Acute lung injury caused by sepsis: how does it happen?

Abstract

Sepsis is a systemic inflammatory disease caused by severe infections that involves multiple systemic organs, among which the lung is the most susceptible, leaving patients highly vulnerable to acute lung injury (ALI). Refractory hypoxemia and respiratory distress are classic clinical symptoms of ALI caused by sepsis, which has a mortality rate of 40%. Despite the extensive research on the mechanisms of ALI caused by sepsis, the exact pathological process is not fully understood. This article reviews the research advances in the pathogenesis of ALI caused by sepsis by focusing on the treatment regimens adopted in clinical practice for the corresponding molecular mechanisms. This review can not only contribute to theories on the pathogenesis of ALI caused by sepsis, but also recommend new treatment strategies for related injuries.

Keywords: acute lung injury; inflammation; pathogenesis; sepsis; treatment.

Figure 1

Acute lung injury in sepsis mainly causes alveolar damage through NF-KB, JAK2/STAT3, mTOR, Notch, and MAPK pathways, leading to impaired gas exchange function and inflammatory exudation.

Figure 2

Monocytes recognize and bind microbial components through Toll-like receptors (TLR) on their surface, releasing a variety of inflammatory mediators and chemokines. Monocytes can also differentiate into macrophages, which are polarized into classical macrophages (M1) and alternative macrophages (M2). M1 and M2 promote the release of pro-inflammatory and anti-inflammatory factors, respectively, causing inflammatory response and injury in the lung.

Figure 3

During sepsis, phagocytes and endothelial cells in the lung tissue release a large number of inflammatory factors, which activate alveolar macrophages, multinucleated leukocytes and other effector cells. Release a large number of oxygen free radicals and be reduced to O₂⁻, most O₂⁻ is disproportionated to H₂O₂ under the action of Superoxide dismutase, H₂O₂ combines with O₂⁻ to form OH, and Myeloperoxidase can oxidize H₂O₂ to produce hypochlorous acid and other toxic substances, it directly damages the alveolar epithelial cells and vascular endothelial cells.

Figure 4

In sepsis, the coagulation system is activated, the damage of vascular endothelial cells leads to thrombosis and fibrin deposition, and the disorder of anticoagulant system, which aggravates lung injury and dysfunction.