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Gallbladder sludge: What is its clinical significance?

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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.

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References and Recommended Reading

  1. Ko CW, Sekijima JH, Lee SP. Biliary sludge. Ann Intern Med 1999, 130:301–311. Excellent review.

    PubMed  CAS  Google Scholar 

  2. Jüngst D, von Ritter C: Biliary crystals, microlithiasis and sludge. In Gallbladder and Biliary Tract Diseases. Edited by Afdhal NH. New York: Marcel Dekker; 2000:455–470. Excellent review.

    Google Scholar 

  3. Conrad MR, Janes JO, Dietchy J: Significance of low level echoes within the gallbladder. AJR Am J Roentgenol 1979, 132:967–972.

    PubMed  CAS  Google Scholar 

  4. Filly RA, Allen B, Minton MJ, et al.: In vitro investigation of the origin of echoes with biliary sludge. J Clin Ultrasound 1980, 8:193–200.

    Article  PubMed  CAS  Google Scholar 

  5. Juniper K, Burson EN: Biliary tract studies. II. The significance of biliary crystals. Gastroenterology 1957, 32:175–211.

    PubMed  Google Scholar 

  6. Frossard JL, Sosa-Valencia L, Amouyal G, et al.: Usefulness of endoscopic ultrasonography in patients with 'idiopathic' acute pancreatitis. Am J Med 2000, 109:196–200. EUS findings in 168 patients with idiopathic pancreatitis were compared with the diagnosis obtained: at surgery in 101, by ERCP in 49, or by bile analysis for crystals and medical follow-up in 18 patients. EUS was abnormal in 135 (80%) patients, 124 of whom had biliary tract disease; 99 (73%) had biliary stones, microlithiasis and/ or sludge. EUS missed five cases (8%) with biliary stones detected at surgery or by bile analysis. In five others, EUS suggested biliary stones, but this was incorrect at subsequent surgery or ERCP. There was no head-to-head comparison with biliary microscopy: only 18 procedures were performed for sediment. EUS was thus able to detect biliary tract disease in 92% of patients thought to have idiopathic pancreatitis.

    Article  PubMed  CAS  Google Scholar 

  7. Allen B, Bernhoft R, Blanckaert N, et al.: Sludge is calcium bilirubinate associated with bile stasis. Am J Surg 1981, 141:51–56.

    Article  PubMed  CAS  Google Scholar 

  8. Lee SP, Nicholls JF: Nature and composition of biliary sludge. Gastroenterology 1986, 90:677–686.

    PubMed  CAS  Google Scholar 

  9. Ko CW, Murakami C, Sekijima JH, et al.: Chemical composition of gallbladder sludge in patients after marrow transplantation. Am J Gastroenterol 1996, 91:1207–1210.

    PubMed  CAS  Google Scholar 

  10. Xia Y, Lambert KJ, Schteingart CD, et al.: Concentrative biliary secretion of ceftriaxone: inhibition of lipid secretion and precipitation of calcium ceftriaxone in bile. Gastroenterology 1990, 99:454–465.

    PubMed  CAS  Google Scholar 

  11. Carey MC, Cahalane MJ: Whither biliary sludge? Gastroenterology 1988, 95:508–523.

    PubMed  CAS  Google Scholar 

  12. Boonyapisit ST, Trotman BW, Ostrow JD: Unconjugated bilirubin, and the hydrolysis of conjugated bilirubin, in gallbladder bile of patients with cholelithiasis. Gastroenterology 1978, 74:70–74.

    PubMed  CAS  Google Scholar 

  13. Ho YC, Ho KJ: Human beta-glucuronidase: measurement of its activity in gallbladder bile devoid of intrinsic interference. Dig Dis Sci 1988, 33:335–342.

    Google Scholar 

  14. Sandstad O, Osnes T, Urdal P, et al.: Brown pigment stones in the common bile duct: reduced bilirubinate deconjugate in bile. Scand J Gastroentol 2000, 35:198–203. Bilirubin diglucuronide is reduced in bile from the common duct of patients with brown pigment stones.

    Article  CAS  Google Scholar 

  15. Spivak W, DiVenuto D, Yuey W: Non-enzymic hydrolysis of bilirubin mono- and diglucuronide to unconjugated bilirubin in model and native bile systems: potential role in the formation of gallstones. Biochem J 1987, 242:323–329.

    PubMed  CAS  Google Scholar 

  16. Lechene de la Porte P, Lafont H, Domingo N, et al.: Composition and immunofluorescence studies of biliary 'sludge' in patients with cholesterol or mixed gallstones. Hepatology 2000, 33:352–360. When gallbladder bile was ultracentrifuged (100,000 g/1 hr), the resultant sediment consisted predominantly of cholesterol and protein (88%), a small amount of mucin (9%), and even less bilirubin pigment (about 5%). There was no difference between these precipitated solutes from the gallbladder bile aspirated at surgery from 49 patients with cholesterol stones (>50% cholesterol) or 16 with mixed gallstones (10% to 50% cholesterol). The sediment composition differed from that of pigment gallstones. The sediment was a mixture of vesicular aggregates and pigment particles. These were linked by a gel matrix of mucin, a pronucleating agent that contained the cholesterol crystals. Such localization in biliary sludge was similar to that previously shown in cholesterol and mixed stones, suggesting that biliary sludge represents an early stage of gallstone formation.

    Article  Google Scholar 

  17. Jüngst D, del Pozo R, Christoph S, et al.: Sedimentation of biliary 'sludge': effect on composition of gallbladder bile from patients with cholesterol, mixed or pigment stones. Scand J Gastroenterol 1996, 31:273–278.

    PubMed  Google Scholar 

  18. Xu QW, Shaffer EA: The potential site of impaired gallbladder contractility in an animal model of cholesterol gallstone disease. Gastroenterology 1996, 110:251–257.

    Article  PubMed  CAS  Google Scholar 

  19. Lee SP: Pathogenesis of biliary sludge. Hepatology 1990, 12:200S-205S.

    PubMed  CAS  Google Scholar 

  20. Feuerstein IM, Shawker TH, Savarese DM: CT demonstration of calcifying sludge balls. J Comput Assist Tomogr 1990, 14:325–326.

    Article  PubMed  CAS  Google Scholar 

  21. Garg PK, Goindi G, Tandon RK: Stimulation of gallbladder by intravenous infusion of amino acid: a new method to obtain duodenal bile for bile analyses. Dig Dis Sci 2000, 45:904–908. Rapid intravenous amino acid infusion can stimulate gallbladder emptying, allowing adequate collection of duodenal bile for microscopic examination.

    Article  PubMed  CAS  Google Scholar 

  22. Parasher VK, Romain K, Sukumar R, Jordon J: Can ERCP contrast agents cause pseudomicrolithiasis? Their effect on the final outcome of bile analysis in patients with suspected microlithiasis. Gastrointest Endosc 2000, 51:401–404. The presence of contrast agents in bile can mimic calcium bilirubinate granules, producing a false-positive interpretation on microscopy. Bile collected during ERCP for microscopy should not be contaminated by a contrast agent.

    Article  PubMed  CAS  Google Scholar 

  23. Ros E, Navarro S, Fernández I, et al.: Utility of biliary microscopy for the prediction of the chemical composition of gallstones and the outcome of dissolution therapy with ursodeoxycholic acid. Gastroenterology 1986, 91:703–712.

    PubMed  CAS  Google Scholar 

  24. Ramond MJ, Dumont M, Belghiti J, Erlinger S: Sensitivity and specificity of microscopic examination of gallbladder bile for gallstone recognition and identification. Gastroenterology 1988, 95:1339–1343.

    PubMed  CAS  Google Scholar 

  25. Buscail L, Escourrou J, Delvaux M, et al.: Microscopic examination of bile directly collected during endoscopic cannulation of the papilla: utility in patients with suspected microlithiasis. Dig Dis Sci 1992, 37:116–120.

    Article  PubMed  CAS  Google Scholar 

  26. Delchier JC, Benfredj P, Preaux AM, et al.: The usefulness of microscopic bile examination in patients with suspected microlithiasis: a prospective evaluation. Hepatology 1986, 6:118–122.

    Article  PubMed  CAS  Google Scholar 

  27. Neoptolemos JP, Davidson BR, Winder AF, Vallance D: Role of duodenal bile crystal analysis in the investigation of 'idiopathic' pancreatitis. Br J Surg 1988, 75:450–453.

    Article  PubMed  CAS  Google Scholar 

  28. Stotland B: Endoscopic ultrasound of the gallbladder and bile ducts. In Gallbladder and Biliary Tract Disease. Edited by Afdhal NH. New York: Marcel Dekker; 2000:437–445. A brief review of this new modality and its role in clinical practice.

    Google Scholar 

  29. Dahan P, Andant C, Levy P, et al.: Prospective evaluation of endoscopic ultrasonography and microscopic examination of duodenal bile in the diagnosis of cholecystolithiasis in 45 patients with normal conventional ultrasonography. Gut 1996, 38:277–281.

    PubMed  CAS  Google Scholar 

  30. Dill JE, Hill S, Berkhouse L, et al.: Combined endoscopic ultrasound and stimulated biliary drainage in cholecystitis and microlithiasis diagnoses and outcomes. Endoscopy 1995, 27:424–427.

    PubMed  CAS  Google Scholar 

  31. Laing FC: Ultrasound diagnosis of choledocholithiasis. Semin Ultrasound CT MR 1987, 8:103–113.

    Google Scholar 

  32. Sugiyama M, Atomi Y: Endoscopic ultrasonography for diagnosing choledocholithiasis: a prospective comparative study with ultrasonography and computer tomography. Gastrointest Endosc 1997, 45:143–146.

    Article  PubMed  CAS  Google Scholar 

  33. Prat F, Amoural PG, Amouyal P, et al.: Prospective controlled study of endoscopic ultrasonography and endoscopic retrograde cholangiography in patients with suspected commonduct lithiasis. Lancet 1996, 347:75–79.

    Article  PubMed  CAS  Google Scholar 

  34. Soto JA, Barish MA, Yurel EK, et al.: Magnetic resonance cholangiography: comparison with endoscopic retrograde cholangiography. Gastroenterology 1996, 110:589–597.

    Article  PubMed  CAS  Google Scholar 

  35. deLedinghen V, Lecesne R, Raymond J-M, et al.: Diagnosis of choledocholithiasis: EUS or magnetic resonance cholangiography? A prospective controlled study. Gastrointest Endosc 1999, 49:26–34.

    Article  PubMed  Google Scholar 

  36. Maringhini A, Ciambra M, Baccelliere P, et al.: Biliary sludge and gallstones in pregnancy: incidence, risk factors, and natural history. Ann Intern Med 1993, 119:116–120.

    PubMed  CAS  Google Scholar 

  37. Gilat T, Konikoff F: Pregnancy and the biliary tract. Can J Gastroenterol 2000, 13(suppl D):550–590. Excellent review of the physiologic changes in pregnancy that lead to sludge/stone formation.

    Google Scholar 

  38. Pitt HA, King W III, Mann LL, et al.: Increased risk of cholelithiasis with prolonged total parenteral nutrition. Am J Surg 1983, 145:106–112.

    Article  PubMed  CAS  Google Scholar 

  39. Shiffman ML, Sugerman HJ, Kellum JM, et al.: Gallstone formation after rapid weight loss: a prospective study in patients undergoing gastric bypass surgery for treatment of morbid obesity. Am J Gastroenterol 1991, 86:1000–1005.

    PubMed  CAS  Google Scholar 

  40. Schaad UB, Tschappeler H, Lentze MJ: Transient formation of precipitations in the gallbladder associated with ceftriaxone therapy. Pediatr Infect Dis 1986, 5:708–710.

    Article  PubMed  CAS  Google Scholar 

  41. Inoue K, Fuchigami A, Higashide S, et al.: Gallbladder sludge and stone formation in relation to contractile function after gastrectomy: a prospective study. Ann Surg 1992, 215:19–26.

    Article  PubMed  CAS  Google Scholar 

  42. Murray FE, Stinchcombe SJ, Hawkey CJ: Development of biliary sludge in patients on intestine care unit: results of a prospective ultrasonographic survey. Gut 1992, 33:1123–1125.

    PubMed  CAS  Google Scholar 

  43. Bolondi L, Gaiani S, Testa S, Labo G: Gallbladder sludge formation during prolonged fasting after gastrointestinal tract surgery. Gut 1985, 26:734–738.

    PubMed  CAS  Google Scholar 

  44. Kim YS, Kestell MF, Lee SP: Gallbladder sludge: lessons from ceftriaxone. J Gastroenterol Hepatol 1992, 7:618–621.

    PubMed  CAS  Google Scholar 

  45. Catnach SM, Anderson JV, Fairclough PD, et al.: Effect of octreotide on gall stone prevalence and gallbladder motility in acromegaly. Gut 1993, 34:270–273.

    PubMed  CAS  Google Scholar 

  46. Hussaini SH, Murphy GM, Kennedy C, et al.: The role of bile composition and physical chemistry in the pathogenesis of octreotide-associated gallbladder stones. Gastroenterology 1994, 107:1503–1513.

    PubMed  CAS  Google Scholar 

  47. Teefey SA, Hollister MS, Lee SP, et al.: Gallbladder sludge formation after bone marrow transplant: sonographic observations. Abdom Imaging 1994, 19:57–60.

    Article  PubMed  CAS  Google Scholar 

  48. Peterseim DS, Pappas TN, Meyers CH, et al.: Management of biliary complications after heart transplant. J Heart Lung Transplant 1995, 14:623–631.

    PubMed  CAS  Google Scholar 

  49. Lorber MI, Van Buren CT, Flechner SM, et al.: Hepatobiliary and pancreatic complications of cyclosporine therapy in 466 renal transplant recipients. Transplantation 1987, 43:35–40.

    Article  PubMed  CAS  Google Scholar 

  50. Lee SP, Maher K, Nicholls JF: Origin and fate of biliary sludge. Gastroenterology 1988, 94:170–176.

    PubMed  CAS  Google Scholar 

  51. Janowitz P, Kratzer W, Zemmler T, et al.: Gallbladder sludge: spontaneous course and incidence of complications in patients with stones. Hepatology 1994, 20:291–294.

    PubMed  CAS  Google Scholar 

  52. Lee SP, Nicholls JF, Park HZ: Biliary sludge as a cause of acute pancreatitis. N Engl J Med 1992, 326:589–593.

    Article  PubMed  CAS  Google Scholar 

  53. Corazziari E, Shaffer EA, Hogan WJ, et al.: Functional disorders of the biliary tract and pancreas. Gut 1999, 45(suppl II):II48-II54.

    Article  PubMed  Google Scholar 

  54. Shaffer EA: Cholescintigraphy in acalculous biliary pain: if abnormal, should cholecystectomy follow? Hepatology 1992, 15:737–739.

    Article  PubMed  CAS  Google Scholar 

  55. Ros E, Navarro S, Bru C, et al.: Occult microlithiasis in 'idiopathic' acute pancreatitis: prevention of relapses by cholecystectomy or ursodeoxycholic acid therapy. Gastroenterology 1991, 101:1701–1709.

    PubMed  CAS  Google Scholar 

  56. May GR, Sutherland LR, Shaffer EA: Efficacy of bile acid therapy for gallstone dissolution: a meta-analysis of randomized trials. Aliment Pharmacol Ther 1993, 7:139–148.

    Article  PubMed  CAS  Google Scholar 

  57. Worobetz LJ, Inglis FG, Shaffer EA: The effect of ursodeoxycholic acid therapy on gallstone formation in the morbidly obese during rapid weight loss. Am J Gastroenterol 1993, 88:1705–1710.

    PubMed  CAS  Google Scholar 

  58. Shiffman ML, Kaplan GD, Brinkman-Kaplan V, Vickers FF: Prophylaxis against gallstone formation with ursodeoxycholic acid in patients participating in a very-low-calorie diet program. Ann Intern Med 1995, 122:899–905.

    PubMed  CAS  Google Scholar 

  59. Sitzmann JV, Pitt HA, Steinborn PA, et al.: Cholecystokinin prevents parenteral nutrition induced biliary sludge in humans. Surg Gynecol Obstet 1990, 170:25–31.

    PubMed  CAS  Google Scholar 

  60. Krznaric Z, Uravic M, Fuckar Z, Zupan Z: Influence on gallbladder volume of early postoperative gastric supply of nutrients. Clin Nutr 2000, 19:413–416. This prospective study of 40 patients after major non-gastrointestinal or hepatobiliary surgery, all in ICU settings, showed that an early postoperative supply of nutrients reduced gallbladder size compared with intravenous crystallized solution alone. The authors conclude that early postoperative delivery of nutrients after such surgery stimulates gallbladder motility and, by preventing biliary stasis, also limits the formation of biliary sludge.

    Article  PubMed  Google Scholar 

  61. Hoy MK, Heshka S, Allison DB, et al.: Reduced risk of liverfunction- test abnormalities and new gallstone formation with weight loss on 3350-kJ (800 kcal) formula diets. Am J Clin Nutr 1994, 60:249–254.

    PubMed  CAS  Google Scholar 

  62. Zapata R, Severin C, Manriques M, Valdiviesco V: Gallbladder motility and lithogenesis in obese patients during dietinduced weight loss. Dig Dis Sci 2000, 45:421–428. In 12 obese patients on a relatively low-caloric diet (800 to 1200 kcal/d), only one developed gallstones over 6 months. The highfat diet (26 g/d) may explain the relatively low frequency of stone formation.

    Article  PubMed  CAS  Google Scholar 

  63. Shiesh S-C, Chen C-Y, Lin X-Z, et al.: Melatonin prevents pigment gallstone formation induced by bile duct ligation in guinea pigs. Hepatology 2000, 32:455–460. Impaired antioxidant defenses resulting in the accumulation of reactive oxygen species and oxidative damage of DNA have been implicated in various degenerative diseases and aging. This animal study suggests a role for oxidative stress in promoting cholesterol crystal formation and in pigment stone formation.

    Article  PubMed  CAS  Google Scholar 

  64. Soloway RD, Winman SA: Oxidative stress as a cause of biliary lithiasis: new possibilities for medical therapy of stones or a false alarm? Hepatology 2000, 32:670–671. Excellent synthesis of how oxidative stress and free radical formation occur and of their consequences.

    Article  PubMed  CAS  Google Scholar 

  65. Muriz JL, Cuevas MJ, El-Mir MY, et al.: Enhancement of bile acid pool size, synthesis and secretion by epomediol in the rat. Dig Dis Sci 2000, 45:1431–1438. Epomediol, a synthetic terpenoid, when administered to rats produces an enlarged bile acid pool from increased synthesis in the liver. This causes an increased bile acid secretion rate and bile flow.

    Article  Google Scholar 

  66. Siegel JH, Veerappan A, Cohen SA, Kasmin FE: Endoscopic sphincterotomy for biliary pancreatitis: an alternative to cholecystectomy in high-risk patients. Gastrointest Endosc 1994, 40:573–575.

    Article  PubMed  CAS  Google Scholar 

  67. Welbourn CRB, Beckly DE, Eyre-Brook IA: Endoscopic sphincterotomy without cholecystectomy for gallstone pancreatitis. Gut 1995, 37:119–120.

    PubMed  CAS  Google Scholar 

  68. Fonseca Chebli JM, Duarte Gaburri P, Meirelles de Souza AF, et al.: 'Idiopathic' acute pancreatitis due to biliary sludge: prevention of relapses by endoscopic biliary sphincterotomy in high-risk patients [letter]. Am J Gastroenterol 2000, 95:3008–3009. Three-year follow-up report on 33 consecutive patients with idiopathic pancreatitis who underwent ERCP and bile analysis for sediment. Twenty-two had either cholesterol crystals (n=18) or bilirubinate granules (n=4). Assuming that microlithiasis and/or biliary sludge was the basis, the authors had 12 of these patients undergo cholecystectomy, and 10 older patients at high risk for surgery underwent endoscopic sphincterotomy. Only one relapse of pancreatitis occurred in the 12 followed for 36 months after cholecystectomy. Endoscopic sphincterotomy was equally effective in the 10 others followed for 27 to 36 months with only one relapse, whereas all had experienced two to six relapses prior to sphincterotomy. This report supports two others in which endoscopic sphincterotomy obviated recurrent pancreatitis and appeared effective in those at high risk for cholecystectomy.

    Article  Google Scholar 

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  1. Faculty of Medicine, Department of Medicine, Foothills Hospital, Room C210, 1403 29th Street NW, T2N 2T9, Calgary, AB, Canada

    Eldon A. Shaffer MD, FRCPC

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Shaffer, E.A. Gallbladder sludge: What is its clinical significance?. Curr Gastroenterol Rep 3, 166–173 (2001). https://doi.org/10.1007/s11894-001-0015-6

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