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Citrate, a calcium chelator, was found to be a regular component of bile in the majority of patients with cholelithiasis. The elevation of citric acid levels was investigated in patients with indwelling T-tubes that were indicative of bile duct exploration for retained bile duct stones following cholecystectomy. The concentration of citrate in gallbladder bile in patients at cholecystectomy was variable. The mean (SEM) 95% confidence interval (CI) concentration in gallbladder bile was 57.8 (4.9) 48.2-67.3 with a range of 0-406 ,moles 1^sup -1^-, and in bile duct bile was 39.6 (11.2) 17.5-61.6 with a range of 0-200 (mu)moles 1^sup -1^. Gallbladder or common duct bile infected with bacteria with at least one species with a CFU of >= 10^sup 5^ recorded significantly lower citrate concentrations. It was not possible in this study significantly to infer that gallbladder bile associated with a particular stone type had an increased or decreased citric acid content. In 7 of 12 patients with indwelling T-tubes owing to choledocholithiasis, an oral citric acid load significantly increased T-tube bile citrate concentrations. This significant outcome prompted the possibility of manipulating citrate levels in bile and the further study of citrate use as an adjuvant in bile acid dissolution of calcified gallstones. Moreover, it is hypothesized that citrate may constitute a naturally occurring anionic chelator of ionized calcium in bile which, when increased in bile and used concurrently with diet management in selected gallstone patients, may augment bile salt dissolution and prevent stone recurrence.
Keywords: bile, calcium, chelator, citrate.
INTRODUCTION
It has been over half a century since citrate was shown to form soluble complexes with calcium [1]. It is a potent complex-forming anion of calcium cations [2]. Citrate is a known inhibitor of the crystallization process of stone-forming calcium salts (oxalate, phosphate) in urine. Moreover, it has also been shown that citrate can inhibit the precipitation of calcium oxalate and calcium phosphate [3-5]. It does so in urine by reducing the urinary saturation of calcium by chelation, thus inhibiting calcium salt nucleation, deposition and crystal growth [6]. Citrate excretion has also been investigated in pancreatic juice. Citrate has been shown to dissolve calcified pancreatic stones both in vitro and in vivo [7, 8].
We have documented the presence of citrate in...