mammals. The aim of the study would be to enable people to control their emotions and, thus, their behavior. This would be of obvious benefit in the rehabilitation of persons who come in conflict with the law because of their violent behavior and, possibly, would allow society to reduce violent crimes. Psychophysiology, which was founded as a separate branch of psychology in 1960, studies psychological or behavioral variables with their respective physiological responses. For example, one of the major preoccupations of psychophysiology is the study of biofeedback, or the control by subjects of their own heart rates or brain function. There is great interest in biofeedback studies, because it is hoped that psychosomatic disturbances could be treated successfully by this technique. In 1949, researchers studied two groups of patients: one group that had recurring head and neck pains, and another that complained of cardiovascular (heart) symptoms. When the researchers administered painful stimuli to the two groups, the members of each group reported an increased intensity in its particular symptoms, although they had been well before the test. The researchers concluded that psychosomatic disorders are caused by the exaggerated response of a particular physiological system, characteristic for the individual. This phenomenon has been named symptom specificity.
History of Stress Research
In ancient Greece, the father of medicine, Hippocrates, taught that in every diseased body there is a natural force that fights the disease from within. Later, in eighteenth century England, John Hunter stated that every injury has the tendency to produce the means for a cure. That is, the concept of being sick includes a battle between the aggressor and the defense mechanisms of the body. Rufus of Ephesus, a Greek physician, around the year 100 c.e. discovered that high fever had a beneficial effect on the progression of many illnesses. This fact was rediscovered by a nineteenth century Viennese psychiatrist, Julius Wagner von Jauregg, who tried to alleviate the mental disease of patients in the last stage of syphilis. In 1883, he observed that the symptoms improved markedly when the patients contracted typhoid fever. Subsequently, he introduced the treatment with malaria and achieved spectacular results, but without knowing the reason for the cure.
The great French physiologist Claude Bernard, in the nineteenth century, taught that a characteristic of living organisms is their ability to maintain a constant internal environment in spite of significant fluctuations in the external conditions in which they live. Walter Bradford Cannon, at Harvard University, gave this phenomenon the name “ homeostasis.” He also coined the term “emergency reaction” to describe the immediate functional changes occurring in the body as a consequence of stressful stimuli. When the homeostatic mechanisms of the body fail to maintain the constancy of the internal medium, disease and eventually death ensue. Although all these findings converged in the treatment of disease by nonspecific means, it was a Viennese physician, Selye, who formulated a scientific theory of the “syndrome of being sick,” or, in other words, the concept of stress and of the general adaptation syndrome.
Selye, who was born in Vienna but immigrated to Canada, discovered in 1936 that the physical response to stress could cause disease and even death. He detected the effects of stress when he injected ovarian extracts into laboratory rats. He found that the extract induced enlargement of the adrenal cortex, shrinkage of the thymus gland, and gastric ulcers. Selye realized that it was the stress caused by the impurities in the extract that induced the characteristic changes. He extrapolated his findings to humans and stated that stress could initiate disease and cause death. In 1950, he published The Physiology and Pathology of Exposure to Stress, in which he gave a detailed description of the general adaptation syndrome concept.
In the beginning, the medical establishment was reluctant to accept the idea that hormones could have a role in the causation of nonspecific aspects of disease; until that time, hormones were known to act only on specific target tissues. They caused disease either by too little or too much of a particular hormone. For example, a lack of growth hormone resulted in dwarfism, whereas too much of the same created a giant. Selye, however, postulated general hormonal effects that transcended their known immediate action on target tissues. Another, unjustified, criticism of his theory was that he attributed too great a role to the hormonal system, neglecting the part played by the nervous system. These criticisms did not hold up in the long run, and Selye’s teachings on stress and the general adaptation syndrome were in the end accepted by medical and physiological researchers.
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