Three-dimensional reconstruction of parenchymal units in the liver of the rat

Abstract

To investigate the parenchymal units in the liver of the rat three-dimensionally, 15 micrometer cryosections were used for the demonstration of glucose-6-phosphatase (G6Pase) activity to visualize the borders of the individual units. Together with the supplying and draining vessels, they were traced through a sequence of 146 sections and reconstructed. A cone-shaped secondary unit with a height of 2.1 mm and a volume of 3.3 mm3 was reconstructed. It was "covered" by a continuous vascular surface, consisting of portal tracts and vascular septa, connecting the portal venular branches. The secondary unit was subdivided by portal tracts and vascular septa, and by branches of a draining central venular tree into 14 primary units. Most of them were tri- to heptahedral in shape. The height varied between 330 and 840 micrometer, and the volume varied between 0.094 and 0.621 mm3. The branches of the portal venular tree, with diameters from 28 +/- 5 micrometer to 61 +/- 14 micrometer, were oriented preferentially along the vertical axis of the units. Most of the primary units were drained by single branches of the central venular tree, located in the center and oriented along the vertical axis of the units. Vessel diameters ranged from 62 +/- 14 micrometer to 216 +/- 9 micrometer. The average length of the sinusoids was 355 +/- 3 micrometer. From the results of this reconstruction study, it was concluded that the concept of the liver acinus cannot be applied to the liver of the rat.

Revelation of simple and complex liver acini after portal transplantation of pancreatic islets or thyroid follicles in rats

“…Recently, studies were published that deny the existence of a TPV in the rat and human liver. 10,11 Regarding the rat liver, these results are now refuted by our study as seen in several of our figures (e.g., Fig. 2C,E; Fig.…”

“…(2) Studies that investigated a peculiar metabolic function of hepatocytes organized in a specific manner within the parenchyma. The hepatic unit organization is then evaluated as a consequence of the distribution pattern of this function, such as the activity of a certain enzyme, 10,11,25,26 or, among others, the selectivity of cell permeabilization following digitonin-pulse perfusion of the liver 27 or colloidal gold uptake. 28 These studies yielded interesting but very contradictory data, and none was able to visualize Rappaport's liver acinus.…”

“…Instead, different types of parenchymal units were newly introduced or revisited, such as the portal lobule, 29 so called "cone-shaped primary lobules", 6-8 of which form a classical (central-vein) but secondary lobule according to Matsumoto,12,13 or "primary lobular units" and "liver modules" with differences to, but basically the same organization as the classic (central vein) liver lobule. 10,11 Using a specific experimental model based on the lownumber intrahepatic portal-embolic transplantation of endocrine tissues it took about 50 years to prove the correctness of RappaportЈs acinus model since his first description in 1954. The following principles can now be concluded from our results:…”

“…This model has been widely accepted, in particular for functional purposes, but has also been questioned by oth-ers, either in conceptual details that lead to several modifications 9 or it has been rejected in general: Some investigators studying the human and rat liver microanatomy strongly oppose the existence of a simple liver acinus and the TPV. [10][11][12][13] The main problem for many investigators when using the acinus concept for practical liver histology is founded on the lack of anatomical structures that help to visualize the outlines of the respective liver acini in particular when considering 3-dimensional aspects. The problem is intensified by the fact that neither in experimental animal models nor in the human liver has anybody yet succeeded in giving a direct visual evidence of a simple, model-propagated liver acinus.…”

In vivo and ex vivo virtual biopsy of the liver with near-infrared, reflectance confocal microscopy

“…Actually, enzymatic studies in ex vivo liver suggest that neither the acini nor the portal units truly define the basic organization of the rat liver, and accordingly, the basic unit would have the shape of a cone, with branches of terminal hepatic vein in its center and portal triads at the periphery. 11 Most in vivo imaging studies convey that in the rat sinusoids and branches of central veins are located on the surface, while their corresponding portal branches lay at a greater depth. This histologic anisotropy contributes to the fact that some structures of the hepatic unit cannot be visualized in vivo with epi-illumination fluorescence microscopy.…”