Biliary Bile-Acid Composition

When the proportion of biliary DCA, expressed as a percentage of total bile acids, was measured in the same three groups of individuals in the Octreotide studies, a similar pattern of results was found to that described above for bile lipids - namely, low values (approximately 12%) in the so-called controls and significantly higher values (approximately 24%) in the two groups of stone carriers.  

11 The Adverse Effects of Increased Proportions of DCA in Bile on Cholesterol Gallstone Formation 

There are multiple ways by which an increase in the percentage DCA in bile may pre-dispose to cholesterol gallstone formation. Carulli et al. showed that DCA-rich bile induces biliary cholesterol hyper-secretion when compared with other bile acids (Graph 8.6). This is likely to be due to the greater hydro-phobicity and detergent efiect of DCA, which would be able to solubilise the lipids in the canalicular cell wall more readily. It may well explain why there have been linear relationships demonstrated between the percentage DCA in bile and (i) the mole percentage cholesterol and (ii) the cholesterol saturation index in bile. This may also explain why there is a link between the 

Graph 8.5 Paired data for the proportion of DCA (percentage of total bile acids) in bile before and during Octreotide treatment (SOOpg/day for 8 months). Data taken from reference 18. 

Graph 8.6 DCA, deoxycholic acid CDCA, chenodeoxycholic acid CA, cholic acid UDCA, ursodeoxycholic acid. Data taken from reference 24. 

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Trautwein, E. A., Rieckhoff, D., Kunath-Rau, A., and Erbersdobler, H. F. (1998). Psyllium, not pectin or guar gum, alters lipoprotein and biliary bile acid composition and fecal sterol excretion in the hamster. Lipids 33, 573-582. 

Samples of gallbladder bile obtained in this way were analysed for bile acids, phospholipids and cholesterol (from which the cholesterol saturation indices were derived). Biliary bile-acid composition was then measured by HPLC. The vesicles were separated from micelles by sucrose density gradient ultra-centrifugation and the cholesterol microcrystal nucleation time measured as described above. 

This specifity for cholate or its conjugates on cholesterol absorption has also been demonstrated by modification of biliary bile acid composition by hormonal perturbations (see[40]). For example, in hypothyroid rats, there is a diminished biliary output of bile acids[41], and a shift in the ratio of biliary cholate and cheno-deoxycholate. This ratio is approximately 3 1 cholate to cheno-deoxycholate in normal rats and is shifted dramatically (9 1) in hypothyroid rats[42]. As might be expected, this hormonal deficiency results in multiple alterations in overall physiology, among which are hypercholesterolemia and increased absorbability of choles-terol[40]. Conversely, administration of thyroid hormones (L-thyroxine or triiodothyronine) results in diminished levels of biliary cholate, and proportional increases in chenodeoxycholate. 

Effects of dietary cholesterol and L-thyroxine on biliary bile acid composition and secretory rate, and on plasma, liver and bile cholesterol levels in rats, Endocrln.Jap., 17 107 (1970). 

For a given bile salt lecithin ratio the interfacial resistance decreases with increasing BS concentration and in the experience of Kwan and coworkers cheno-rich bile dissolves Ch three times as fast as bile with normal biliary bile acid composition. 

Crosignani, A., Podda, M., Battezzati, P.M., Bertoilnl, E., Zuin, M., Watson, D., Setchell, K.D.R. Changes in bile acid composition in patients with primary biliary cirrhosis induced by ursodeoxycholic acid administration. Hepatology 1991 14 1000-1007... 

The hydrolysis of bile acid conjugates is probably the initial reaction catalyzed by intestinal bacteria. Therefore, primarily free bile acids are isolated from the feces of man and animals [1-5]. The bulk of the free bile acids in feces of man is deoxycholic acid and lithocholic acid which are generated by the 7 -dehydroxylation of cholic acid and chenodeoxycholic acid, respectively. A portion of fecal acids is absorbed from the intestinal tract, returned to the liver where they are conjugated and again secreted via biliary bile. Therefore, the final composition of biliary bile acids is the result of a complex interaction between liver enzymes and enzymes in intestinal bacteria. 

The liver secretes about 1 L of bile daily. Bile flow and composition depend on the secretory activity of the hepatic cells that line the biliary canaliculi. As the bile flows through the biliary system of ducts, its composition can be modified in the ductules and ducts by the processes of reabsorption and secretion, especially of electrolytes and water. For example, osmotically active compounds, including bile acids, transported into the bile promote the passive movement of fluid into the duct lumen. In the gallbladder, composition of the bile is modified further through reabsorptive processes. 

PBS and gently blotted to remove blood and tissue fluids, then suspended over the lip of a small (250 pi) microcentrifuge tube and punctured with a needle to allow the bile to drain into the tube. Store frozen until assay. There is usually enough material to measure lipid composition (bile acids, cholesterol, phospholipids) with standard colorimetric kits (<1 pi needed for each assay). In addition to biliary cholesterol levels, it is important to take note of bile salt concentrations, since these are the detergents which suspend dietary lipids in micelles and deliver them to the intestinal epithelium for absorption by enterocytes. Differences in bile salt concentration alone could lead to differences in cholesterol absorption. 

There is a large production of hepatic lymph which appears to arise by passage of fluid from the perisinusoidal space, from bile duct area and in the portal tract area (A12). It has been suggested that blood, lymph, and bile enter into an equilibrium in the portal tract (Review article, 2). The lymphatics could also act as a transport system between the liver lobule and the biliary epithelium (All). A detailed study of the relative concentrations of BSP and its metabolites in lymph, bile, and plasma indicated that the composition of lymph differs from that of bile and plasma (K20). Thus, it seems unlikely that lymphatics were the transport system for BSP from liver cells to bile. During biliary stasis there is a rapid rise in lymphatic BSP levels (B32, G12) and the relative concentrations of BSP metabolites approach those found in bile (K20). On ligation of the bile duct the level of bilirubin and bile acids in lymph also rises (G12) as does the plasma level of BSP (BIO) and rose bengal (B22). 

Deoxycholic acid is present in substantial amounts only in mammalian bile. It is a bacterial artifact produced from cholic acid during enterohepatic circulation and is not formed by the liver. The first observations of bacterial contribution to biliary composition were made in studies with deoxycholic acid (105, 106). The absence of this acid from rabbit fistula bile was observed as early as 1930 (107) but the importance of bacterial metabolites in the composition of bile was not appreciated until discovered by the Swedish workers (108). Several other bile acids have now been recognized as secondary, resulting from similar alterations in the gut during enterohepatic circulation rather than from hepatic biosynthesis (4, 9). 

The effects of diets and/or of bile acid sequestrants on plasma lipid levels is well established (1,2) The role of changes in the biliary composition in eliciting the lipoprotein changes is, however, less clear. Object of this report will be to describe the pattern of abnormalities of bile acid (BA) composition in hyperlipoproteinemic patients moreover, the effects of different diets (high polyunsaturates high fiber soy proteins) and of BA sequestrants will be evaluated. 

Vitamins K and Kj are absorbed by an active process in the proximal small intestines. Bile of normal composition is necessary to facilitate the absorption. The bile component principally concerned in the absorption and transport of fat-soluble vitamin K from the digestive tract is thought to be Jcoxycholic acid. The molecular compound of vitamin K with deoxycholic acid was effective on oral administration to rats with biliary fistula. Vitamin K is absorbed through the lymph in chylomicrons. It is tran.sportcd to the liver, where it is concentrated, but no significant storage occurs. 

At the same time the pancreatic enzymes start the cleavage of triglycerides (to mono, diglycerides and fatty acids), of cholesterol esters and of lecithin (to lysolecithin and fatty acids). As the digestion progresses bile is diluted and micelles enlarge since they include the products of lipolysis thus, intestinal micelles are markedly different, in size and composition, from biliary micelles. 

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