Quantitative aspects of the parenchyma-stroma relationship in experimentally induced cholestasis

In order to quantify changes of the parenchyma/stroma relations in the progression of experimentally induced biliary fibrosis in the rat, localisation of lactate dehydrogenase activity and Sirius Red staining were used as criteria to detect parenchymal cells and collagen fibers, respectively. Blood levels of bilirubin, alkaline phosphatase, anti-thrombin III activity, alpha 2-antiplasmin, factor II and factor X were related to the data obtained by histomorphometric measurements in sections gathered 1, 2, 4 and 6 weeks after the onset of cholestasis in three animals and after 8 weeks in one animal. Histophotometry showed a reduction in volume density of the parenchymal cell mass of 96%, 78%, 76%, 62% and 59% of the control values, respectively. During the same period, the collagen increased 5-fold in 4 weeks time, levelling off afterwards. Newly formed collagen appeared in the portal areas in close association with proliferating ductules, invading with the latter into the parenchymal mass. After 6 weeks, regressive changes were observed in the ductule complexes formed, manifested by a lowering of the epithelium in which extensive apoptotic cell death was observed with the electron microscope. Of the blood parameters analyzed, the clotting factor X showed the best inverse correlation with the Sirius Red readings (rs = -0.84), i.e. the volume density of collagenous fibers.