A clinical and histochemical study of cholestasis

Extrahepatic obstructive cholestasis reverses the bile salt secretory polarity of rat hepatocytes.

“…These findings indicate basolateral accumulation of functionally active canalicular bile salt carriers in cholestatic hepatocytes rather than an increased contamination of "cholestatic" blLPM vesicles with canalicular membranes, since the relative enrichments of canalicular marker enzyme activities remained similar in blLPM vesicles of normal and cholestatic liver (Table I). Thus, the results provide direct evidence for structural and functional reversal of the bile salt secretory polarity in hepatocytes during extrahepatic cholestasis, thereby corroborating previous enzymatic, histochemical and immunofluorescence studies with various canalicular enzymes (2,(8)(9)(10) and with different domain specific antigens of unknown functions (1 1), respectively. These earlier observations indicate that loss ofthe hepatocellular surface polarization during biliary obstruction is a general phenomenon that affects a variety of both canalicular (8)(9)(10)(11) and sinusoidal (11) domain specific proteins.…”

“…Thus, the results provide direct evidence for structural and functional reversal of the bile salt secretory polarity in hepatocytes during extrahepatic cholestasis, thereby corroborating previous enzymatic, histochemical and immunofluorescence studies with various canalicular enzymes (2,(8)(9)(10) and with different domain specific antigens of unknown functions (1 1), respectively. These earlier observations indicate that loss ofthe hepatocellular surface polarization during biliary obstruction is a general phenomenon that affects a variety of both canalicular (8)(9)(10)(11) and sinusoidal (11) domain specific proteins. The present study provides no conclusive evidence with respect to an altered polarization of plasma membrane constituents other than cBSTP in cholestatic hepatocytes, although in cholestatic blLPM canalicular marker enzyme activities were considerably less decreased compared with cholestatic cLPM or even unaltered when compared with normal blLPM (Tables I and II).…”

“…Especially intriguing is the observation of retrograde vesicle-mediated transport from bile to blood for lipoprotein X (6) and for dimeric IgA (7), suggesting that retrograde passage via the transcellular route might represent an important pathway for "regurgitation" of bile constituents into blood plasma. Such retrograde diacytosis might also be involved, at least in part, in the described topographic shift of some histochemically demonstrable enzymes (8)(9)(10) and antigens (11) from the canalicular to the basolateral (sinusoidal and lateral) membrane domain. Although these findings have been interpreted to reflect a "reversed secretory polarity" in cholestatic hepatocytes (2,7), direct structural and functional proof for this hypothesis has so far not been obtained.…”

Actin filaments of hepatocytes in experimental rat cholestasis - Observations using a fluorescent staining method by DACM labeled heavy meromyosin.

“…Liver treated with common bile duct ligation showed the subcellular changes frequently localized to bile canaliculi and nearby structure (30). In the present experiments, actin filaments increased in the peripheral cytoplasma, particularly around bile canaliculi.…”

The amazing universe of hepatic microstructure†

“…84 The heterogeneous appearance of canaliculi in cholestatic liver tissue was explained, at least in part, by new development of canaliculi attempting to rescue bile secretory function 85 along a mechanism analogous to canalicular development studied by Chris Peeters in fetal liver. [86][87][88] Altogether, the findings allowed one to summarize that in prolonged cholestasis new canaliculi develop, and bile regurgitates through several pathways: directly from canaliculi through leaky tight junctions, from inside the cell by reversed vesicle-mediated transcytosis, and by reversed transmembrane secretion at the sinusoidal side 89,90 (Fig. 6).…”