Red cell carriage of label: its limiting effect on the exchange of materials in the liver.

The red cell membrane is a permeability barrier that limits the equilibration of a variety of solutes between red cell and plasma water. We utilized the multiple indicator dilution technique to investigate the effect of this barrier on the exchange in the liver of a group of tracer substances that are not removed in net fashion from the hepatic circulation: thiourea, urea, and chloride. We demonstrated that, after preequilibration of the label with red cells, a red cell carriage effect appeared (the trapping and translocation of label in the red cells), that this effect was most marked when the permeability of the red cell was relatively low for the substance under consideration (thiourea), and that the effect became small when the permeability of the red cells was large for the exchanging substance (urea and chloride). We developed a theoretical description of the retarding effect of the red cell permeability barrier on the extravascular exchange of label and were able to use this description to obtain estimates of the red cell permeability from the in vivo dilution curves. We examined the effect of plasma injection, of changing the input in such a fashion that the label was not preequilibrated with red cells, and found both experimentally and theoretically, that for substances of low permeability the transit time from these experiments, if multiplied by the total water flow or solute flux, gave an overestimate of both the apparent total volume of distribution and the mass of traced material in the system. This last effect is of great importance for the practical design of many biological experiments. Reliable volume and mass estimates can be made only when the labeled material has been preequilibrated with red cells.