The streaming liver II. Hepatocyte life history

ABSTRACT— Thirty male adult rats, were injected with [ 3 H]‐thymidine, [ 3 H]TdR. The animals were killed in groups of five, at the following times: 1 h, 14, 30, 60, 90 and 120 days. The livers were fixed in formalin, embedded in paraffin and cut into 5‐μ‐thick sections, which were then dipped into liquid emulsion and exposed for 3 weeks. The grain content of each sampled cell was counted and its distance from the nearest portal tract rim measured. Since the cells were labelled once and the label was available only for a short period, cell displacement could be followed with time. One hour after labelling, most labelled cells were confined within the 300 μm distance from the portal space rim. From then on, labelled cells advanced at a daily velocity of 2.5 μm toward the terminal hepatic vein. The liver acinus is composed of two compartments: a progenitor compartment extending up to 300 μm from the portal tract and a functional compartment covering the remaining acinus portion. Such an arrangement is known as a two‐compartment cell renewal system, and is found in renewing tissues like cryptvillus and epidermis. The hepatocyte moves from the portal space toward the terminal hepatic vein, proceeding along a trajectory, denominated as tissue radius. Since cells move in one direction, the further a cell is from the portal tract, the older it is. One may therefore estimate cell age by measuring its distance from the origin. Since the tissue radius portrays cells of all ages, it describes the entire life history of one cell. The advancing hepatocytes traverse the three acinus zones. Each represents, therefore, a differentiation stage of one cell, and since in each zone cells perform different functions, the metabolic activity of the hepatocyte is age‐dependent. When young it is engaged, among other activities, in gluconeogenesis, turning in old age to glycolysis.