Figure 2.

Schematic of the HPA axis and the Stress Response to Surgery. Different anesthetics have different effects on the HPA axis and immune system (see Effects of Anesthesia on the Surgical Stress Response). During surgical stress, activation of the HPA axis is controlled by a relatively small number of neurons located in the paraventricular nucleus (PVN) of the hypothalamus. These neurons release neural factors, such as corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) into the hypophyseal portal circulation, which stimulates the anterior pituitary gland to release ACTH into the blood and activates the adrenal gland to release the stress hormones, catecholamines, and cortisol. Under normal exposure to stress, the HPA axis is held in check via multiple negative feedback mechanisms. However, during major surgery, trauma, infection or burns, imbalances occur and the action of stress hormones are potentiated by cytokines IL-1beta, IL-6 and TNF-alpha, prostaglandin-2 (PGE-2), and nitric oxide (NO), which predispose the body to further injury from ischemia, inflammation, and coagulopathy. Older surgical patients appear to be more vulnerable to surgical stress because their hypothalamus and pituitary are less sensitive to negative feedback from both cortisol and ACTH (7–9). The medullary Nucleus Tractus Solitarus (NTS) is also influenced by the stress response as it receives sensory neural inputs from the arterial baroreceptors, integrates this information with the hypothalamus, and other parts of the brain, and regulates the sympathetic and parasysmpathetic outflows to the body (7, 64–72).