Metabolic response to injury and infection

Published on 27/02/2015 by admin

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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

Following directed adhesion to endothelium and migration into tissue, neutrophils undergo an oxidative burst, producing a large variety of free radicals (species with one or more unpaired electrons) and reactive oxygen species (ROS), overwhelming natural scavenging and antioxidant defences, such as superoxide dismutase and glutathione peroxidase. These free radicals and ROS directly damage cells. Proteases, arachidonic acid metabolites (leukotrienes, thromboxanes and prostaglandins) and adhesion molecules are produced, amplifying the inflammatory cascade. Inducible nitric oxide synthase is activated, and nitric oxide is produced. Tissue macrophages become primed and activated.

CYTOKINES

Cytokines are soluble, non-antibody, regulatory proteins released from the activated immunocytes, and are responsible primarily for the inflammatory and counter-inflammatory response. Injury and infection cause cytokine release from activated leukocytes, endothelial cells and fibroblasts. T-helper type 1 (TH1) lymphocytes primarily impact cell-mediated immunity and secrete tumour necrosis factor-α (TNF-α), interleukin-2 (IL-2) and interferon-γ (IFN-γ), while TH2 lymphocytes impact antibody-mediated immunity and secrete IL-4 and IL-10. The TH1/TH2 cytokine profile determines the immunostimulatory/immunosuppressive balance. Cytokines generally exert their effects in a paracrine fashion, but in severe injury and infection, they enter the circulation and act as hormones. The following are major cytokines involved in the response to stress:

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: