Hypocapnic but not metabolic alkalosis impairs alveolar fluid reabsorption

Acid-base disturbances, such as metabolic or respiratory alkalosis, are relatively common in critically ill patients. We examined the effects of alkalosis (hypocapnic or metabolic alkalosis) on alveolar fluid reabsorption in the isolated and continuously perfused rat lung model. We found that alveolar fluid reabsorption after 1 hour was impaired by low levels of CO ₂ partial pressure (PCO ₂; 10 and 20 mm Hg) independent of pH levels (7.7 or 7.4). In addition, PCO ₂ higher than 30 mm Hg or metabolic alkalosis did not have an effect on this process. The hypocapnia-mediated decrease of alveolar fluid reabsorption was associated with decreased Na,K-ATPase activity and protein abundance at the basolateral membranes of distal air-spaces. The effect of low PCO ₂ on alveolar fluid reabsorption was reversible because clearance normalized after correcting the PCO ₂ back to normal levels. These data suggest that hypocapnic but not metabolic alkalosis impairs alveolar fluid reabsorption. Conceivably, correction of hypocapnic alkalosis in critically ill patients may contribute to the normalization of lung ability to clear edema.