Chapter 86 Metabolic response to injury and infection
Injury and infection evoke in the host a hypermetabolic inflammatory response and a compensatory hypometabolic hypoimmune response. The magnitude of the response is proportional to the extent of injury. Additional components of illness, such as ischaemia and reperfusion or resuscitation, nutritional status, surgical procedures, transfusions, drugs and anaesthetic techniques, genetic polymorphisms and concurrent diseases, impact on the response. Some components of the metabolic response, or the failure to regulate the response, are destructive, and its modulation may improve patient survival.1
MEDIATORS OF THE METABOLIC RESPONSE
CYTOKINES
NEUROENDOCRINE MEDIATORS
Cytokine release from the site of injury or infection triggers vagal afferent impulses to the dorsal vagal complex (DVC) in the medulla oblongata. Synaptic connections with the rostroventral medulla and locus ceruleus, and the hypothalamic nuclei, activate the sympathetic nervous system and the HPA axis respectively.2 High circulating cytokine levels may also cross the blood–brain barrier, or affect neurons at circumventricular organs lacking a blood–brain barrier, such as the area postrema. In general, a biphasic response is observed following injury and infection: an initial neuroendocrine ‘storm’ followed by a decrease. The following are some neuroendocrine mediators involved in the response to stress:
THE METABOLIC RESPONSE
The metabolic response to injury and infection begins with the activation of receptors throughout the body by the above mediators. These receptors include toll-like receptors (TLR)-2 and TLR-4, and the receptor for advanced glycation end products (RAGE). Subsequent intracellular activation of the NF-κB pathway leads to gene induction and production of mRNA for the synthesis of proinflammatory cytokines. Catecholamines can initiate rapid functional changes via protein phosphorylation, which does not require gene induction. Behavioural effects such as anorexia, possibly due to elevated leptin levels, also affect the metabolic response. The metabolic effects may be described at three levels.