scholarly journals Caroli's Disease: Current Knowledge of Its Biliary Pathogenesis Obtained from an Orthologous Rat Model

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Yasunori Sato ◽  
Xiang Shan Ren ◽  
Yasuni Nakanuma
Keyword(s):  
Bile Duct ◽  
Primary Cilia ◽  
Current Knowledge ◽  
Intrahepatic Bile Duct ◽  
Fluid Secretion ◽  
Polycystic Kidney ◽  
Caroli's Disease ◽  
Caroli’S Disease ◽  
Cell Matrix ◽  
Cell Matrix Interactions

Caroli's disease belongs to a group of hepatic fibropolycystic diseases and is a hepatic manifestation of autosomal recessive polycystic kidney disease (ARPKD). It is a congenital disorder characterized by segmental saccular dilatations of the large intrahepatic bile duct and is frequently associated with congenital hepatic fibrosis (CHF). The most viable theory explaining its pathogenesis suggests that it is related to ductal plate malformation. The development of the polycystic kidney (PCK) rat, an orthologous rodent model of Caroli's disease with CHF as well as ARPKD, has allowed the molecular pathogenesis of the disease and the therapeutic options for its treatment to be examined. The relevance of the findings of studies using PCK rats and/or the cholangiocyte cell line derived from them to the pathogenesis of human Caroli's disease is currently being analyzed. Fibrocystin/polyductin, the gene product responsible for ARPKD, is normally localized to primary cilia, and defects in the fibrocystin from primary cilia are observed in PCK cholangiocytes. Ciliopathies involving PCK cholangiocytes (cholangiociliopathies) appear to be associated with decreased intracellular calcium levels and increased cAMP concentrations, causing cholangiocyte hyperproliferation, abnormal cell matrix interactions, and altered fluid secretion, which ultimately result in bile duct dilatation. This article reviews the current knowledge about the pathogenesis of Caroli's disease with CHF, particularly focusing on studies of the mechanism responsible for the biliary dysgenesis observed in PCK rats.

Intrahepatic bile duct primary cilia in biliary atresia

2018 ◽  
Vol 48 (8) ◽  
pp. 664-674 ◽  
Author(s):  
Roberta Frassetto ◽  
Filippo Parolini ◽  
Salvatore Marceddu ◽  
Giulia Satta ◽  
Valeria Papacciuoli ◽  
...  
Keyword(s):  
Bile Duct ◽  
Biliary Atresia ◽  
Primary Cilia ◽  
Intrahepatic Bile Duct

Cystic Bile Duct Dilatations and Caroli’s Disease

2015 ◽  
pp. 111-127
Author(s):  
Felice Giuliante ◽  
Agostino Maria De Rose ◽  
Gennaro Nuzzo
Keyword(s):  
Bile Duct ◽  
Caroli's Disease ◽  
Caroli’S Disease

scholarly journals Caroli’s disease: a diagnostic challenge

2018 ◽  
Vol 5 (11) ◽  
pp. 3750
Author(s):  
Padmini Yadav ◽  
Shailesh Adhikari ◽  
Narendra Pandit ◽  
Lalijen Awale ◽  
Keerthi Vasan ◽  
...  
Keyword(s):  
Bile Duct ◽  
Open Cholecystectomy ◽  
Poor Performance ◽  
Left Lobe ◽  
Tube Placement ◽  
Diagnostic Challenge ◽  
Caroli's Disease ◽  
Caroli’S Disease ◽  
T Tube ◽  
Intrahepatic Bile Ducts

Caroli’s disease is a rare congenital hepatobiliary disease characterized by multifocal segmental dilatation of intrahepatic bile ducts affecting all or parts of the liver. It predisposes to biliary stasis and consequent lithiasis, cholangitis, abscesses, and septicemia. Sometimes it is difficult to diagnose and differentiate it from other similar disease conditions. 60-year-old female presented with features of recurrent cholangitis with hepatolithiasis and multiple cyst in liver, cholelithiasis was planned for cholecystectomy and drainage procedure. Patient underwent open cholecystectomy with common bile duct (CBD) exploration with T-tube placement due to intraoperative instability. Post-operative T tube cholangiogram was done. Post-operative T tube cholangiogram showed bilobar major duct cystic dilatation with predominant left lobe involvement, with few cysts containing calculi. Patient was planned for left hepatectomy with bile duct excision but patient refused to undergo aforementioned surgery. Therefore ERCP and sphincterotomy was done in view of poor performance status.Caroli’s disease being a rare disease is sometimes difficult to diagnose and treat in an old age patient with bilobar involvement and poor general conditions.

Cl−-dependent secretory mechanisms in isolated rat bile duct epithelial units

2001 ◽  
Vol 281 (2) ◽  
pp. G438-G446 ◽  
Author(s):  
Satish K. Singh ◽  
Albert Mennone ◽  
Alessandro Gigliozzi ◽  
Flavia Fraioli ◽  
James L. Boyer
Keyword(s):  
Bile Duct ◽  
Intrahepatic Bile Duct ◽  
Fluid Secretion ◽  
Intracellular Camp ◽  
Camp Concentration ◽  
Uptake Pathway ◽  
Duct Epithelium ◽  
Bile Duct Epithelium ◽  
Rat Bile ◽  
Intracellular Camp Concentration

Cholangiocytes absorb and secrete fluid, modifying primary canalicular bile. In several Cl−-secreting epithelia, Na+-K+-2Cl− cotransport is a basolateral Cl− uptake pathway facilitating apical Cl− secretion. To determine if cholangiocytes possess similar mechanisms independent of CO2/HCO[Formula: see text], we assessed Cl−-dependent secretion in rat liver isolated polarized bile duct units (IBDUs) by using videomicroscopy. Without CO2/HCO[Formula: see text], forskolin (FSK) stimulated secretion entirely dependent on Na+ and Cl−and inhibited by Na+-K+-2Cl−inhibitor bumetanide. Carbonic anhydrase inhibitor ethoxyzolamide had no effect on FSK-stimulated secretion, indicating negligible endogenous CO2/HCO[Formula: see text] transport. In contrast, FSK-stimulated secretion was inhibited ∼85% by K+ channel inhibitor Ba2+ and blocked completely by bumetanide plus Ba2+. IBDU Na+-K+-2Cl− cotransport activity was assessed by recording intracellular pH during NH4Cl exposure. Bumetanide inhibited initial acidification rates due to NH[Formula: see text] entry in the presence and absence of CO2/HCO[Formula: see text]. In contrast, when stimulated by FSK, a 35% increase in Na+-K+-2Cl− cotransport activity occurred without CO2/HCO[Formula: see text]. These data suggest a cellular model of HCO[Formula: see text]-independent secretion in which Na+-K+-2Cl−cotransport maintains high intracellular Cl−concentration. Intracellular cAMP concentration increases activate basolateral K+ conductance, raises apical Cl−permeability, and causes transcellular Cl− movement into the lumen. Polarized IBDU cholangiocytes are capable of vectorial Cl−-dependent fluid secretion independent of HCO[Formula: see text]. Bumetanide-sensitive Na+-K+-2Cl− cotransport, Cl−/HCO[Formula: see text] exchange, and Ba2+-sensitive K+ channels are important components of stimulated fluid secretion in intrahepatic bile duct epithelium.

scholarly journals Inhibition of Intrahepatic Bile Duct Dilation of the Polycystic Kidney Rat with a Novel Tyrosine Kinase Inhibitor Gefitinib

2006 ◽  
Vol 169 (4) ◽  
pp. 1238-1250 ◽  
Author(s):  
Yasunori Sato ◽  
Kenichi Harada ◽  
Shinichi Furubo ◽  
Kazuo Kizawa ◽  
Takahiro Sanzen ◽  
...  
Keyword(s):  
Bile Duct ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Intrahepatic Bile Duct ◽  
Polycystic Kidney
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