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.

Permeation patterns of polar nonelectrolytes across the guinea pig biliary tree

1984 ◽  
Vol 247 (5) ◽  
pp. G527-G536 ◽  
Author(s):  
N. Tavoloni
Keyword(s):  
Steady State ◽  
Bile Acid ◽  
Bile Duct ◽  
Guinea Pig ◽  
Bile Acids ◽  
Bile Flow ◽  
Biliary Tree ◽  
Canalicular Membrane ◽  
Biliary Clearance ◽  
Spontaneous Secretion

The biliary permeation of polar nonelectrolytes was studied in anesthetized, bile duct-cannulated guinea pigs with functional cholecystectomy and nephrectomy. During spontaneous secretion, the steady-state bile-to-plasma ratio (B/P) of [14C]urea, [14C]erythritol, [14C]mannitol, [3H]sucrose, and [3H]inulin was 1.02, 0.90, 0.38, 0.12, and 0.04, respectively. Differently structured hydroxy bile acids, but not taurodehydrocholate, reversibly diminished [14C]erythritol and [14C]mannitol B/P during choleresis, and with some of them, particularly taurocholate and glycochenodeoxycholate, the biliary clearance of either solute declined below precholeretic levels. For any given hydroxy bile acid, the degree of B/P diminution was directly related to the molecular radii of these two inert carbohydrates. All bile acids failed to decrease [14C]urea, [3H]sucrose, and [3H]inulin B/P. On the contrary, most of them irreversibly increased [3H]sucrose and [3H]inulin permeability. These results suggest that in the guinea pig 1) hydroxy bile acids diminish the size or rearrange the architecture of the canalicular membrane "aqueous pores" through which [14C]erythritol and [14C]mannitol enter the canaliculus, and 2) solutes of the size of or smaller than [14C]mannitol enter bile primarily through a transcellular route, whereas [3H]sucrose, and [3H]inulin permeate mainly via a transjunctional shunt pathway. These studies indicate that [14C]erythritol and [14C]mannitol cannot be used to estimate canalicular bile flow in this species.

[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.

scholarly journals Hepatic versus gallbladder bile composition: in vivo transport physiology of the gallbladder in rainbow trout

2000 ◽  
Vol 278 (6) ◽  
pp. R1674-R1684 ◽  
Author(s):  
M. Grosell ◽  
M. J. O'Donnell ◽  
C. M. Wood
Keyword(s):  
Rainbow Trout ◽  
Bile Acid ◽  
Oncorhynchus Mykiss ◽  
Bile Acids ◽  
Bile Flow ◽  
Gallbladder Bile ◽  
Apical Surface ◽  
Hepatic Bile ◽  
Bile Composition

Ion and water transport across the teleost Oncorhynchus mykiss gallbladder were studied in vivo by comparing flow and composition of hepatic bile, collected by chronic catheter, to volume and composition of terminally collected gallbladder bile. Differences in composition were comparable with those of other vertebrates, whereas bile flow (75 μl ⋅ kg− 1 ⋅ h− 1) was below values reported for endothermic vertebrates. The gallbladder concentrates bile acids five- to sevenfold and exhibits higher net Cl− than Na+ transport in vivo, in contrast to the 1:1 transport ratio from gallbladders under saline/saline conditions. Transepithelial potential (TEP) in the presence of bile, at the apical surface, was −13 mV (bile side negative) but +1.5 mV in the presence of saline. Bile acid in the apical saline reversed the TEP, presumably by a Donnan effect. We propose that ion transport across the gallbladder in vivo involves backflux of Na+ from blood to bile resulting in higher net Cl− than Na+ flux. This Na+backflux is driven by a bile side negative TEP and low Na+activity in bile due to the complexing effects of bile acids.

Function of rat hepatocyte tight junctions: studies with bile acid infusions

1991 ◽  
Vol 260 (1) ◽  
pp. G167-G174
Author(s):  
W. G. Hardison ◽  
E. Dalle-Molle ◽  
E. Gosink ◽  
P. J. Lowe ◽  
J. H. Steinbach ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Bile Acid ◽  
Bile Acids ◽  
Bile Flow ◽  
Biliary Tree ◽  
Isolated Hepatocytes ◽  
Paracellular Permeability ◽  
Molecular Weights ◽  
Charge Selectivity ◽  
Constant Rate

To determine the effects of alteration of biliary paracellular permeability on bile flow and composition, we measured the biliary outputs of compounds highly concentrated in bile, all infused at a constant rate in the isolated rat liver perfused with Krebs-Henseleit buffer in a one-pass fashion. Paracellular permeability was increased by infusing 10(-8) M vasopressin (VP). The cholephilic compounds were three cations of various molecular weights, tributylmethylammonium (TBuMA), N-acetylprocainamide ethobromide (APAEB), and propidium iodide, and two anions, taurocholate (TC), a micelle-forming bile acid, and taurodehydrocholate (TDHC), an nonmicelle former. When TC was infused and paracellular permeability increased with VP, neither bile flow nor TC output changed, whereas outputs of cations fell. When TDHC was infused, TDHC output fell, as did outputs of all cations. The decrements in cation outputs exceeded that of TDHC and were inversely related to the molecular weight of the cation. To document that these changes were not related to reduced uptake of these compounds, we tested the uptakes of TBuMA, APAEB, and TDHC into isolated hepatocytes. In no case did 10(-8) M VP significantly reduce uptake. The data demonstrate that micelle-forming bile acids, with their high effective molecular weights, do not efflux from the biliary tree when permeability is increased with VP, whereas nonmicelle-forming bile acids do. Cations efflux more readily than anions, and within this group efflux rate is inversely related to molecular weight. The data confirm the size and charge selectivity of biliary tree permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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)

Bile secretion of sulfated glycolithocholic acid is required for its cholestatic action in rats

1992 ◽  
Vol 262 (2) ◽  
pp. G267-G273
Author(s):  
F. Kuipers ◽  
M. J. Hardonk ◽  
R. J. Vonk ◽  
R. van der Meer
Keyword(s):  
Intravenous Injection ◽  
Biliary Drainage ◽  
Bile Flow ◽  
Wistar Rats ◽  
Parent Compound ◽  
Biliary Tree ◽  
Bile Secretion ◽  
Biliary Secretion ◽  
Contrast Administration ◽  
Bile Formation

To test our hypothesis that the cholestatic action of sulfated glycolithocholic acid (SGLC) in the rat is related to its interaction with calcium in the biliary tree [R. van der Meer, R. J. Vonk, and F. Kuipers. Am. J. Physiol. 254 (Gastrointest. Liver Physiol. 17): G644-G649, 1988], we have now compared its effects on bile formation in control Wistar rats and mutant Groningen Yellow (GY) Wistar rats. Intravenous injection of 0.6 mumol/100 g body wt of [14C]SGLC in unanesthetized rats with permanent biliary drainage did not induce cholestasis in either of the strains; however, its biliary secretion was strongly impaired in GY rats (12% dose at 1 h after injection vs. 95% dose in controls). Injection of 6.0 and 12.0 mumol/100 g body wt of [14C]SGLC caused an almost complete cessation of bile flow in control rats within 3 and 1 h, respectively. In contrast, administration of the same doses did not cause cholestasis in GY rats. Cholestasis in control rats was preceded by coprecipitation of [14C]SGLC and calcium in bile and incomplete biliary recovery of radioactivity. The hepatic content 15 min after injection of [14C]SGLC (6.0 mumol/100 g body wt) was similar in control and GY rats, 51 and 49% of the dose, respectively. Administration of glycolithocholic acid, the unsulfated parent compound of SGLC (6.0 mumol/100 g body wt), induced a rapid but reversible cessation of bile flow in both controls and GY rats; in this case no precipitation was observed in bile. This study shows that rapid bile secretion of SGLC is required for the induction of cholestasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic bile formation: bile acid transport and water flow into the canalicular conduit

2020 ◽  
Vol 319 (5) ◽  
pp. G609-G618
Author(s):  
Norman B. Javitt
Keyword(s):  
Bile Acid ◽  
Water Flow ◽  
Bile Flow ◽  
Organic Anion ◽  
Osmotic Gradient ◽  
Acid Transport ◽  
Hepatic Bile ◽  
Bile Formation ◽  
Bile Acid Concentration ◽  
Bile Acid Transport

Advances in molecular biology identifying the many carrier-mediated organic anion transporters and advances in microscopy that have provided a more detailed anatomy of the canalicular conduit make updating the concept of osmotically determined canalicular flow possible. For the most part water flow is not transmembrane but via specific pore proteins in both the hepatocyte and the tight junction. These pores independently regulate the rate at which water flows in response to an osmotic gradient and therefore are determinants of canalicular bile acid concentration. Review of the literature indicates that the initial effect on hepatic bile flow of cholestatic agents such as Thorazine and estradiol 17β-glucuronide are on water flow and not bile salt export pump-mediated bile acid transport and thus provides new approaches to the pathogenesis of drug-induced liver injury. Attaining a micellar concentration of bile acids in the canaliculus is essential to the formation of cholesterol-lecithin vesicles, which mostly occur in the periportal region of the canalicular conduit. The other regions, midcentral and pericentral, may transport lesser amounts of bile acid but augment water flow. Broadening the concept of how hepatic bile flow is initiated, provides new insights into the pathogenesis of canalicular cholestasis.

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