Multiple Organ Failure as an Endocrine-Mediated Response to Chronic Stress via the HypothalamoPituitary Adrenal (HPA) axis

Homeostasis is the coordinated system of physiological and biochemical processes which regulate and maintain most of the steady states in the organism, attempting to keep the internal conditions relatively constant, for example: pH, internal temperature, etc; in a state of equilibrium. This concept is essential to the understanding of stress.

In everyday life, there are numerous factors that recurrently disrupt homeostasis, such as, environmental factors or internal and external stimuli. This coordinated system then works to keep the organism in an incessant flux around particular variables that could be considered optimal conditions for it to live and survive. Any deviation relatively far from the optimal equilibrium and the organism’s specific response, involving a number of processes which strive to restore normal body conditions, can be perceived as Stress.

As per the particular event, response to stress is by Sympathetic nervous system (SNS) activation which leads to the so-called Fight-or-Flight response, or Cannon’s reaction. This state cannot be maintained for extended periods of time as it could be detrimental to the physical and mental health of the organism. The Parasympathetic system seeks to returns the conditions to the more optimal range. This restoration consumes a lot of energy and resources, putting a lot of strain on the body, but seeks to focus it to repress the immediate problem. One such process to overcome chronic stress is multiple organ failure caused by the organism's own system.

Endocrine Response to Stress

HypothalamoPituatary Adrenal Axis

The HypothalamoPituataryAdrenal (HPA) axis, is an intricate set of interactions among three endocrine glands, being the hypothalamus, pituitary gland, and adrenal glands. These interactions constitute a major part of the neuroendocrine system responsible for the response to stress, as well numerous body processes that affect the organism both physically and mentally. These include regulation of energy stores and energy expenditure, sexuality, digestion, the immune system as well as emotions.

Fundamentally, the HPA axis responds to stressors through the release of cortisol in a long term, delayed process. The Hypothalamus secretes Corticotropin Releasing Hormone (CRH) and Vasopressin (ADH) into the portal circulation of the pituitary gland by neurons of the Paraventricular nucleus (PVN). These elicit the release of Pro-Opiomelanocortin polypeptide (POMC) from the Adenohypophysis, which can then be cleaved into several hormones. This includes Adrenocotricotropic hormone (ACTH), . ACTH, through systemic circulation, arrives at the cortex of the Adrenal gland and stimulates the release of Cortisol. CRH itself, also takes part in the physio- and psychological response to stressors (Del Giudice et al., 2011).

General Adaptation Syndrome

General Adaptation Syndrome (GAS) outlines an organism’s stress response. It is mediated by the interactions of the HPA axis, and can be distinguished into four phases:

ACTH

Multiple Organ Failure

Sepsis and other critical illnesses lead to a biphasic inflammatory, immune, hormonal, and metabolic response. A pronounced increase in the secretion of the stress hormones with an associated increase in mitochondrial and metabolic activity, marks the acute phase. As a result of the changes in the endocrine profile and intense inflammation, energy production, metabolic rate, and normal cellular processes decrease drastically, thereby resulting in Multiple Organ Dysfunction or failure (Singer et al., 2004).

Conclusion

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References

Charmandari, E., Tsigos, C., & George, G. (2005). Endocrinology of the Stress Response. Annual Review of Physiology, 67, 259-284.

Del Giudice, M., Ellis, B., & Shirtcliff, E. (2011). The Adaptive Calibration Model of stress responsivity. Neurosci Biobehav Rev, 35(7), 1562–1592.-1562–1592.

McEwen, B. (2008). Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators. European Journal of Pharmacology, 583(2-3), 174-185.

Singer, M., De Santis, V., Vitale, D., & Jeffcoate, W. (2004). Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation. Lancet, 7-13.

Taylor, Shelley, and Sirois, Fuschia. (2012). Health Psychology 2nd Canadian Edition