ABSTRACT
Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are devastating illnesses. ARDS is the severe endpoint of acute lung injury and is defined as a syndrome of inflammation and increased permeability in the absence of left heart failure. ARDS is commonly associated with trauma, sepsis, pneumonia, and shock. Anything that can diffusely injury the lung can lead to ARDS. Regardless of the etiology, the pathophysiology and clinical manifestations are the same and can be divided into three phases: the acute or oxidative phase, the proliferative phase, and the fibrotic or reparative phase. While the immediate processes leading to ALI and ARDS are not known, direct injury could occur either to lung endothelium and/or epithelium and trigger an inflammatory response. Alternatively, the inflammatory cascade, if activated systemically, could itself indirectly cause endothelial or epithelial injury through reactive oxidant species, proteases, and cytokines. The result is widespread capillary leak and exudation of protein-and fibrin-rich fluids into the interstitium and the alveolar space. Leakage of protein leads to activation of coagulant pathways and influences a secondary release of growth factors and profibrotic mediators, presumably leading to healing and repair, but occasionally contributing to ongoing inflammation and damage to the lung. This chapter will summarize the current understanding of the contribution and regulation of the different mediators, both biochemical and cellular, that are believed important to the pathogenesis of acute lung injury.
