Clinical meaning
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection (Sepsis-3 definition, 2016). The pathophysiology begins when pathogen-associated molecular patterns (PAMPs) such as bacterial endotoxin (LPS) activate innate immune receptors (Toll-like receptors, TLR4) on macrophages and neutrophils. This triggers a massive release of pro-inflammatory cytokines (TNF-alpha, IL-1, IL-6) creating a cytokine storm. The inflammatory cascade causes: (1) Endothelial dysfunction with increased capillary permeability leading to third-spacing and tissue edema; (2) Nitric oxide-mediated vasodilation causing decreased SVR and distributive shock; (3) Activation of the coagulation cascade creating microvascular thrombosis (DIC), further impairing tissue oxygen delivery; (4) Mitochondrial dysfunction (cytopathic hypoxia) where cells cannot utilize oxygen even when delivered; (5) Myocardial depression from circulating cardiodepressant factors (IL-1, TNF-alpha) reducing contractility. Septic shock is defined as sepsis with persistent hypotension requiring vasopressors to maintain MAP >65 mmHg AND serum lactate >2 mmol/L despite adequate fluid resuscitation. The qSOFA score (quick Sequential Organ Failure Assessment) uses three bedside criteria (RR >22, altered mentation GCS <15, SBP <100 mmHg) to identify patients at risk outside the ICU. The full SOFA score tracks six organ systems to quantify dysfunction. The Surviving Sepsis Campaign (SSC) Hour-1 Bundle mandates: measure lactate, obtain blood cultures before antibiotics, administer broad-spectrum antibiotics, begin 30 mL/kg crystalloid for hypotension or lactate >4, and start vasopressors if hypotensive during or after fluid resuscitation.