Paracellular fluid transport by epithelia.

The evidence that a major fraction of water crosses the paracellular route during isotonic fluid transfer is reviewed together with a description of the theory and experimental results derived from extracellular probe studies. Four transporting epithelia which have been studied using the method are gallbladder, intestine, Malpighian tubule, and salivary gland. It is concluded that paracellular probe flows are not due to simple convection generated by osmotic flow through the junctions but are generated by active fluid transport within the junction: a mechano-osmotic process. The geometry of the pathway involved would indicate that some salt accompanies the paracellular fluid, representing a hypo-osmotic flow. Transport of salt by the cell route, which may be accompanied by some water, represents a hypertonic flow. The problem then becomes one of balancing the two to produce an isotonic transportate. We suggest, using recent data from knockout mice, that some aquaporins are functioning in different epithelial tissues as osmo-comparators within a feedback loop that regulates the paracellular fluid flow rate. This results in an overall quasi-isotonic transport by the epithelium. The model is applied to forward-facing systems such as proximal tubule and backward-facing systems such as exocrine glands.