PATHOPHYSIOLOGY OF SIRS
A mild systemic inflammatory response to an injury, infection, or other bodily insult may nor-mally have salutatory effects. However, a marked or prolonged response, such as that associated with severe infections, is often deleterious and can result in widespread organ dysfunction. Although gram-negative organisms account for most cases of infection-related SIRS, many other infectious agents are capable of inducing the same syndrome. These organisms either elaborate toxins or stimu-late release of substances that trigger this response. The most commonly recognized initiators are the lipopolysaccharides, which are released by gram-negative bacteria. Lipopolysaccharide is composed of an O polysaccharide, a core, and lipid A. The O polysaccharide distinguishes between different types of gram-negative bacteria, whereas lipid A, an endo-toxin, is responsible for the compound’s toxicity. The resulting response to endotoxin involves a complex interaction between macrophages/monocytes, neu-trophils, lymphocytes, platelets, and endothelial cells that can affect nearly every organ.
The central mechanism in initiating SIRS appears to be the abnormal secretion of cyto-kines. These low-molecular-weight peptides and glycoproteins function as intercellular mediators regulating such biological processes as local and systemic immune responses, inflammation, wound healing, and hematopoiesis. The most important cytokines released during SIRS are interleukin-6, adrenomedullin, soluble CD 14, the adhesion molecule sELAM-1, macrophage inflammatory protein-1α, extracellular phospholipase A 2, and C-reactive pro-tein. The resulting inflammatory response includes release of potentially harmful phospholipids, attrac-tion of neutrophils, and activation of the comple-ment, kinin, and coagulation cascades.
Increased phospholipase A2 levels release ara-chidonic acid from cell membrane phospholip-ids. Cyclooxygenase converts arachidonic acid to thromboxane and prostaglandins, whereas lipoxy-genase converts arachidonic acid into leukotrienes (slow-reacting substances of anaphylaxis). Increased phospholipase A 2 and acetyltransferase activities result in the formation of another potent proinflam-matory compound, platelet-activating factor. Attrac-tion and activation of neutrophils releases a variety of proteases and free radical compounds that dam-age vascular endothelium. Activation of monocytes causes them to express increased amounts of tissue factor, which in turn can activate both the intrinsic and extrinsic coagulation cascades.
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