Epithelial solute permeability, ion transport and tight junction morphology in the developing lung of the fetal lamb

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Abstract
Experiments were performed on exteriorized fetal lambs of between 69 days gestation and term (147 days) to observe changes in lung volume and lung liquid secretion rate, and to delineate any alterations in solute permeability, ion transport and tight junction morphology in the maturing lung epithelium. While it was technically possible to measure solute permeability as early as 69 days it was not feasible to apply the Ussing flux ratio technique before 84 days. Fetal lung liquid volume and secretion rate, when normalized for body weight, increase linearly with gestation, whereas tracheal volume expressed in the same manner remains constant. When expressed in terms of pore theory, epithelial permeability to small polar non-electrolytes does not change between 69 days and term (equivalent pore radius 0.66 and 0.64 nm, respectively). In the immature fetus of 69-76 days, mean epithelial tight junction strand number is 8.3, whereas by the end of gestation it has fallen to 4.6. The transfer constants (min-1) for Na+ and Cl- movement in the direction lung liquid to plasma are, respectively, some 6 and 4 times greater at 84-87 days than at term. As in the mature fetus, the lung epithelium at 84-87 days transports Cl- from plasma to lung lumen, albeit with a slightly reduced transport e.m.f. [electromotive force]. Na movement does not, at any gestational age, differ from the predictions for passive transfer. In lung liquid the concentrations of Cl- and K+ increase and that of HCO3- decreases during gestation, while that of Na+ does not change. The rises in lung liquid Cl- and K+ concentrations follow those in plasma, maintaining plasma/lung liquid ratios of 0.7 and 0.95, respectively. Plasma HCO3- remains constant and the plasma/lung liquid ratio for HCO3- rises from 3 at 69-76 days to 20 near term as the lung liquid HCO3- falls from 9.8 to under 2 mmol kg-1 H2O.