The Biliary Excretion of Sulphated and Non-Sulphated Bile Acids and Bilirubin in Patients with External Bile Drainage

1984 ◽  
Vol 67 (1) ◽  
pp. 61-68 ◽  
Author(s):  
James S. Dooley ◽  
Carl Bartholomew ◽  
John A. Summerfield ◽  
Barbara H. Billing
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Biliary Excretion ◽  
Total Bilirubin ◽  
Serum Bilirubin ◽  
Bilirubin Concentration ◽  
Biliary Decompression ◽  
Bilirubin Excretion ◽  
Bile Drainage ◽  
The Difference

1. The biliary excretion of total bilirubin and bile acids, and the fate of tracer doses of radioactive sulphated and non-sulphated bile acids, were studied in patients with percutaneous transhepatic bile drainage. 2. Non-sulphated bile acids were excreted in bile early after biliary decompression, and the serum total 3α-hydroxy bile acid concentrations fell rapidly to normal. Biliary bilirubin excretion was both less than and delayed compared with that of bile acids, and the serum bilirubin concentration fell more slowly. 3. The serum disappearance of [3H]chenodeoxycholate-3-sulphate was slower than that of [14C]glycocholate in all patients with bile drainage, the difference being more marked in the jaundiced patients. 4. The radioactive sulphated bile acids were recovered predominantly in the urine of the jaundiced patients. In contrast [14C]glycocholate was excreted almost exclusively in bile. In an anicteric patient, radioactive sulphated bile acid disappeared from the serum more quickly, and biliary recovery exceeded that in the urine. 5. The studies demonstrate the differences in handling of total bilirubin, and sulphated and non-sulphated bile acids in man after the relief of bile duct obstruction. The biliary excretion of radioactive labelled sulphated bile acids is low for at least 1 week after biliary drainage, but later becomes the predominant route for excretion in the anicteric patient.

Modulation of hepatic biotransformation and biliary excretion of bile acid by age and sinusoidal bile acid load

1987 ◽  
Vol 252 (1) ◽  
pp. G114-G119 ◽  
Author(s):  
U. Baumgartner ◽  
K. Miyai ◽  
W. G. Hardison
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Residence Time ◽  
Biliary Excretion ◽  
Bile Acid Concentration ◽  
Acid Processing ◽  
Acid Load ◽  
The Difference ◽  
Rat Livers ◽  
Hepatic Biotransformation

Pericentral hepatocytes excrete bile acids more slowly and biotransform them more than periportal cells. This may reflect adaptation to low pericentral bile acid concentration or may be intrinsic. We studied two models in which pericentral bile acid concentrations are high: the 72-h choledocho-caval shunt (CCS) rat and the 3- to 4-wk-old rat. Livers were perfused forward or backward to assess periportal or pericentral hepatocyte function. Taurodeoxycholate (TDC) was infused at 32 nmol X min-1 X g liver-1, and a bolus of [3H]TDC was given to assess metabolism and excretion of bile acids. In CCS livers perfused backward, pericentral cells resembled periportal cells of controls in that time to excrete 50% of administered [3H]TDC (t50) was reduced by two-thirds and [3H]TDC biotransformation was reduced by about half. In young livers t50 was half that of adult livers when perfused backward. Biotransformation, however, was not reduced. Young livers biotransformed more than adult controls for any given residence time of bile acid in the liver. We conclude that the difference between pericentral and periportal cells as regards bile acid processing is adaptive. Livers from young rats biotransform more bile acid than those from controls under similar conditions.

scholarly journals A nomogram based on pretreatment levels of serum bilirubin and total bile acid levels predicts survival in colorectal cancer patients

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yinghao Cao ◽  
Shenghe Deng ◽  
Lizhao Yan ◽  
Junnan Gu ◽  
Jia Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factors ◽  
Bile Acid ◽  
Bile Acids ◽  
Cancer Patients ◽  
Serum Bilirubin ◽  
Cox Regression ◽  
Total Bile Acid ◽  
Cox Regression Analysis ◽  
Colorectal Cancer Patients

Abstract Background Serum bilirubin and total bile acid (TBA) levels have been reported to be strongly associated with the risk and prognosis of certain cancers. Here, we aimed to investigate the effects of pretreatment levels of serum bilirubin and bile acids on the prognosis of patients with colorectal cancer (CRC). Methods A retrospective cohort of 1474 patients with CRC who underwent surgical resection between January 2015 and December 2017 was included in the study. Survival analysis was used to evaluate the predictive value of pretreatment levels of bilirubin and bile acids. X-Tile software was used to identify optimal cut-off values for total bilirubin (TBIL), direct bilirubin (DBIL) and TBA in terms of overall survival (OS) and disease-free survival (DFS). Results DBIL, TBIL, and TBA were validated as significant prognostic factors by univariate Cox regression analysis for both 3-year OS and DFS. Multivariate Cox regression analyses confirmed that high DBIL, TBIL and TBA levels were independent prognostic factors for both OS (HR: 0.435, 95% CI: 0.299–0.637, P < 0.001; HR: 0.436, 95% CI: 0.329–0.578, P < 0.001; HR: 0.206, 95% CI: 0.124–0.341, P < 0.001, respectively) and DFS (HR: 0.583, 95% CI: 0.391–0.871, P = 0.008; HR:0.437,95% CI: 0.292–0.655, P <0.001; HR: 0.634, 95% CI: 0.465–0.865, P = 0.004, respectively). In addition, nomograms for OS and DFS were established according to all significant factors, and the c-indexes were 0.819 (95% CI: 0.806–0.832) and 0.835 (95% CI: 0.822–0.849), respectively. Conclusions TBIL, DBIL and TBA levels are independent prognostic factors in colorectal cancer patients. The nomograms based on OS and DFS can be used as a practical model for evaluating the prognosis of CRC patients.

Cholestasis induced by Sulphated Glycolithocholic Acid in the Rat: Protection by Endogenous Bile Acids

1985 ◽  
Vol 68 (2) ◽  
pp. 127-134 ◽  
Author(s):  
Folkert Kuipers ◽  
Rick Havinga ◽  
Roel J. Vonk
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Biliary Excretion ◽  
Hepatic Clearance ◽  
Recovery Phase ◽  
Bile Acid Pool ◽  
Acid Pool ◽  
Hepatotoxic Effect ◽  
Biliary Excretion Rate ◽  
Bile Production

1. Sulphated glycolithocholic acid (SGLC) causes cholestasis in experimental animals, despite its sulphated form. In the present study, the cholestatic potency and the pharmacokinetics of SGLC were investigated in rats under two conditions: (a) in the presence of an intact circulating bile acid pool and (b) after exhaustion of the bile acid pool by 24 h of bile diversion. 2. Intravenous administration of SGLC (8 μmol/ 100 g body weight) to rats with an intact bile acid pool did not cause cholestasis. However, biliary phospholipid and cholesterol concentrations were reduced by 40% and 29% respectively during the first hour after administration. When the same dose of the bile acid was injected in rats with a 24 h biliary drainage, a complete cessation of bile production was observed within 1 h. Twelve hours after the onset of cholestasis, bile production gradually increased again, showed a marked overshoot, and reached control levels after 3 days. In the recovery phase, biliary phospholipid and cholesterol concentrations were greatly reduced. 3. The absence of endogenous bile acids did not change the hepatic clearance rate of a tracer dose of radiolabelled SGLC, but markedly decreased its biliary excretion rate. 4. It was concluded that the hepatotoxic effect of SGLC is much more pronounced in rats with an exhausted bile acid pool, possibly due to a slower biliary excretion of the toxic compound. This phenomenon may have clinical implications for patients with a contracted bile acid pool.

scholarly journals Differential hepatic processing and biliary secretion of head-group and acyl chains of liposomal phosphatidylcholines

1991 ◽  
Vol 275 (1) ◽  
pp. 139-144 ◽  
Author(s):  
H J Verkade ◽  
J T Derksen ◽  
A Gerding ◽  
G L Scherphof ◽  
R J Vonk ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Degradation Products ◽  
Acyl Chain ◽  
Quantitative Difference ◽  
Biliary Secretion ◽  
Synthesis Rate ◽  
Head Group ◽  
Bile Drainage ◽  
Acyl Chains

To investigate the contribution of plasma-derived phosphatidylcholine (PC) to bile PC, the hepatic processing and biliary secretion of liposome-associated PC was studied in rats. For this purpose, small unilamellar vesicles (SUV), containing trace amounts of [2-palmitoyl-9,10-3H]dipalmitoylphosphatidylcholine ([palmitoyl-3H]DPPC), [choline-14C]-dipalmitoylphosphatidylcholine ([choline-14C]DPPC), di[14C]palmitoylphosphatidylcholine ([14C]DPPC) or di[1-14C]-oleoylphosphatidylcholine ([14C]DOPC), were administered intravenously to unanaesthetized rats, equipped with permanent catheters in heart and bile duct. Biliary secretion of the 14C-head-group label of DPPC was very slow (0.3% of injected dose in 4 h), whereas the [3H]palmitoyl label was secreted at a much higher rate (16% in 4 h), but only after substantial catabolism of the acyl chain. To study the latter process in more detail, we compared hepatic metabolism and biliary secretion of [1-14C]acyl-labelled DPPC and DOPC. In rats with an 8-day bile drainage, degradation products of the oleoyl chain were utilized for synthesis of bile acids, which were subsequently secreted into the bile (2% in 6 h). A much smaller fraction (0.6% in 6 h) was secreted as PC and lyso-PC. When bile drainage was started immediately after SUV injection, i.e. a situation with a low hepatic bile acid synthesis rate and a high phospholipid secretion, the secretion of [14C]DOPC-derived radioactivity in the form of bile acids was decreased (0.2% in 6 h), and that as (lyso-)PC increased (1.5% in 6 h). Biliary secretion of DPPC palmitoyl chains in bile-diverted rats was much less than that of the oleoyl chains, and occurred predominantly as PC and lyso-PC (0.6%, compared with 0.4% as bile acids in 6 h). Breath analyses demonstrated that a considerable fraction of both acyl chains was oxidized to CO2 and expired: 25.1% of the administered label for oleoyl chains and 13.4% for palmitoyl chains respectively in a 4 h period. The results of this study indicate that liposomal PC is only minimally secreted into bile via a direct pathway; the bulk is extensively degraded in the liver. Resulting products are partly secreted into bile, as bile acid or as resynthesized PC. There appears to be a quantitative difference in the metabolism of oleoyl and palmitoyl acyl chains.

Bilirubin production in healthy term infants as measured by carbon monoxide in breath

1994 ◽  
Vol 40 (10) ◽  
pp. 1934-1939 ◽  
Author(s):  
D K Stevenson ◽  
H J Vreman ◽  
W Oh ◽  
A A Fanaroff ◽  
L L Wright ◽  
...  
Keyword(s):  
Total Bilirubin ◽  
Serum Bilirubin ◽  
Coombs Test ◽  
Bilirubin Concentration ◽  
Term Infants ◽  
Rh Incompatibility ◽  
Insulin Dependent ◽  
End Tidal ◽  
Positive Direct ◽  
Test Result

Abstract To describe total bilirubin production in healthy term infants, we measured the end-tidal breath CO, corrected for ambient CO (ETCOc), with an automated sampler and electrochemical (EC) CO instrument. For infants of mothers with a negative Coombs' test, the ETCOc was 1.3 +/- 0.7 microL/L (n = 397) and the serum bilirubin on day 3 postpartum was 73 +/- 35 mg/L (n = 381). In contrast, the ETCOc for infants with ABO or Rh incompatibility, a positive direct Coombs' test, and bilirubin &gt; 130 mg/L (n = 9) was significantly higher, 1.8 +/- 0.8 microL/L, than for those who had a positive Coombs' test result but whose bilirubin was &lt; or = 130 mg/L (n = 12), 1.0 +/- 0.5 microL/L (P &lt; 0.05). At 2 to 8 h postpartum seven term babies from mothers with insulin-dependent diabetes had ETCOc of 1.8 +/- 0.7 microL/L, significantly higher than that in the other term infants [1.3 +/- 0.7 microL/L (n = 390), P &lt; 0.04]. Their bilirubin concentration at 72 +/- 12 h was also higher: 121 +/- 45 mg/L (n = 7) vs 73 +/- 34 mg/L (n = 374; P = 0.03). We conclude that ETCOc measurements may be helpful in understanding the mechanisms of jaundice in healthy term infants in a variety of conditions.

The Enhancement of Maximal Bilirubin Excretion with Taurocholate–Induced Increments in Bile Flow

1974 ◽  
Vol 52 (3) ◽  
pp. 389-403 ◽  
Author(s):  
Carl A. Goresky ◽  
Henry H. Haddad ◽  
Warren S. Kluger ◽  
Brita E. Nadeau ◽  
Glen G. Bach
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Bile Flow ◽  
Low Flow ◽  
Molar Ratio ◽  
Bile Formation ◽  
Bilirubin Excretion ◽  
Anesthetized Dogs ◽  
Bile Flow Rate ◽  
Biliary Excretion Rate

Of the processes involved in the handling of a bilirubin load, the biliary secretory maximum or Tm for bilirubin has been regarded as rate limiting, and as a characteristic of liver function. In the present study, bile flow was varied by use of bile acid infusions, in order to determine whether the Tm is indeed constant or whether it varies with flow. Anesthetized dogs, with bile flow stabilized by cholinergic blockade, were studied during taurocholate infusions. In these animals the ductular component of flow is relatively inhibited and the bile flow rate increases approximately in proportion to the rate of excretion of taurocholate. The maximal biliary excretion rate of bilirubin was found to increase linearly with flow and taurocholate excretion, in a significant fashion, but, in contrast to the relation between taurocholate excretion and flow, a significantly large intercept remained on linear extrapolation towards zero flow. The basis for the large intercept is a great increase in the bilirubin concentration in bile as the flow is decreased. This results in a simultaneous sharp increase in the molar ratio (bilirubin/taurocholate) at very low flow rates.We have inferred, on the basis of the preceding data, that the capacity for bilirubin transport is linked to the secretion of bile acids into bile. At low rates of supply of bile acids, little of the material will reach the centers of the hepatic lobules, and the contribution of bile acids to bile flow at that site will be relatively low. At higher rates of bile acid infusion or supply, increased amounts of the bile acids will reach the centers of the lobules and contribute to increased bile formation in these areas. It appears that this is the mechanism which underlies the change in the transport maximum for bilirubin with change in the rate of bile salt excretion.

scholarly journals Effectiveness of single and double phototherapy on indirect hyperbilirubinemia in neonates

2011 ◽  
Vol 51 (6) ◽  
pp. 316 ◽  
Author(s):  
Nanda Susanti Milyana ◽  
Guslihan Dasa Tjipta ◽  
Muhammad Ali ◽  
Emil Azlin ◽  
Bugis Mardina Lubis ◽  
...  
Keyword(s):  
Neonatal Jaundice ◽  
Total Bilirubin ◽  
Serum Bilirubin ◽  
Controlled Trial ◽  
Spectral Irradiance ◽  
Bilirubin Concentration ◽  
Randomized Controlled ◽  
Significant Difference ◽  
Term Newborns ◽  
The Mean

Background Hyperbilirubinemia is a common problem in full term newborns and phototherapy is the most widespread treatment for lowering bilirubin concentration in neonates. Double phototherapy could increase the effectiveness of treatment.Objective To compare the effectiveness of single and double phototherapy and increasing spectral irradiance for decreasing serum bilirubin levels in neonates for indirect hyperbilirubinemia.Methods An open, randomized, controlled trial was conducted at H. Adam Malik and Pirngadi Hospitals, Medan, from May to December 2009. Subjects were divided into two groups, those who received single phototherapy (n=30) and those who received double phototherapy (n=30) treatments. We included term newborns with neonatal jaundice in the first week of life. Serum bilirubin and average spectral irradiation levels were measured at baseline and after 12 hours and 24 hours of phototherapy treatment.Results The mean total bilirubin levels of the single and double phototherapy groups at the beginning of therapy were 17.6 mg/dL (SD1.41) and 17.5 mg/dL (SD 1.32), respectively, with no significant difference between values. During the study period the sum of average spectral irradiance by double phototherapy was significantly higher than that of single phototherapy (P < 0.05). A significantly greater decrease in bilirubin levels was observed in the double phototherapy group at 12 hours and 24 hours of phototherapy compared to the single phototherapy group (P = 0.001).Conclusion Double phototherapy is more effective than single phototherapy in reducing bilirubin levels in jaundiced newborns.

Conjugation is rate limiting in hepatic transport of ursodeoxycholate in the rat

1982 ◽  
Vol 243 (3) ◽  
pp. G208-G213 ◽  
Author(s):  
I. Zouboulis-Vafiadis ◽  
M. Dumont ◽  
S. Erlinger
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Liver Toxicity ◽  
Hepatic Transport ◽  
Secretory Rate ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
The Difference ◽  
Conjugation Process ◽  
Rate Limiting

It has been reported that biliary secretion is the limiting step in the hepatic transport of bile acids by the hepatocyte from plasma to canalicular bile. The aim of the present study was to examine the role of conjugation in the transport process using ursodeoxycholate (UDCA) and tauroursodeoxycholate (TUDCA), two bile acid with low liver toxicity. Rats were given constant intravenous infusions of cholate (C), taurocholate (TC), UDCA, or TUDCA at progressively increasing rates. The biliary maximum secretory rate (SRm), in nmol . min-1 . 100 g body wt-1, for TC (1,835.2 +/- 135.5, mean +/- SE) was not significantly different from that of C (1,749.4 +/- 85.6). In contrast, the SRm for TUDCA (5,909.4 +/- 304.4) was approximately sevenfold that of UDCA (802.1 +/- 134.2), the difference being statistically significant (P less than 0.001). The SRm of UDCA in the presence of a taurine infusion (1,367 +/- 84.4) was higher than that of UDCA infused alone but still much lower than that of TUDCA. Phenobarbital sodium pretreatment did not increase SRm of UDCA alone or in the presence of a taurine infusion. These results suggest that in the rat 1) conjugation is the rate-limiting step in the overall transport of UDCA (and perhaps other bile acids) by the liver, and 2) the conjugation process itself is limiting, rather than the availability of taurine. They support the view that, although not mandatory for secretion into bile, conjugation of bile acids confers a biological advantage, possibly by increasing the solubility of the bile acid.

Bile acid structure and biliary lipid secretion. II. A comparison of three hydroxy and two keto bile acids.

1978 ◽  
Vol 234 (6) ◽  
pp. E637
Author(s):  
N E Hoffman ◽  
R B Sewell ◽  
R A Smallwood
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Biliary Lipid ◽  
Lipid Secretion ◽  
Dihydroxy Acid ◽  
Intracellular Effect ◽  
The Difference ◽  
Acid Structure ◽  
Cholanoic Acid ◽  
Anesthetized Cat

The effect of five bile acids on biliary lipid secretion was studied in the pentobarbital-anesthetized cat. The dihydroxy acid, taurohyodeoxycholic acid, was indistinguishable from another dihydroxy acid, taurochenodeoxycholic acid, but secretion of both phospholipid and cholesterol was considerably reduced with two mono-keto dihydroxy acids, tauro-3alpha,12alpha-dihydroxy-7-keto-5beta-cholanoic acid and tauro-3alpha,7alpha-dihydroxy-12-keto-5beta-cholanoic acid. The effect of a trihydroxy bile acid, taurocholic acid was as previously described. The effect of the keto bile acids may be explained by the ability of these bile acids to solubilize lipid, but such an explanation is inadequate for the difference between di- and trihydroxy bile acids. An intracellular effect of bile acid is postulated.

scholarly journals Bile acid conjugation and hepatic taurine concentration in rats fed on pectin

1989 ◽  
Vol 62 (3) ◽  
pp. 539-550 ◽  
Author(s):  
T. Ide ◽  
M. Horii ◽  
K. Kawashima ◽  
T. Yamamoto
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Biliary Excretion ◽  
The Other ◽  
Acid Excretion ◽  
Citrus Pectin ◽  
Taurine Concentration ◽  
Dietary Level ◽  
Biliary Bile Acid ◽  
Conjugated Bile Acids

A relationship between bile acid conjugation and hepatic taurine concentration was investigated in rats fed on citrus pectin. When rats were fed on the diets containing varying amounts of pectin (10, 30, 60 and 100 g/kg dietary levels), biliary excretion of bile acids increased as the dietary levels of pectin increased. The increase was entirely due to the glycine-conjugated bile acids. The biliary excretion of taurine-conjugated bile acid was somewhat decreased as the dietary level of the fibre increased. Consequently, most of the bile acids were conjugated with glycine in rats fed on the diet containing 100 g pectin/kg. On the other hand, dietary cellulose (60 and 100 g/kg) did not affect the biliary bile acid excretions. The major proportion of bile acids in rats receiving a fibre-free diet and the diets containing cellulose were conjugated with taurine. Hepatic taurine concentrations decreased as the dietary levels of pectin, but not of cellulose, increased. Although dietary pectin (100 g/kg) also slightly decreased the taurine concentration in the kidney, those concentrations in other non-hepatic tissues examined (heart, brain and serum) were unaffected by the dietary fibre. Supplementation of the diet containing 100 g pectin/kg with methionine (10 g/kg) and taurine (10 and 50 g/kg) strikingly increased hepatic taurine concentrations. In this situation, the conjugation of bile acid with glycine was almost abolished and taurine conjugates became abundant in the bile of these animals. It is suggested that dietary pectin mediated an increase in the biliary bile acid excretion which may have depleted the hepatic pool of taurine available for bile acid conjugation and, thus, increased glycine conjugation of bile acids.

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