Annals of Biomedical Engineering

, Volume 39, Issue 2, pp 786–800 | Cite as

A Mechanical Model for CCK-Induced Acalculous Gallbladder Pain

  • W. G. Li
  • X. Y. Luo
  • N. A. Hill
  • R. W. Ogden
  • A. Smythe
  • A. Majeed
  • N. Bird
Article
First Online:
Received:
Accepted:

Abstract

This study investigates the potential correlation between acalculous biliary pain and mechanical stress during the bile-emptying phase. This study is built on the previously developed mathematical model used to estimate stress in the gallbladder wall during emptying [Li, W. G., X. Y. Luo, et al. Comput. Math. Methods Med. 9(1):27–45, 2008]. Although the total stress was correctly predicted using the previous model, the contribution from patient-specific active stress induced by the cholecystokinin (CCK) test was overlooked. In this article, we evaluate both the active and passive components of pressure in a gallbladder, which undergoes isotonic refilling, isometric contraction and emptying during the infusion of CCK. The pressure is estimated from in vivo ultrasonographical scan measurements of gallbladder emptying during CCK tests, assuming that the gallbladder is a thin ellipsoidal membrane. The passive stress is caused by the volume and shape changes during refilling at the gallbladder basal pressure, whereas the active stress arises from the pressure rise during the isometric gallbladder contraction after the CCK infusion. The effect on the stress estimates of the gallbladder to the liver is evaluated to be small by comparing numerical simulations of a gallbladder model with and without a rigid ‘flat top’ boundary. The model was applied to 51 subjects, and the peak total stress was found to have a strong correlation with the pain stimulated by CCK, as measured by the patient pain score questionnaires. Consistent with our previous study for a smaller sample, it is found that the success rate in predicting of CCK-induced pain is over 75%.

Keywords

Gallbladder Active stress Passive stress Acalculous biliary pain Emptying Refilling Isometric contraction Isotonic refilling CCK 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgment

The project was supported by EPSRC through grant EP/G015651.

References

  1. 1.
    Almkvist, G., and B. Berndt. Gauss, Landen, Ramanujan, the arithmeticgeometric mean, ellipses, π and the ladies diary. Am. Math. Mon. 95:585–608, 1988.CrossRefGoogle Scholar
  2. 2.
    Barlow, J., H. Gregersen, et al. Identification of the biomechanical factors associated with the perception of distension in the human esophagus. Am. J. Physiol. Gastrointest. Liver Physiol. 282(4):683–689, 2002.Google Scholar
  3. 3.
    Bathe, K. J. Finite Element Procedures. Englewood Cliffs, NJ: Prentice Hall, 1996.Google Scholar
  4. 4.
    Beckingham, I. J. ABC of diseases of liver, pancreas, and biliary system: gallstone disease. Br. Med. J. 322(7278):91, 2001.CrossRefGoogle Scholar
  5. 5.
    Body, L., L. Højgaard, et al. Human gallbladder pressure and volume: validation of a new direct method for measurements of gallbladder pressure in patients with acute cholecystitis. Clin. Physiol. Funct. Imaging 16(2):145–156, 2008.Google Scholar
  6. 6.
    Brotschi, E., K. Crocker, et al. Effect of low extracellular calcium on gallbladder contractionin vitro. Dig. Dis. Sci. 34(3):360–366, 1989.CrossRefPubMedGoogle Scholar
  7. 7.
    Chijiiwa, K., T. Yamasaki, et al. Direct contractile response of isolated gallbladder smooth muscle cells to cholecystokinin in patients with gallstones. J. Surg. Res. 56(5):434–438, 1994.CrossRefPubMedGoogle Scholar
  8. 8.
    Claus, P., M. McLaughlin, et al. Estimation of active myocardial force development: a feasibility study in a potentially clinical setting. Proceedings of the 25th Annual International Conference of the IEEE EMBS, Cancun, Mexico, September 17–21, 2003.Google Scholar
  9. 9.
    Cozzolino, H., F. Goldstein, et al. The cystic duct syndrome. JAMA 185(12):920, 1963.PubMedGoogle Scholar
  10. 10.
    Dodds, W. J., W. J. Hogan, et al. Motility of the biliary system. In: Handbook of Physiology: the Gastrointestinal System, Vol. 1, Section 6, Part 2(28), edited by S. G. Schultz. Betheda, Maryland: American Physiological Society, 1989, pp. 1055–1101.Google Scholar
  11. 11.
    Drewes, A., H. Gregersen, et al. Experimental pain in gastroenterology: a reappraisal of human studies. Scand. J. Gastroenterol. 38(11):1115–1130, 2003.CrossRefPubMedGoogle Scholar
  12. 12.
    Ferris, D., and J. Vibert. The common bile duct: significance of its diameter. Ann. Surg. 149(2):249–251, 1959.CrossRefPubMedGoogle Scholar
  13. 13.
    Fuller, R. A., J. A. Kuhn, et al. Laparoscopic cholecystectomy for acalculous gallbladder disease. Proc. (Bayl. Univ. Med. Cent.) 13(4):331–333, 2000.Google Scholar
  14. 14.
    Gaensler, E. Quantitative determination of the visceral pain threshold in man. J. Clin. Invest. 30:406, 1951.CrossRefPubMedGoogle Scholar
  15. 15.
    Gao, C., L. Arendt-Nielsen, et al. Sensory and biomechanical responses to ramp-controlled distension of the human duodenum. Am. J. Physiol. Gastrointest. Liver Physiol. 284(3):461, 2003.Google Scholar
  16. 16.
    Herman, I. P. Physics of the Human Body. Berlin: Springer, p. 214, 2007.Google Scholar
  17. 17.
    Herring, P., and S. Simpson. The pressure of bile secretion and the mechanism of bile absorption in obstruction of the bile duct. Proc. R. Soc. Lond., B, Biol. Sci. 79(535):517–532, 1907.Google Scholar
  18. 18.
    Hould, F. S., G. M. Fried, et al. Progesterone receptors regulate gallbladder motility. J. Surg. Res. 45(6):505–512, 1988.CrossRefPubMedGoogle Scholar
  19. 19.
    Hunter, P., and B. Smaill. The analysis of cardiac function: a continuum approach. Prog. Biophys. Mol. Biol. 52(2):101–164, 1988.CrossRefPubMedGoogle Scholar
  20. 20.
    Ishizuka, J., M. Murakami, et al. Age-related changes in gallbladder contractility and cytoplasmic Ca2+ concentration in the guinea pig. Am. J. Physiol. Gastrointest. Liver Physiol. 264(4):624, 1993.Google Scholar
  21. 21.
    Lambert, R., and J. Ryan. Response to calcium of skinned gallbladder smooth muscle from newborn and adult guinea pigs. Pediatr. Res. 28(4):336, 1990.CrossRefPubMedGoogle Scholar
  22. 22.
    Langley, G. B., and H. Sheppeard. The visual analogue scale: its use in pain measurement. Rheumatol. Int. 5(4):145–148, 1985.CrossRefPubMedGoogle Scholar
  23. 23.
    Lee, K., P. Biancani, et al. Calcium sources utilized by cholecystokinin and acetylcholine in the cat gallbladder muscle. Am. J. Physiol. Gastrointest. Liver Physiol. 256(4):785, 1989.Google Scholar
  24. 24.
    Li, W. G., X. Y. Luo, et al. One-dimensional models of the human biliary system. J. Biomech. Eng.-Trans. ASME 129(2):164–173, 2007.CrossRefGoogle Scholar
  25. 25.
    Li, W. G., X. Y. Luo, et al. Correlation of mechanical factors and gallbladder pain. Comput. Math. Methods Med. 9(1):27–45, 2008.CrossRefGoogle Scholar
  26. 26.
    Luo, X. Y., W. G. Li, et al. On the mechanical behaviour of the human biliary system. World J. Gastroenterol. 13:1384–1392, 2007.Google Scholar
  27. 27.
    MacPherson, B., G. Scott, et al. The muscle layer of the canine gallbladder and cystic duct. Cells Tissues Organs 120(3):117–122, 1984.CrossRefGoogle Scholar
  28. 28.
    Mahour, G., K. Wakim, et al. The common bile duct in man: its diameter and circumference. Ann. Surg. 165(3):415, 1967.CrossRefPubMedGoogle Scholar
  29. 29.
    Meiss, R. Graded activation in rabbit mesotubarium smooth muscle. Am. J. Physiol. 229(2):455, 1975.PubMedGoogle Scholar
  30. 30.
    Melzack, R. The McGill Pain Questionnaire: major properties and scoring methods. Pain 1(3):277–299, 1975.CrossRefPubMedGoogle Scholar
  31. 31.
    Middelfart, H. V., P. Jensen, et al. Pain patterns after distension of the gallbladder in patients with acute cholecystitis. Scand. J. Gastroenterol. 33(9):982–987, 1998.CrossRefPubMedGoogle Scholar
  32. 32.
    Morales, S., P. Camello, et al. Characterization of intracellular Ca2+ stores in gallbladder smooth muscle. Am. J. Physiol. Gastrointest. Liver Physiol. 288(3):G507, 2005.CrossRefPubMedGoogle Scholar
  33. 33.
    Ness, T. J., and G. F. Gebhart. Visceral pain: a review of experimental studies. Pain 41(2):167–234, 1990.CrossRefPubMedGoogle Scholar
  34. 34.
    Novozhilov, V. V. Thin Shell Theory. Groningen: P. Noordhoff Ltd, pp. 124–1130, 1964.Google Scholar
  35. 35.
    Ooi, R. C., X. Y. Luo, et al. The flow of bile in the human cystic duct. J. Biomech. 37(12):1913–1922, 2004.CrossRefPubMedGoogle Scholar
  36. 36.
    Parkman, H., A. Pagano, et al. Electric field stimulation-induced guinea pig gallbladder contractions (role of calcium channels in acetylcholine release). Dig. Dis. Sci. 42(9):1919–1925, 1997.CrossRefPubMedGoogle Scholar
  37. 37.
    Parkman, H., R. Garbarino, et al. Myosin light chain phosphorylation correlates with contractile force in guinea pig gallbladder muscle. Dig. Dis. Sci. 46(1):176–181, 2001.CrossRefPubMedGoogle Scholar
  38. 38.
    Pauletzki, J., M. Sackmann, et al. Evaluation of gallbladder volume and emptying with a novel three-dimensional ultrasound system: comparison with the sum-of-cylinders and the ellipsoid methods. J. Clin. Ultrasound 24(6):277–285, 1996.CrossRefPubMedGoogle Scholar
  39. 39.
    Petersen, P., C. Gao, et al. Pain intensity and biomechanical responses during ramp-controlled distension of the human rectum. Dig. Dis. Sci. 48(7):1310–1316, 2003.CrossRefPubMedGoogle Scholar
  40. 40.
    Renzetti, L., M. Wang, et al. Contribution of intracellular calcium to gallbladder smooth muscle contraction. Am. J. Physiol. Gastrointest. Liver Physiol. 259(1):G1, 1990.Google Scholar
  41. 41.
    Ryan, J. Calcium and gallbladder smooth muscle contraction in the guinea pig: effect of pregnancy. Gastroenterology 89(6):1279, 1985.PubMedGoogle Scholar
  42. 42.
    Ryan, J., and S. Cohen. Gallbladder pressure-volume response to gastrointestinal hormones. Am. J. Physiol. 230(6):1461, 1976.PubMedGoogle Scholar
  43. 43.
    Schoetz, Jr., D., W. LaMorte, et al. Mechanical properties of primate gallbladder: description by a dynamic method. Am. J. Physiol. Gastrointest. Liver Physiol. 241(5):376, 1981.Google Scholar
  44. 44.
    Shaffer, E. A. Epidemiology of gallbladder stone disease. Best Pract. Res. Clin. Gastroenterol. 20(6):981–996, 2006.CrossRefPubMedGoogle Scholar
  45. 45.
    Shaffer, E., A. Bomzon, et al. The source of calcium for CCK-induced contraction of the guinea-pig gallbladder. Regul. Pept. 37(1):15–26, 1992.CrossRefPubMedGoogle Scholar
  46. 46.
    Shimada, T. Voltage-dependent calcium channel current in isolated gallbladder smooth muscle cells of guinea pig. Am. J. Physiol. Gastrointest. Liver Physiol. 264(6):1066, 1993.Google Scholar
  47. 47.
    Shoucri, R. Theoretical study of pressure-volume relation in left ventricle. Am. J. Physiol. Heart Circ. Physiol. 260(1):H282, 1991.Google Scholar
  48. 48.
    Shoucri, R. Studying the mechanics of left ventricular contraction. IEEE Eng. Med. Biol. Mag. 17(3):95–101, 1998.CrossRefPubMedGoogle Scholar
  49. 49.
    Shoucri, R. Active and passive stresses in the myocardium. Am. J. Physiol. Heart Circ. Physiol. 279(5):H2519, 2000.PubMedGoogle Scholar
  50. 50.
    Smythe, A., A. Majeed, et al. A requiem for the cholecystokinin provocation test? Gut 43(4):571, 1998.CrossRefPubMedGoogle Scholar
  51. 51.
    Smythe, A., R. Ahmed, et al. Bethanechol provocation testing does not predict symptom relief after cholecystectomy for acalculous biliary pain. Dig. Liver Dis. 36(10):682–686, 2004.CrossRefPubMedGoogle Scholar
  52. 52.
    Streeter, Jr., D., R. Vaishnav, et al. Stress distribution in the canine left ventricle during diastole and systole. Biophys. J. 10(4):345–363, 1970.CrossRefPubMedGoogle Scholar
  53. 53.
    Washabau, R., M. Wang, et al. Effect of muscle length on isometric stress and myosin light chain phosphorylation in gallbladder smooth muscle. Am. J. Physiol. Gastrointest. Liver Physiol. 260(6):920, 1991.Google Scholar
  54. 54.
    Washabau, R., M. Wang, et al. Role of myosin light-chain phosphorylation in guinea pig gallbladder smooth muscle contraction. Am. J. Physiol. Gastrointest. Liver Physiol. 266(3):G469, 1994.Google Scholar
  55. 55.
    Williamson, R. Acalculous disease of the gallbladder. Gut 29(6):860, 1988.CrossRefPubMedGoogle Scholar
  56. 56.
    Yamasaki, T., K. Chijiiwa, et al. Direct contractile effect of motilin on isolated smooth muscle cells from human gallbladder. J. Surg. Res. 56(1):89–93, 1994.CrossRefPubMedGoogle Scholar
  57. 57.
    Zhang, L., A. Bonev, et al. Ionic basis of the action potential of guinea pig gallbladder smooth muscle cells. Am. J. Physiol., Cell Physiol. 265(6):C1552, 1993.Google Scholar

Copyright information

© Biomedical Engineering Society 2010

Authors and Affiliations

  • W. G. Li
    • 1
  • X. Y. Luo
    • 1
  • N. A. Hill
    • 1
  • R. W. Ogden
    • 1
  • A. Smythe
    • 2
  • A. Majeed
    • 2
  • N. Bird
    • 2
  1. 1.School of Mathematics and StatisticsUniversity of GlasgowGlasgowUK
  2. 2.Academic Surgical Unit, Royal Hallamshire HospitalSheffieldUK

Personalised recommendations