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

Abstract

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.

Factors Affecting Plasma Clearance of [14C]Cholic Acid in Patients with Cirrhosis

“…This study confirms a previous observation (Blum & Spritz, 1966) that cirrhotic patients clear ['4C]cholic acid more slowly from the intravascular compartment than do normal subjects. Since there is good evidence (Berson & Yalow, 1952) that for practical purposes intravascular mixing of a substance given by rapid intravenous injection is complete within 5 min, we chose to express serum radioactivity values as a percentage of the amount of radioactivity present in serum 5 min after radioisotope injection.…”

“…concentrations are elevated (Rudman & Kendall, 1957;Osborn, Wootton, da Silva & Sherlock, 1959;Sandberg, Sjovall, Sjovall & Turner, 1965), the ratio of trihydroxy to dihydroxy bile acids in the serum is reduced (Carey, 1958), urinary excretion of bile acids is increased (Gregg, 1968;Blum & Spritz, 1966) and the concentration of secondary bile acids in bile is reduced (Vlahcevic, Buhac, Bell & Swell, 1970). Blum & Spritz (1966) showed that the initial serum clearance of ['4C]cholic acid was impaired in cirrhotic patients, and that significant amounts of labelled bile acid remained in their serum for several days.…”

“…Blum & Spritz (1966) showed that the initial serum clearance of ['4C]cholic acid was impaired in cirrhotic patients, and that significant amounts of labelled bile acid remained in their serum for several days. The aims of the present study were to obtain more detailed information about the disappearance from the serum of ['4C]cholic acid in cirrhotics, and to identify the mechanisms responsible for delayed clearance.…”

Estimation of Cholesterol and Bile Acid Turnover in Man by Kinetic Analysis

“…The fractional turnover rates for cholic and chenodeoxycholic acids obtained in this cirrhotic were greater than those previously published (27) by a labeled bile acid method. The slower catabolic rates observed in the labeled bile acid studies may in part be explained by the slower uptake of labeled bile acid from the circulation into the liver and the greater reflux from the liver, both of which produce a larger extrahepatic bile acid pool in cirrhotics (28). This alteration in the hepatic clearance of plasma bile acid could have the effect of producing a prolonged infusion of labeled bile acid into the biliary tract, creating a spuriously slow biliary exponential decay.…”

Studies on Cholesterol Metabolism in Experimental Diabetic Rat

“…Furthermore, the great difference between two groups was also obtained in expiratory It has been shown that the formation of conjugated cholic acids with amino acid was decreased in liver disease of human (Gattfries et al, 1966), and consequently the bile acid concentration in plasma was elevated (Carey 1958;Osborn et al, 1959;Blum and Spritz 1966;Theodor et al, 1968). It is well known that the conjugated step with amino acid should be proceeded for secretion of cholic acid into the bile and it was affected by the impairment of liver function.…”