Overview of Bile Secretion

Hawkins

et al. 1997

Microsc. Res. Tech.

Although there is a large body of data on the gallbladder and the importance of the cystic duct in surgical procedures, there is insufficient data regarding the morphology of the human cystic duct. In the present study, transmission electron microscopic (TEM) and scanning electron microscopic (SEM) survey of several surgical and autopsy cystic ducts in cholelithiasis and cholesterolosis is reported. In cholelithiasis, similar to gallbladder epithelium, the cystic duct epithelial cells display minor‐to‐severe alterations of the epithelial surface accompanied by variable erosion of the epithelium. Areas of intact surface epithelium demonstrate microvilli‐covered cells coated by a rich glycocalyx and mucous production. In other areas, apical excrescences are associated with mucus hyperproduction and secretory events. Lipoid bodies are also present in many cells and especially in many of the cells' subluminal apical areas. In cholesterolosis, mucous secretory granules appear dilated, fatty deposits are infrequent, and peculiar intracellular cholesterol deposits can be detected in the apical and subapical region of cells and around condensed mitochondria. Following elective cholecystectomies, predominantly in association with cholelithiasis, eroded areas were detected; therefore, it appears that the action of intraluminal calculi may be a principal causative factor in discrete epithelial erosions of the cystic duct. Intraluminal calculi/debris, along with the alteration of mucus, cell sloughing, and a decreased pool of bile acids and motility may participate in the gallstone nucleation process. The peculiar cholesterol inclusions may also play a role in that nucleating process. Microsc. Res. Tech. 39:22–38, 1997. © 1997 Wiley‐Liss, Inc.

Section: Cholelithiasismentioning

confidence: 83%

Ultrastructural aspects of human cystic duct epithelium as a result of cholelithiasis and cholesterolosis

Hawkins

et al. 1997

Microsc. Res. Tech.

“…Bile consists mostly of water, and normal bile-water flow is necessary to keep small bile ducts open and to prevent the precipitation of biliary constituents so that flow is not Aquaporin-1 gene transfer improved cholestasis J Marrone et al obstructed. 22 Besides, biliary aqueous phase functions as the liquid vehicle for vesicles and micelles in bile to transport them to the intestine and thus permit their excretion. The function of biliary water is mostly self-protection 22 and therefore, a normal canalicular water transport would reduce the risk of bile secretory dysfunction.…”

Section: Resultsmentioning

confidence: 99%

Adenoviral transfer of human aquaporin -1 gene to rat liver improves bile flow in estrogen-induced cholestasis

et al. 2014

Estrogens can cause liver cholestatic disease. As downregulation of hepatocyte canalicular aquaporin-8 (AQP8) water channels has been involved in estrogen-induced bile secretory failure, we tested whether the archetypal water channel AQP1 improves 17α-ethinylestradiol (EE)-induced cholestasis. EE administration to rats reduced bile flow by 50%. A recombinant adenoviral (Ad) vector encoding human AQP1 (hAQP1), AdhAQP1, or a control vector was administered by retrograde bile ductal infusion. Hepatocyte canalicular hAQP1 expression was confirmed by liver immunostaining and immunoblotting in purified membrane fractions. Accordingly, canalicular osmotic water permeability was markedly increased. Bile flow, either basal or bile salt-stimulated was significantly augmented by over 50%. The choleretic efficiency of endogenous bile salts (that is, volume of bile per μmol of excreted bile salt) was significantly increased by 45% without changes in the biliary bile salt composition. Our data suggest that the adenoviral transfer of hAQP1 gene to the livers of EE-induced cholestatic rats improves bile flow by enhancing the AQP-mediated bile salt-induced canalicular water secretion. This novel finding might have potential therapeutic implications for cholestatic diseases.

“…In a few species – for example, the guinea pig – bicarbonate appears to be the dominant primary solute. Water and filterable solutes (plasma electrolytes, amino acids, glucose and short chain fatty acids) enter bile paracellularly by solvent drag; these molecules that enter bile passively have been termed ‘secondary solutes’ (4). This view of canalicular bile formation neglects the role of pericanalicular actin filaments that probably serve to drive canalicular bile into the biliary ductules (5).…”

mentioning

confidence: 99%

Cholestatic liver disease: pathophysiology and therapeutic options

Hofmann

2002

Liver

Cholestasis results from defective canalicular secretion of bile or obstruction to bile flow distal to the canaliculus. In early primary biliary cirrhosis, bile secretion continues, because of the secretory pressure of bile or because some ductules are not obstructed. With complete cholestasis, a bile acid deficiency occurs in the small intestinal lumen leading to lipid maldigestion and fat-soluble vitamin malabsorption. Bacterial proliferation, bacterial translocation to lymph nodes and endotoxemia may also occur leading to an acute phase reaction. Retention of bile acids in the hepatocyte leads to apoptosis. Accumulation of bile acids in the systemic circulation leads to pruritus, and may contribute to endothelial injury in the lungs and kidney. Early attempts to mimic hepatic excretory function by hemoperfusion over adsorbent columns were unsuccessful for a variety of reasons. Extracorporeal dialysis against albumin offers promise of a realistic albeit partial simulation of hepatic excretory function.