The Importance of Conjugation with Glutathione for Sulfobromophthalein Sodium (BSP) Transfer from Blood to Bile*

Although elevated concentrations of serum bile acids have frequently been demonstrated in patients with liver disease (2, 3), little other information concerning the effect of hepatic impairment on the metabolism of these substances is known. Josephson (4), utilizing a nonisotopic intravenous cholic acid tolerance test, found that obstructive jaundice could be differentiated from hepatoparenchymal disease by increased retention of cholic acid in the serum 5 and 30 minutes after injection of a 0.5-g test dose. More recently, Carey (2) showed that the ratio of concentrations of serum trihydroxy-to dihydroxy-bile acid, rather than the absolute concentrations in patients with liver disease, may provide important diagnostic and prognostic information.In the present study, bile acid metabolism in human liver disease was further investigated after the intravenous injection of isotopically labeled cholic acid into patients with Laennec's cirrhosis and into normal subjects. Comparisons were then made of the first 60-minute plasma clearance of radioactivity, the rate of conjugation, and the late clearance of plasma cholic acid in both groups; finally, from these data and the plasma cholic acid concentration, cholic acid pool sizes and turnover rates were calculated in the cirrhotic group.

Section: Methodsmentioning

confidence: 86%

The metabolism of intravenously injected isotopic cholic acid in Laennec's cirrhosis.

Blum¹,

Spritz²

1966

“…In keeping with such a hypothesis is the fact that BSP is largely conjugated in the liver with glutathione (19), a process catalyzed presumably by a specific enzyme (20). Although it is established that conjugation is not essential to biliary excretion, the possibility cannot be excluded that conjugation in some way facilitates biliary transfer of the dye (21 (15). Nevertheless, the finding of a normal splanchnic blood volume suggests that the splanchnomegaly is associated with a relative reduction in the volume of actively circulating blood in the splanchnic bed.…”

Section: Discussionmentioning

confidence: 99%

Volumetric, hemodynamic, and excretory characteristics of the liver in acromegaly.

Preisig¹,

Morris²,

Shaver³

et al. 1966

Comprehensive autopsy studies (1, 2) have disclosed that enlargement of the viscera, including the heart, lungs, kidneys, pancreas, adrenals, and particularly the liver, is a prominent and consistent feature of acromegaly. The detailed structural changes responsible for visceromegaly in patients with this disease are poorly understood. Studies of the functional alterations of the hypertrophied organs are few and have been focused almost exclusively on the kidneys. Increased renal plasma flow, glomerular filtration rate, and proximal tubular functions have been demonstrated (3-5). It seemed reasonable, therefore, to expect that blood flow and excretory function of the liver might also be augmented.Precise appraisal of liver size by clinical examination alone is difficult; furthermore, evaluation of hepatic hyperfunction cannot be made with routine liver function tests. The introduction of methods for measurement of splanchnic blood flow and volume (6, 7) and for estimation of sulfobromophthalein (BSP) kinetics (8, 9) has made quantitative determination of hepatic function possible. Correlation of function with hepatic size is feasible owing to the development of techniques for quantification of "liver volume" (10).The results of such studies, carried out in 11 pa-

“…The removal of sulfobromophthalein sodium (BSP) from plasma and its excretion into bile involves hepatic uptake, storage, glutathione conjugation, and transport of the dye into the canaliculi (1)(2)(3)(4)(5). As in the case of other organic anions, such as bilirubin, fluorescein, and land, Ohio.…”

Section: Introductionmentioning

confidence: 99%

The effect of sodium taurocholate on the hepatic metabolism of sulfobromophthalein sodium (BSP). The role of bile flow

Boyer¹,

Scheig²,

Klatskin³

1970

A B S T R A C T The influence of bile salts on the hepatic metabolism of sulfobromophthalein sodium (BSP) was studied in the perfused rat liver. During sodium taurocholate infusions, hepatic uptake of BSP from plasma was increased and appeared to be related to an enhanced transit of BSP from liver into bile. BSP-glutathione conjugation was not affected by the bile salt infusions, although bile salts inhibited the enzyme system in vitro.The major effect of bile salts was to increase the BSP transport maximum (Tm). When sodium taurocholate was infused in saline at a rate of 30 /moles/hr, both bile flow and the BSP Tm increased, and remained at peak levels of 1.5 ±0.12 Al/min per g liver and 21 ±3.0 lg/min per g liver, respectively. In contrast, during saline infusion alone both levels were significantly lower (1.06 ±0.17 /Al/min per g liver and 15.8 ±4.16 .g/min per g liver, respectively), and both fell progressively after the 2nd hr of perfusion. This decline in bile flow and BSP Tm was associated with a decrease in biliary bile salt excretion and was reversed by adding bile salts to the perfusate. Since the biliary concentration of BSP remained within a narrow range in all experiments, the BSP Tm was primarily determined by the rate of bile flow.Dependence of BSP Tm on the rate of bile production was further confirmed by changing the temperature of the perfusate during a constant infusion of taurocholate. BSP Tm paralleled temperature-induced changes in bile flow irrespective of changes in the level of bile salt excretion.Since the biliary concentration of BSP remained within a narrow range in all experiments, the concen-