Functional Disorders of the Biliary Tract and Cholelithiasis: Analysis of a Possible Relationship
https://doi.org/10.22416/1382-4376-2024-34-4-94-103
Abstract
Aim: Diagnostic criteria for functional disorders of the biliary tract are presented in the materials of the Rome IV consensus, as well as expert councils of Russian and foreign specialists. Episodes of functional biliary pain are caused by a violation of bile outflow through the cystic duct and sphincter of Oddi. It has been suggested that there is a “biliary continuum” in which in some patients’ biliary dysfunction is transformed into cholelithiasis.
Key points. Lithogenic bile is considered as the pathophysiological basis for the development of biliary dyskinesia and cholelithiasis. Lithogenic bile provokes inflammation of low grades in the mucous membrane of the biliary tract, decreased contractility of the gallbladder and impaired relaxation of the biliary sphincters, impaired physiological response to cholecystokinin. Changes in motility of the biliary tract may be associated with the influence of hydrophobic bile salts and impaired eicosanoid metabolism. Hyperplasia of the epithelium and muscle layer, hypersecretion of mucin and cholesterol precipitation further impair the outflow of bile. Experimental data and some clinical observations indicate the possibility of transformation of biliary dysfunction into cholelithiasis. Dysfunction of the sphincter of Oddi is one of the possible consequences of cholecystectomy and, in fact, acts as a variant of postcholecystectomy syndrome. The basis for the treatment of biliary dysfunctions are antispasmodics of different classes, which can be combined with ursodeoxycholic acid. The biliary tract-selective antispasmodic hymecromone has shown high effectiveness in relieving biliary pain, which also has a moderate choleretic effect and the ability to prevent the crystallization of cholesterol in bile and can be used both for functional diseases and for cholelithiasis. The domestic drug hymecromone “Odecromone” entered the pharmaceutical market.
Conclusion. There is no doubt that the relevance of further study of the patterns of development of biliary dysfunctions and GI is obvious. The study of this problem will contribute to the development of effective preventive approaches, including in the field of nutraceuticals.
About the Authors
Yu. O. ShulpekovaRussian Federation
Yulia O. Shulpekova, Cand. Sci. (Med.), Associate Professor
Department of Internal Diseases Propedeutics, Gastroenterology and Hepatology
119991; Pogodinskaya str., 1, build. 1; Moscow
I. R. Popova
Russian Federation
Irina R. Popova, Dr. Sci. (Med.), Professor
Department of Internal Diseases Propedeutics, Gastroenterology and
Hepatology
119435; Pogodinskaya str., 1, build. 1; Moscow
V. M. Nechaev
Russian Federation
Vladimir M. Nechaev, Cand. Sci. (Med.), Associate Professor
Department of Internal Diseases Propedeutics, Gastroenterology and Hepatology
119435; Pogodinskaya str., 1, build. 1; Moscow
References
1. Ivashkin V.T., Mayev I.V., Shulpekova Yu.O., Baranskaya Ye.K., Okhlobystin A.V., Trukhmanov A.S., et al. Diagnostics and treatment of biliary dyskinesia: clinical guidelines of the Russian gastroenterological Association. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2018;28(3):63–80. (In Russ.) DOI: 10.22416/1382-4376-2018-28-3-63-80
2. Nersesov A.V., Kaibullaeva D.A., Vasnev O.S., Tashenova L.K., Sakhipov M.M., Berestimov G.T., et al. A modern conception of postcholecystectomy syndrome (based on materials from the expert council held on May 4, 2019, in Almaty, Kazakhstan). Farmakoekonomika. Modern Pharmacoeconomics and Pharmacoepidemiology. 2020;13(2):205–19. (In Russ.) DOI: 10.17749/2070-4909/farmakoekonomika.2020.036
3. Cotton P.B., Elta G.H., Carter C.R., Pasricha P.J., Corazziari E.S. Rome IV. Gallbladder and sphincter of Oddi disorders. Gastroenterology. 2016:150(6):1420–9. E2. DOI: 10.1053/j.gastro.2016.02.033
4. Bueverova E.L., Zolnikova O.Yu., Dzhakhaya N.L., Sedova A.V., Ivashkin V.Т. Pathogenesis of functional biliary pain and pharmacology of trimebutin. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2024;34(1):7–14. (In Russ.) DOI: 10.22416/1382-4376-2024-34-1-7-14
5. Velanovich V. Biliary dyskinesia and biliary crystals: A prospective study. Am Surg. 1997;63(1):69–74.
6. Yap L., Wycherley A.G., Morphett A.D., Toouli J. Acalculous biliary pain: Cholecystectomy alleviates symptoms in patients with abnormal cholescintigraphy. Gastroenterology. 1991;101(3):786–93. DOI: 10.1016/0016-5085(91)90540-2
7. Dave R.V., Pathak S., Cockbain A.J., Lodge J.P., Smith A.M., Chowdhury F.U., et al. Management of gallbladder dyskinesia: Patient outcomes following positive 99mtechnetium (Tc)-labelled hepatic iminodiacetic acid (HIDA) scintigraphy with cholecystokinin (CCK) provocation and laparoscopic cholecystectomy. Clin Radiol. 2015;70(4):400–7. DOI: 10.1016/j.crad.2014.12.006
8. Reshetnyak V.I. Concept of the pathogenesis and treatment of cholelithiasis. World J Hepatol. 2012;4(2):18–34. DOI: 10.4254/wjh.v4.i2.18
9. Sviridov D., Mukhamedova N., Miller Y.I. Lipid rafts as a therapeutic target. J Lipid Res. 2020;61(5):687–95. DOI: 10.1194/jlr.TR120000658
10. Wang H.H., Portincasa P., Liu M., Tso P., Wang D.Q. An update on the lithogenic mechanisms of cholecystokinin a receptor (CCKAR), an important gallstone gene for Lith13. Genes (Basel). 2020;11(12):1438. DOI: 10.3390/genes11121438
11. Portincasa P., Di Ciaula A., Bonfrate L., Stella A., Garruti G., Lamont J.T. Metabolic dysfunction-associated gallstone disease: Expecting more from critical care manifestations. Intern Emerg Med. 2023;18(7):1897–918. DOI: 10.1007/s11739-023-03355-z
12. Li N., Li X., Ding Y., Liu X., Diggle K., Kisseleva T., et al. SREBP regulation of lipid metabolism in liver disease, and therapeutic strategies. Biomedicines. 2023;11(12):3280. DOI: 10.3390/biomedicines11123280
13. Ershova A.I., Al Rashi D.O., Ivanova A.A., Aksenova Yu.O., Meshkov A.N. Secondary hyperlipidemias: Etiology and pathogenesis. Russian Journal of Cardiology. 2019;5:74–81. (In Russ.)
14. van Erpecum K.J., Wang D.Q., Moschetta A., Ferri D., Svelto M., Portincasa P., et al. Gallbladder histopathology during murine gallstone formation: relation to motility and concentrating function. J Lipid Res. 2006;47(1):32–41. DOI: 10.1194/jlr.M500180-JLR200
15. Zhu G.Y., Jia D.D., Yang Y., Miao Y., Wang C., Wang C.M. The effect of Shaoyao Gancao decoction on sphincter of Oddi dysfunction in hypercholesterolemic rabbits via protecting the enteric nervous system – interstitial cells of Cajal — smooth muscle cells network. J Inflamm Res. 2021;14:4615–28. DOI: 10.2147/JIR.S326416
16. Lavoie B., Nausch B., Zane E.A., Leonard M.R., Balemba O.B., Bartoo A.C., et al. Disruption of gallbladder smooth muscle function is an early feature in the development of cholesterol gallstone disease. Neurogastroenterol Motil. 2012;24(7):e313–24. DOI: 10.1111/j.1365-2982.2012.01935.x
17. Dias I.H., Borah K., Amin B., Griffiths H.R., Sassi K., Lizard G., et al. Localisation of oxysterols at the sub-cellular level and in biological fluids. J Steroid Biochem Mol Biol. 2019;193:105426. DOI: 10.1016/j.jsbmb.2019.105426
18. Cong P., Pricolo V., Biancani P., Behar J. Effects of cholesterol on CCK-1 receptors and caveolin-3 proteins recycling in human gallbladder muscle. Am J Physiol Gastrointest Liver Physiol. 2010;299(3):G742–50. DOI: 10.1152/ajpgi.00064.2010
19. Lavoie B., Balemba O.B., Godfrey C., Watson C.A., Vassileva G., Corvera C.U., et al. Hydrophobic bile salts inhibit gallbladder smooth muscle function via stimulation of GPBAR1 receptors and activation of KATP channels. J Physiol. 2010;588(Pt 17):3295–305. DOI: 10.1113/jphysiol.2010.192146
20. Sheng W., Ji G., Zhang L. The effect of lithocholic acid on the gut-liver axis. Front Pharmacol. 2022;13:910493. DOI: 10.3389/fphar.2022.910493
21. Ding F., Hu Q., Wang Y., Jiang M., Cui Z., Guo R., et al. Smooth muscle cells, interstitial cells and neurons in the gallbladder (GB): Functional syncytium of electrical rhythmicity and GB motility (Review). Int J Mol Med. 2023;51(4):33. DOI: 10.3892/ijmm.2023.5236
22. Xiao Z.L., Amaral J., Biancani P., Behar J. Impaired cytoprotective function of muscle in human gallbladders with cholesterol stones. Am J Physiol Gastrointest Liver Physiol. 2005;288(3):G525–32. DOI: 10.1152/ajpgi.00261.2004
23. Simon D.A., Friesen C.A., Schurman J.V., Colombo J.M. Biliary dyskinesia in children and adolescents : A mini review. Front Pediatr. 2020;8:122. DOI: 10.3389/fped.2020.00122
24. Di Paola F.W., Heubi J.E., Bezerra J.A., Mack C.L., Shneider B.L. Diseases of the gallbladder in infancy, childhood, and adolescence. In: Suchy F.J., Sokol R.J., Balistreri W.F. (eds.) Liver disease in children. Cambridge University Press; 2021:255–72.
25. Costa C.J., Nguyen M.T.T., Vaziri H., Wu G.Y. Genetics of gallstone disease and their clinical significance : A narrative review. J Clin Transl Hepatol. 2024;12(3):316–26. DOI: 10.14218/JCTH.2023.00563
26. Takeda S., Aburada M. The choleretic mechanism of coumarin compounds and phenolic compounds. J Pharmacobiodyn. 1980;4(9):724–34. DOI: 10.1248/bpb1978.4.724
27. Hoffmann R.M., Schwarz G., Pohl C., Ziegenhagen D.J., Kruis W. Bile acid-independent effect of hymecromone on bile secretion and common bile duct motility. Dtsch Med Wochenschr. 2005;130(34–35):1938–43. (In German). DOI: 10.1055/s-2005-872606
28. Draese K., Hirche H. Pharmacological effects on the motor activity of Oddi's sphincter. Postoperative electromanometric measurements of the bile ducts. Fortschr Med. 1980;98(39):1529–33. (In German)
29. Abate A.L., Dimartino V., Spina P., Costa P.L., Lombardo C., Santini A., et al. Hymecromone in the treatment of motor disorders of the bile ducts: A multicenter, double-blind, placebo-controlled clinical study. Drugs Exp Clin Res. 2001;27(5–6):223–31.
30. Bordin D.S., Dubtsova E.A., Selezneva E. Ya., Kukoleva E.O., Lashko M.L., Chebotareva M.V., et al. Efficacy and safety of hymecromone various doses in patients who have undergone cholecystectomy. Effective Pharmacotherapy. 2021;17(39):34–8. (In Russ.) DOI: 10.33978/2307-3586-2021-17-39-34-38
31. Selezneva E.Ya., Mechetina T.A., Orlova Yu.N., Koricheva E.S., Voinovan I.N., Bezaeva I.V., et al. A comparative study of the effectiveness of UDCA monotherapy and the combination of UDCA with hymecromone in patients with stage 2 biliary sludge. Experimental and Clinical Gastroenterology. 2016;10(134):94–8. (In Russ.)
32. Okhlobystin A.V., Ufimtseva A.K., Tatarkina M.A., Okhlobystina O.Z., Ivashkin V.T. Efficacy of hymecromone in post-cholecystectomy patients. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2021;31(4):37–44. (In Russ.) DOI: 10.22416/1382-4376-2021-31-4-37-44
33. Minushkin O.N. Biliary dysfunction, choice of antispasmodic. Gastroenterologiya Sankt-Peterburga. 2013(1):11–4. (In Russ.)
34. Nersesov A.V., Kaybullaeva D.A., Rakhmetova V.S., Lozinskaya I.A., Kurmangalieva A.K., Ayupova V.S., et al. Hymecromone administration in real clinical practice: Results of the prospective multicentre observational study in the Republic of Kazakhstan. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2021;31(5):34–50. (In Russ.) DOI: 10.22416/1382-4376-2021-31-5-34-50
35. Okhlobystin A.V., Ufimtseva A.K. Hymecromone in the treatment of biliary diseases: Options and prospects. Pediatric Nutrition. 2020;18(5):66–74. (In Russ.) DOI: 10.20953/1727-5784-2020-5-66-74
Review
For citations:
Shulpekova Yu.O., Popova I.R., Nechaev V.M. Functional Disorders of the Biliary Tract and Cholelithiasis: Analysis of a Possible Relationship. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2024;34(4):94-103. https://doi.org/10.22416/1382-4376-2024-34-4-94-103