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.

The contribution of the extrahepatic bile ducts to bile formation

1976 ◽  
Vol 54 (5) ◽  
pp. 757-763 ◽  
Author(s):  
S. M. Strasberg ◽  
C. N. Petrunka ◽  
R. G. Ilson
Keyword(s):  
Bile Acid ◽  
Bile Flow ◽  
Bile Ducts ◽  
Bilirubin Concentration ◽  
Bile Formation ◽  
Fed State ◽  
Extrahepatic Bile Ducts ◽  
Bile Flow Rate ◽  
Two Sides ◽  
Bile Samples

This study was performed to determine the contribution of the extrahepatic bile ducts to bile flow in the rhesus monkey. Bile flow from the two sides of the liver was divided. The major extrahepatic bile ducts remained connected to one side of the liver only. Bile flow, and the concentrations of [14C]erythritol, bicarbonate, bile acid, and bilirubin in bile samples from the two sides of the liver, in the fed state were measured and compared. An estimate of the net flow from the extrahepatic ducts was obtained from the [14C]erythritol concentrations on the two sides of the liver and the bile flow rate on the side with the extrahepatic ducts. The [14C]erythritol bile–plasma ratio was significantly lower in bile collected from the side with the extrahepatic bile ducts, than in bile from the other side of the liver. About 10% of total hepatic bile flow originated in the extrahepatic bile ducts, in the fed state. The bicarbonate-[14C]erythritol concentration ratio was significantly higher in bile from the side with the extrahepatic bile ducts. Bicarbonate – bile acid, and bicarbonate–bilirubin concentration ratios were also significantly higher in bile from the side of the liver with the extrahepatic ducts. The extrahepatic bile ducts have a physiologically significant role in the secretion of bile water. Bicarbonate is secreted in association with water in the extrahepatic ducts.

Bile Flow and Composition During Bile Acid Depletion and Administration

1974 ◽  
Vol 52 (2) ◽  
pp. 334-348 ◽  
Author(s):  
Curtis D. Klaassen
Keyword(s):  
Bile Acid ◽  
Bile Salt ◽  
Bile Acids ◽  
Bile Flow ◽  
Enterohepatic Circulation ◽  
Acid Excretion ◽  
Bile Formation ◽  
Bile Acid Excretion ◽  
Rat Bile ◽  
Acid Administration

Relatively similar concentrations of the inorganic ions were detected in rat, rabbit, and dog bile; however, dog bile had a higher concentration of protein, cholesterol, phospholipid phosphorous, and percentage solids than rat bile, and rabbit bile had the lowest concentration. The biliary excretion of bile acids was altered in each species by: (1) interruption of the enterohepatic circulation; (2) rapid administration of an exogenous load of bile acids; and (3) constant infusion of an exogenous load of bile acids. Bile acid and phospholipid phosphorous concentration and percentage solids increased after bile acid administration in all three species; however, species differences in bilirubin concentration were observed and a marked decrease was detected in rabbit and dog bile but it markedly increased in rat bile. When the enterohepatic circulation was interrupted in the dog and rat, the bile acid concentration markedly decreased with only minor changes in bile flow. This not only supports the theory that there is a bile salt independent fraction of bile formation, but also demonstrates that canalicular bile formation can be maintained at relatively normal rates with almost no excretion of bile acids. Marked discrepancy between bile acid excretion and bile flow was observed in the rat after bile acid administration, in that a marked increase in bile acid excretion was observed but little or no increase in flow. When bile flow was plotted against bile acid excretion for the three species, the slope of the line was less during bile acid administration than during depletion, indicating that the bile acids are accompanied by less water during bile acid administration than during depletion. Variation in the bile flow intercept with zero bile acid excretion (thought to represent the bile salt-independent fraction) was relatively large, which is probably due in part to alteration in the production of the bile salt independent fraction when bile acid secretion is altered. It appears that both the choleretic property of bile acids varies during various rates of bile acid excretion and the bile salt-independent fraction is not constant. Therefore, calculation of the bile salt independent fraction as previously performed should be interpreted with extreme caution. Thus, it appears difficult to determine the quantitative importance of bile acid excretion in bile formation.

Relation between biliary glutathione excretion and bile acid-independent bile flow

1989 ◽  
Vol 256 (1) ◽  
pp. G22-G30 ◽  
Author(s):  
N. Ballatori ◽  
A. T. Truong
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Bile Flow ◽  
Sodium Arsenite ◽  
Driving Forces ◽  
Similar Function ◽  
Bile Formation ◽  
Treatment Groups ◽  
Pooled Data ◽  
Straight Line

Glutathione efflux into bile of the fluorocarbon-perfused isolated rat liver was altered with eight different agents (L-buthionine-[S,R]-sulfoximine, cefamandole, sodium arsenite, phenobarbital, furosemide, nitrofurantoin, aminopyrine, and benzylamine), and correlations were established between bile flow and biliary excretion of 1) glutathione, 2) endogenous bile acids, and 3) glutathione plus bile acids. Biliary efflux of endogenous bile acids was relatively low (0.5-5 nmol.min-1.g liver-1) and was minimally affected by these agents. Biliary glutathione excretion in control livers was between 4 and 9 nmol.min-1.g-1 and in treated livers ranged from 1 to 21 nmol.min-1.g-1. For each of the various interventions, an increase or decrease in glutathione excretion was always accompanied by a change in bile flow in the same direction; however, these changes were not always directly proportional when comparisons were made between treatment groups. Nevertheless, when bile flow (microliter.min-1.g-1; ordinate) was plotted against glutathione excretion into bile for the pooled data, a significant correlation was observed that was adequately described by a straight line: y = 0.071 chi + 0.72 (r2 = 0.62, P less than 0.001). A similar function described the relation between bile flow and the sum of bile acids and glutathione in bile: y = 0.077 chi + 0.55 (r2 = 0.62, P less than 0.001). In contrast, the taurocholate- or glycocholate-induced choleresis had only minimal effects on glutathione efflux. These findings support the hypothesis that glutathione is one of the osmotic driving forces in bile acid-independent bile formation.(ABSTRACT TRUNCATED AT 250 WORDS)

[14C]erythritol clearance and canalicular bile acid-independent flow in the baboon

1982 ◽  
Vol 242 (5) ◽  
pp. G475-G480
Author(s):  
S. M. Strasberg ◽  
R. G. Ilson ◽  
C. N. Petrunka
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Bile Flow ◽  
Quantitative Assessment ◽  
Sodium Taurocholate ◽  
Hepatic Bile ◽  
Bile Formation ◽  
Canalicular Bile

The use of [14C]erythritol for the quantitative assessment of hepatic bile formation has been studied in baboons using sodium taurocholate to generate canalicular bile flow. It has been found that increments in [14C]erythritol clearance are equal to taurocholate-induced increments in bile flow, but there was no change in [14C]erythritol clearance when bile flow was increased by secretin. No evidence was found to support the view that bile acids affect bile acid-independent bile flow.

History of hepatic bile formation: old problems, new approaches

2014 ◽  
Vol 38 (4) ◽  
pp. 279-285 ◽  
Author(s):  
Norman B. Javitt
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Water Flow ◽  
Bile Flow ◽  
Water Movement ◽  
Sodium Taurocholate ◽  
Biliary System ◽  
Hepatic Bile ◽  
Bile Formation ◽  
Osmotic Effect

Studies of hepatic bile formation reported in 1958 established that it was an osmotically generated water flow. Intravenous infusion of sodium taurocholate established a high correlation between hepatic bile flow and bile acid excretion. Secretin, a hormone that stimulates bicarbonate secretion, was also found to increase hepatic bile flow. The sources of the water entering the biliary system with these two stimuli were differentiated by the use of mannitol. An increase in its excretion parallels the increase in bile flow in response to bile acids but not secretin, which led to a quantitative distinction between canalicular and ductular water flow. The finding of aquaglyceroporin-9 in the basolateral surface of the hepatocyte accounted for the rapid entry of mannitol into hepatocytes and its exclusion from water movement in the ductules where aquaporin-1 is present. Electron microscopy demonstrated that bile acids generate the formation of vesicles that contain lecithin and cholesterol after their receptor-mediated canalicular transport. Biophysical studies established that the osmotic effect of bile acids varies with their concentration and also with the proportion of mono-, di-, and trihydroxy bile acids and provides a basis for understanding their physiological effects. Because of the varying osmotic effect of bile acids, it is difficult to quantify bile acid independent flow generated by other solutes, such as glutathione, which enters the biliary system. Monohydroxy bile acids, by markedly increasing aggregation number, severely reduce water flow. Developing biomarkers for the noninvasive assessment of normal hepatic bile flow remains an elusive goal that merits further study.

Biliary excretion of inorganic electrolytes: its role in hepatic bile formation

1985 ◽  
Vol 63 (10) ◽  
pp. 1245-1251 ◽  
Author(s):  
Nicola Tavoloni
Keyword(s):  
Bile Acid ◽  
Guinea Pig ◽  
Bile Acids ◽  
Bile Flow ◽  
Major Change ◽  
Biliary Tree ◽  
Bile Secretion ◽  
Bicarbonate Concentration ◽  
Hepatic Bile ◽  
Bile Formation

To define the role of inorganic electrolyte secretion in hepatic bile formation, the effects of secretin, glucagon, and differently structured bile acids on bile flow and composition were studied in the dog, guinea pig, and rat. In the dog and guinea pig, secretin (2.5–10 clinical units∙kg−1∙30 min−1) increased bile flow and bicarbonate concentration in bile, a finding consistent with the hypothesis that the hormone stimulates a bicarbonate-dependent secretion possibly at the level of the bile ductule–duct. In the rat, secretin (5–15 CU∙kg−1∙30 min−1) failed to increase bile secretion. Glucagon (1.25–300 μg∙kg−1∙30 min−1) increased bile flow in all the three species, and produced no changes in biliary bicarbonate concentrations in the dog and rat. In the guinea pig, however, glucagon choleresis was associated with an increase in bicarbonate concentration in bile, similar to that observed with secretin. The choleretic activities of various bile acids (taurocholate, chenodeoxycholate, glycochenodeoxycholate, tauroursodeoxycholate, and ursodeoxycholic acid, infused at 30–360 μmol∙kg−1∙30 min−1) were similar in the rat (6.9–7.2 μL/μmol), but different in the guinea pig (11–31 μL/μmol). In the latter species, the more hydrophobic the bile acid, the greater was its choleretic activity. In all instances, bile acid choleresis was associated with a decline in the biliary concentrations of chloride, but with no major change in bicarbonate levels. The prominent finding of these studies is that, regardless of whether bile flow was stimulated by hormones or different bile acids, bicarbonate concentrations in bile were always similar to or higher than those in plasma. This is construed to support the view that bicarbonate is transported into bile, possibly at multiple sites within the biliary tree. Its excretion most likely provides the driving force for hormone-induced choleresis, and may in part account for the flow of bile associated with bile acid secretion.

scholarly journals AGE RELATED FEATURES OF THE BOMBESIN EFFECT ON HEPATIC BILE FORMATION

2020 ◽  
Vol 66 (5) ◽  
pp. 46-54
Author(s):  
O.F. Moroz ◽  
◽  
S.P. Veselsky ◽  
T.P. Lyaschenko ◽  
◽  
...  
Keyword(s):  
Body Weight ◽  
Bile Acids ◽  
Bile Flow ◽  
Bile Salts ◽  
Aged Rats ◽  
Hepatic Bile ◽  
Adult Rats ◽  
Bile Formation ◽  
Age Related ◽  
Bile Flow Rate

Hepatic bile formation under bombesin action (1 µg/100 g body weight, intraportally) was examined in acute experiments on 30 male rats of three age categories: juvenile (body weight 130-175 g), adult (200-250 g) and elder (more than 300 g). Changes in the bile flow rate were recorded and the amount of various bile acids (BA) was detected using thin layer chromatography/densitometry. Bombesin caused the increase of the bile flow rate in juvenile and adult rats without any effect on it in old animals. The concentration of free bile acids increased in juvenile and adult rats and decreased in old animals. This peptide stimulated secretion of taurocholic and glicocholic acids in adult and aged rats but had no effect on the secretion of tauroconjugated dihydroxycholates. Secretion of dihydroxy bile salts conjugated with glycine was more potently enhanced by bombesin in adult rats but in the elder group this parameter dropped below the control. Bombesin had a lower effect on the BA secretion in aged rats but its influence on the juvenile animals was bidirectional. In this group the peptide stimulates free bile salts formation and, without affecting de novo synthesis, inhibits BA conjugation with amino acids in aged group. Bombesin activated classic pathway of BA biosynthesis in juvenile rats and suppressed it in aged animals. The data obtained demonstrate that different effect of bombesin on bile acids content in rats of different age could change biliary lipid-solubilizing capacity under age related damage of the gut with impairment of normal bombesin release.

Differing effects of norcholate and cholate on bile flow and biliary lipid secretion in the rat

1984 ◽  
Vol 246 (1) ◽  
pp. G67-G71
Author(s):  
E. R. O'Maille ◽  
S. V. Kozmary ◽  
A. F. Hofmann ◽  
D. Gurantz
Keyword(s):  
Bile Acid ◽  
Acid Secretion ◽  
Bile Acids ◽  
Bile Flow ◽  
Critical Micellar Concentration ◽  
Biliary Lipid ◽  
Lipid Secretion ◽  
Unit Increase ◽  
Cholesterol Secretion ◽  
Bile Acid Secretion

The effects of norcholate (a C23 bile acid that differs from cholate in having a side chain containing four rather than five carbon atoms) on bile flow and biliary lipid secretion were compared with those of cholate, using the anesthetized rat with a bile fistula. Norcholate and cholate were infused intravenously over the range of 0.6-6.0 mumol X min-1 X kg-1. Both bile acids were quantitatively secreted into bile; norcholate was secreted predominantly in unconjugated form in contrast to cholate, which was secreted predominantly as its taurine or glycine conjugates. The increase in bile flow per unit increase in bile acid secretion induced by norcholate infusion [17 +/- 3.2 (SD) microliters/mumol, n = 8] was much greater than that induced by cholate infusion (8.6 +/- 0.9 microliters/mumol, n = 9) (P less than 0.001). Both bile acids induced phospholipid and cholesterol secretion. For an increase in bile acid secretion (above control values) of 1 mumol X min-1 X kg-1, the increases in phospholipid secretion [0.052 +/- 0.024 (SD) mumol X min-1 X kg-1, n = 9] and cholesterol secretion (0.0071 +/- 0.0033 mumol X min-1 X kg-1, n = 9) induced by norcholate infusion were much less than those induced by cholate infusion (0.197 +/- 0.05 mumol X min-1 X kg-1, n = 9, and 0.024 +/- 0.011 mumol X min-1 X kg-1, n = 9, respectively; P less than 0.001 for both phospholipid and cholesterol). The strikingly different effects of norcholate on bile flow and biliary lipid secretion were attributed mainly to its possessing a considerably higher critical micellar concentration than cholate.

Effect of protoporphyrin IX on ursodeoxycholate-induced hypercholeresis in the rat

1988 ◽  
Vol 75 (6) ◽  
pp. 593-599
Author(s):  
J. J. Garcia-Marin ◽  
J. G. Redondo-Torres ◽  
F. Perez-Barriocanal ◽  
M. M. Berenson
Keyword(s):  
Body Weight ◽  
Bile Acid ◽  
Bile Flow ◽  
Sodium Taurocholate ◽  
Protoporphyrin Ix ◽  
Inhibitory Effect ◽  
Bicarbonate Secretion ◽  
Bile Formation ◽  
Dose Dependent ◽  
Bile Acid Secretion

1. It is known that the perfusion of rat livers with solutions containing protoporphyrin IX induces a decrease in bile flow which is not due to inhibition of bile acid secretion but rather to decreased electrolyte transport into bile. By contrast, ursodeoxycholate induces hypercholeresis, partly due to a marked stimulation of biliary bicarbonate secretion. The aim of the present work was to investigate the effect of protoporphyrin IX on ursodeoxycholate-induced choleresis in anaesthetized male Wistar rats. 2. Protoporphyrin IX infusion at rates of 10, 20 and 40 μg min−1 100 g−1 body weight into the jugular vein induced a dose-dependent inhibitory effect on bile flow as well as on bile acid and electrolyte secretion. The lowest infused rate only induced slight and non-significant changes in spontaneous bile formation and functional variables such as glycaemia, packed cell volume, blood pH, Pco2, Po2 and bicarbonate concentration, and in hepatic carbonic anhydrase activity. It was thus considered as a subtoxic dose. 3. Sodium taurocholate was infused (0.5 μmol min−1 100 g−1 body weight) over the second hour of the lowest dose of protoporphyrin IX infusion. In these rats, no significant changes in bile flow or bile acid and electrolyte secretion were observed as compared with animals receiving sodium taurocholate plus saline solution. 4. Bile acid secretion induced by ursodeoxycholate infusion (1 μmol min−1 100 g−1 body weight) was similar both in rats receiving ursodeoxycholate plus saline solution and in animals infused with this bile acid over the second hour of the lowest dose of protoporphyrin IX infusion. However, bile flow and biliary bicarbonate secretion induced by ursodeoxycholate were markedly impaired (− 43% and − 56%, respectively) by protoporphyrin IX. 5. These results indicate that in the rat, in vivo, protoporphyrin IX impairs bile formation in a dose-dependent manner. They suggest that the mechanism(s) involved in ursodeoxycholate-induced bicarbonate secretion, and hence hypercholeresis, are particularly sensitive to the inhibitory effect of protoporphyrin IX.

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