The stress response involves two primary neuroendocrine pathways: the sympathetic-adrenal-medullary (SAM) axis for immediate 'fight-or-flight' and the hypothalamic-pituitary-adrenal (HPA) axis for sustained stress adaptation. The SAM axis: stressors activate the hypothalamus, which stimulates the sympathetic nervous system via preganglionic neurons. Postganglionic fibers release norepinephrine at target organs, and the adrenal medulla releases epinephrine and norepinephrine into the bloodstream, producing immediate effects: increased heart rate and contractility, bronchodilation, blood glucose elevation (glycogenolysis), pupil dilation, and blood shunting from digestive organs to skeletal muscle. The HPA axis: the hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the anterior pituitary to release ACTH, which stimulates the adrenal cortex to release cortisol. Cortisol provides sustained energy through gluconeogenesis, protein catabolism, and lipolysis; suppresses the immune system; promotes sodium retention; and provides negative feedback to the hypothalamus and pituitary. Chronic stress causes allostatic overload: persistently elevated cortisol leads to insulin resistance, visceral fat deposition, hypertension, immunosuppression, hippocampal atrophy (impaired memory), disrupted sleep, and increased cardiovascular risk. Understanding these mechanisms helps nurses recognize stress-related illness exacerbations, medication adjustments needed during physiological stress, and the importance of stress...