Skip to main content
SpringerLink
Log in

Progress in the study on the composition and formation mechanism of gallstone

  • Published:
Science in China Series B: Chemistry Aims and scope Submit manuscript

Abstract

Our serial studies from {dy1970}s on chemical composition, structure determination and formation mechanism of gallstones were reviewed. The chemical component investigation of brown-pigment gallstone demonstrated that it consists of macromolecules such as proteins, glycoproteins, polysaccharides, bilirubin polymers and pigment polymers, and biomolecules such as cholesterol, bile salts, calcium salts of carbonate, phosphate, fatty acids and bilirubinate as well as various metal ions. The binding of metal ions with bile salts and bilirubin plays important roles in gallstone formation, i.e., calcium bilirubinate complex is the major constitute of brown-pigment gallstones, and copper bilirubinate complex is critical in the black color appearance of black-pigment gallstone. The cross section of many gallstones exhibits a concentric ring structure composed of various small particles with a fractal character. This is nonlinear phenomenon in gallstone formation. Atypical model system of metal ions-deoxycholate (or cholate)-gel was chosen to mimic an in vitro pattern formation system. The experimental results suggested that a nonlinear scientific concept should be considered in understanding gallstone formation. Minor changes in the chemical composition and/or the microenvironment may lead to very different precipitate patterns with a variety of shapes, colors, appearances, and structures. A new model was suggested that periodical templets of periodical and fractal patterns were formed in the initial stage, then the spatio-temporal patterns grew gradually on it. Furthermore, the interaction between divalent metal ions and bile saltsin vitro was investigated, and the results indicated that non-stoichiometric M(DC)2-NaDC mixed complexes with mixed micelles structure can be formed in physiological condition.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Soloway, R. D., Trotman, B. W., Maddrey, W. C. et al., The influence of hemolysis, infection and stasis on the calcium salts in pigment gallstones, Dig. Dis. Sci., 1986, 31: 454–460.

    Article  CAS  Google Scholar 

  2. Cheng, L. J., Zhang, Y., Ma, J. S. et al., Chemical preparation and properties of ditaurobilirubin disodium salt, Chemical Reagents, 2000, 22(2): 70–71.

    Google Scholar 

  3. Ma, J. S., Wang, C. Q., Yan, F., Hypocrellin A-sensitized photooxidation of bilirubin in aprotic solvents, Photographic Science and Photochemistry, 1991,9(1): 58–61.

    CAS  Google Scholar 

  4. Yang, Z. H., Wang, K., Liu, X. T., Studies of electron-spin-resonance on bilirubin free radicals, Science in China, Series B, 1992, 35(9): 1093–1100.

    CAS  Google Scholar 

  5. Ostrow, J. D., Overview the bile pigment metabolism, in Bile Pigments and Jaundice: Molecular, Metabolic, and Medical Aspects (ed. Ostrow, J. D.), New York: Marcel Dekker, 1986,1–6.

    Google Scholar 

  6. Ouyang, J. M., Li, C., Li, Y. Q. et al., Monolayer and Langmuir-Blodgett films of bilirubin dihexadecyl ester, Thin Solid Films, 1999, 348: 242–247.

    Article  CAS  Google Scholar 

  7. Wu, J. G., Shen, G. R., Zhou, X. S. et al., Structure characteristics of bilirubin gallstone, Chinese Science Bulletin, 1979, 24: 1054–1056.

    CAS  Google Scholar 

  8. Zhou, X. S., Wang, S. S., Wu, J. G. et al., Pigment gallstones study, Chinese Medical Journal, 1982, 95(12): 905–911.

    CAS  Google Scholar 

  9. Wu, J. G., Shen, G. R., Zhou, X. S. et al., Study on the composition, structure and mechanism of formation of bilirubin gallstone, ActaScientiarumNaturaliumUniversitatisPekinensis, 1980, 1:34–43.

    Google Scholar 

  10. Zhou, X. S., Shen, G. R., Wu, J. G. et al., A spectroscopic study of pigment gallstone in China, Biospectroscopy, 1997, 3(3): 371–380.

    Article  CAS  Google Scholar 

  11. Soloway, R. D., Wu, J. G., Analysis of Gallstones, Boca Raton, Ann Arbor, London, Tokyo: CRC Press, 1995,167–190.

    Google Scholar 

  12. Yang, Z. L., Weng, S. F., Wu, J. G., Study on the composition of pigment gallstones, Acta Scientiarum Naturalium Univer- sitatis Pekinensis, 1998, 34(4): 429–434.

    CAS  Google Scholar 

  13. Soloway, R. D., Song, Y. Y., Wu, J. G. et al., Serial Fourier transform infrared and FT-Raman spectroscopy with increasing temperature to examine bilirubinates and black gallstones, Gastroenterology, 1999, 116(4): G0136.

    Google Scholar 

  14. Song, Y. Y., Xu, Z. H., Wu, J. G. et al., SERS of bilirubin and its complexes, Spectroscopy and Spectral Analysis, 1999, 19(2): 165–167.

    CAS  Google Scholar 

  15. Xu, Z. Y., Li, W. H., Wu, J. G. et al., FT-Raman study on gallstones, Chinese Journal of Light Scattering, 1995, 7(23): 172–176.

    Google Scholar 

  16. Yang, Z. L., Soloway, R. D., Wu, J. G. et al., NMR-H1 evidence for the variability of probonated bilirubin and bilirubinate (BR) configuration in different solvents: Why sodium BR is soluble and calcium BR precipitates, Gastroenterology, 1997, 112(4):A529.

    Google Scholar 

  17. Soloway, R. D., Wu, J. G., Xu, D. F., Pigment gallstones and secondary calcification of gallstones, in Gallstone Disease, Pathophysiology and Therapeulic Approaches (ed. Swobodink, W., Ditshuneit, H., Soloway, R. D.), Berlin: Springer- Verlag, 1990, 35–46.

    Google Scholar 

  18. Xu, Y. Z., Chen, Z. D., Wu, J. G. et al., The fractal phenomena in molecular mechanics calculation, Science in China, Series B, 1997, 40(4): 419–427.

    CAS  Google Scholar 

  19. Xu, Y. Z., Tao, J., Xu, Z. H. et al., Structural basis for the discrepancy of spectral behavior in C-H stretching band between steroids and long chain hydrocarbon compounds, Science in China, Series B, 1999, 42(2): 178–184.

    Article  CAS  Google Scholar 

  20. Xu, Y. Z., Chen, Z., D., Wu, J. G. et al., Molecular mechanics investigation of the intra-molecular hydrogen bond stability of bile acids, Acta Scientiarum Naturalium Universitatis Pekinensis, 1996, 32(4): 425–430.

    CAS  Google Scholar 

  21. Xu, Y. Z., Weng, S. F., Wu, J. G. et al., 2DIR spectroscopic studies on cholic acid, Two-Dimensional Correlation Spec- troscopy, 1999, CP503: 303–306.

    Google Scholar 

  22. Soloway, R. D., Wu, J. G., Shen, G. R. et al., Protein trapping of salts as a mechanism of black pigment gallstone nidation and growth, Gastroenterology, 1987, 92 (5): Part 2, 1780–1802.

    Google Scholar 

  23. Hou, R. Z., Wu, J. G., Soloway, R. D. et al., Fourier transform infrared photoacoustic spectroscopy of dental calculus, Mi- crochim. Acta, 1988, 2: 133–136.

    Google Scholar 

  24. Taylor, D. R., Crowther, R. S., Wu, J. G. et al., Calcium carbonate in cholesterol gallstones: polymorphism, distribution, and hypotheses about pathogenesis, Hepatology, 1995, 22 (2): 488–496.

    CAS  Google Scholar 

  25. Liu, J. H., Soloway, R. D., Wu, J. G. et al., How does Ca bilirubinate bind to protein in gallstones? Gastroenterology, 1994, 106 (4): A346.

    Google Scholar 

  26. Wagner, A. J., Wu, J. G., Soloway, R. D. et al., Does the structure of calcium bilirubinate provide special properties contributing to its precipitation in bile? A comparison with other metal bilirubinates by Fourier transform infrared spectroscopy (FT-IR), Hepatology, 1987, 7 (5): 1138–1139.

    Google Scholar 

  27. Wu, J. G., Soloway, R. D., Xu, D. F. et al., FT-IR study on calcium ions binding to bilirubin, 7th International Conference on FTS, Abstract Program p2.6, SPIE, 1989, 1145:264.

  28. Yang, Z. L., Soloway, R. D., Wu, J. G. et al., Calcium binds with both the carboxyl and pyrrole groups of bilirubinate in vitro formation of non-stoichoimetric salt, Gastroenterology, 1991, 100 (5): A813.

    Google Scholar 

  29. Yang, B. J., Wu, J. G., Soloway, R. D. et al., Normal coordinate analysis of bilirubin vibrational spectra: effects of intramolecular hydrogen bonding, SpectrochimicaActa, 1993, 49A (12): 1735–1746.

    Article  CAS  Google Scholar 

  30. Soloway, R. D., Wu, J. G., Yang, Z. L. et al., Why does Ca++ vary from 3 to 12% in non-stoichiometric calcium bilirubinates? Gastroenterology, 1994, 106 (4): A359.

    Google Scholar 

  31. Wu, E., Wu, J. G., Xu, G. X. et al., Gallstone analysis by ESR spectroscopy, Chinese Science Bulletin, 1989, 34 (23): 1996–2000.

    Google Scholar 

  32. Guo, H., Soloway, R. D., Wu, J. G. et al., Dependence of equilibrium swelling on an interaction between calcium bilirubinate and protein, Gastroenterology, 1990, 98 (5): A249.

    Google Scholar 

  33. Shen, G. R., Li, W. H., Wu, J. G. et al., Measurement and characterization of black gallstone composition using extraction with serial solvents, Gastroenterology, 1997, 112(4): A523.

    Google Scholar 

  34. Soloway, R. D., Wu, J. G., Pigment Oxidation and Polymers with Emphasis on the Role of Copper Complexes, Trieste: Bilirubin Workshop, April 6–8, 1995.

    Google Scholar 

  35. Li, W. H., Soloway, R. D., Wu, J. G. et al., Copper forms black bilirubinate salts related to the formation of free radicals and causes alternation of the pyrrole rings and tetrapyrrole structure, Trieste: Bilirubin Workshop, 1992.

    Google Scholar 

  36. Ferraro, J. R., Wu, J. G., Li, W. H. et al., Copper binding to bilirubin as determined by FT-IR and EPR spectroscopy, Applied Spectroscopy, 1996, 50 (7): 922–934.

    Article  CAS  Google Scholar 

  37. Li, W. H., Shen, G. R., Wu, J. G. et al., Copper bilirubinate and black pigment gallstone, Biospectroscopy, 1995, 1 (2): 149–156.

    Article  CAS  Google Scholar 

  38. Shi, J. S., Qiu, S. M., Wu, J. G. et al., FT-IR study on black-pigment gallstone, Chinese Surgical Journal, 1988, 26 (11): 149 -156.

    Google Scholar 

  39. Wu, J. G., Xu, D. F., Zhou, X. S. et al., Do ring form in gallstone during growth due to the Liesegang phenomenon or periodic desposition? Gastroenterology, 1990, 98 (5): A254.

    Google Scholar 

  40. Li, X. F., Soloway, R. D., Wu, J. G. et al., Chaotic and periodic precipitation in a Ca-Cu bile salt system: relation to gallstone formation, Clinical Research, 1993, 41 (2): A158.

    Google Scholar 

  41. Peng, Q., Wu, J. G., Xu, D. F. et al., Periodic and chaotic precipitation phenomena in bile salt system related to gallstone formation, Biospectroscopy, 1997, 3: 195–205.

    Article  CAS  Google Scholar 

  42. Li, X. F., Soloway, R. D., Wu, J. G. et al., Liesegang Rings phenomenon and gallstone formation, Science in China, Series B (in Chinese), 1996, 26 (1): 52–56.

    Google Scholar 

  43. Wang, L. B., Hu, T. D., Wu, J. G. et al., Micro FT-IR and EXAFS studies on periodic and chaotic precipitations in bile salt systems, Mikrochimi Acta, 1997, [Suppl.]14: 345–347.

    CAS  Google Scholar 

  44. Xie, D. T., Wu, J. G., Xu, G. X. et al., Three-dimensional periodic and fractal precipitation in metal ion-deoxycholate sys- tem: Amodel for gallstone formation, J. Phys. Chem. B, 1999, 103 (40): 8602–8605.

    Article  CAS  Google Scholar 

  45. Xie, D. T., Xu, Y. Z., Wu, J. G. et al., Development of a three dimensional metal-bile salt-gel system to study periodic and chaotic precipitation as a model of gallstone growth, Gastroenterology, 1997, 112(4): A528.

    Google Scholar 

  46. Wu, J. G., Zhou, X. S., Xu, D. F. et al., A spectroscopic investigation of the formation mechanism of pigment gallstones, Biospectroscopy (invited review), 1997, 3: 381–391.

    Article  CAS  Google Scholar 

  47. Peng, Q., Li, W. H., Wu, J. G. et al., Other components of bile influence the pattern of metal-deoxycholate precipiation in agar gel, Gastroenterology, 1997, 112(4): A520.

    Google Scholar 

  48. Yang, Z. L., Wu, J. G., Xu, G. X. et al., Influence of cholesterol, lecithin, and bilirubin on patterns of precipitates of bile acid-divalent metals, Gastroenterology, 1997, 112 (4): A529.

    Google Scholar 

  49. Liu, Z. J., Soloway, R. D., Wu, J. G. et al., Ca++ increases bile salt mixed micelle size and cholesterol solubility, Clinical Research, 1993, 41(2): A159.

    Google Scholar 

  50. Liu, Z. J., Wu, J. G., Xu, G. X. et al., Studies on the influence of metal ions on the colloid properties of sodium taurocho- late by laser scattering and fluoresence spectroscopy, Acta Scientiarum Naturalium Universitatis Pekinensis, 1994, 30(6): 641–657.

    CAS  Google Scholar 

  51. Sun, Y., Yang, Z. L., Soloway, R. D. et al., The effects of varying the proportions of Co(DC)2-NaDC in mixed micelles on the resulting precipitates, Gastroenterology, 1999, 116(4): G0146.

    Google Scholar 

  52. Sun, Y., Yang, Z. L., Wu, J. G. et al., Study on the Co(DC)2-NaDC mixed micelle system, Spectroscopy and Spectral Anly- sis, 1999, 19 (2): 172–176.

    CAS  Google Scholar 

  53. Sun, Y., Yang, Z. L., Wu, J. G. et al., Effectt of various divalent metal ions (Co2+, Ca2+ and Cu2+) on the cation composition of precipitates from a mixed micelle (M(DC)2-NaDC) system, Gastroenterology, 2000, 118(4): 306.

    Google Scholar 

  54. Sun, Y., Yang, Z. L., Wu, J. G. et al., Study on the interaction of Ca2+, La3+and Eu3+ with NaDC micelle, Acta Phys- ico-Chimica Sinica, 2000, 16 (10): 873–878.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Chemistry and Molecular Engineering, Department of Chemical Biology, Peking University, 100871, Beijing, China

    Ying Sun, Zhanlan Yang, Guorong Shen, Yong Zhou, Jinguang Wu & Guangxian Xu

  2. College of Medicine, Peking University, 100871, Beijing, China

    Xiaosi Zhou

Authors
  1. Ying Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhanlan Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guorong Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yong Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaosi Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jinguang Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Guangxian Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sun, Y., Yang, Z., Shen, G. et al. Progress in the study on the composition and formation mechanism of gallstone. Sc. China Ser. B-Chem. 44, 449–456 (2001). https://doi.org/10.1007/BF02880673

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02880673

Keywords

Search

Navigation