External solution driving forces for isotonic fluid absorption in proximal tubules

We have explored evidence that suggests that lateral intercellular spaces is the mammalian proximal nephron do not serve as a hypertonic "central compartment" driving volume absorption. A primary consideration is the very low transepithelial resistance of this tissue as demonstrated by several laboratories. By making the reasonable assumption that passive ion permeation occurs via a paracellular route, we have concluded that the diffusion resistance of the spaces in insufficient to allow the development of a significant compositional difference between the spaces and the peritubular medium. This conclusion led us to look for potential osmotic gradients existing between the luminal and peritubular solutions. From the perfusion rate dependence of osmotic volume flow in the absence of active transport in isolated convoluted and straight proximal tubules, we calculated that both segments have very high hydraulic conductances, on the order of 3,000-5,000 micron/sec. Consequently, slight differences in the effective osmolality of the external solutions are sufficient to explain net volume absorption both in vivo and in vitro. We have provided evidence for two such driving forces. First, the development of asymmetrical anion concentration differences along the length of the proximal nephron due to preferential reabsorption of HCO-3 provides a driving force if the reflection coefficient for HCO-3 exceeds that for Cl-. Second, slight luminal hypotonicity may develop as a consequence of active solute absorption. Although both mechanisms probably occur simultaneously in vivo, we consider the former to be quantitatively the most important.