Kinetic interpretation of hepatic multiple-indicator dilution studies.

The single-injection, multiple-indicator dilution approach, together with an analysis based on a model of microcirculatory events, provides a way of determining the composition of and the rates of processes in the liver. By comparison with a vascular reference, labeled red cells, a set of interstitial materials are found to enter the Disse space in a delayed-wave, flow-limited fashion, larger materials being excluded from a proportion of the space, and labeled water is found to undergo flow-limited distribution into the liver cells. In contrast, many other substances exhibit barrier-limited exchange with the liver cells; their tracer outflow profiles consist of throughput material (which has entered the interstitium but not the liver cells) and of returning material (which has entered the cells, later to return to the vascular space). Intracellular metabolic sequestration or biliary secretion reduces the outflow recovery of returning tracer; it also results in decreasing steady-state concentrations along sinusoids and cells and, where the cell membrane is limiting, in a step-down in concentration across it.