Bile acid pool size in relation to functional status of gallbladder and biliary lipid composition in Chinese

Abstract

Bile acid pool size was measured in 10 Chinese without gallstones, 14 with pigment stones, and 10 with mixed stones by an isotope dilutin technique. Functional status of gallbladder was evaluated by intravenous cholecystogram and its gross appearance at surgery. Biliary lipid composition was also determined. The control subjects had a bile acid pool size comparable to that of Caucasians. Regardless of the nature of gallstones, bile acid pools of stone patients with functioning gallbladder were within normal range, whereas the pools of those with non- or poorly-functioning gallbladder diminished to about two-thirds of the control. Thus, the diminution of bile acid pool size was apparently the consquence of loss of storage function of gallbladder rather than the cause of production of lithogenic bile. The common bile duct bile obtained from stone patients with nonfunctioning gallbladder had a relatively high lithogenic index, at least partly related to its low total lipid concentration.

Gallbladder bile supersaturated with cholesterol in gallstone patients preferentially develops from shortage of bile acids

“…1, panel A2; Table 1). In line with these findings, 19–53% reduced GB mmol/l BA levels presented in patients with GSD in 12 of the 13 referred studies from 11 different countries, including Australia (28), Chile (15), China (21), Denmark (25), England (17), Germany (24), Japan (27), New Zealand (20), Pakistan (19), Sweden (12, 22), and USA (23, 26). GB mmol/l PLs were significantly reduced in five of the 13 referred studies (Table 1), while in the remaining eight studies, PLs were unaltered in GS patients.…”

Pathogenesis of cholesterol gallstones: a parsimonious hypothesis

“…Gallstone subjects on a high cholesterol diet demonstrate further contraction of their bile salt pools acutely [34], possibly because a greater fraction of hepatic bile is diverted into the duodenum as a result of augmented gallbladder motor dysfunction with further suppression of bile salt synthesis upon its return [89]. This was also demonstrated in humans with gall-stones and non-functioning gallbladders [88] and in fact in Chinese gallstone subjects [91] it was demonstrated as early as 1980 that, regardless of the category of stones (most had pigment gallstones), bile salt pools of patients with functioning gallbladders were within normal limits, whereas in stone patients with nonor poorly-functioning gallbladder the pools were diminished by about one-third. This was also demonstrated in humans with gall-stones and non-functioning gallbladders [88] and in fact in Chinese gallstone subjects [91] it was demonstrated as early as 1980 that, regardless of the category of stones (most had pigment gallstones), bile salt pools of patients with functioning gallbladders were within normal limits, whereas in stone patients with nonor poorly-functioning gallbladder the pools were diminished by about one-third.…”

“…As notable examples, when measured by isotope dilution in dogs, a contracted bile salt pool results from implantation of prosthetic gallstones in the gallbladder [90], as does sham cholecystostomy without implantation of a prosthesis [90]. Flying in the face of the prevailing paradigm at that time [16] Ho et al [91] concluded correctly that diminuation of bile salt pool size was the consequence of loss of gallbladder storage function rather than the cause of lithogenic bile production. Flying in the face of the prevailing paradigm at that time [16] Ho et al [91] concluded correctly that diminuation of bile salt pool size was the consequence of loss of gallbladder storage function rather than the cause of lithogenic bile production.…”

“…As notable examples, when measured by isotope dilution in dogs, a contracted bile salt pool results from implantation of prosthetic gallstones in the gallbladder [90], as does sham cholecystostomy without implantation of a prosthesis [90]. This was also demonstrated in humans with gall-stones and non-functioning gallbladders [88] and in fact in Chinese gallstone subjects [91] it was demonstrated as early as 1980 that, regardless of the category of stones (most had pigment gallstones), bile salt pools of patients with functioning gallbladders were within normal limits, whereas in stone patients with nonor poorly-functioning gallbladder the pools were diminished by about one-third. Flying in the face of the prevailing paradigm at that time [16] Ho et al [91] concluded correctly that diminuation of bile salt pool size was the consequence of loss of gallbladder storage function rather than the cause of lithogenic bile production.…”

Development of a mechanistic biokinetic model for hepatic bile acid handling to predict possible cholestatic effects of drugs

“…The bile acid synthesis rate was scaled to a million human hepatocytes. Ho et al described a bile acid pool of 0.136 mmol/kg body weight (Ho et al, 1980) in a 70 kg person with 1.5 kg of liver. This results in a bile acid synthesis rate of 0.22 pmol bile acid/min/g liver, which is 1.8 pmol bile acids/min/10 6 hepatocytes, assuming a hepatocellularity of 122 × 10 6 ·hepatocytes per gram liver (Arias, 1988;Wilson et al, 2003;Sohlenius-Sternbeck, 2006) (Arias, 1988;Sohlenius-Sternbeck, 2006;Wilson et al, 2003).…”