Experimental obstructive cholestasis: the wound-like inflammatory liver response

Abstract

Obstructive cholestasis causes hepatic cirrhosis and portal hypertension. The pathophysiological mechanisms involved in the development of liver disease are multiple and linked. We propose grouping these mechanisms according to the three phenotypes mainly expressed in the interstitial space in order to integrate them.Experimental extrahepatic cholestasis is the model most frequently used to study obstructive cholestasis. The early liver interstitial alterations described in these experimental models would produce an ischemia/reperfusion phenotype with oxidative and nitrosative stress. Then, the hyperexpression of a leukocytic phenotype, in which Kupffer cells and neutrophils participate, would induce enzymatic stress. And finally, an angiogenic phenotype, responsible for peribiliary plexus development with sinusoidal arterialization, occurs. In addition, an intense cholangiocyte proliferation, which acquires neuroendocrine abilities, stands out. This histopathological finding is also associated with fibrosis.It is proposed that the sequence of these inflammatory phenotypes, perhaps with a trophic meaning, ultimately produces a benign tumoral biliary process -although it poses severe hepatocytic insufficiency. Moreover, the persistence of this benign tumor disease would induce a higher degree of dedifferentiation and autonomy and, therefore, its malign degeneration.

Remote ischemic conditioning: Short-term effects on rat liver ischemic-reperfusion injury

“…Az egyik felszíni mérőfej a máj bal lateralis lebenyén [12] mindig azonos lokalizációban került felhelyezésre. A másik mérőfej a bal m. biceps femoris felett került rögzítésre.…”

A half century (1961-2011) of applying microsurgery to experimental liver research

“…An advantage of the microsurgical technique of extrahepatic cholestasis in the rat is the absence of biliary pseudocyst formation, hepatopulmonary infection, and thus the prevention of mortality related to sepsis [22,23] . In rats with microsurgical extrahepatic cholestasis, the weekly administration of antibiotics and vitamin K allows rodents to survive for more than 8 wk [24,25] . In the long-term evolution, both macrosurgical (BDL) and microsurgical experimental cholestasis models develop hepatomegaly with a marked ductular proliferation and fibrosis, but the loss of normal liver architecture, typical of cirrhosis, is seldom found [24][25][26] .…”

“…In rats with microsurgical extrahepatic cholestasis, the weekly administration of antibiotics and vitamin K allows rodents to survive for more than 8 wk [24,25] . In the long-term evolution, both macrosurgical (BDL) and microsurgical experimental cholestasis models develop hepatomegaly with a marked ductular proliferation and fibrosis, but the loss of normal liver architecture, typical of cirrhosis, is seldom found [24][25][26] . In relation to extrahepatic alterations, jaundice, choluria, PH with enlarged spleen and collateral portosystemic circulation, hepatic encephalopathy and ascites, stand out [25,27] .…”

Involvement of cholangiocyte proliferation in biliary fibrosis

“…Cholangiopathies are characterized by cholestasis, the loss of cholangiocytes through necrosis or apoptosis, with cholangiocyte proliferation resulting in the formation of new side branches to ducts in an effort to regain function [13,26,27] , and portal/periportal inflammation [26] . Obstructive cholestasis contributes to hepatic cirrhosis and portal hypertension [28] . Portal fibroblasts and hepatic stellate cells (HSCs) are recruited to the area, and followed by parenchyma invasion and biliary fibrosis [26] .…”