The pathophysiology of sepsis-2021 update: Part 1, immunology and coagulopathy leading to endothelial injury

Abstract

Purpose: To provide an overview of current literature on the pathophysiology of sepsis, with a focus on mediators of endothelial injury and organ dysfunction.

Summary: Sepsis is a dysregulated response to infection that triggers cascades of interconnected systems. Sepsis has been a significant cause of mortality worldwide, and the recent viral pandemic that may produce severe sepsis and septic shock has been a major contributor to sepsis-related mortality. Understanding of the pathophysiology of sepsis has changed dramatically over the last several decades. Significant insight into the components of the inflammatory response that contribute to endothelial injury and trigger coagulation pathways has been achieved. Similarly, characterization of anti-inflammatory pathways that may lead to secondary infections and poor outcome has illustrated opportunities for improved therapies. Description of an increasing number of important mediators and pathways has occurred and may point the way to novel therapies to address immune dysregulation. Pharmacists will need a fundamental understanding of the overlapping pathways of the immune response to fully prepare for use of novel treatment options. While pharmacists typically understand coagulation cascade how to utilize anticoagulants, the issues in sepsis related coagulopathy and role of mediators such as cytokines and complement and role of activated platelets and neutrophils require a different perspective.

Conclusion: Pharmacists can benefit from understanding both the cellular and organ system issues in sepsis to facilitate assessment of potential therapies for risk and benefit.

Keywords: coagulopathy; cytokines; endothelial injury; immune response; inflammation; sepsis.