Hypoxia-induced alveolar epithelial dysfunction

Abstract

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 ...