ASPECTOS INTESTINALES DE LA FORMACION DE CALCULOS BILIARES DE COLESTEROL

ASPECTOS INTESTINALES DE LA FORMACION DE CALCULOS BILIARES DE COLESTEROL

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El intestino parece desempeñar un papel importante en el desarrollo de la litiasis vesicular por cálculos de colesterol debido a las interacciones complejas, integradas y sutiles con el sistema biliar.
portincasa9.jpg Autor:
Portincasa, Piero
Columnista Experto de SIIC

Institución:
Clinica Medica "Augusto Murri" Department of Internal Medicine and Public Medicine (DIMIMP) University Medical School of Bari Bari, Italy


Artículos publicados por Portincasa, Piero
Coautores
Karel J van Erpecum*  Marcin Krawczyk** 
MD, PhD. University of Utrecht Medical School, The Netherlands*
Medical student – Socrates Erasmus European mobility programmeUniversity of Lublin Medical School, Poland**
Recepción del artículo
3 de Mayo, 2004
Aprobación
27 de Mayo, 2004
Primera edición
4 de Marzo, 2005
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
La litiasis vesicular por cálculos de colesterol puede considerarse como una enfermedad que prevalece en el mundo occidental. La patogénesis es multifactorial e incluye la sobresaturación biliar de colesterol, la cristalización promovida por proteínas y el deterioro de la motilidad posprandial de la vesícula. Algunas investigaciones recientes indican que el intestino también desempeña un papel importante en la patogénesis de los cálculos de colesterol, si se consideran diversos factores. Una variedad de proteínas transportadoras está involucrada en el proceso de absorción intestinal de colesterol y podría vincularse con el incremento de su sobresaturación biliar. Más aun, el tránsito intestinal prolongado podría incrementar el riesgo de cálculos a través del aumento de la formación en el lumen intestinal de desoxicolato, una sal biliar hidrófoba secundaria y prolitogénica. Además, en personas normales existe relación estrecha entre la motilidad intestinal y la de la vesícula biliar en el período de ayuno (interdigestivo). Encontramos alteración en la motilidad intestinal, ausencia de contracción vesicular y liberación anormal de la hormona motilina en el período interdigestivo en pacientes con litiasis vesicular. Estos trastornos podrían contribuir a la formación de litos vesiculares y se discuten en el presente trabajo.

Palabras clave
Motilidad gastrointestinal, músculo liso, cristales de colesterol, motilidad de la vesícula biliar


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Abstract
Cholesterol gallstone disease can be considered a mass disease in the Western world. Pathogenesis is multifactorial, including biliary cholesterol supersaturation, crystallization-promoting proteins and impaired postprandial gallbladder motility. Recent studies indicate that the intestine also plays an important role in pathogenesis of cholesterol gallstones, if one considers several factors. A number of transport proteins are involved in the process of intestinal cholesterol absorption and might provide links to increased biliary cholesterol supersaturation. Moreover, prolonged intestinal transit could increase gallstone risk by enhancing formation in the intestinal lumen of the secondary hydrophobic and pro-lithogenic bile salt deoxycholate. Furthermore, in normal subjects there is an intimate relationship between gallbladder and intestinal motility in the fasting (interdigestive) state. We found disordered intestinal motility, absent gallbladder contraction and abnormal release of the hormone motilin in the interdigestive state in gallstone patients. These disturbances could contribute to gallstone formation and are discussed in the present article.

Key words
Gastrointestinal motility, smooth muscle, cholesterol crystals, gallbladder motility


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Especialidades
Principal: Nefrología y Medio Interno
Relacionadas: Atención Primaria, Diagnóstico por Imágenes, Medicina Interna



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Bibliografía del artículo
  1. Attili AF, Carulli N, Roda E et al. Epidemiology of gallstone disease in Italy: prevalence data of the multicenter italian study on cholelithiasis (MICOL). Am J Epidemiology 1995; 141:158-165.
  2. Sherlock S, Dooley J. Diseases of the liver and biliary system. Oxford: Blackwell Science, 2002.
  3. Metzger AL, Adler R, Heymsfield S. Diurnal variations in biliary lipid composition. N Engl J Med 1973; 288:333-336.
  4. Hyogo H, Tazuma S, Cohen DE. Cholesterol gallstones. Curr Opinion Gastroenterol 2002; 18:366-371.
  5. Marinelli RA, LaRusso NF. Solute and water transport pathways in cholangiocytes. Semin Liver Dis 1996; 16(2):221-229.
  6. Marinelli RA, LaRusso NF. Aquaporin water channels in liver: their significance in bile formation. Hepatology 1997; 26(5):1081-1084.
  7. Apstein MD, Carey MC. Pathogenesis of cholesterol gallstones: a parsimonious hypothesis. Eur J Clin Invest 1996; 26:343-352.
  8. Staggers JE, Hernell O, Stafford RJ et al. Physical-chemical behavior of dietary and biliary lipids during intestinal digestion and absorption. 1. Phase behavior and aggregation states of model lipid systems patterned after aqueous duodenal contents of healthy adult human beings. Biochemistry 1990; 29(8):2028-2040.
  9. Acton S, Rigotti A, Landschulz KT et al. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science 1996; 271(5248):518-520.
  10. Drobnik W, Lindenthal B, Lieser B et al. ATP-binding cassette transporter A1 (ABCA1) affects total body sterol metabolism. Gastroenterology 2001; 120(5):1203-1211.
  11. Hauser H, Dyer JH, Nandy A et al. Identification of a receptor mediating absorption of dietary cholesterol in the intestine. Biochemistry 1998; 37(51):17843-17850.
  12. Altmann SW, Davis Jr HR, Zhu L et al. Niemann-Pick C1 Like 1 Protein Is Critical for Intestinal Cholesterol Absorption. Science 2004; 303:1201-1204.
  13. Berge KE, Tian H, Graf GA et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 2000; 290(5497):1771-1775.
  14. Lee MH, Lu K, Hazard S et al. Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nat Genet 2001; 27(1):79-83.
  15. Lu K, Lee MH, Patel SB. Dietary cholesterol absorption; more than just bile. Trends Endocrinol Metab 2001; 12(7):314-320.
  16. Repa JJ, Berge KE, Pomajzl C et al. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta. J Biol Chem 2002; 277(21):18793-18800.
  17. Yu L, Hammer RE, Li-Hawkins J et al. Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion. Proc Natl Acad Sci USA 2002; 99:16237-16242.
  18. Yu L, Li-Hawkins J, Hammer RE et al. Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol. J Clin Invest 2002; 110(5):671-680.
  19. Mendez-Sanchez N, Rahbar-Tabrizi N, King-Martinez AC et al. Risk factors for cholesterol gallstone formation are associated with common polymorphisms of ABCG5/ABCG8, the genes encoding the biliary cholesterol half-transporters, in german and mexican gallstone patients. Hepatology 38 (Suppl.1), A474. 2003.
  20. Wang DQH. New concepts of mechanisms of intestinal cholesterol absorption. Annals Hepatology 2003; 2:113-121.
  21. Wang DQH, Lammert F, Cohen DE et al. Cholic acid aids absorption, biliary secretion, and phase transitions of cholesterol in murine cholelithogenesis. Am J Physiol 1999; 276:G751-60.
  22. Wang DQ, Tazuma S, Cohen DE et al. Feeding natural hydrophilic bile acids inhibits intestinal cholesterol absorption: studies in the gallstone-susceptible mouse. Am J Physiol Gastrointest Liver Physiol 2003; 285(3):G494-G502.
  23. Voshol PJ, Havinga R, Wolters H et al. Reduced plasma cholesterol and increased fecal sterol loss in multidrug resistance gene 2 P-glycoprotein-deficient mice. Gastroenterology 1998; 114(5):1024-1034.
  24. Schwarz M, Russell DW, Dietschy JM et al. Alternate pathways of bile acid synthesis in the cholesterol 7alpha-hydroxylase knockout mouse are not upregulated by either cholesterol or cholestyramine feeding. J Lipid Res 2001; 42(10):1594-1603.
  25. Wang DQH, Paigen B, Carey MC. Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: physical-chemistry of gallbladder bile. J Lipid Res 1997; 38:1395-1411.
  26. Wang DQH, Carey MC. Measurement of intestinal cholesterol absorption by plasma and fecal dual-isotope ratio, mass balance, and lymph fistula methods in the mouse: an analysis of direct versus indirect methodologies. J Lipid Res 2003; 44(5):1042-1059.
  27. Ponz dL, Iori R, Barbolini G et al. Influence of small-bowel transit time on dietary cholesterol absorption in human beings. N Engl J Med 1982; 307(2):102-103.
  28. Traber MG, Ostwald R. Cholesterol absorption and steroid excretion in cholesterol-fed guinea pigs. J Lipid Res 1978; 19(4):448-456.
  29. Shoda J, He BF, Tanaka N et al. Increased deoxycholate in supersaturated bile of patients with cholesterol gallstones disease and its correlation with de novo syntheses of cholesterol and bile acids in liver, gallbladder emptying, and small intestinal transit. Hepatology 1995; 21:1291-1302.
  30. Berr F, Pratschke E, Fischer S et al. Disorders of bile acid metabolism in cholesterol gallstone disease. J Clin Invest 1992; 90:859-868.
  31. Heuman R, Norrby S, Sjodahl R et al. Altered gallbladder bile composition in gallstone disease. Relation to gallbladder wall permeability. Scand J Gastroenterol 1980; 15:581-586.
  32. Carulli N, Loria P, Bertolotti M. Effects of acute changes of bile acid pool composition on biliary lipid secretion. J Clin Invest 1984; 74:614-624.
  33. Heaton KW, Emmett PM, Symes CL et al. An explanation for gallstones in normal-weight woman: slow intestinal transit. Lancet 1993; 341:8-10.
  34. Thomas LA, Veysey MJ, Bathgate T et al. Mechanism for the transit-induced increase in colonic deoxycholic acid formation in cholesterol cholelithiasis. Gastroenterology 2000; 119(3):806-815.
  35. Xu QW, Scott RB, Tan DTM et al. Slow intestinal transit: a motor disorder contributing to cholesterol gallstone formation in the ground squirrel. Hepatology 1996; 23:1664-1672.
  36. Van Erpecum KJ, Wang DQH, Lammert F et al. Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: soluble pronucleating proteins in gallbladder and hepatic biles. J Hepatol 2001; 35:444-451.
  37. Denson LA, Sturm E, Echevarria W et al. The orphan nuclear receptor, shp, mediates bile acid-induced inhibition of the rat bile acid transporter, ntcp. Gastroenterology 2001; 121(1):140-147.
  38. Gerloff T, Stieger B, Hagenbuch B et al. The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver. J Biol Chem 1998; 273(16):10046-10050.
  39. Lu TT, Makishima M, Repa JJ et al. Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol Cell 2000; 6(3):507-515.
  40. Goodwin B, Jones SA, Price RR et al. A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol Cell 2000; 6(3):517-526.
  41. Van Erpecum KJ, Carey MC. Influence of bile salts on molecular interactions between sphingomyelin and cholesterol: relevance to bile formation and stability. Biochim Biophys Acta 1997; 1345:269-282.
  42. Hussaini SH, Pereira SP, Murphy GM et al. Deoxycholic acid influences cholesterol solubilization and microcrystal nucleation time in gallbladder bile. Hepatology 1995; 22(6):1735-1744.
  43. Wang DQH, Carey MC. Complete mapping of crystallization pathways during cholesterol precipitation from model bile: influence of physical-chemical variables of pathophysiologic relevance and identification of a stable liquid crystalline state in cold, dilute and hydrophilic bile salt-containing system. J Lipid Res 1996; 37:606-630.
  44. Moschetta A, vanBerge-Henegouwen GP, Portincasa P et al. Cholesterol crystallization in model biles. Effects of bile salt and phospholipid species composition. J Lipid Res 2001; 42(8):1273-1281.
  45. Hussaini SH, Murphy GM, Petit R et al. The role of bile composition and physical chemistry in the pathogenesis of octreotide-associated gallbladder stones. Gastroenterology 1994; 107:1503-1513.
  46. Low-Beer TS, Nutter S. Colonic bacterial activity, biliary cholesterol saturation, and pathogenesis of gallstones. Lancet 1978; 2(8099):1063-1065.
  47. Van Berge-Henegouwen GP, van der Werf SDJ, Ruben AT. Effect of lactulose on biliary lipid composition. J Lipid Res 1986; 3:328-332.
  48. Van Berge-Henegouwen GP, Portincasa P, van Erpecum KJ. Effect of lactulose and fiber-rich diets on bile in relation to gallstone disease: an update. Scand J Gastroenterol 1997; 32(Suppl. 22):68-71.
  49. Thornton JR, Heaton KW. Do colonic bacteria contribute to cholesterol gall-stone formation Effects of lactulose on bile. Br Med J (Clin Res Ed) 1981; 282:1018-1020.
  50. Pomare EW, Heaton KW, Low-Beer TS et al. The effect of wheat bran upon bile salt metabolism and upon the lipid composition of bile in gallstone patients. Am J Dig Dis 1976; 21(7):521-526.
  51. Thornton JR, Emmett PM, Heaton KW. Diet and gall stones: effects of refined and unrefined carbohydrate diets on bile cholesterol saturation and bile acid metabolism. Gut 1983; 24:2-6.
  52. Veysey MJ, Malcolm P, Mallet AI et al. Effects of cisapride on gall bladder emptying, intestinal transit, and serum deoxycholate: a prospective, randomised, double blind, placebo controlled trial. Gut 2001; 49(6):828-834.
  53. Jorgensen T. Abdominal symptoms and gallstone disease: an epidemiological investigation. Hepatology 1989; 9:856-860.
  54. Dukas L, Leitzmann MF, Willett WC et al. Association of bowel movement frequency and use of laxatives with the occurrence of symptomatic gallstone disease in a prospective study of women. Am J Gastroenterol 2001; 96(3):715-721.
  55. Stolk MFJ, van Erpecum KJ, Smout AJPM et al. Motor cycles with phase III in antrum are associated with high motilin levels and prolonged gallbladder emptying. Am J Physiol 1993; 264:G596-G600.
  56. Van Erpecum KJ, Van Berge-Henegouwen GP, Stoelwinder B et al. Bile concentration is a key factor for nucleation of cholesterol crystals and cholesterol saturation index in gallbladder bile of gallstone patients. Hepatology 1990; 11:1-6.
  57. Stolk MF, Van Erpecum KJ, Peeters TL et al. Interdigestive gallbladder emptying, antroduodenal motility, and motilin release patterns are altered in cholesterol gallstone patients. Dig Dis Sci 2001; 46(6):1328-1334.
  58. Jazrawi RP, Pazzi P, Petroni ML et al. Postprandial gallbladder motor function: refilling and turnover of bile in health and cholelithiasis. Gastroenterology 1995; 109:582-591.
  59. Pauletzki JG, Cicala M, Holl J et al. Correlation between gallbladder fasting volume and postprandial emptying in patients with gallstones and healthy controls. Gut 1993; 34:1443-1447.
  60. Stolk MFJ, Van Erpecum KJ, Renooij W et al. Gallbladder emptying in vivo, bile composition and nucleation of cholesterol crystals in patients with cholesterol gallstones. Gastroenterology 1995; 108:1882-1888.
  61. Portincasa P, Di Ciaula A, Baldassarre G et al. Gallbladder motor function in gallstone patients: sonographic and in vitro studies on the role of gallstones, smooth muscle function and gallbladder wall inflammation. J Hepatol 1994; 21:430-440.
  62. Xu QW, Shaffer EA. The potential site of impaired gallbladder contractility in an animal model of cholesterol gallstone disease. Gastroenterology 1996; 110:251-257.
  63. Chen Q, Amaral J, Biancani P et al. Excess membrane cholesterol alters human gallbladder muscle contractility and membrane fluidity. Gastroenterology 1999; 116:678-685.
  64. Amaral J, Xiao ZL, Chen Q et al. Gallbladder muscle dysfunction in patients with chronic acalculous disease. Gastroenterology 2001; 120(2):506-511.
  65. Chen Q, Amaral J, Oh S et al. Gallbladder relaxation in patients with pigment and cholesterol stones. Gastroenterology 1997; 113:930-937.
  66. Schneider H, Sanger H, Hanisch E. In vitro effects of cholecystokinin fragments on human gallbladders. Evidence for an altered CCK-receptor structure in a subgroup of patients with gallstones. J Hepatol 1997; 26:1063-1068.
  67. Upp JR, Jr., Nealon WH, Singh P et al. Correlation of cholecystokinin receptors with gallbladder contractility in patients with gallstones. Ann Surg 1987; 205:641-648.
  68. Chen Q, Yu P, De Petris G et al. Distinct muscarinic receptors and signal transduction pathways in gallbladder muscle. J Pharmacol Exp Ther 1995; 273:650-655.
  69. Chen Q, De Petris G, Yu P et al. Different pathways mediate cholecystokinin actions in cholelithiasis. Am J Physiol 1997; 272:G838-44.
  70. Yu P, Chen Q, Xiao Z et al. Signal transduction pathways mediating CCK-induced gallbladder muscle contraction. Am J Physiol 1998; 275:G203-11.
  71. Behar J, Rhim BY, Thompson W et al. Inositol trisphosphate restores impaired human gallbladder motility associated with cholesterol stones. Gastroenterology 1993; 104:563-568.
  72. Zhu XG, Greeley GH, Newman J et al. Correlation of in vitro measurements of contractility of the gallbladder with in vivo ultrasonographic findings in patients with gallstones. Surg Gynecol Obstet 1985; 161:470-472.
  73. Lennon F, Feeley TM, Clanachan AS et al. Effects of histamine receptor stimulation on diseased gallbladder and cystic duct. Gastroenterology 1984; 87:257-262.
  74. Martinez-Cuesta MA, Moreno L, Morillas J et al. Influence of cholecystitis state on pharmacological response to cholecystokinin of isolated human gallbladder with gallstones. Dig Dis Sci 2003; 48(5):898-905.
  75. Kano M, Shoda J, Satoh S et al. Increased expression of gallbladder cholecystokinin: a receptor in prairie dogs fed a high-cholesterol diet and its dissociation with decreased contractility in response to cholecystokinin. J Lab Clin Med 2002; 139(5):285-294.
  76. Xiao ZL, Rho AK, Biancani P et al. Effects of bile acids on the muscle functions of guinea pig gallbladder. Am J Physiol Gastrointest Liver Physiol 2002; 283(1):G87-G94.
  77. Trevisani M, Amadesi S, Schmidlin F et al. Bradykinin B2 receptors mediate contraction in the normal and inflamed human gallbladder in vitro. Gastroenterology 2003; 125(1):126-135.
  78. Kano M, Shoda J, Irimura T et al. Effects of long-term ursodeoxycholate administration on expression levels of secretory low-molecular-weight phospholipases A2 and mucin genes in gallbladders and biliary composition in patients with multiple cholesterol stones. Hepatology 1998; 28:302-313.
  79. Stolk MFJ, van de Heijning BJM, van Erpecum KJ et al. Effect of bile salts on in vitro gallbladder motility: preliminary study. Ital J Gastroenterol Hepatol 1996; 28:105-110.
  80. Xu QW, Freedman SM, Shaffer EA. Inhibitory effect of bile salts on gallbladder smooth muscle contractility in the guinea pig in vitro. Gastroenterology 1997; 112:1699-1706.

 
 
 
 
 
 
 
 
 
 
 
 
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