New Insights into Functional Aspects of Liver Morphology

Abstract

The liver is structurally and functionally complex and has been considered second only to brain in its complexity. Many mysteries still exist in this heterogeneous tissue whose functional unit of the lobule has continued to stump morphologists for over 300 years. The primary lobule, proposed by Matsumoto in 1979, has been gaining acceptance as the functional unit of the liver over other conceptual views because it's based on vessel architecture and includes the classic lobule as a secondary feature. Although hepatocytes comprise almost 80% of the liver, there are at least another dozen cell types, many of which provide "cross-talk" and play important functional roles in the normal and diseased liver. The distribution and functional roles of all cells in the liver must be carefully considered in both the analysis and interpretation of research data, particularly data in the area of genomics and "phenotypic anchoring" of gene expression results. Discoveries regarding the functional heterogeneity of the various liver cell types, including hepatocytes, hepatic stellate cells, sinusoidal endothelia, and Kupffer cells, are providing new insights into our understanding of the development, prevention and treatment of liver disease. For example, functional differences along zonal patterns (centrilobular or periportal) have been demonstrated for sinusoidal endothelium, Kupffer cells, and hepatocytes and can explain the gradients and manifestations of disease observed within lobules. Intralobular gradients of bile uptake, glycogen depletion, glutamine synthetase, and carboxylesterase by hepatocytes; widened fenestrations in centrilobular sinusoidal lining cells; and differences in the components of centrilobular extracellular matrix or function of Kupffer cells have been demonstrated. Awareness of the complexities and heterogeneity of the liver will add to a greater understanding of liver function and disease processes that lead to toxicity, cancer, and other diseases.

Pluripotent plasticity of stem cells and liver repopulation

“…22 In contrast to hepatocytes that occupy almost 80% of the total liver volume and perform the majority of numerous liver functions, nonparenchymal liver cells, which contribute only 6.5% to the liver volume, but 40% to the total number of liver cells, are localized in the sinusoidal compartment of the tissue. [24][25][26] Although hepatocytes comprise almost 80% of the liver, there are at least another ten cell types, many of which provide ''cross-talk'' and play important functional roles in the normal and diseased liver. 25,26 It has been increasingly recognized that both under normal and pathological conditions, many hepatocyte functions are regulated by substances released from neighboring non-parenchymal cells.…”

“…[24][25][26] Although hepatocytes comprise almost 80% of the liver, there are at least another ten cell types, many of which provide ''cross-talk'' and play important functional roles in the normal and diseased liver. 25,26 It has been increasingly recognized that both under normal and pathological conditions, many hepatocyte functions are regulated by substances released from neighboring non-parenchymal cells. 24,27 Liver sinusoidal endothelial cells constitute the lining or wall of the hepatic sinusoid.…”

“…24 To the key mediators involved in the intercellular communication in the liver belong prostanoids, nitric oxide, endothelin-1, TNF-a, interleukins, and chemokines, many growth factors (transforming growth factor-beta (TGF-b), PDGF, IGF-I, HGF), and reactive oxygen species (ROS). 24,25 Sinusoidal blood flow is, to a great extent, regulated by hepatic stellate cells that can contract due to the presence of smooth muscle a-actin. The main vaso-active substances that affect constriction or relaxation of hepatic stellate cells derive both from distant sources and from neighboring hepatocytes (carbon monoxide, leukotrienes), endothelial cells (endothelin, nitric oxide, prostaglandins), Kupffer cells (prostaglandins, NO), and stellate cells themselves (endothelin, NO).…”

“…These cells differentiate into intermediate hepatocyte-like cells after a regenerative challenge. 24,25,28,65 Animal data indicate that oval cells are activated when oxidative stress inhibits the regenerative capability of more mature hepatocytes. 66,68 Oxidative stress is thought to play a major role in the pathogenesis of both alcoholic and NAFLD.…”

Características Estereológicas del Hígado de Rata (Rattus norvergicus) sometidas a Menopausia Inducida por Ovariectomía

“…El hígado es estructural y funcionalmente un tejido complejo, a pesar de que el hepatocito constituye en un tejido normal casi el 80% del tejido hepático, existen al menos otra docena de células que desempeñan importantes funciones (Malarkey et al, 2005). Weibel et al (1969) informaron un 83,1% de hepatocitos en el hígado de ratas Wistar y Valenca et al (2008), una densidad de volumen de 48% y densidad de número de 42, 2 ± 0,98 x103 mm 3 .…”