Sepsis and Septic Shock

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is its most severe subset, in which circulatory, cellular, and metabolic abnormalities are profound enough to substantially increase mortality. Together they represent the prototypical example of how an infection can drive the systemic pathophysiology of critical illness.

Definition

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection; septic shock is a subset of sepsis with persisting circulatory and cellular/metabolic dysfunction associated with a higher risk of death than sepsis alone.

Scope

This entry covers the conceptual definition of sepsis and septic shock, the host-response biology that distinguishes them from uncomplicated infection, and the burden they impose. It is reference and educational material describing pathophysiology and definitions; it does not provide diagnostic thresholds or treatment instructions for individual patients.

Core questions

• What converts an infection into sepsis — that is, into organ dysfunction driven by the host response?
• How does septic shock differ mechanistically from sepsis without shock?
• Why does a dysregulated host response damage organs distant from the site of infection?
• How have consensus definitions of sepsis changed and why?

Key concepts

• Dysregulated host response to infection
• Organ dysfunction as the defining feature
• Distributive (vasodilatory) shock
• Cellular and metabolic dysfunction
• Pro-inflammatory and immunosuppressive phases
• Sepsis-3 versus earlier SIRS-based definitions

Mechanisms

Infection is recognised by innate immune receptors, provoking release of inflammatory mediators. In sepsis this response is dysregulated: excessive and disordered signalling injures the endothelium, increases vascular permeability, and impairs vasomotor tone, producing distributive shock with maldistribution of microcirculatory flow. Concurrently the host response couples inflammation to coagulation and disturbs cellular metabolism, so that even with restored blood pressure, cells may fail to extract or use oxygen. A counter-regulatory, often immunosuppressive phase follows, contributing to secondary infection and late mortality. The net effect is organ dysfunction remote from the original infection (Hotchkiss & Karl, 2003; Angus & van der Poll, 2013).

Clinical relevance

Sepsis and septic shock are leading causes of admission to and death within intensive care, and the concepts in this entry underpin how clinicians recognise that an infection has become a systemic, organ-threatening process. The material explains definitions and mechanisms for orientation and study; it is not a protocol and does not give dosing or individualised management guidance, which belong to current clinical guidelines such as the Surviving Sepsis Campaign (Evans et al., 2021).

Epidemiology

Sepsis is a major global health burden. A systematic review of population-level data estimated tens of millions of hospital-treated sepsis cases annually with substantial mortality, while noting that most data came from high-income countries and that the true global burden is likely underestimated (Fleischmann et al., 2016).

History

Definitions of sepsis evolved from the 1991 consensus, which tied sepsis to SIRS plus infection, through a 2001 revision, to the 2016 Sepsis-3 consensus, which redefined sepsis as life-threatening organ dysfunction from a dysregulated host response and septic shock by persistent hypotension and metabolic derangement. In parallel, mechanistic understanding shifted from a purely hyperinflammatory model toward one recognising concurrent immunosuppression (Hotchkiss & Karl, 2003; Singer et al., 2016).

Debates

How should sepsis be defined and identified?

The move from SIRS-based criteria to the organ-dysfunction-centred Sepsis-3 definition improved conceptual clarity but generated debate about operational criteria, screening tools, and applicability across settings, including resource-limited environments under-represented in the evidence.

Key figures

• Mervyn Singer
• Derek C. Angus
• Tom van der Poll
• Richard S. Hotchkiss
• Konrad Reinhart

Seminal works

• singer-2016
• angus-2013
• hotchkiss-2003

Frequently asked questions

What is the difference between sepsis and septic shock?

Sepsis is life-threatening organ dysfunction from a dysregulated response to infection; septic shock is a more severe subset in which circulatory and cellular/metabolic abnormalities persist and carry a substantially higher risk of death.

Is sepsis the same as an infection in the bloodstream?

No. Sepsis is defined by organ dysfunction caused by a dysregulated host response, not simply by the presence of bacteria in the blood; an infection can be present without sepsis, and sepsis can arise from infection at many sites.