HEPATIC-UPTAKE OF PROTEIN-BOUND LIGANDS - EFFECT OF AN UNSTIRRED DISSE SPACE

Uptake of protein-bound substances by the liver was modeled considerin g concurrent depletion of unbound ligand (i.e., not bound to protein)a long the length of a sinusoid as well as within a 0.5-mu m unstirred b oundary layer at the surface of the hepatic parenchymal cells. The dev elopment completes a previous exploration of Weisiger et al. [Am. J. P hysiol. 261 (Gastrointest. Liver Physiol. 24): G872-G884, 1991]. Ligan d is carried across the unstirred layer by albumin, producing a deviat ion from binding equilibrium inside and outside the unstirred layer. T he resulting differential equations have a closed solution. In the cas e of tight binding, the unbound ligand in the sinusoid is in a quasi-s teady state, and the unbound fraction becomes constant along the flow path, except for a very short section at its beginning. During hepatic oleate uptake, the unbound oleate concentration rises from 39% of the equilibrium value at 0.1 mu M albumin and 0.01 mu M oleate to 78% at 0.5 mu M albumin and 0.05 mu M oleate. Diffusion through the unstirred layer and across the cell membrane was found, in the model, to contri bute to the overall resistance to oleate uptake in a complementary fas hion.