By Robert F. Betts, Stanley W. Chapman MD, Robert L. Penn MD
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Extra info for Reese and Betts' A Practical Approach to Infectious Diseases
Furthermore, the enzyme responsible for degrading PAF to an inactive metabolite is decreased in patients who die from sepsis . The important role PAF plays in the sepsis cascade prompted research into developing antagonists that prevent associated adverse physiologic events. Encouraging results from experimental studies culminated in clinical trials investigating PAF receptor antagonist use for treating patients with severe sepsis (see section IV). 4. NO plays a central role in regulating vascular tone and determining responsiveness to endogenous and exogenous vasopressors .
Proinflammatory cytokines and other factors that activate PLA, de facto, also trigger PAF production. Conversely, drugs that inhibit PLA, such a glucocorticoids, decrease PAF production. PAF binds to specific receptors present on numerous inflammatory cells, activates neutrophils, aggregates platelets, and facilitates nitric oxide (NO) production. PAF is implicated in sepsis-associated coagulation abnormalities, pulmonary hypertension, myocardial depression, and gut ischemia. Like other proinflammatory mediators, PAF increases during sepsis.
As developed, SIRS deliberately presents low threshold clinical evidence for defining systemic inflammatory response regardless of cause. The definition of SIRS may be refined as prospective studies using the consensus definitions identify new variables that will improve prognostic accuracy and clinical applicability . As it stands currently, the new term highlights the systemic inflammatory response as a syndrome, or constellation of signs and symptoms, that warrants early recognition and aggressive search for the underlying cause.