Endocrinology/Objectives/Lecture 21

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Contents 1 Stress and the endocrine system 1.1 Discuss Cannon's concept of homeostasis and fight-flight responses. 1.2 List major neuroendocrine systems involved in stress. 1.3 List metabolic and biochemical changes during stress. 1.4 Describe responses to mental stress of the cardiovascular, respiratory, gastrointestinal, neural, and hormonal systems. 1.5 Describe neuroendocrine and cardiovascular responses to physical stress (exercise, cold, gravity). 1.6 Explain how body responses change with chronic exposure to stress; define habituation and sensitization. 1.7 Discuss the role of stress in the development of diseases, particularly in hypertension, endocrine, and immune system disorders.

Stress and the endocrine system

Discuss Cannon's concept of homeostasis and fight-flight responses.

Walter Bradford Cannon developed a theory of homeostasis that hinged on a number of synergistic and antagonizing systems working in concert to maintain constancy. At its essence, Cannon's theory claimed that each time the system strayed from normal, an opposing process must mediate the return of the system to normal.

Cannon also coined the term fight or flight to describe an organism's response to stress (specifically, the threat of harm). The fight-or-flight response is driven by the sympathetic nervous system, which by and large is stimulatory.

List major neuroendocrine systems involved in stress.

Per usual, the hypothalamus and pituitary gland are intimately involved in the stress response. CRH released from the peraventricular nucleus stimulates corticotropes in the anterior pituitary to release ACTH, which is released into the blood and causes the adrenal cortex to release cortisol.

In addition, the central nervous system may respond to stress by activating sympathetic outflow, which evokes the release of catecholamines from the adrenal medulla. Epinephrine and norepinephrine synergize with cortisol to bring about the stress response, which includes the liberation of substrates (e.g. glucose) necessary to mount a successful flight-or-fight response.

List metabolic and biochemical changes during stress.

Cortisol and epinephrine (and also glucagon) are the chief mediators of the metabolic changes that occur in response to stress. These changes include:

• ↑Glycogenolysis (and ↓glycogen synthesis)
• ↑Gluconeogenesis
• ↑Lipolysis
• ↑Protein catabolism

Describe responses to mental stress of the cardiovascular, respiratory, gastrointestinal, neural, and hormonal systems.

Mental stress results in sympathetic outflow, with norepinephrine causing an increase in cardiac contractility, elevated heart rate, and increased blood pressure. This is exacerbated by norepinephrine binding α₁-adrenergic receptors on vascular smooth muscle, causing vasoconstriction and a rise in peripheral resistance. Sustained vasoconstriction results in vascular smooth muscle hypertrophy, which further narrows the vessel lumen. Sympathetic outflow to the kidney also enhances vasoconstriction through the renin-angiotensin system, which results in increased angiotensin II (a potent vasoconstrictor) and aldosterone. The latter causes sodium retention and expansion of the extracellular fluid compartment (hypervolemia) with a consequent rise in blood pressure.

Via β₂-adrenergic receptors, epinephrine released in response to stress causes dilation of the bronchioles.

CRH enhances colon motility (while decreasing stomach contractility and emptying), decreasing the amount of time the colon has to absorb water from the feces, resulting in frequent defecation and diarrhea (and potentially irritable bowel syndrome). In addition, CRH may cause rupture of enterocytes, potentially allowing antigenic peptides to pass from the intestinal lumen and evoking an immune response. Dimished gastric contractility and emptying is mediated by CRH's inhibition of vagal outflow, while enhanced colonic motility is due to norepinephrine (from the locus coeruleus in response to CRH) acting on sacral parasympathetic neurons.

Describe neuroendocrine and cardiovascular responses to physical stress (exercise, cold, gravity).

The CNS responds to stress with increased sympathetic outflow, which results in more norepinephrine binding to β₁ receptors on the heart, increasing contracility. Additionally, sympathetic outflow acts on the adrenal medulla to stimulate the release of norepinephrine and epinephrine, which also increase cardiac contractility via β₁ receptors, and also cause peripheral vasoconstriction via α₁ receptors on vascular smooth muscle. This is especially important in response to cold, in which vasoconstriction allows blood to be shunted to vital tissues from the skin and other nonvital tissues.

Explain how body responses change with chronic exposure to stress; define habituation and sensitization.

Chronic stress is associated with excessively high cortisol, whose metabolic functions become catabolic rather than anabolic at high levels.

One has habituated to a stressor when repeated presentations of the homotypic (same) stressor fails to elicit a stress response (or elicits a nominal one). This is mediated by decreased release of catecholamines in response to a homotypic stressor. The habituation can be removed by sensitization, in which a heterotypic (different) stressor elicits an increased response compared to the homotypic stimulus.

Habituation occurs via the sequestration of catecholamines in the adrenal medulla. Homotypic stressors may still elicit the synthesis of medullary catecholamines, but fail to stimulate their systemic secretion. However, sensitization with a heterotypic stressor succeeds in stimulating catecholamine release, and because so many catecholamines have been sequestered in the adrenal medulla, the resulting sensitization is substantial.

Discuss the role of stress in the development of diseases, particularly in hypertension, endocrine, and immune system disorders.

• ↑CRH → ↑catecholamines → ↑vasoconstriction, ↑cardiac contractility ↑hypertension
• ↑Cortisol → ↑blood glucose → ↑insulin → insulin resistance (type II diabetes)
• ↑Cortisol → leukopenia, ↓cytokines → immunosuppression
• ↑Norepinephrine, ↑epinephrine → ↓leukocyte proliferation → immunosuppression