1
|
Abstract
BACKGROUND The gallbladder filling and emptying cycle controls bile flow into the duodenum. Disruption of this emptying and refilling cycle leads to bile stasis and subsequent gallstone formation. The bile flow rate is inversely proportional to its viscosity. Moreover, bile is a complex material with varying density in different people because of its diverse components. These density changes alter the viscosity. Prediction of shear viscosity from density measurements may thus contribute to medical assessment and treatment of the patient. OBJECTIVE To investigate the relationship between the shear viscosity and density of bile. METHODS Natural and filtered bile samples were prepared for density, viscosity and pressure drop measurements. The density and shear viscosity were measured by a density meter and viscometer, respectively, and a relationship was established between them. Measurements of the pressure drop in a glass tube were used to estimate the apparent viscosity and compared with shear viscosity obtained with the viscometer. RESULTS The natural bile with higher density showed a greater shear viscosity than the filtered bile, especially at low shear rates. Bile viscosity was proportional to density. In addition, the pressure drop of the natural samples was greater than that of the filtered sample. The viscosity measured by the viscometer deviated from the results obtained using Poiseuille's law and the tube pressure drop measurements. The density difference between the natural and filtered bile samples was smaller than 1%. However, the viscosities of the natural and filtered bile samples varied by up to >30%. CONCLUSIONS Porcine bile viscosity is proportional to density. Based on the bile density, one can easily evaluate the shear viscosity using a linear relationship. The density considerably influences the bile viscosity, with small density increases greatly increasing the shear viscosity.
Collapse
Affiliation(s)
- Nguyen Ngoc Minh
- Department of Mechanical Systems Engineering, Tokyo Metropolitan University, Hachioji, Tokyo, Japan
| | - Hiromichi Obara
- Department of Mechanical Systems Engineering, Tokyo Metropolitan University, Hachioji, Tokyo, Japan
| |
Collapse
|
2
|
Vilkin A, Nudelman I, Morgenstern S, Geller A, Bar Dayan Y, Levi Z, Rodionov G, Hardy B, Konikoff F, Gobbic D, Niv Y. Gallbladder inflammation is associated with increase in mucin expression and pigmented stone formation. Dig Dis Sci 2007; 52:1613-20. [PMID: 17385041 DOI: 10.1007/s10620-006-9162-9] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2005] [Accepted: 12/01/2005] [Indexed: 12/11/2022]
Abstract
Mucin is a high molecular weight glycoprotein that plays an important role in protecting the gallbladder epithelium from the detergent effect of bile. However, it also participates in gallstone formation. There is little information about a possible relationship between gallbladder inflammation and mucin expression or gallbladder stones' characteristics. The aims of this study were to investigate stone characteristics and patterns of mucin expression in the gallbladder epithelium and bile of gallstone patients, in relation to inflammation. Gallbladder bile and tissue samples from 21 patients were obtained at surgery. Mucin content was evaluated by gel filtration on a Sepharose CL-4B column. Dot blot for bile mucin apoproteins and immunohistochemistry staining for gallbladder mucosal mucin apoproteins were performed with antibodies to MUC2, MUC3, MUC5AC, MUC5B and MUC6. Staining intensity score (0-3) was used for assessment of antigen expression and the level of inflammation. Gallstone cholesterol content was determined in 16 patients. MUC 5AC and MUC 5B were demonstrated in 95.4 and 100% of gallbladder bile samples, respectively. Immunohistochemistry staining with antibodies to MUC 2, MUC 3, MUC 5AC, MUC 5B and MUC 6 were positive in 0, 100, 85.7, 100 and 95.4% of the gallbladder mucosal samples, respectively. Pigmented brown stones were associated with a higher level of gallbladder inflammation. Mucin species expressed in gallbladder epithelium are MUC3, MUC5AC, MUC5B and MUC6. MUC5AC and MUC5B are secreted into bile. Inflammation of the gallbladder is accompanied by a higher level of MUC5AC expression and is associated with pigmented brown stones.
Collapse
Affiliation(s)
- Alexander Vilkin
- Department of Gastroenterology, Rabin Medical Center, Beilinson Campus, Tel Aviv University, Petach Tiqwa, Israel
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
3
|
Abstract
'Sludge' is the solid material which results from the slow settling of particles dispersed in a liquid medium. Biliary sludge in the gallbladder can be detected by transabdominal ultrasonography, and the typical echoes derive mainly from pigment precipitates mixed with cholesterol crystals. A portion of biliary sludge contains comparatively large particles (1-3 mm) called microliths, the formation of which is an obligatory intermediate step in the development of all types of gallstone. Microlithiasis and sludge in bile may cause colicky pain, cholecystitis, cholangitis, and acute pancreatitis, and are thus of clinical relevance. In these patients treatment follows the guidelines of symptomatic gallstone disease, and strategies include long-term application of ursodeoxycholic acid, endoscopic papillotomy, or preferably laparoscopic cholecystectomy.
Collapse
Affiliation(s)
- Christoph Jüngst
- Department of Medicine I, Universitätsklinikum Bonn, Sigmund-Freud Str. 25, 53105 Bonn, Germany
| | | | | |
Collapse
|
4
|
Jüngst D, Gussmann E, Zündt B, Meyer G, Jüngst C, Del Pozo R, Fischer S. Solubility of cholesterol in the crystal-free gallbladder bile of gallstone patients. ACTA ACUST UNITED AC 2004; 144:134-40. [PMID: 15454882 DOI: 10.1016/j.lab.2004.04.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Supersaturation of bile with cholesterol is generally considered the driving force of cholesterol precipitation. However, in most investigations the amount of cholesterol crystals is included in the calculation of the cholesterol saturation index (CSI). We therefore studied the solubility of cholesterol in crystal-free gallbladder bile from gallstone patients. Our results demonstrate significantly ( P <.05) higher CSIs (1.4 +/- 0.5 and 1.4 +/- 0.4 vs 1.1 +/- 0.4, mean +/- SD) in crystal-free gallbladder bile from 66 patients with cholesterol stones and 21 patients with mixed stones compared with those in 30 patients with pigment stones and a significant difference ( P <.001) in the amount of cholesterol in vesicles (19.2% +/- 13.7% and 14.3% +/- 11.6 % vs 4.2% +/- 5.9%) and of the crystal-observation time (COT; 1-21 days, median 2 days and 1-21 days, median 3 days, vs 3-21 days, median 21 days). We detected a positive correlation ( r =.24, P <.01) between the percentage of cholesterol in vesicles and the CSI and a negative correlation between COT and CSI ( r = -.23, P <.02 ) and COT and the percentage of cholesterol in vesicles ( r = -.52, P <.001 ). However, in 14 of 30 gallbladder-bile specimens from patients with pigment stones but in just 5 of 21 specimens from patients with mixed stones patients and 12 of 66 specimens from patients with cholesterol stones, the distribution of cholesterol in different phases (mixed micelles, vesicles, and crystals) was within the limits of solubility determined in previous studies of model bile. Therefore, in addition to the relative composition of biliary lipids, nonlipid components exert considerable influence on the solubility of cholesterol in the gallbladder bile of gallstone patients.
Collapse
Affiliation(s)
- Dieter Jüngst
- Department of Medicine II, Klinikum Grsshadern, Ludwig-Maximillians University, Munich, Germany.
| | | | | | | | | | | | | |
Collapse
|
5
|
Abstract
Biliary sludge is a mixture of particulate matter which has precipitated from bile. It generally consists of cholesterol monohydrate crystals, calcium bilirubinate or other calcium salts. In a clinical setting, biliary sludge is almost always an ultrasonographic diagnosis. Although it is less clinically applicable, direct microscopic examination of gallbladder bile is far more sensitive than ultrasonography into sludge detection, and has to be regarded as the diagnostic gold standard. The overall prevalence of sludge in the general population is relatively low. However, several clinical conditions are associated with a particularly high prevalence of biliary sludge, including pregnancy, rapid weight loss, total parenteral nutrition, octreotide therapy, bone marrow or solid organ transplantation. The clinical course of biliary sludge varies, and complete resolution, a waxing and waning course, and progression to gallstones are all possible outcomes. It may cause complications usually associated with gallstones, such as biliary colic, acute cholecystitis, and acute pancreatitis. The main pathogenic mechanism involved in sludge formation is probably gallbladder dismotility, and in selected patients measures aimed to maintain adequate gallbladder contractions has been shown to effectively prevent sludge development.
Collapse
Affiliation(s)
- P Pazzi
- Department of Gastroenterology and Digestive Endoscopy, S. Anna Hospital, Ferrara, Italy.
| | | | | | | |
Collapse
|
6
|
Jüngst D, Niemeyer A, Müller I, Zündt B, Meyer G, Wilhelmi M, del Pozo R. Mucin and phospholipids determine viscosity of gallbladder bile in patients with gallstones. World J Gastroenterol 2001; 7:203-7. [PMID: 11819761 PMCID: PMC4723523 DOI: 10.3748/wjg.v7.i2.203] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: An increased viscosity of gallbladder bile has been considered an important factor in the pathogenesis of gallstone disease. Besides lipids and proteins, mucin has been suggested to affect the viscosity of bile. To further clarify these issues we compared mucin, protein and the lipid componEnts of hepatic and gallbladder bile and its viscosity in patients with gallstones.
METHODS: Viscosity of bile (mPa.s) was measured using rotation viscosimetry in regard to the non Newtonian property of bile at low shear rates.
RESULTS: Biliary viscosity was markedly higher in gallbladder bile of patients with cholesterol (5.00 ± 0.60 mPa.s, mean ± SEM, n = 28) and mixed stones (3.50 ± 0.68 mPa.s; n = 8) compared to hepatic bile (0.92 ± 0.06 mPa.s, n = 6). A positive correlation between mucin and viscosity was found in gallbladder biles (r = 0. 65; P < 0.001) but not in hepatic biles. The addition of physiologic and supraphysiologic amounts of mucin to gallbladder bile resulted in a dose dependent non linear increase of its viscosity. A positive correlation was determined between phospholipid concentration and viscosity (r = 0.34, P < 0.005) in gallbladder biles. However, no correlation was found between total protein or the other lipid concentrations and viscosity in both gallbladder and hepatic biles.
CONCLUSION: The viscosity of gallbladder bile is markedly higher than that of hepatic bile in patients with gallstones. The concentration of mucin is the major determinant of biliary viscosity and may contribute by this mechanism to the role of mucin in the pathogenesis of gallstones.
Collapse
Affiliation(s)
- D Jüngst
- Department of Medicine II, Klinikum Grosshadern, Marchioninistr. 15, 81377 Munich, Germany
| | | | | | | | | | | | | |
Collapse
|
7
|
Abstract
Biliary sludge is a mixture of particulate solids that have precipitated from bile. Such sediment consists of cholesterol crystals, calcium bilirubinate pigment, and other calcium salts. Sludge is usually detected on transabdominal ultrasonography. Microscopy of aspirated bile and endoscopic ultrasonography are far more sensitive. Biliary sludge is associated with pregnancy; with rapid weight loss, particularly in the obese; with critical illness involving low or absent oral intake and the use of total parenteral nutrition (TPN); and following gastric surgery. It is also associated with biliary stones with common bile duct obstruction; with certain drugs, such as ceftriaxone and octreotide; and with bone marrow or solid organ transplantation. The clinical course of biliary sludge varies. It often vanishes, particularly if the causative event disappears; other cases wax and wane, and some go on to gallstones. Complications caused by biliary sludge include biliary colic, acute cholangitis, and acute pancreatitis. Asymptomatic patients with sludge or microlithiasis require no therapy. When patients are symptomatic or if complications arise, cholecystectomy is indicated. For the elderly or those at risk from the surgery, endoscopic sphincterotomy can prevent recurrent episodes of pancreatitis. Medical therapy is limited, although some approaches may show promise in the future.
Collapse
Affiliation(s)
- E A Shaffer
- Faculty of Medicine, Department of Medicine, Foothills Hospital, Room C210, 1403 29th Street NW, Calgary, AB T2N 2T9, Canada.
| |
Collapse
|
8
|
de la Porte PL, Lafont H, Domingo N, Meyer G, Müller I, Zündt B, Jüngst D. Composition and immunofluorescence studies of biliary "sludge" in patients with cholesterol or mixed gallstones. J Hepatol 2000; 33:352-60. [PMID: 11019989 DOI: 10.1016/s0168-8278(00)80269-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
Abstract
BACKGROUND/AIMS Gallbladder bile from patients with cholesterol or mixed gallstones frequently contains biliary "sludge", a suspension of cholesterol monohydrate crystals and pigment granules embedded in mucin and proteins. The composition of biliary "sludge" and the preferential localization of mucin and proteins could be an indicator for its potential role in gallstone formation. METHODS Ultracentrifugation (100000 g/l h) was used to precipitate "sludge" from bile, and the concentration difference of its main components between native bile and ultracentrifuged bile samples was calculated. After purification of the sediment, immunolocalization was performed for the detection of mucin, IgA, albumin, aminopeptidase, and anionic polypeptide fraction using polyclonal and monoclonal antibodies. RESULTS The amount of sludge in gallbladder bile was 4.26 mg/ml-0.78 (mean+/-SEM) in patients with cholesterol and 2.51 mg/ml+/-0.39 in patients with mixed stones and cholesterol was the main component (48.9+/-4.6% and 44.4+/-7.1%). The sediment appeared as a mixture of vesicular aggregates and pigment particles which were linked by a gel matrix of mucin containing cholesterol crystals. While anionic polypeptide fraction and aminopeptidase were associated to pigments, IgA was uniformly spread in the crystalline parts of "core-like" structures, and albumin, when it was present, appeared as randomly located small spots. CONCLUSIONS Our study demonstrates that the cholesterol content and the distribution pattern of mucin and different proteins is similar in the sediments of biliary "sludge" to that previously shown in cholesterol and mixed gallstones. This suggests that biliary "sludge" represents an early stage of gallstone formation in these patients.
Collapse
Affiliation(s)
- P L de la Porte
- INSERM Unite 476, Nutrition Humaine et Lipides, Marseille, France
| | | | | | | | | | | | | |
Collapse
|
9
|
Jüngst D, Müller I, Kullak-Ublick GA, Meyer G, Frimberger E, Fischer S. Deoxycholic acid is not related to lithogenic factors in gallbladder bile. THE JOURNAL OF LABORATORY AND CLINICAL MEDICINE 1999; 133:370-7. [PMID: 10218768 DOI: 10.1016/s0022-2143(99)90068-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The influence of deoxycholic acid (DCA) on the factors in gallbladder bile responsible for cholesterol gallstone disease has been a controversial subject of discussion. This might be partially due to patient selection or inappropriate methods. Therefore, we investigated the relationship between the percentage of DCA and lithogenic factors in the gallbladder bile of patients with cholesterol gallstones and with normal or moderately impaired gallbladder contractility. Patients with pigment stones served as a control group. The percentage of DCA in the gallbladder bile of 20 patients with cholesterol stones (23.2%+/-6.5%; mean+/-SD) was comparable to the DCA percentage in the gallbladder bile of 11 patients with pigment stones (26.5%+/-8.5%). No correlation was seen between the DCA percentage of total bile acids and the crystal observation time, cholesterol saturation index (CSI), total protein value, mucin level, and amount of cholesterol in vesicles or crystals in the total group of patients or in the subgroups with cholesterol or pigment stones, respectively. The lack of correlation between DCA percentage and CSI was determined in native bile (r = 0.048) as well as in crystal-free bile after ultracentrifugation (r = 0.107). Our findings demonstrate that in patients with gallstones, the percentage of DCA in gallbladder bile is not related to any of the known biliary factors associated with cholesterol gallstone disease. We conclude that in patients with normal or moderately impaired gallbladder function, an elevated DCA level in the gallbladder bile is of minor pathophysiologic significance for the formation of cholesterol gallstones.
Collapse
Affiliation(s)
- D Jüngst
- Department of Medicine II, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Germany
| | | | | | | | | | | |
Collapse
|
10
|
Catala I, Domingo N, Juste C, Gueugneau AM, Thorin B, Lutton C, Corring T, Lafont H. Effect of beta-cyclodextrin dietary supplementation on biliary proteins and their resulting cholesterol nucleating activity in pigs. BIOCHIMICA ET BIOPHYSICA ACTA 1998; 1394:74-84. [PMID: 9767121 DOI: 10.1016/s0005-2760(98)00101-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
We explored the possibility that the biliary protein fraction may support part of the variation in the nucleating activity previously measured in gallbladder biles of pigs. Eighteen gallbladder aspirates freshly obtained from three dietary groups (0, 5, or 10% beta-cyclodextrin) of six pigs were chromatographed to purify their total protein fraction. Proteins were quantified, and analysed through electrophoresis and immunoblotting or enzyme-linked immunosorbent assay for albumin, and five putative effectors of cholesterol crystallisation, mucins, immunoglobulin A, 130 kDa, apolipoprotein A-I, and anionic polypeptide fraction. Each total protein fraction was also assayed for its ability to influence cholesterol precipitation, when added to supersaturated model bile. The current data provided evidence that the cholesterol crystallisation-promoting activity of biliary proteins in model biles increased with the beta-cyclodextrin dietary content. This occurred without any significant change in the total biliary protein content, but was associated with a significant decrease in the concentration of albumin and apolipoprotein A-I, resulting in changes in the overall balance of proteins in bile. Comparison of these results with the crystallisation figures previously obtained from the corresponding native biles led us to conclude that biliary proteins might influence the outcome of the crystallisation process, namely the final crystal concentration at equilibrium, but would not systematically represent a major driving force for determining the velocity of crystal formation in native bile of pigs.
Collapse
Affiliation(s)
- I Catala
- Laboratoire d'Ecologie et de Physiologie du Système Digestif, INRA, 78352 Jouy-en-Josas Cedex, France
| | | | | | | | | | | | | | | |
Collapse
|
11
|
Juste C, Catala I, Riottot M, André M, Parquet M, Lyan B, Béguet F, Ferézou-Viala J, Sérougne C, Domingo N, Lutton C, Lafont H, Corring T. Inducing cholesterol precipitation from pig bile with beta-cyclodextrin and cholesterol dietary supplementation. J Hepatol 1997; 26:711-21. [PMID: 9075681 DOI: 10.1016/s0168-8278(97)80439-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND/METHODS In this study, pigs fed for 3 weeks a well-balanced semi-purified diet enriched with 0.3% cholesterol and 0, 5 or 10% beta-cyclodextrin were proposed as new animal donors of gallbladder bile exhibiting different rates of cholesterol crystallization, in order to gain insight into the early mechanisms underlying cholesterol precipitation in vivo. The appearance and growth of cholesterol crystals were monitored in the incubated freshly collected gallbladder biles through light microscopy and concomitant time-sequential determination of crystallized cholesterol concentration, and interpreted in terms of the composition of the bile. RESULTS Although the concentration of total lipids and proteins and the relative proportions of bile acids, phospholipids, and cholesterol remained unchanged under beta-cyclodextrin, the cholesterol crystallization increased in the following order: 0<<10<5% beta-cyclodextrin. Concomitantly, the proportion of chenodeoxycholic acid in bile, and the hydrophobicity index of the biliary bile acid mixture increased in the following order: 0<5<10% beta-cyclodextrin (the same as reported elsewhere for the decrease in the antinucleating ApoA1), while sn-2 arachidonoyl biliary lecithins were specifically increased with 5% beta-cyclodextrin in the diet. CONCLUSIONS We hypothesized that lecithin molecular species may be the determinant factor in modulating high cholesterol crystallization rates in biles otherwise enriched with hydrophobic bile acids.
Collapse
Affiliation(s)
- C Juste
- Laboratoire d'Ecologie et de Physiologie du Système Digestif, INRA, Jouy-en-Josas, France
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|