Pathophysiology of sepsis

Abstract

The roles of inflammation and coagulation in the pathophysiology of sepsis are described. Sepsis results when an infectious insult triggers a localized inflammatory reaction that then spills over to cause systemic symptoms of fever or hypothermia, tachycardia, tachypnea, and either leukocytosis or leukopenia. These clinical symptoms are called the systemic inflammatory response syndrome. Severe sepsis is defined by dysfunction of one of the major organ systems or unexplained metabolic acidosis. The inflammatory reaction is mediated by the release of cytokines, including tumor necrosis factor-alpha, interleukins, and prostaglandins, from neutrophils and macrophages. The cytokines activate the extrinsic coagulation cascade and inhibit fibrinolysis. These overlapping processes result in microvascular thrombosis; thrombosis is one potential factor producing organ dysfunction. Activation of the coagulation system leads to consumption of endogenous anticoagulants (e.g., protein C and antithrombin); this may be an important factor in the development of microvascular coagulation. Antiinflammatory mediators as well as inflammatory mediators have a role in sepsis, and an excess of either can result in poor patient outcomes. Sepsis is a complex syndrome involving activation of a variety of systems.