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Pathophysiology of sepsis

Remi Neviere, MD
Section Editors
Scott Manaker, MD, PhD
Daniel J Sexton, MD
Deputy Editor
Geraldine Finlay, MD


The normal host response to infection is a complex process that localizes and controls bacterial invasion, while initiating the repair of injured tissue. It involves the activation of circulating and fixed phagocytic cells, as well as the generation of proinflammatory and antiinflammatory mediators. Sepsis results when the response to infection becomes generalized and involves normal tissues remote from the site of injury or infection.

The pathophysiology of sepsis and mechanisms of multiple organ system dysfunction are reviewed here. The definition and management of sepsis are discussed separately. (See "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis" and "Evaluation and management of suspected sepsis and septic shock in adults".)


The host response to an infection is initiated when innate immune cells, particularly macrophages, recognize and bind to microbial components. This may occur by several pathways:

Pattern recognition receptors (PRRs) on the surface of host immune cells may recognize and bind to the pathogen-associated molecular patterns (PAMPs) of microorganisms [1]. There are three families of PRRs: toll-like receptors (TLRs), nucleotide-oligomerization domain (NOD) leucine-rich repeat proteins, and retinoic-acid-inducible gene I (RIG-I)-like helicases. Examples include the peptidoglycan of Gram-positive bacteria binding to TLR-2 on host immune cells, as well as the lipopolysaccharide of Gram-negative bacteria binding to TLR-4 and/or lipopolysaccharide-binding protein (CD14 complex) on host immune cells.

PRRs can also recognize endogenous danger signals, so-called alarmins or danger-associated molecular patterns (DAMPs) that are released during the inflammatory insult. DAMPs are nuclear, cytoplasmic, or mitochondria structures acquiring new functions when released in the extracellular environment. Examples of DAMPs include high mobility group box-1 protein HMGB1, S100 proteins, and mitochondrial DNA [2].

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Literature review current through: Nov 2017. | This topic last updated: Dec 15, 2016.
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