Stress (physiology)

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This article is about the pathological process. For other uses of the term Stress, please see Stress (disambiguation).

Stress, as defined by Hans Selye (who is regarded as the first to formulate the concept of stress in physiological terms) is "the nonspecific response of the body to any demand, whether is caused by, or results in, pleasant or unpleasant conditions. Stress as such, like temperature as such, is all-inclusive, embodying both the positive and the negative aspects of these concepts."[1] All living organisms have stressors and stress responses, but this article deals only with those of vertebrates.

By Selye's understanding, stress is not a reaction to any specific thing; it has a characteristic form and composition, but no particular cause; it might be produced by virtually any agent, and the effects can differ from one individual to another [2]. But stress is not a nonspecific reaction: in animals, it affects certain organs - notably the adrenal and the pituitary glands, the thymus, and the gastrointestinal tract in a very selective manner.

"Stress cannot and should not be avoided. Everybody is always under some degree of stress. Even while quietly asleep our heart must continue to beat, our lungs to breathe, and even our brain works in the form of dreams. Stress can be avoided only by dying." From 'The Nature of Stress' by Hans Selye

The hypothalamo-pituitary-adrenal axis

Any demand made upon the body - whether physical or emotional, whether from internal or external causes, produces a nonspecific stimulus (a "stressor"). This is converted into nervous signals that may be carried by any of many different neural pathways in the brain, but eventually it acts upon certain neuroendocrine cells in the paraventricular nucleus of the hypothalamus. These cells transform the nervous signals into a humoral messenger, (corticotrophin releasing hormone, CRH), which is secreted from nerve endings into portal blood vessels which carry it to the anterior pituitary gland. There, CRH stimulates the corticotroph cells to secrete adrenocorticotrophic hormone (ACTH) into the general circulation. Upon reaching the adrenal cortex, ACTH causes secretion of glucocorticoids (cortisol or corticosterone). These induce glyconeogenesis, supplying energy for the adaptive reactions necessary to meet the demands faced by the body, facilitate other enzymatically regulated adaptive metabolic responses, and suppress immune reactions as well as inflammation. Glucocorticoids subsequently feedback to the brain and pituitary to terminate the stress response by reducing the responsiveness of neurones in the hypothalamus and elsewhere, and by attenuating the synthesis of CRH and ACTH.

This hypothalamo-pituitary-adrenal axis (HPA axis) plays a pivotal role in physiological and behavioral adaptation to environmental change in all vertebrates: its proteins, gene structures, and signaling pathways were present in the earliest vertebrates and appear to have been tightly conserved through subsequent evolution [3] The HPA axis is organized hierarchically, with feedbacks operating at several points. In all vertebrates studied, it is controlled centrally by peptides of the CRH family. These effects are mediated by at least two distinct G protein-coupled receptors and modulated by a secreted binding protein. These neuropeptides are also released within the brain and influence stress-related behaviors, such as anxiety and fear.

The "Fight or Flight" response

The flight or fight response, also called the "acute stress response" was first described by Walter Cannon in the 1920s as a theory that animals react to threats with a general discharge of the sympathetic nervous system.[4]

[5] In response to acute stress, acetylcholine is released from preganglionic sympathetic nerves that innervate the chromaffin cells of the adrenal medulla. As a consequence, the chromaffin cells secrete the hormone epinephrine (adrenaline) into the general circulation. This provides readily available sources of energy by forming glucose from glycogen depots and [[free fatty acid]s from the triglyceride stores of adipose tissue; it quickens the pulse and raises arterial blood pressure, but also accelerates blood coagulation and thereby protects against blood loss in the event of injury.

More recently, ethologists working with nonhuman primates have established four distinct fear responses that proceed sequentially in response to increasing threat. The sequence begins with "the freeze response" - "stop, look, and listen" . Next comes an attempt to flee, then an attempt to fight. Finally, comes tonic immobility. ("playing dead"). Thus, "freeze, flight, fight, or fright" may be a more complete and nuanced alternative to "fight or flight." [6]

Chronic stress

  • McEwen BS, Kalia M (2010) The role of corticosteroids and stress in chronic pain conditions.

Metabolism 59 Suppl 1:S9-15 PMID 20837196



  1. Selye H (1985) The nature of stress Basal Facts. 1985;7:3-11 PMID 2990402
  2. Kudielka BM, Wüst S (2010) Human models in acute and chronic stress: assessing determinants of individual hypothalamus-pituitary-adrenal axis activity and reactivity Stress 13:1-14. PMID: 20105052
  3. Denver RJ (2009) Structural and functional evolution of vertebrate neuroendocrine stress systems Ann N Y Acad Sci 1163:1-16 PMID 19456324
  4. Cannon WB (1914) The emergency function of the adrenal medulla in pain and the major emotions. Am J Physiol 33:356-72
  5. Cannon WB (1929) Bodily Changes in Pain, Hunger, Fear and Rage: An Account of Recent Research Into the Function of Emotional Excitement, 2nd ed. New York, Appleton-Century-Crofts
  6. Bracha HS et al. (2004) Does "Fight or Flight" need updating? Psychosomatics 45:448-9
  7. Hans Selye
    • Selye H (1950)Stress and the general adaptation syndrome Br Med J 1:1383-92 PMID 15426759
    • Selye H (1976) The stress concept Can Med Assoc J 115:718 PMID 20312787
    • Selye H (1976) Forty years of stress research: principal remaining problems and misconceptions Can Med Assoc J 115:53-6 PMID 1277062
    • Neylan TC (1998) Hans Selye and the Field of. Stress Research. J Neuropsych 10:230
    • Szabo S (1985) The creative and productive life of Hans Selye: a review of his major scientific discoveries Experientia 41:564–567