Hypoxia-induced Alveolar Epithelial Dysfunction

摘要

Alveolar hypoxia occurs in patients with acute respiratory distress syndrome (ARDS) as a result of flooded alveoli, and is associated with decreased edema fluid clearance and, thus, increased mortality. The mechanisms of impaired alveolar fluid clearance in epithelial injury are incompletely understood. Hypoxia-mediated impairment of lung edema clearance is closely related to the inhibition of Na,K-adenosine triphosphatase (Na,K-ATPase), an enzyme that consumes up to 40% of cellular ATP production. Within a short period of time, hypoxia inhibits Na,K-ATPase activity by promoting its endocytosis from the plasma membrane to intracellular compartments in alveolar epithelial cells. More prolonged hypoxia appears to result in both downregulation and degradation of Na,K-ATPase. By decreasing Na,K-ATPase activity, there is decreased ATP demand and oxygen consumption, crucial elements for cellular survival under hypoxic conditions. Better understanding of these mechanisms may lead to novel therapeutic approaches for the treatment of ARDS.