Hepatic enzymic zonation: A reevaluation of the concept of the liver acinus

Abstract

The distribution pattern of a periportal enzyme (carbamoylphosphate synthetase) and a pericentral enzyme (glutamine synthetase) in human and rat liver has provided an objective parameter to delineate the zonal boundaries of the liver acinus. On sections, the pericental zone (zone 3) is circular and discrete rather than star-like and reticular, as predicted by the acinar concept, whereas the periportal zone (zone 1) is reticular, i.e. contiguous between adjacent acini rather than discrete. Three-dimensionally, the composite of pericentral zones (the pericentral compartment) follows the branching pattern of the terminal hepatic (central) vein, whereas the composite of periportal zones (the periportal compartment) envelops the pericentral compartment as a three-dimensional network (reticulum). This modified concept that is based upon the three-dimensional distribution of hepatocyte-specific enzymes is supported by data from the literature regarding the three-dimensional angioarchitecture of the liver, the perfusion pattern of the liver and the three-dimensional pattern of tissue oxygenation. Hence, a unified concept of the liver architecture that is based upon the observed distribution pattern of blood flow, of gene expression and of metabolism can be established.

The portal lobule in rat liver fibrosis: A re-evaluation of the liver unit

“…An important point of this concept is to consider that zone 3, with the worst portal blood supply, surround CVs and extend to interlobular portal veins from which TPBs arise. The concept of the liver acinus has become the most accepted description during the past 40 years and is thought to explain many pathologic lesions of the liver; however, in recent years several studies on liver lobular angioarchitectures [15][16] and enzyme distributions, [17][18][19] both of which reflect the microcirculation, provide contradictions to the acinus concept.…”

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

“…Other authors, investigating the activities of single or a combination of certain enzymes, were critical to this approach regarding the exact boundaries or overall number of the different zones or opposed the acinus concept in general. [9][10][11] Our model is not designed to study the subdivision of the liver acinus into metabolic zones in detail. However, we found examples (Fig.…”

“…The 3-dimensional outlines of the acinus are thus understood as an ellipsoid. 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.…”

Now you see it, now you don't

“…16 Mall described a "portal lobule" with a portal tract at its center, 17 whereas for the so-called "biliary lobule" of Brissaud and Sabourin 18 the portal tract also forms the axis but here the bile drainage component is considered dominant. Functional liver lobules have also been defined according to metabolic characteristics of the hepatocytes 19 or the regulatory effects of oxygen gradients. 20 However, compared with all of these and several other models, the landmark acinar concept of the fundamental liver unit in animals and humans devised by Rappaport 21,22 and developed out of his university thesis presentation, 23 has attracted the most attention and captured the imagination of hepatologists and pathologists alike for more than 40 years, at least until recently.…”

“…19 The avant-garde hepatic microvascular unit has been defined as an elongated pyramidal or conical radial sector of the classic lobule, fed at its base on the periphery by the smallest branches of the portal veins (inlet venules) that colocalize with the canals of Hering. This newly appreciated structure is currently thought to qualify best for the title of choleohepaton, the elementary morphofunctional unit of the liver.…”