Modeling the proximal tubule: complications of the paracellular pathway.

When the proximal tubule epithelium is represented as cellular and lateral intercellular (LIS) compartments, the presence of a paracellular pathway can render the overall phenomenologic equations quite an indirect representation of intraepithelial transport processes. 1) Active sodium transport into the LIS may create a hypertonic region that drives water movement from lumen to peritubular blood, i.e., a term for active water transport may appear in the overall transport equations. The correlate of this uphill water flux is a solute polarization effect, such that the measured epithelial water permeability is less than that of the cell membranes. 2) Basolateral uptake of potassium by the cell may lower the LIS concentration and promote diffusive entry of K across the tight junction. Even without cellular uptake of K from the lumen, the epithelial transport equations may contain a term for active K reabsorption. The solute polarization correlate is a low epithelial reflection coefficient that does not represent a convective flux of K through a specific channel. 3) When there is convective flux of Na and Cl through the tight junction but none through the cell, then a fluid circuit around junction and cell may be present, even when net epithelial volume flux is absent. In this case, part of the net epithelial Cl flux must be represented in the overall transport equations as electroneutral Na-Cl cotransport.