Transcapillary Exchange of Water and of Other Substances in Certain Organs of the Dog

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Abstract
Data are presented on the relative rates of passage of a number of substances (e.g., deuterium or tritium oxide, Na-22, K-42, Cl-36, thiocyanate, inulin, p-amino-hippurate (PAH)) across the capillary walls of several organs of anesthetized dogs. Injection of several test substances together with a reference substance (such as the blue dye T-1824) to permit correction for dilution is made into the main vessel to an organ and blood is obtained by a catheter in the main vessel from the organ. By means of an automatic sampling device (described) some 15-30 samples of blood are obtained each representing a collection period of 0.5-3.0 seconds. From the concentrations of the test and reference substances in each sample and the concentrations in the injection solution, time-concentration ratio curves are plotted. In the hind leg, head, liver and spleen the curves for the substances with the greater diffusion coefficients are lower than the curves for the substances with the smaller diffusion coefficients and similar volumes of distribution. In the kidney the curves for PAH are lower than for any other substance including labeled water because of the uptake of PAH by the tubule cells when sufficiently small amounts of PAH are injected. In this organ the curves for the test substances are markedly displaced relative to the references curve: maxima occur later the the curves for the test substances are higher, after the maxima, than the reference curve. This displacement indicates that return of the test substances to the blood stream occurs. Corrections for this return are made, based on the assumption that the rising, initial, portions of the curves represent the amount remaining without return. Net losses, thus corrected for return, amount to 50-98% for labeled water with correspondingly smaller losses for larger test substances. Fifty to 98% of the water passing through an organ crosses the capillary walls and returns. It is concluded that the bulk filtration hypothesis of passage of substances across capillary walls is not compatible with these results. It is also concluded that the results can be interpreted on the basis and in the framework of the hypothesis that diffusion is the mechanism of passage and that most, if not all, of the capillary surface area is involved in the passage. A recently proposed pore filtration hypothesis is examined briefly; it is not compatible with the results obtained here and is invalid on physico-chemical grounds. In an appendix, a derivation is presented of Starling''s equilibrium condition based on the diffusion hypothesis and on the concept of chemical potentials. It is concluded that had diffusion been considered earlier in terms of gradients of chemical potentials (i.e., in terms of gradients of pressure as well as of concentration) the hypothesis of filtration through pores would not have been necessary.