Intact Enterohepatic Circulation Research Articles

The effect of gastric antral stimulation upon the secretion of hepatic bile.

SummarySeven dogs were prepared with completely separated vagally denervated antral pouches, gastrojejunostomy, and cholecystectomy. A duodenal cannula was placed opposite the opening of the common bile duct in each animal. In 3 of these dogs, a Heidenhain pouch was also constructed whereas in the other 4 animals a gastric cannula was placed in the ventral wall of the stomach. Biliary volume and composition were studied by catheterization of the common bile duct during constant i.v. infusion of 2% sodium taurocholate to maintain an intact enterohepatic circulation of bile salts. In the dogs with Heidenhain pouches or when the gastric cannula was closed, perfusion of the antral pouch with buffered 4% choline chloride solution at pH 7.5, caused highly significant increases in biliary volume, HCO3 concentration and output, Cl concentration and output and total outputs of Na, K, bile salts, and bile solids. The concentration of Na and K was unchanged but the concentration of bile salts and solids was decrease...

Importance of Bile Acids and of an Intact Distal Small Intestine for Fat Absorption

Summary 1.The enterohepatic recirculation of sodium taurocholate-24-C 14 was studied in 2 volunteer medical students and 2 patients with disorders of the distal small intestine. One patient had a jejunocolic fistula created surgically for the management of obesity, and the other had irradiation for a carcinoma of the cervix. 2.In the normal subjects, the exponential decline in specific activity, counts per minute per milligram, of sodium taurocholate-C 14 in duodenal samples permitted estimation of the kinetics of the enterohepatic circulation. These observations, when compared with previous investigations, suggest that approximately 30% of the cholate pool in normal man consists of cholic acid conjugated with taurine. 3.Significant steatorrhea was demonstrable in both patients. However, their proximal small intestine appeared normal from morphological and biochemical studies. The Schilling test was abnormal in both patients. 4.A virtual absence of enterohepatic recirculation for sodium taurocholate-C 14 was demonstrated in 2 patients. In addition, recirculation of unconj ugated or newly conjugated cholate-C 14 was negligible. 5.These experiments demonstrate clearly the importance of the distal small intestine in maintaining the enterohepatic recirculation of sodium taurocholate. They also point up the importance of an intact enterohepatic circulation of bile salts to the over-all process of lipid absorption in man.

The Effect of Bile Duct Ligation, Bile Duct Cannulation, and Hypothermia on α-Naphthylisothiocyanate-Induced Hyperbilirubinemia and Cholestasis in Rats

The hyperbilirubinemic and cholestatic responses to alpha-naphthylisothiocyanate (ANIT) in the rat were altered by subjecting test animals to various environmental and surgical manipulations. Studies utilizing hypo- and hyperthermic conditions showed that a positive correlation exists between the rectal temperature and the effects of ANIT. In addition, it was observed that ANIT produced an apparent poikilothermic response, in that treated rats were unable to maintain normal rectal temperatures. Bile duct ligation inhibited the cholestatic and altered the hypothermic responses to ANIT treatment. Cannulation of the bile duct prior to ANIT administration significantly inhibited the hyperbilirubinemia and cessation of bile flow. These data demonstrate the importance of an intact enterohepatic circulation and normal body temperature in the actions of ANIT. The effect of the various parameters on the ANIT-induced hyperbilirubinemia and cholestasis suggests the involvement of a biotransformation product of ANIT.

On the Formation of Hyodeoxycholic Acid in the Rat: BILE ACIDS AND STEROIDS 154

1. Lithocholic acid-24-14C was administered to rats and labeled hyodeoxycholic acid was isolated from feces and from bile collected after 3 days of intact enterohepatic circulation. Labeled 3α-hydroxy-6-keto-5β-cholanoic acid was isolated from feces. No labeled hyodeoxycholic acid was formed when lithocholic acid-24-14C was administered to bile fistula rats. One of the major metabolites in these experiments was 3α,6β-dihydroxy-5β-cholanoic acid. 2. After administration of 3α,6β-dihydroxy-5β-cholanoic acid-24-14C to intact rats, labeled hyodeoxycholic acid was isolated from feces and bile. Labeled 3α-hydroxy-6-keto-5β-cholanoic acid was isolated from feces. In the bile fistula rat, 3α,6β-dihydroxy-5β-cholanoic acid-24-14C was metabolized mainly into β-muricholic acid and no labeled hyodeoxycholic acid was formed. 3. In the intact rat, 3α-hydroxy-6-keto-5β-cholanoic acid-24-14C was transformed mainly into hyodeoxycholic acid, whereas in the bile fistula rat 3α,6β-dihydroxy-5β-cholanoic acid was the main metabolite. 4. It was suggested that hyodeoxycholic acid is formed from lithocholic acid through the following reactions Lithocholic acid (liver)/→ 3α,6β-dihydroxy-5β-cholanoic acid (intestine)/→ 3α-hydroxy-6-keto-5β-cholanoic acid (intestine)/→ hyodeoxycholic acid