Developmental changes in lung epithelial ion transport and liquid movement

Abstract

During fetal life, the lungs are filled with liquid that flows from the pulmonary circulation across the epithelium in response to the osmotic force generated by Cl- secretion of airway and distal lung epithelial cells. As birth approaches, net Cl- secretion across the respiratory tract epithelium decreases, and this is associated with a reduction in the flow of liquid into the lung lumen. The cause for this change is unknown, but several recent studies indicate that it may be related to alterations in the hormonal milieu to which the lung epithelium is exposed late in gestation. The switch from placental to pulmonary gas exchange at birth requires rapid removal of liquid from the lung lumen. During labor and the immediate postnatal period, the pulmonary epithelium changes from a predominantly Cl-(-)secreting membrane to a predominantly Na(+)-absorbing membrane, with resultant reversal of the direction of flow of lung liquid. There is considerable evidence that this change reflects an active metabolic process involving increased Na(+)-K(+)-ATPase activity in lung epithelial cells, which drives liquid from the lung lumen into the interstitium, with subsequent absorption into the pulmonary circulation. This Na(+)-K(+)-ATPase-dependent process persists in the bronchopulmonary epithelium of the mature lung and probably has an important role in clearance of alveolar edema associated with heart failure or lung injury.