The systemic inflammatory response in sepsis is triggered by the release of pathogen-associated molecular patterns (PAMPs) — structural components of bacteria, viruses, and fungi such as lipopolysaccharide (LPS, from gram-negative bacteria cell walls) and lipoteichoic acid (from gram-positive bacteria). These are recognised by pattern-recognition receptors (including Toll-like receptors) on circulating monocytes, macrophages, and dendritic cells, triggering an overwhelming inflammatory cascade.

This cascade releases pro-inflammatory cytokines — TNF-alpha, IL-1, IL-6, and many others — which cause widespread endothelial activation and damage. The consequences include increased vascular permeability (causing oedema and relative hypovolaemia), loss of vascular tone (causing vasodilation and distributive shock), activation of the coagulation cascade (causing disseminated intravascular coagulation, DIC), and direct cellular toxicity leading to mitochondrial dysfunction and impaired oxygen utilisation even when oxygen delivery is restored.

The result is a combination of inadequate oxygen delivery (from hypotension and reduced cardiac output) and impaired oxygen utilisation (from mitochondrial dysfunction) — both contributing to cellular energy failure and organ dysfunction. Lactate — produced by anaerobic metabolism when oxygen utilisation fails — is therefore both a marker of severity and a treatment target.