Osmotic water flow in leaky epithelia

Abstract

I review three currently unsolved and controversial problems in understanding solute-linked water transport in epithelia. 1. Values of osmotic water permeability (Posm) calculated from steady-state osmotic flow in response to a gradient of a probe molecule tend to be underestimates, because of three unstirred-layer (USL) effects. These are: dissipation of the probe's gradient by diffusion in USL's; reduction of the probe's gradient, due to the sweeping-away effect of water flow generated by the probe itself; and solute polarization (creation of an opposing gradient of an initially symmetrically distributed solute by the sweeping-away effect). These errors increase with probe permeability, USL thickness, Posm, and concentration ratio of symmetrically distributed solute to probe, and vary inversely as the fractional area available for water flow (e.g., lateral intercellular space width). The form of an osmotic transient, and the possibility of extracting a true Posm value from the transient, depend on the relative values of three time constants: those for solute diffusion in USL's, for solute polarization by water flow in USL's and for measuring water flow. Sweeping-away effects cause major underestimates (by one or more orders of magnitude) in epithelial Posm determinations, as shown by apparent streaming potentials during osmotic flow and by transiently reversed flows after removal of the proble. True Posm values for leaky epithelia probably exceed 10(-3) or 10(-2) cm/sec.osm. The necessary conditions for resolving osmotic transients are set out. 2. I illustrate the difficulties in deciding what fraction of transepithelial water flow is via the cells, and what fraction via the junctions. There is no existing method for answering this question. 3. Controversies about the validity, or need for modification, of the standing-gradient theory are discussed. Progress in this field requires new methods: to resolve osmotic transients; to separate transcellular and transjunctional water flows; and to measure solute concentrations in lateral intercellular spaces directly.

Paracellular non‐electrolyte permeation during fluid transport across rabbit gall‐bladder epithelium

“…He has also pointed out, however, that at low osmolalities the epithelium becomes 'leaky' to phenol red and sucrose (Diamond, 1964b(Diamond, , 1979. In an attempt to understand this latter phenomenon in terms of the model for non-electrolyte permeation described in this paper, the fractional transported concentrations of several non-electrolytes have been measured first as a function of mucosal osmolality and second as a function of time during transport at reduced osmolality.…”

The roles of paracellular and transcellular pathways and submucosal space in isotonic water absorption by rabbit ileum.

“…Thus, as well as increasing the rate of solute equilibration between the mucosa and submucosa, the presence of the shunt pathway prevents concentration polarization and 'sweeping away' effects within the submucosa, as predicted by Diamond (1979), because the salt gradients will be dissipated via the shunts. This means that the measured Lp of the transcellular route can be considered to be an accurate estimate of the true value.…”

“…This means that Diamond's (1979) view that the unstirred layer effects can nullify the effect of a step change in external tonicity on osmotic flow into the lateral intercellular space, so that the Lp of the lateral intercellular space boundary is indeterminate, is correct.…”

“…The slow rise in submucosal tonicity following an increase in concentration of the mucosal solution indicates: (a) that the solute tonicity within the submucosal compartment can differ from that in either the serosal bathing solution or the lateral intercellular space; (b) that there is a relatively slow rate of solute equilibration between the submucosa and serosal solution; if solute equilibration between the submucosa and serosal solution were rapid, no significant rise in submucosal concentration could occur on raising the mucosal solute concentration; (c) the solute concentration within the submucosa is not controlled solely by the Na+-pump activity ofthe mucosa and/or unstirred layer effects, as suggested by Diamond (1979) and Barry & Diamond (1984); if this were true, then recovery of inflow after a step increase in mucosal tonicity should be the same whether NaCl, sucrose or macromolecular solute is added to the mucosal solution. The rebound rise in inflow after raising the mucosal NaCl tonicity and the absence of rebound when macromolecules are added demonstrates that the rebound recovery phase is due to low molecular weight solute equilibration across the wide shunt pathway between the mucosal and submucosal solutions and not to concentration polarization.…”

“…Hence, the appropriate Lp to generate the osmotic gradient required for fluid absorption is that ofthe channels which reflect NaCl. Diamond (1979) has argued that the real Lp of this route in rabbit gall-bladder is very high, but is apparently low because solute polarization within the lateral intercellular space reduces the osmotic pressure gradient across the mucosa. This argument can be refuted, for rabbit small intestine at least, by the results presented here and in the previous paper (Naftalin & Tripathi, 1985).…”