Porth's Essentials of Pathophysiology, 4e

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Stress and Adaptation

C h a p t e r 9

Neuroendocrine Responses The stress response is mediated by anatomical structures found in both the central nervous system and peripheral tissues. Manifestations of the stress response are strongly influenced by both the nervous and endocrine sys- tems. 9,16,17 The neuroendocrine systems integrate signals received along neurosensory pathways and from circulat- ing mediators that are carried in the bloodstream. In addi- tion, the immune system both affects and is affected by the stress response. Table 9-1 summarizes the action of hor- mones involved in the neuroendocrine responses to stress. Results of the coordinated release of these neurohor- mones include mobilization of energy, a sharpened focus and awareness, increased cerebral blood flow and glu- cose utilization, enhanced cardiovascular and respiratory functioning, redistribution of blood flow to the brain and muscles, modulation of the immune response, inhibition of reproductive function, and a decrease in appetite. 16,17 The stress response is a normal, coordinated physiologic system intended to increase the probability of survival, but importantly, it also is designed to be an acute response. That is, optimally it is turned on when necessary to bring the body back to a stable state and turned off when the challenge to homeostasis abates. Therefore, under normal circumstances, the neural responses and hormones that are released during the response do not persist long enough to cause damage to vital tissues. Since the early 1980s, the term allostasis has been used by some investigators to describe the interactive physiologic changes in the neuro- endocrine, autonomic, and immune systems that occur in response to either real or perceived challenges to homeo- stasis. More recently, others have proposed that allosta- sis is the body’s attempt to maintain stability through change, thereby adequately or inadequately adapting to

threatening or unpredictable stimuli. 18 The persistence or accumulation of these allostatic changes (e.g., immuno- suppression, activation of the sympathetic nervous and renin-angiotensin-aldosterone systems) has been called an allostatic load, and this concept has been used to measure the cumulative effects of stress on humans. 16–21 Allostatic load can result in weakening a person’s ability to respond to repeated stressors, and it may provide insight into how one might respond to future stressors. A number of indices have been suggested for measuring allostatic load, includ- ing blood pressure, cortisol, C-reactive protein, body mass index (BMI), and cholesterol. 22 Integration of the components of the stress response, occurring at the level of the central nervous system (CNS), is complex and not completely understood. 23,24 It relies on communication along neuronal pathways of the cerebral cortex, limbic system, thalamus, hypo- thalamus, pituitary gland, and reticular activating sys- tem (RAS). The cerebral cortex is involved in vigilance, cognition, and focused attention, while the limbic sys- tem is associated with emotional components (e.g., fear, excitement, rage, anger) of the stress response (Fig. 9-2). The thalamus functions as the relay center and is impor- tant in receiving, sorting out, and distributing sensory input. The hypothalamus coordinates responses of the endocrine system and autonomic nervous system (ANS). The RAS modulates mental alertness, ANS activity, and skeletal muscle tone using input from other neural struc- tures. The musculoskeletal tension that occurs during the stress response reflects increased activity of the RAS and its influence on reflex circuits that control muscle tone. Adding to the complexity of this system is the fact that individual brain circuits that participate in media- tion of the stress response interact and regulate each other’s activities. For example, reciprocal connections

Hormones Involved in the Neuroendocrine Responses to Stress

TABLE 9-1

Hormones Associated with the Stress Response

Source of the Hormone

Physiologic Effects

Catecholamines (norepinephrine, epinephrine)

Locus ceruleus, adrenal medulla

Produces a decrease in insulin release and an increase in glucagon release resulting in increased glycogenolysis, gluconeogenesis, lipolysis, proteolysis, and decreased glucose uptake by the peripheral tissues; an increase in heart rate, cardiac contractility, and vascular smooth muscle contraction; and relaxation of bronchial smooth muscle Stimulates ACTH release from anterior pituitary and increased activity of neurons in locus ceruleus Potentiates the actions of epinephrine and glucagon; inhibits the release and/or actions of the reproductive hormones and thyroid-stimulating hormone; and produces a decrease in immune cells and inflammatory mediators Stimulates the synthesis and release of cortisol

Corticotropin-releasing factor (CRF)

Hypothalamus

Adrenocorticotropic hormone (ACTH) Glucocorticoid hormones (e.g., cortisol)

Anterior pituitary Adrenal cortex

Mineralocorticoid hormones (e.g., aldosterone)

Adrenal cortex

Increases sodium absorption by the kidney

Antidiuretic hormone (ADH, vasopressin)

Hypothalamus,

Increases water absorption by the kidney; produces vasoconstriction of blood vessels; and stimulates the release of ACTH

posterior pituitary