Studies on the sterol and lipid composition of bile

McAllister, Ronald Andrew (1972) Studies on the sterol and lipid composition of bile. MSc(R) thesis, University of Glasgow.

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Abstract

The initial stage of these investigations was concerned with estimates of the precision of analytical methods for the determination of phospholipids, cholesterol and bile salts in human and canine bile samples. During the course of these studies a new method for the determination of cholesterol was developed. This was based on the determination of the hexoses present in the side chain at C(3) in cholesterol digitonide, by means of the cysteine-sulphuric acid reaction. The procedure was found to give an approximate tenfold gain in sensitivity over the Sperry and Webb method, and was about six times more sensitivity than procedures using the anthrone reaction. Since bile samples in these investigations were stored in the frozen state, the effect of freezing and thawing on cholesterol solubilisation in bile was studied. Data were presented to show that considerable amounts of cholesterol were brought out of solution in gallbladder bile from patients with gallstones as a result of freezing and thawing. It was suggested that this finding might explain some of the discrepancies found in the literature. The first part of the thesis reported a study that was made of the supposed increased in the incidence of gallstone disease in patients who have undergone vagotomy. Initially it was shown that bile obtained by duodenal intubation following the injection of cholecystokinin was representative of gallbladder bile. This method was then used to obtain bile samples from a group pre-operative duodenal ulcer patients and pre-operative gallstone patients, the latter group serving as controls. Samples of bile so obtained were analysed from cholesterol, phospholipide and bile salts. When the relative compositions were plotted on phase diagrams, bile from gallstone patients lay close the limits of cholesterol solubility, whereas bile from pre-operative duodenal ulcer patients lay within the micellar zone. The determinations were then repeated on the duodenal ulcer patients after vagotomy and drainage. No significant changes could be found in bile from these patients in the 8 to 10 period after operation. This did not exclude the possibility of later changes in bile composition that might predispose to gallstone formation. In the second part of this thesis, a study was made of the sterol and lipid composition of hepatic and gallbladder bile in patients with diagrams, hepatic bile from these patients was found to be saturated with cholesterol, whereas gallbladder bile lay within the micellar zone. It was concluded that supersaturation of hepatic bile is not the sole factor responsible for the precipitation of cholesterol. Part 3 described a model for the study of bile flow in the dog. This permitted total diversion of bile composition were found to take place if ten per cent was sampled for chemical analysis. There was therefore no significant diversion of the enterohepatic circulation of bile salts. When the relative composition of canine gallbladder and hepatic bile were compared, the former was found to contain significantly more bile salts and significantly less phospholipid than the latter. There was no significant difference in the relative amounts of cholesterol. When these data were plotted on phase diagrams, both gallbladder and hepatic bile lay well within the micellar zone. This might explain why cholesterol gallstones are rare in dogs. The bile salt excretion and pool size were measured in dogs by a direct method. With the gallbladder intact, the pool size was 6.60 m-moles +/- S.E. 0.7. After cholecystectomy it was 4.6 m-moles +/- S.E. 0.3. From these values and measurement of the bile salt output it was calculated that in the cholecystectomised dog, the pool size circulated about 6 times per diem. The pool size was found to be large when compared with man and monkey. This might reflect differences in the eating habits of the different species. Patients with gallstones are reported to have a reduced bile salt pool. This was studied in dogs by measuring the bile salt pool before and after cholecystectomy. There was a significant reduction in the pool size. Since removal of the gallbladder reduces the storage space of the extra-hepatic biliary tree, it was concluded that in patients the presence of stones in the gallbladder may effectively reduce the pool size. This suggested that a reduced bile salt pool in gallstone patients may be a result and not a cause of the disease. The final part of the thesis elaborates on the clinical observations made in Part 1 in which studies were made on bile composition before and after vagotomy. Dogs with chronic biliary fistulae were used to study the effect of vagal stimulation by insulin hypoglycaemia. Data was presented to show that vagal stimulation by this means produced a water choleresis. This could be blocked by stropine either when given together with insulin, or one hour after insulin. This suggested that insulin choleresis is mediated via the vagus. Atropine was also shown to inhibit the secretion of bile salts, phospholipids and cholesterol. This observation was made here for the first time.

Item Type: Thesis (MSc(R))
Qualification Level: Masters
Additional Information: Adviser: A W Kay
Keywords: Biochemistry
Date of Award: 1972
Depositing User: Enlighten Team
Unique ID: glathesis:1972-72885
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Jun 2019 11:06
Last Modified: 11 Jun 2019 11:06
URI: http://theses.gla.ac.uk/id/eprint/72885

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