Hypocapnic but not metabolic alkalosis impairs alveolar fluid reabsorption

Abstract

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 CO2 partial pressure (PCO2; 10 and 20 mm Hg) independent of pH levels (7.7 or 7.4). In addition, PCO2 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 airspaces. The effect of low PCO2 on alveolar fluid reabsorption was reversible because clearance normalized after correcting the PCO2 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.

Figure 1.

(A) Alveolar fluid reabsorption (AFR) decreased during progressive hypocapnic alkalosis (pH 7.50, 7.60, and 7.70). (B) AFR was also impaired by effect of low partial pressure CO₂ (PCO₂; ∼ 10, ∼ 20, and ∼ 30 mm Hg, and pH 7.40). (C) Metabolic alkalosis (pH 7.70; PCO₂, ∼ 40 mm Hg) did not affect AFR. Bars represent mean ± SEM. *p < 0.05; **p < 0.01; n = 5.

Figure 2.

AFR was plotted against PCO₂. There was a significant correlation between them (r² = 0.961, p < 0.001). Values are mean ± SEM, n = 5.

Figure 3.

AFR was restored to normal levels after correcting the hypocapnia from low to normal pH values in 3-hour experiments: normal pH (7.40) during the first hour, low PCO₂ to a pH of 7.70 during the second hour, and back to normal PCO₂ and pH during the third hour. Bars represent mean ± SEM. **p < 0.01, n = 5.

Figure 4.

(A) Na,K-ATPase activity (assessed as ouabain inhibitable hydrolysis of ³²P-ATP) decreased at the basolateral membranes (BLM) of peripheral lung tissues during hypocapnic alkalosis as compared with control animals. (B) Na,K-ATPase α1-subunit protein abundance at the BLM of peripheral lung tissues was decreased during hypocapnic alkalosis as compared with control animals. (C) Representative Western blot. Graphs represent the mean ± SEM. *p < 0.05, n = 3. TM = total membranes.