Effects of capillary heterogeneity on rates of steady uptake of substances by the intact liver

Abstract

Steady elimination of substances by a heterogeneous perfused organ is investigated for general uptake kinetics, with special reference to saturation kinetics. In the case of uptake of substances by hepatocellular enzymes according to Michaelis-Menten kinetics, the theory is brought to bear on published data on the elimination of galactose by isolated perfused pig livers. Using a statistical sample-splitting method, it is shown that the data are inconsistent with functional homogeneity of liver sinusoids ( P < 0.002), and a reinterpretation of the pooled data is carried through in terms of a model incorporating capillary heterogeneity. The limitations of such analyses in the case of several parallel biochemical pathways of uptake are discussed.