Pathophysiology of sepsis

INTRODUCTION

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 and the systemic inflammatory response syndrome: Definitions, epidemiology, and prognosis" and "Evaluation and management of severe sepsis and septic shock in adults".)

NORMAL RESPONSE TO INFECTION

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.
  • The triggering receptor expressed on myeloid cell (TREM-1) and the myeloid DAP12-associating lectin (MDL-1) receptors on host immune cells may recognize and bind to microbial components [2].

The binding of immune cell surface receptors to microbial components has multiple effects:

                  

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Literature review current through: Apr 2013. | This topic last updated: Mar 2, 2013.
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