Severe cholestasis leads to vitamin D depletion without perturbing its C‐25 hydroxylation in the dog

• Published in: Hepatology (Baltimore, Md.) Md.), 1988-11, Vol.8 (6), p.1577-1585
• Main Authors: Plourde, Victor, Gascon‐Barré, Marielle, Willems, Bernard, Huet, P.‐Michel
• Format: Article
• Language: English
• Subjects: Animals; Bile Ducts - metabolism; Biological and medical sciences; Calcifediol - blood; Calcifediol - metabolism; Cholestasis - metabolism; Disease Models, Animal; Dogs; Female; Gastroenterology. Liver. Pancreas. Abdomen; Hydroxylation; Liver - anatomy & histology; Liver - metabolism; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Other diseases. Semiology; Vitamin D Deficiency - metabolism
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.1840080618

The role of the liver as a contributory factor in the vitamin D deficiency of cholestatic liver disease has been studied in vivo in dogs with chronic bile duct ligation, whereas controls underwent diversion of the bile flow through the urinary bladder via a choledococystostomy anastomosis. The hepatic extraction of vitamin D3 was evaluated by the multiple indicator dilution technique, and the formation of 25‐hydroxyvitamin D3 was assessed by directly sampling the hepatic effluent for up to 150 min after vitamin D3 administration. The serum and hemodynamic data indicate that dogs with chronic bile duct ligation had severe cholestasis and hepatocel‐lular injury; histologically, macronodular cirrhosis was present. Dogs with choledococystostomy anastomosis had normal livers and normal liver function. The data indicate that the absence of normal bile flow into the intestinal lumen led to a progressive depletion of vitamin D reserve in both animals with choledococystostomy anastomosis and those with chronic bile duct ligation. However, neither the hepatic fractional extraction of vitamin D3, its hepatic clearance nor its transformation into 25‐hydroxyvitamin D3 was significantly changed by chronic bile duct ligation. The results of the present studies indicate that the hepatic handling of vitamin D3 including its C‐25 hydroxylation, is well preserved in the presence of severe cholestasis. They also suggest that the state of vitamin D depletion which often accompanies chronic cholestatic liver disease can largely be accounted for by factors such as secondary malabsorption of the vitamin due to the absence of adequate amounts of bile salts in the intestinal lumen, or by other factors which seem independent of the hepatic metabolism of vitamin D.