Endotoxic shock (ES) is mostly caused by Gram-negative bacillus endotoxin, and the main clinicopathological process is vascular regulatory dysfunction, hypotension caused by vasodilation, and organ tissue damage caused by a systemic inflammatory response. The main pathophysiological change in ES is systemic inflammatory response syndrome (SIRS), which often leads to multiple organ dysfunction syndrome (MODS). Lipopolysaccharide (LPS), the main active ingredient of endotoxin, can activate or induce various endogenous inflammatory mediators such as complement, kinin, and various cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL- 1β) and interferon-γ (IFN-γ), etc. Previous experiments have proved that many inflammatory mediators themselves are vasoactive substances, which are the main factors involved in the occurrence and development of shock. However, in ES, the exact pathogenesis of inflammatory injury in organs and tissues of circulatory failure has not been elucidated, and it is still a very difficult problem in clinical treatment.
Figure 1. Pathophysiology of endotoxic shock. (Pillitteri M, et al., 2023)
LPS is composed of three parts, including O-specific side chain, core polysaccharide, and lipid A, of which lipid A is its main toxic component. Endotoxin can be released into the blood or act directly on a variety of effector cells (monocyte phagocytes, neutrophils, endothelial cells, etc.), and it is the promoter of the body's immune response to induce the occurrence of ES. Vasodilation, increased permeability, decreased blood flow, and blood stasis can occur in ES, resulting in pathophysiological changes in microcirculation. The specific mechanism includes the following four parts:
In summary, the occurrence of ES is mediated by LPS. When effector cells interact with cells, a number of signaling pathways are activated in the cells, leading to the overexpression of inflammatory mediators, primary cell damage, septic shock, and multiple organ failures due to the overexpression of inflammatory mediators. As a special type of shock, ES has a very high fatality rate, and the mortality rate can reach 25-50%. The transition time from the reversible stage to the irreversible stage in the shock process is very short, generally only a few seconds to a few minutes, so it is often too late for timely and correct diagnosis and effective and definite treatment. It is helpful to detect endotoxin in the blood of healthy individuals to make a diagnosis of ES since normal blood does not contain endotoxin. The determination of endotoxin in blood by the Limulus test can predict the occurrence of ES, which has important practical significance in clinical practice.
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