Morphologic, biophysical, and biochemical consequences of ligation of the common biliary duct in the dog.

Common biliary ducts of 32 adult mongrel dogs were ligated for a period of 2 days to 6 weeks. Sham-operated animals served as controls. Bile ducts were removed at sacrifice, and biophysical, morphologic, and biochemical parameters were measured. Our study shows that biliary duct ligation results in an immediate increase of intraductular pressure and is followed quickly by significant increase in the rate of collagen synthesis and the activity of prolyl hydroxylase. Histologic data show subepithelial inflammation followed by marked increases in periductular fibrosis. This fibroproliferative response is paralleled by peak levels of prolyl hydroxylase activity at 2 weeks prostligation. Paradoxically, bile ducts continuously distend throughout the ligation period despite increased fibroplasia. We present here the first topographic (SEM) study of normal and ligated common bile duct epithelium. Following 2 weeks of ligation large crater-like fenestrae are seen ductular epithelial surfaces. This is followed by focal epithelial sloughing. We speculate that the continuous distention and epithelial necrosis seen in the present study may be due to biliary stasis and/or subepithelial infiltration of bile through epithelial fenestrae. This hypothesis is supported by our studies which show that collagen extractibility is markedly increased by the addition of bile to the homogenate.