title: Pathophysiology of acute lung injury.
abstract: The acute respiratory distress syndrome (ARDS) is a life-threatening syndrome that may occur in any patient without any predisposition and that is mostly triggered by underlying processes such as sepsis, pneumonia, trauma, multiple transfusions, and pancreatitis. ARDS is defined by (1) acute onset, (2) bilateral infiltrates in chest x-rays, (3) absence of left ventricular failure, and (4) severe arterial hypoxemia with a PaO2/FiO2 ratio less than 200 mmHg. Still, ARDS is feared (mortality 30-40%) and relatively frequent (incidence between 13.5 per 100,000 to 75 per 100,000). Acute lung injury (ALI) describes a similar, but less severe, clinical condition, with PaO2/FiO2 values between 200 and 300 mmHg. Despite ongoing and intensive scientific research in this area, the mechanisms underlying ALI/ARDS are still not completely understood, and until recently, there were no studies demonstrating any beneficial effect of a single treatment modality in ARDS. The recent report that a specific approach to ventilatory support can significantly reduce mortality in ARDS underscores the need for better understanding of the pathophysiological events occurring in this syndrome. This review therefore summarizes the current pathophysiological concepts underlying the evolution of acute hypoxemic respiratory failure and focuses on: (1) possible reasons for the development of ALI/ARDS; (2) cellular and humoral mediator responses leading to a sustained and self-perpetuating inflammation of the lung; (3) consequences with regard to fluid balance, pulmonary perfusion, ventilation, and efficiency of gas exchange; and (4) mechanisms underlying the aggravating complications commonly seen in ARDS, especially ventilator-associated lung injury, ventilator-associated pneumonia, and lung fibrosis.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Justus-Liebig-University Giessen, Klinikstrasse 36, D-35392 Giessen, Germany. andreas.guenther@innere.med.uni-giessen.de
authors.forename: A
authors.initials: A
authors.lastname: Günther
authors.forename: D
authors.initials: D
authors.lastname: Walmrath
authors.forename: F
authors.initials: F
authors.lastname: Grimminger
authors.forename: W
authors.initials: W
authors.lastname: Seeger