The processes of cellular uptake and exchange in the liver

The multiple indicator dilution technique has been utilized to examine the exchange between blood and tissue in the liver. With the use of labeled red cells and albumin and a set of classic compartment labels (inulin, sucrose, sodium, and water), we find the sinusoidal endothelium to be freely permeable to all of the dissolved labels; delayed wave flow-limited distribution of each occurs into its respective space. For the group of extracellular materials (albumin, inulin, sucrose, and sodium) an exclusion phenomenon, increasing with molecular size, restricts access to the interstitial space. The hepatocyte cellular membrane is the principal barrier in the system. Analytical solutions to the equations describing exchange across this barrier (which extend to the flow-limited extreme, exemplified by labeled water) have been developed. These allow one to analyze the outflow dilution curves for materials penetrating cells. For materials penetrating less well, outflow curves consist of throughput material, which emerges without entering cells, and exchanging material, which has entered. Two extreme examples are reviewed: labeled rubidium, which enters the cells concentratively, so that its early outflow profile consists almost exclusively of throughput material; and D-glucose, which enters nonconcentratively, so that its throughput and exchanging components overlap in intimate fashion.