Examining Stress: The HPA Axis & Sympathetic-Adrenal-Medullary System

// Corey Schuler, RN, MS, CNS, DC


While the adrenal glands are often pointed to as responsible for handling the normal stress response, they may instead be target organs of two intersecting systems. The hypothalamus-pituitary-adrenal (HPA) axis is the endocrine response to stressors producing adrenocorticotropic hormone (ACTH) from the pituitary gland with measurable changes in levels of plasma cortisol and salivary cortisol as produced in the adrenal cortex. The sympathetic-adrenal-medullary system produces epinephrine and norepinephrine and measurable changes in heart rate are seen. It is important not to oversimplify this relationship as HPA responses habituate to repeated stress exposure. In effect, the body responds better and better to the same stressor. The sympathetic system shows rather uniform activation patterns with repeated stress exposure.1

The Role of Rumination

Even in primary care settings, our encouragement to reduce rumination within our patients may offer benefit when the stress response is a factor in one’s health goals.

The HPA may also not habituate to repeated stress exposure. In this situation, the same stressor causes the same set of physiological functions as if it were a new, unique stressor. Repetitive and unwanted past-centered negative thinking, also known as rumination, is related with non-habituation of the HPA axis stress response.2 Even in primary care settings, our encouragement to reduce rumination within our patients may offer benefit when the stress response is a factor in one’s health goals.

Combining information from both systems provides a cross-reference to determine if the stress response is in an early-, mid-, or late-stage. The adrenal release of cortisol may be under dual control of both ACTH and preganglionic sympathetic neurons.3

Salivary Cortisol Testing

Salivary cortisol is also affected by psychological stimulation.4 However, its utility as a predictable marker has come into question. Saliva is probably one of the most studied oral correlates of stress. Being controlled by both sympathetic and parasympathetic fibers, the salivary glands are controlled by various factors. While stimulation of the parasympathetic fibers leads to normal vasodilation and increased secretion of saliva, sympathetic stimulation produces a complex series of reactions with little or no effect. Experiments on emotional states on salivary composition suggest that pH of saliva changes under stress.5 One measureable marker in saliva that changes in response to stress is the immune function marker secretory IgA (S-IgA).6 7 8 9

Ultimately, knitting together a patient’s story in regards to responses to new stressors, repeated stressors, immune function, and certain physiological measures are critical components to direct the methods in which we choose to support our patients under stress.

HPA Axis Optimization Program

1. Schommer NC, Hellhammer DH, Kirschbaum C. Dissociation between reactivity of the hypothalamus-pituitary-adrenal axis and the sympathetic-adrenal-medullary system to repeated psychosocial stress. Psychosom Med. 2003 May-Jun;65(3):450-60.
2. Gianferante D, Thoma MV, Hanlin L, et al. Post-stress rumination predicts HPA axis responses to repeated acute stress. Psychoneuroendocrinology. 2014 Aug 1;49C:244-252.
3.Hellhammer DH, Wust S, Kudielka BM. Salivary cortisol as a biomarker in stress research. Psychoneuroendocrinology 2009; 34:163–171.
4.Kakimoto Y, Nakamura A, Tarui H, Nagasawa Y, Yagura S. Crew workload in JASDF C-1 transport flights: I. Change in heart rate and salivary cortisol. Aviat Space Environ Med. 1988 Jun;59(6):511-6.
5.Morse DR, Schacterle GR, Furst L, Zaydenberg M, Pollack RL. Oral digestion of a complex-carbohydrate cereal: effects of stress and relaxation on physiological and salivary measures. Am J Clin Nutr. 1989 Jan;49(1):97-105.
6.Jemmott JB, Magloire K. Academic stress, social support, and secretory immunoglobulin A. J Pers Soc Psychol. 1988 Nov;55(5):803-10.
7.Jemmott JB, Borysenko JZ, Borysenko M, et al. Academic stress, power motivation, and decrease in secretion rate of salivary secretory immunoglobulin A. Lancet. 1983 Jun 25;1(8339):1400-2.
8.Jasnoski ML, Kugler J. Relaxation, imagery, and neuroimmunomodulation. Ann N Y Acad Sci. 1987;496:722-30.
9. McClelland DC, Floor E, Davidson RJ, Saron C. Stressed power motivation, sympathetic activation, immune function, and illness. J Human Stress. 1980;6(2):11-9.

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