Role of alveolar epithelial sodium transport in high altitude pulmonary edema (HAPE).

Alveolar edema results from an imbalance between fluid filtration into the alveolar space and removal by reabsorption. Hypoxia increases filtration by raising pulmonary capillary pressure and increasing endothelial and epithelial permeability allowing fluid and blood cells to access the alveoli. Active Na-reabsorption drives the fluid reabsorption from the alveolar space, but hypoxia inhibits reabsorption by inhibition of epithelial Na-channels (ENaC) and Na/K-ATPase. A (genetically determined) low activity of alveolar reabsorption in normoxia and further inhibition by hypoxia might cause HAPE-susceptibility, since at some point the depressed reabsorption may not keep pace with increased filtration. Na-reabsorption might even prove totally inefficient in the presence of large leaks of the alveolar barrier. Alveolar Na-reabsorption has not been measured in HAPE. Nasal epithelial Na-transport has been used as surrogate marker based on similarities in subunit expression of ENaC in nasal, airway, and alveolar epithelium. At high altitude cold, dryness, and nasal infections affect the nasal potential making any extrapolation to processes at the alveolar epithelium unreliable. The variability in nasal Na- and Cl-transport reduces the usefulness of nasal potentials to diagnose HAPE-susceptibility.