Systemic inflammatory response syndrome (SIRS) begins with a cellular response to an invading organism or antigen. Neutrophils, monocytes (macrophages), and lymphocytes begin the phagocytosis process and release inflammatory mediators and proteases into the bloodstream. Activated monocytes and damaged endothelial cells release tumor necrosis factor alpha (TNFα), a proinflammatory cytokine, into the local area of infection. TNFα stimulates monocytes and promotes the release of tissue factor and platelet activating factor. In SIRS, the plasma level of TNFα is elevated—possibly due to an overwhelming presence of pathogens. [Early intervention for infection is associated with lower mortality rates.] Other cytokines released by monocytes include interleukin-1 (IL-1)—which produces hypotension—and interleukin-6 (IL-6)—which manifests with fever and results in
- release of tissue factor
production of C-reactive protein
- activation of T-cell lymphocytes
Anti-inflammatory responses include the production of interleukin-8 by monocytes and interleukin-10 by many types of leukocytes to reduce the production of pro-inflammatory cytokines. When a patient develops SIRS, the pro-inflammatory mediators are overwhelming the anti-inflammatory mediators.
During SIRS, a coagulation process is also initiated to contain the invading organism within a localized area. Tissue factor initiates the coagulation cascade by promoting synthesis of VIIIa, then Va, and finally thrombin formation to convert fibrinogen into fibrin. [Prothrombin time (PT) is a valuable parameter for tracking the evolution of sepsis from SIRS]. In a homeostatic response to the coagulation process, certain anticoagulation factors contain the coagulation process to a localized area. TF pathway inhibitor (TFPI) limits the effects of tissue factor. Activated protein C limits the coagulation process to the localized area. Plasminogen activator promotes the fibrinolysis—dissolving of clots—in the vascular system. However, as SIRS evolves into sepsis, plasminogen activator inhibitor (PAI-1) and thrombin activatable fibrinolysis inhibitor (TAFI) inhibit the fibrinolytic process upsetting the balance of homeostasis in favor of clot development.
Hence, the pathophysiology of SIRS involves systemic evolution of (1) an inflammatory response and—as sepsis evolves—(2) a predominantly coagulation process usually in microvasculature along the endothelial walls of capillaries.