Stress is a biological state in which homeostasis is threatened, triggering coordinated activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic-adrenomedullary (SAM) system. The hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates pituitary secretion of adrenocorticotropic hormone (ACTH). ACTH acts on the adrenal cortex zona fasciculata to produce cortisol. Cortisol is a steroid hormone that crosses cell membranes, binds intracellular glucocorticoid receptors, and alters gene transcription to regulate metabolism, immune function, and cardiovascular tone. Negative feedback from cortisol normally limits HPA activation, but chronic or excessive stress can dysregulate this loop. The nurse monitors vital signs, reports signs of stress-related complications such as hyperglycemia or hypertension, and supports patient comfort and stress-reduction strategies as directed.