Water and solute exchanges. How far have we come in 100 years? What's next?

Two approaches have been used in descriptions of transvascular exchanges and net transfers of water and small solutes. The classical approach is based on Starling's four factors, vascular and interstitial hydrostatic and osmotic pressures, and on the concept of filtration in bulk without separation of solvent water from small solutes. In a physicochemical approach based on nonequilibrium thermodynamics and on multiple indicator-dilution experiments, diffusion is considered the dominant mechanism in transvascular exchanges of water with net transfers related primarily to the permeability and net passage of small solutes such as sodium and chloride ions (osmotic buffering). Reconciliation of the two approaches is proposed in the hypothesis that small solute controls are dominant over a period of seconds while oncotic pressure factors are operative over minutes. Interpretation of multiple indicatordilution experiments is classically based on linear models developed by Goresky for solute extravascular distributions and by Crone for permeability calculations. Recurrent nonlinear models are required in the kidneys and for gases and volatile substances, including water, in the lungs where Kety's model may be applicable. Aquaporins may be important but their role has not been completely defined. Incorporation of these findings into the physiome concept remains a challenge only partially met.