Bile Pigments of Jaundice*

Hoffman, Harry N.; Whitcomb, Fred F.; Butt, Hugh R.; Bollman, Jesse L.

doi:10.1172/jci104011

Cited by 41 publications

(14 citation statements)

References 19 publications

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“…The data in Table I confirm earlier reports that unconjugated bilirubin is found consistently in mammalian bile, as detected by the indirect diazo reaction (present paper, [49][50][51], solvent partition methods (52,53), or chromatographically as Pigment I (53)(54)(55)(56)(57), an equimolar complex of bilirubin and its diglucuronide (13,58,59). The presence of unconjugated bilirubin is not, as others have claimed (49,60,61), simply an artefact produced by hydrolysis of excreted conjugate, since: (a) in this investigation, indirect bilirubin was detected in biles collected freshly on ice and in the dark, conditions that virtually abolished in vitro hydrolysis of bilirubin conjugates; and (b) in an individual bile sample, the per cent of unconjugated bilirubin was unrelated to the rate of hydrolysis of conjugated bilirubin in vitro.…”

Section: Resultssupporting

confidence: 89%

Absorption of Bile Pigments by the Gall Bladder*

Ostrow¹

1967

J. Clin. Invest.

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Abstract. A technique is described for preparation in the guinea pig of an in situ, isolated, vascularized gall bladder that exhibits normal absorptive functions. Absorption of labeled bile pigments from the gall bladder was determined by the subsequent excretion of radioactivity in hepatic bile.Over a wide range of concentrations, unconjugated bilirubin-14C was well absorbed, whereas transfer of conjugated bilirubin proceeded slowly. Mesobilirubinogen-8H was absorbed poorly from whole bile, but was absorbed as rapidly as unconjugated bilirubin from a solution of pure conjugated bile salt.Bilirubin absorption was not impaired by iodoacetamide, 1.5 mm, or dinitrophenol, 1.0 mm, even though water transport was affected. This indicated that absorption of bilirubin was not dependent upon water transport, nor upon energy-dependent processes. The linear relationship between absorption and concentration of pigment at low concentrations in bile salt solutions suggested that pigment was transferred by passive diffusion. At higher pigment concentrations or in whole bile, this simple relationship was modified by interactions of pigment with bile salts and other constituents of bile. These interactions did not necessarily involve binding of bilirubin in micelles.The slow absorption of the more polar conjugates and photo-oxidative derivatives of bilirubin suggested that bilirubin was absorbed principally by nonionic, and partially, by ionic diffusion.Concentrations of pure conjugated bile salts above 3.5 mm were found to be injurious to the gall bladder mucosa. This mucosal injury did not affect the kinetics of bilirubin absorption.During in vitro incubation of bile at 370C, decay of bilirubin and hydrolysis of the conjugate proceeded as first-order reactions. The effects of these processes on the kinetics of bilirubin absorption, and their possible role in the formation of "white bile" and in the demonstrated appearance of unconjugated bilirubin in hepatic bile, are discussed.

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Section: Resultssupporting

confidence: 89%

Absorption of Bile Pigments by the Gall Bladder*

Ostrow¹

1967

J. Clin. Invest.

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“…fer from normal (14). It may be that the damaged cells are unable to excrete conjugated pigment I into the bile.…”

Section: Commentmentioning

confidence: 99%

Sulfate and Glucuronide Conjugates of Bilirubin in Experimental Liver Injury*

Schoenfield¹,

Bollman²,

Hoffman³

1962

J. Clin. Invest.

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Free, water-insoluble, indirect-reacting bilirubin is conjugated prior to excretion, predominantly as an ester monoglucuronide and a diglucuronide, forming the water-soluble, direct-reacting pigments I and II, respectively (1-6). The conjugation of bilirubin with glucuronic acid, in the presence of uridine diphosphate glucuronic acid which serves as a glucuronyl donor, is brought about by the enzyme, glucuronyl transferase. It has been shown that conjugated bilirubin also contains nonglucuronide conjugates (7-13).Isselbacher and McCarthy (12), using S35-labeled sulfate, identified bilirubin sulfate chromatographically and radioautographically in the bile of rats, cats, and humans and in the serum and urine of rats with ligated bile ducts. They observed that the enzymatic biosynthesis of bilirubin sulfate in vitro involves active sulfate and requires adenosine triphosphate. These same authors speculated that the proportions of glucuronide and sulfate conjugates might be altered in certain disease states.The present study was designed to investigate the relative proportions of glucuronide and sulfate conjugates of bilirubin of laboratory animals after hepatic injury. We also examined the relative proportions of pigments I and II under these same conditions (14). MATERIALS AND METHODSExperimental conditions. Male Wistar rats, weighing 250 to 300 g, were used. Each experimental group contained 6 animals except those groups used for study of bile from the isolated liver, each of which contained 4 animals. To accomplish acute injury, animals were exposed in a closed chamber to vapors of carbon tetrachloride of constant concentration (25 mg CC1, per 50 L air) for 7 hours. Bile fistulas were prepared by cannulating the common bile ducts with polyethylene catheters. The common bile duct was ligated securely with two ties of * Abridgment of thesis submitted by Dr. Schoenfield to the Faculty of the Graduate School of the University of Minnesota in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Medicine.4-0 braided silk and the duct was cut between the ties for studies of short (acute) obstruction (24 hours) and of prolonged obstruction (6 to 10 days). In one group acute obstruction was accomplished after exposure to CCl4. This was done to study the added effect of carbon tetrachloride injury on the plasma pigments inasmuch as the exposure alone did not produce jaundiced plasma. Rat liver perfusion preparations (15) were utilized in the study of pigments in bile produced by the isolated liver in response to acute CC14 injury.After bile fistulas were prepared in the control groups and in the other groups in which CC14 was given later, 100 tec inorganic radioactive sulfate (S3O,) in normal saline solution was injected intraperitoneally or into the isolated liver system. Bile was then collected for 5 hours on ice and in the dark. For study of the plasma pigments the radioactive-labeled sulfate was administered immediately after obstruction in the acute experiments and 24 hours prior to the ti...

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“…Although hepatectomy experiments [I, 6,7,10,[13][14][15] have shown that extrahepatic bilirubin production is possible, questions on origin and meta bolic distribution of bile pigment formed outside the liver have not been answered. Furthermore, the chemical structure of the bilirubin conjugated in nonhepatic tissues is only partially known [6,7,10,17,18].…”

Section: Discussionmentioning

confidence: 99%

“…Bilirubin formation out of the liver has been known since 1923 [13,14]; H o ffm a n et al [10] brought out the first evidence of extrahepatic conjuga tion. However, many aspects of this metabolic pathway are still unclear.…”

mentioning

confidence: 99%

“…However, many aspects of this metabolic pathway are still unclear. After total hepatectomy, the dogs develop moderate hyperbilirubinemia and bilirubinuria [1], Pigment I (bilirubin monoglucuronide) has been considered to be the main conjugated pigment in these animals [10], the remainder being unconjugated (UCB). Further studies [18] have favored the hypothesis that pigment II (bilirubin diglucuronide) is formed only within the liver, directly from bilirubin as well as from the extrahepatic pigment I.…”

mentioning

confidence: 99%

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Extrahepatic Bilirubin Formation and Conjugation in the Dog

Royer¹,

Noir²,

Sfarcich³

et al. 1974

Digestion

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After total hepatectomy in the dog, increased bilirubin concentrations were found in the circulating plasma or bound to tissues. Small amounts of the accumulated pigment were also excreted in the urine. Both unconjugated (UCB) and direct-reacting (DB) serum bile pigments increased significantly – especially after bilirubin loading. Analysis of the bile pigments in the serum and urine of hepatectomized dogs showed that approximately 10% of the conjugates were present as bilirubin xyloside and 25% as bilirubin glucoside. By performing an enterectomy and/or a splenectomy and also a nephrectomy, it was possible to demonstrate that the spleen, intestine, and kidney may be sites of bilirubin formation and conjugation in the hepatectomized dog.

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Bile Pigments of Jaundice*

Cited by 41 publications

References 19 publications

Absorption of Bile Pigments by the Gall Bladder*

Absorption of Bile Pigments by the Gall Bladder*

Sulfate and Glucuronide Conjugates of Bilirubin in Experimental Liver Injury*

Extrahepatic Bilirubin Formation and Conjugation in the Dog

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