Endocrine and molecular responses to surgical stress.
Successful adaptation to stress is a prerequisite for the survival of all organisms living in an environment in which noxious stimuli are constantly present. Higher organisms, including human beings, have developed complex mechanisms to tolerate the myriad of insults that occur to cellular constituents and organ systems after trauma with its resultant blood loss and tissue injury. Surgical stress can be conceptualized in this context, and it is therefore not surprising that human beings have developed an array of integrated stress-response axes that work in concert to return the host to a sustainable homeostatic plateau. The most important aspects of these axes are depicted in Figure 24. Surgical stress activates the higher cortical center of the brain and the spinal and baroreceptor reflexes that stimulate the hypothalamus to secrete CRH. CRH stimulates the release of ACTH from the pituitary gland, which causes the release of glucocorticoids from the adrenal cortex. Simultaneously, in a parallel fashion, surgical stress activates the sympathetic system to release catecholamines. Glucocorticoids and catecholamines are the major effectors of stress adaptation and interact at multiple levels in a synergistic fashion. They bind to specific receptors that are present in virtually every organ, although the number and affinity of a given tissue's receptor vary dramatically for individual ligands. Receptor occupancy results in short-term and long-term effects that ultimately improve the host's prospects of tolerating the stressful event. The short-term effects result in rapid actions, such as cardiovascular and metabolic responses that benefit the host in a "fight or flight" reaction. The long-term effects generally occur through alterations in gene transcription that prepare the host for, or adapt the host to, repetitive or chronic stress. Changes in the phosphorylation state of intracellular proteins are a common mode of action for both the short-term and long-term responses. These stress-responsive proteins have an enormous functional capacity: they alter enzymatic pathways, modulate hormone levels, and act as transcription factors to modify the expression of stress-responsive genes. During the last decade considerable progress has been made in explaining the complex signal transduction pathways mediating these responses. The importance of the HSPs in the host response to acute stress and their intimate association with activation of the HPA axis and sympathetic nervous system have recently been appreciated. The HSPs are likely to be induced early during organ rejection or ischemia and thus serve as diagnostic indicators.(ABSTRACT TRUNCATED AT 400 WORDS)
Udelsman
R
R
Johns Hopkins University School of Medicine, Baltimore, Maryland.
Holbrook
N J
NJ
D000210:Acute-Phase Reaction / Q000235:genetics / Q000503:physiopathology; D000324:Adrenocorticotropic Hormone / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D005938:Glucocorticoids / Q000502:physiology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000502:physiology*; D013312:Stress, Physiological / Q000235:genetics / Q000503:physiopathology*; D013514:Surgical Procedures, Operative
D005938:Glucocorticoids; D006360:Heat-Shock Proteins; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone