Secretion of Bile Acids by the Liver and Their Role in the Formation of Hepatic Bile

Wheeler, Henry O.

doi:10.1001/archinte.1972.03650040063006

Cited by 74 publications

(13 citation statements)

References 70 publications

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“…In addition to the disease, two other shortcomings should be considered: the postoperative alterations in biliary function, and the interruption of the enterohepatic circulation. Postoperative alterations in biliary function were reflected in our study by a low bile flow from the 2nd to the 6th postoperative days; a low flow has already been observed in the early postoperative period in man (8,9) and in the rhesus monkey (10); in the rhesus monkey, the decreased flow was associated with a decreased secretion of bile acids, phospholipids and cholesterol and returned to normal within 2 weeks (10). In man, biliary function has been considered to return to normal within approximately one week (8, 1 1 , 12); this is in agreement with the stabilization of bile flow 7 days after oDeration in our patients and representative days have been included.…”

Section: Discussionmentioning

confidence: 99%

Canalicular Bile Production in Man*

Prandi

Erlinger

Glasinovic

et al. 1975

Eur J Clin Investigation

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Bile flow, erythritol clearance (measured after administration of 14-C-erythritol) and bile acid excretion were studied in 8 non-icteric patients operated upon for gallstone disease without biliary obstruction in whom a T-tube had been inserted. Bile flow increased from the 2nd (0.27 plus or minus SEM 0.01 ml/min) to the 7th (0.50 plus or minus SEM 0.05 ml/min) postoperative days and remained stable thereafter. Because the values obtained between the 7th and the 15th postoperative days (average: 0.46 plus or minus SEM 0.02 ml/min) were not lower and were of the same order of magnitude as those previously reported in the literature for quantitative bile collections, it was assumed that bile collection had been complete. Bile-to-plasma concentration ratio of erythritol was 0.77 plus or minus SEM 0.04. The regression line between erythritol clearance and bile flow had a slope of 0.99 (indicating that increments in clearance were followed by equivalent increments of flow) and an intercept for a zero-clearance of 0.11, suggesting a ductular/ductal secretion of 0.11 ml/min. The relationship between erythritol clearance and bile acid excretion suggested that canalicular bile was formed both of a bile acid-dependent flow (11 mul of water being excreted per mumol of bile acid secreted) and a bile acid-independent flow of 0.16 ml/min (or 35 percent of the average bile flow). These findings indicate that erythritol clearance provides a valid estimate of canalicular bile flow in man and that the three bile fractions previously postulated in animals (canalicular bile acid-dependent, canalicular bile acid-independent and ductular/ductal) may also be present in man.

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Section: Discussionmentioning

confidence: 99%

Canalicular Bile Production in Man*

Prandi

Erlinger

Glasinovic

et al. 1975

Eur J Clin Investigation

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“…This is the purpose of the present review. The excellent reviews by Wheeler (174,175) and a later comprehensive summary by FORKER Erlinger (46) should be consulted for a detailed review of earlier work.2 The empha sis here is on recent developments.…”

Section: Introduction +1174mentioning

confidence: 99%

Mechanisms of Hepatic Bile Formation

Forker¹

1977

Annu. Rev. Physiol.

163

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It should be evident from this review of recent investigations that we are still very far from a consistent description of bile formation, much less a satisfactory understanding. Nevertheless certain broad conclusions emerge. Four distinct kinds of active solute transport can be identified, and because bile always has nearly the same osmotic pressure as plasma, each of them is a determinant of bile flow. 1. Concentrative transport of water-soluble organic constituents, of which bile acids are quantitatively most important, occurs in the canaliculi accompanied by the passive flow of water and inorganic electrolytes. Owing to micelle formation the osmotic force for this flow is largely attributable to Na+ ions that accompany the bile acids anions. 2. The canalicular flow obligated by the excretion of bile acids is supplemented by the entry of additional fluid, the so-called bile acid-independent canalicular fraction. Because no organic component has been identified to account for this phenomenon, the active transport of one or more inorganic ions is probably responsible. The limited evidence available at present suggests that Na+ ions is the most likely candidate. 3. The extralobular biliary epithelium can modify the flow and composition of bile by the reabsorption of inorganic ions--a process which resembles reabsorption from the gallbladder in the sense that bile in the lumen remains iso-osmotic with plasma while bile acids and the other organic constituents are concentrated. 4. Under the influence of secretin, and to a lesser degree other intestinal hormones, the ducts or ductules can secrete additional fluid in which HCO3- is concentrated with respect to plasma. A fifth component of bile is generated by the canalicular excretion of phospholipid and cholesterol, but these are insoluble in water and are incorporated into micelles, and, therefore exert no osmotic force. The existence of these processes is inferred from studies of many different species, and it should be emphasized that the picture is a composite one. For example, distal fluid reabsorption has been convincingly demonstrated only in dogs and monkeys, and secretin is not a choleretic in rats or rabbits. It should also be clear that the actual mechanisms of solute transport remain poorly defined. Thus the term active transport in the present context should be thought of in its general thermodynamic sense rather than as denoting any particular transport mechanism. For the future, the most pressing problems are methodologic. To mention only three that seem especially important: ways must be found to sample bile closer to its origin; the proper interpretation of studies with isolated liver cell membranes will require unambiguous methods to certify their source; and descriptions of transport kinetics must somehow be refined to reflect the effective intracellular concentration of solutes as well as their distribution within the liver lobule.

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“…The relative contribution of canalicular and ductular bile flow has major species-related differences. Bile flow is largely canalicular in rodents [87], whereas it is evenly divided among BSDF, BSIF and ductular bile flow in humans [88].…”

Section: Physiological Mechanisms Of Bile Formationmentioning

confidence: 99%

Silymarin as a New Hepatoprotective Agent in Experimental Cholestasis: New Possibilities for an Ancient Medication

Crocenzi¹,

Roma²

2006

CMC

100

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Silymarin is a purified extract from milk thistle (Silybum marianun (L.) Gaertn), composed of a mixture of four isomeric flavonolignans: silibinin (its main, active component), isosilibinin, silydianin and silychristin. This extract has been empirically used as a remedy for almost 2000 years, and remains being used as a medicine for many types of acute and chronic liver diseases. Despite its routinely clinical use as hepatoprotectant, the mechanisms underlying its beneficial effects remain largely unknown. This review addresses in detail a number of recent studies showing a novel feature of silymarin as a hepatoprotective drug, namely: its anticholestatic properties in experimental models of hepatocellular cholestasis with clinical correlate. For this purpose, this review will cover the following aspects: 1. The chemistry of silymarin, including chemical composition and properties. 2. The current clinical applications of silymarin as a hepatoprotective agent, including the mechanisms by which silymarin is thought to exert its hepatoprotective properties, when known. 3. The physiological events involved in bile formation, and the mechanisms of hepatocellular cholestasis, focusing on cellular targets and mechanisms of action of drugs used to reproduce experimentally cholestatic diseases of clinical interest, in particular estrogens and monohydroxylated bile salts, where anticholestatic properties of silymarin have been tested so far. 4. The recent findings describing the impact of silymarin on normal bile secretion and its novel, anticholestatic properties in experimental models of cholestasis, with particular emphasis on the cellular/molecular mechanisms involved, including modulation of bile salt synthesis, biotransformation/depuration of cholestatic compounds, changes in transporter expression/activity, and evocation of signaling pathways.

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Secretion of Bile Acids by the Liver and Their Role in the Formation of Hepatic Bile

Cited by 74 publications

References 70 publications

Canalicular Bile Production in Man*

Canalicular Bile Production in Man*

Mechanisms of Hepatic Bile Formation

Silymarin as a New Hepatoprotective Agent in Experimental Cholestasis: New Possibilities for an Ancient Medication

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