Cholesterol gallstone disease

When Reuben et al., measured the hourly secretion rates of phospholipids, bile acids and cholesterol in obese and nonobese individuals with and without cholesterol gallstone disease, they found that the pattern of results was quite different in the obese and the nonobese gallstone carriers. The obese had hypersecretion of cholesterol but normal bile-acid output, while the nonobese had normal cholesterol secretion but a reduced bile-acid output. The authors speculated that the most likely explanation for the high biliary cholesterol secretion rates in the obese was their increased total body cholesterol synthesis. Conversely, nonobese gallstone carriers often have a reduced total bile-acid pool size, and if the enterohepatic cycling frequency of this small bile-acid pool remains unchanged (controversial), it could explain the reduced bile-acid secretion rate seen in the normal weight (nonobese) individuals. 

This profile of changes was comparable to that seen in patients with conventional cholesterol gallstone disease, the only difference being that, as a result of OT, the chemistry probably developed in days or weeks, as opposed to months or years in the case of spontaneous gallstone formation. ... 

If more cholesterol enters the bile than can be solubilized by the available bile salts and phosphatidylcholine, cholesterol gallstone disease (cholelithiasis) can occur. This is generally caused by gross malabsorption of bile acids from the intestine, obstruction of the biliary tract, or severe hepatic dysfunction, leading to abnormalities in bile or bile salt production. 

A 53-year-old male patient with elevated levels of low-density lipoprotein (LDL) cholesterol, signs of premature cholesterol gallstone disease and substantially elevated triglycerides visited his physician for a follow-up to check his current status. The patient had received various statin, HMG-CoA-reductase inhibitors therapies for the past 2 years. However, after blood work done at this follow-up visit, complications had still not subsided. This patient has similar problems as two of his siblings. Which of the following best explains this patients dyslipidemia ... 

In London, the Guy s Hospital group d wished to see if they could extrapolate validly from OT-treated acromegalic patients to those with sporadic gallstone disease. They also wished to study further the mechanism whereby prolongation of colonic transit might influence DCA metabolism, biliary cholesterol secretion and saturation, and therefore the risk of cholesterol gallstone formation. To study this, Thomas et developed a working hypothesis... 

The initial steps in BA synthesis are characterised by the introduction of a hy-droxylic group in the la position, or in position 27, followed by another in the la position into the cholesterol nucleus. Both synthetic pathways (the neutral and the acidic pathways) possess a distinct microsomal 7-oxysterol hydroxylase, which is regulated by different genes. The most recently described disorder of BA synthesis is cholesterol 7a-hydroxylase deficiency, in which their decreased production through the classical pathway is partially balanced by activation of the alternative pathway. Cholesterol levels increase in the liver, with a consequent low-density lipoprotein hypercholesterolemia, and cholesterol gallstones may result, although there is no liver disease. In contrast, a defect in the conversion of 27-hydroxy-cholesterol to la,27-dihydroxy-cholesterol due to deficiency of the oxysterol 7a-hydroxylase specific for the alternate pathway, causes severe neonatal liver disease [8]. 

These drugs should be avoided in patients with hepatic or renal dysfunction. There appears to be a modest increase in the risk of cholesterol gallstones, reflecting an increase in the cholesterol content of bile. Therefore, fibrates should be used with caution in patients with biliary tract disease or in those at high risk such as women, obese patients, and Native Americans. 

Juzyszyn Z, Kurzawski M, Lener A, Modizejew-ski A, Pawlik A, Drozdzik M (2008) Cholesterol 7a-hydrolase (CYP7A1) C.-278 A>C promoter polymorphism in gallstone disease patients. Genet Test 12 97-100... 

The research areas covered by the Meeting are very wide, having to do with the liver and biliary pathophysiology, nutrition, gallstone disease and atherosclerosis prevention. Scientists from the major clinical and basic disciplines provided an update overview of the complex mechanisms regulating the biosynthesis and catabolism of cholesterol and the formation and metabolism of bile acids. 

Another experimental approach to gallstone therapy is the use of phenobarbital. In Rhesus monkeys it increases bile salt and phospholipid secretion into bile without significantly changing cholesterol secretion.98 Furthermore, it has been reported to decrease cholesterol saturation in hepatic bile in man.99 Phenobarbital s ability to decrease the relative cholesterol content in bile may allow dissolution of cholesterol gallstones after long-term therapy. Neither lecithin nor cholestyramine are effective in human gallstone disease.100... 

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