摘要:

AbstractDifficulties in obtaining proper bile samples are due to inaccessibility of the biliary tree and to distortions induced by sampling methods. One must be cognizant of the effects of diet on bile secretion and gallbladder motility. Experimental methods which interrupt the enterohepatic circulation or alter the intestinal migrating myoelectric complex induce spurious changes in bile flow and composition. Biliary tract pressure‐flow relationships must be maintained or the gallbladder will be made functionless. Dead space errors lead to distortions unless studies are performed in the steady state, or dead space is measured and corrections are applied. Surgery has major effects on some parameters of interest, and animals should be allowed to recover when these are studied. The effect of the mixing of bile with other secretions in the duodenum must be considered when using bile‐rich duodenal fluid. For some parameters of bile secretion, mixing is unimportant but for others, special precautions for handling bile and interpreting results are requi

ISSN:0270-9139    

DOI:10.1002/hep.1840040802

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractA brief review is given of the chemistry of bile acids, emphasizing the relationship between chemical structure, physical properties and enterohepatic cycling of the major primary and secondary bile acids. Features of the enterohepatic circulation of primary and secondary bile acids in man are summarized. The effects of bile acid feeding on the composition of the enterohepatic circulation in man are reviewed. Methods for characterizing the enterohepatic circulation of bile acids in man are tabulated.

ISSN:0270-9139    

DOI:10.1002/hep.1840040803

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

ISSN:0270-9139    

DOI:10.1002/hep.1840040804

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractA major limitation in understanding bile formation has been technical. The liver and ductular epithelium are relatively inaccessible, necessitating indirect techniques of uncertain validity. This is well seen in attempts to define the role of electrolyte secretion in bile. It is widely agreed that bile salts stimulate a component of canalicular flow and that inorganic electrolyte secretion is stimulated by bile salts. The choleretic efficiency of a bile salt is directly related to the magnitude of the electrolyte effect. But there is no consensus regarding how and where bile salts stimulate electrolyte secretion. Some evidence points to a paracellular route by processes of solvent drag and diffusion. Other studies suggest stimulation of specific transcellular electrolyte pathways. It has been believed that canalicular bile salt‐independent bile flow is generated by active blood‐to‐bile electrolyte transport. Actually, available methods do not permit us to conclude with absolute certainty that there is canalicular bile salt‐independent flow, although there is considerable evidence for it. New studies suggest that electrolyte transport in this type of flow is passive and that flow is due to transport of organic anions. Ductular flow does seem to be due to active transport of electrolytes, particularly bicarbonate. Better and more direct techniques are required to settle the controversies in th

ISSN:0270-9139    

DOI:10.1002/hep.1840040805

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractThe secretory compartment for biliary lecithin and cholesterol secretion probably resides in the smooth endoplasmic reticulum of the hepatocyte. The secretory compartment for bile salts lies predominantly in the enterohepatic circulation which fluxes bile salts continuously through the smooth endoplasmic reticulum compartment and extracts lipids for secretion into bile. Most of bile lecithin is newly synthesized by the liver; most of bile cholesterol is derived from extrahepatic sources. Both cholesterol and lecithin secretion are coupled to bile salt secretion and describe output curves which can be fitted by rectangular hyperbolae: since bile salt secretion is a linear function of input, the relative proportions of cholesterol to bile salts plus lecithin in bile increase at low bile salt outputs. In health, an adequate bile salt (+ lecithin) secretion coupled with normal cholesterol secretion maintains the relative composition of bile in a stable state: fasting compositions usually lie within the micellar zone or metastable supersaturated zone of a triangular coordinate‐phase diagram plot. In cholesterol gallstone disease, mean bile salt (+ lecithin) secretion rates are subnormal and/or mean cholesterol secretion rates are supranormal, especially in the fasting state. If individuals are obese there is also enhanced hypersecretion of biliary cholesterol. Either or both secretory defects lead to an elevation and persistence of cholesterol supersaturation of bile. The physical state of the secreted lipids in bile is complex and fluctuant, and probably involves vesicle structures and mixed micelles at high water and cholesterol concentrations and predominantly micellar structures at low water and cholesterol concentrations. In lithogenic bile, the physical state, proportions and nucleation potential of the lipid aggregates are probably different. Further, the respective proportions of biliary mixed micelles and vesicles are probably influenced by the mean hydrophilicity of the bile salt poo

ISSN:0270-9139    

DOI:10.1002/hep.1840040806

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractBilirubin is a linear tetrapyrrole whose conformation is affected by internal hydrogen bonds formed between the carboxyl side chains and dipyrromethenone rings. Structural variations include: constitutional isomerism of the vinyl or carboxyethyl side chains, geometric isomerism of the methene bridges, tautomerism of the lactam groups, conformational rotations about the central methylene bridge and ionization of one or both carboxyl groups. Aggregation of the dianion into dimers and multimers may occur. The pKa' values of the two carboxyl groups are affected greatly by the environment and may differ widely in micellar solutions like bile. Solubility of bilirubin in water is less than 1 nMat pH = 7 and about 0.1μMat pH = 8. Nonetheless, it dissolves poorly in most lipid solvents, except for asymmetrical chloroalkanes. Hydrogen bond‐breaking solvents, especially dimethyl sulfoxide, are most effective in solubilizing bilirubin. In bile salt solutions, solubility of bilirubin is well above the concentrations of unconjugated bilirubin found in normal human gallbladder bile, and is impaired by lecithin but unaffected by cholesterol. At physiological pH in bile salt solutions, bilirubin is predominantly in its monoanion form that binds readily to the micelles. In such solutions, addition of physiological concentrations of calcium precipitates calcium bilirubinate, leaving residual bilirubin concentrations of up to 15μMin 50mMtaurocholate or close to the maximum bilirubin concentrations in normal bile. Studies in which disodium bilirubinate is dissolved in bile salt solutions and pH is adjusted to the physiological range reveal that metastable supersaturation with bilirubin may occur and that a mesophase may also form in the presence of lecithin, akin to that seen with cholesterol. These results form a basis for understanding the precipitation of calcium bilirubinate from bile during pigment gallstone format

ISSN:0270-9139    

DOI:10.1002/hep.1840040807

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractThe study of biliary proteins has grown enormously in the last 10 years. Although much has been recently learned about the nature, origin and hepatobiliary transport of these proteins, little is known of their function in bile or their effect on its physical state. This review will focus on description of the proteins and mechanisms by which they are secreted into bile.

ISSN:0270-9139    

DOI:10.1002/hep.1840040808

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractA critical step in the formation of cholesterol gallstones is nucleation (i.e., the formation of cholesterol monohydrate crystals from supersaturated bile). The rate of nucleation of cholesterol depends upon a critical balance between pronucleating and antinucleating factors in bile. Mucin, a high molecular weight glycoprotein secreted by the gallbladder and biliary duct epithelium, is a pronucleating agent in experimental and human gallstone disease. Gallbladder mucin shares with other epithelial mucins the ability to bind lipids and bile pigment. The hydrophobic binding sites in the polypeptide core of mucin may provide a favorable environment for nucleation of cholesterol monohydrate from supersaturated bile. In nearly all animal models of cholelithiasis, mucin hypersecretion is prominent. The stimulus for gallbladder mucin hypersecretion appears to be a component of lithogenic bile. Prostaglandins regulate mucin release in gallbladder epitheliumin vitroand probablyin vivo.In the cholesterol‐fed prairie dog, blockage of mucin release with aspirin inhibits gallstone formation. These findings suggest that inhibition of mucin release may prevent cholesterol stone formation during high‐risk periods or after dissolution therapy with bile sa

ISSN:0270-9139    

DOI:10.1002/hep.1840040809

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractWater and electrolyte absorption leading to increased intraluminal concentrations of lipids and other solutes comprise the primary physiologic effect of the gallbladder. The dynamics of entero‐hepatic circulation can lead to confinement of up to 60% of the bile acid pool within the gallbladder during prolonged fasting. This bile acid sequestration markedly reduces both the bile salt secretory rate and total solute concentration in comparison with the nonfasting state producing hepatic bile that is more than normally dilute especially in comparison with gallbladder bile. These conditions favor formation of small low‐density vesicles in hepatic bile which are more buoyant than the concentrated biliary micelles found in anatomically dependent regions of the gallbladder. Vesicle formation in hepatic bile may explain the “stratification” phenomenon often noted within the gallbladder. This observation could be accounted for by inhomogeneous mixing of the dissimilar lipid particles, i.e., vesicles and micelles. If vesicles are present and stratified as presumed, the overall cholesterol transporting capability of the total lipid particles, including these regionalized vesicles, would be considerably enhanced. The net effect of this process would lead to anoverestimationof the true degree of metastable cholesterol supersaturation for the biliary micellar system within the gallbladder on the incorrect assumption of homogeneous mixing of

ISSN:0270-9139    

DOI:10.1002/hep.1840040810

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractRecent research has suggested that self‐association of bile salts does not follow the micellar pattern of self‐association exhibited by typical flexible chain surfactants and detergents. A working model for the self‐association of bile salts is proposed. It includes a mild degree of cooperativity in the early stages of the growth of aggregates and coexistence of a number of aggregates of different aggregation numbers. The polydispersity implies an increase in the average aggregation number with increasing concentration of the bile salt. Bile salts can be purified by foam fractionation. Surface tension data for sodium cholate are in agreement with the above qualitative model of self‐association. An isoextraction method is useful for estimating monomer activities. Results for sodium deoxycholate suggest little self‐association in dilute solutions and a mildly cooperative self‐association at higher concentrations. A comparative study of the interactions of the fluorescent probe, 2‐p‐toluidinyl‐naphthalene‐6‐sulfonate, with sodium alkyl sulfates and sodium deoxycholate indicates that bile salts may differ significantly from classical micellar systems in their solubilization characteristics also. The evidence suggests strongly that a specific adduct formation with an optimum number of bile salt anions may be important in solubilization brought about by the rigidity and the complex shape of

ISSN:0270-9139    

DOI:10.1002/hep.1840040811

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY