Mechanisms of lung vascular injury and edema induced by pulmonary microembolism

Abstract

Pulmonary vascular injury in adult respiratory distress syndrome is a multifactorial process. Activation of the clotting cascade during sepsis or tissue injury deposits fibrin microthrombi in pulmonary vessels. The fibrin clots act as a ‘sink’ for the residual α-thrombin and other clotting factors. Fibrin-induced plasminogen activation activates the complement system, resulting in the formation of neutrophil-activating peptides (C5a), which contribute to neutrophil sequestration in pulmonary microvessels. In addition, α-thrombin promotes neutrophil-endothelial adherence by effects on the endothelial cell. Macrophages may enhance increased vascular permeability by the secretion of monokines (TNF and IL-1) and lead to the recruitment and activation of neutrophils. The sequestration of neutrophils in the lung and the generation of toxic oxygen radicals and proteases in close proximity to the endothelial cell are the ultimate mediators of endothelial cell injury and increased vascular permeability.