Overview
Clinical Meaning
The sepsis cascade transforms localized infection into systemic inflammatory response with multi organ dysfunction.
The sepsis cascade transforms localized infection into systemic inflammatory response with multi-organ dysfunction. PAMPs (LPS from gram-negatives, lipoteichoic acid from gram-positives) bind toll-like receptors (TLR4 for LPS) on innate immune cells, activating NF-κB signaling and releasing pro-inflammatory cytokines: TNF-alpha, IL-1β, IL-6 (cytokine storm). Effects: (1) Endothelial dysfunction — tissue factor activates coagulation, selectins recruit neutrophils, increased permeability causes capillary leak; (2) Vasodilation — iNOS produces massive nitric oxide causing profound refractory hypotension; (3) Microvascular thrombosis — DIC from tissue factor activation with consumption of protein C, antithrombin III; (4) Mitochondrial dysfunction — cytopathic hypoxia means cells cannot use oxygen even when delivery is adequate (explains paradoxically elevated ScvO2 in sepsis). The result is distributive shock with relative hypovolemia, microvascular ischemia, cellular energy failure, and multi-organ failure.
