Porth's Essentials of Pathophysiology, 4e

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Stress and Adaptation

C h a p t e r 9

Immune system (cytokines)

Hypothalamus

CRF

Brain stem

Adrenal gland

Locus ceruleus

Pituitary ACTH

Cortisol

Autonomic nervous system manifestations

FIGURE 9-3. Neuroendocrine–immune system regulation of the stress response. ACTH, adrenocorticotropic hormone; CRF, corticotropin-releasing factor.

peripherally delivered or locally produced, also has CNS effects; angiotensin II type 1 (AT 1 ) receptors are widely dis- tributed in the hypothalamus and locus ceruleus. Through these receptors, angiotensin II enhances CRF formation and release, contributes to the release of ACTH from the pituitary, enhances stress-induced release of vasopressin from the posterior pituitary, and stimulates release of nor- epinephrine from the locus ceruleus. Results from animal studies on the effect of AT 1 receptor blockade suggest that receptor antagonists attenuate activation of the stress response and may be an effective treatment for chronic stimulation of the stress response. 26,27 Other Hormones. A wide variety of other hormones, including growth hormone, thyroid hormone, and reproductive hormones, are responsive to stressful situa- tions as well. 16,17,28 Systems responsible for reproduction, growth, and immunity are directly linked to the stress system, and hormonal effects of the stress response pro- foundly influence these systems. Although growth hormone is initially elevated with the onset of stress, prolonged presence of cortisol leads to sup- pression of growth hormone, insulin-like growth factor 1 (IGF-1), and other growth factors, exerting a chronically inhibitory effect on growth. In addition, CRF directly increases somatostatin, which in turn inhibits growth hor- mone secretion. Although the connection is speculative, effects of stress on growth hormone may provide one of the vital links to understanding failure to thrive in children. Stress-induced cortisol secretion also is associ- ated with decreased levels of thyroid-stimulating hor- mone and inhibition of conversion of thyroxine (T 4 ) to the more biologically active triiodothyronine (T 3 ) in peripheral tissues (see Chapter 32). Both changes may serve as a means to conserve energy at times of stress.

of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland into the systemic circulation. Adrenocorticotropic hormone, in turn, stimulates the adrenal gland to synthesize and secrete glucocorticoid hormones (e.g., cortisol). 25 Cortisol is the primary glucocorticoid in humans, representing a major subclass of steroid hormones that regulate metabolic, cardiovascular, immune, and behav- ioral responses. A glucocorticoid negative feedback sys- tem exists, whereby the HPA axis is subject to feedback inhibition from circulating glucocorticoids. These gluco- corticoids have a number of direct or indirect physiologic effects that mediate the stress response, enhance the action of other stress hormones, or suppress other components of the stress system. In this regard, cortisol acts not only as a mediator of the stress response but also as an inhibitor so that overactivation of the stress response does not occur. 21,23 Cortisol maintains blood glucose levels and enhances the effect of catecholamines on the cardiovascular system. Blood glucose levels are elevated rapidly, in part by mobi- lization of glucose stores and by inhibition of further stor- age through the antagonizing effects of insulin. 21 Cortisol also suppresses osteoblast activity, hematopoiesis, protein and collagen synthesis, and immune responses. All of these functions are meant to protect the organism against the effects of a stressor and to focus energy on regaining bal- ance in the face of an acute challenge to homeostasis. Angiotensin II. Stimulation of the SNS also activates the peripheral renin-angiotensin-aldosterone system (RAAS), which mediates a peripheral increase in vascular tone and renal retention of sodium and water (see Chapter 18). These changes contribute to the physiologic alterations that occur with the stress response; if prolonged, they may contribute to pathologic changes. Angiotensin II,