Biliary sludge: more than a curiosity

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Biliary sludge: more than a curiosityBiliary sludge was first recognised

ultrasonographically, and was defined as an echogenicmaterial that forms in layers in the most dependentportion of the gallbladder, varies with posture, and,unlike gallstones, does not cast an acoustic shadow.1The composition of biliary sludge is now known, and,it is increasingly recognised both as a precursor ofgallstOnes2,3 and as an important cause of "idiopathic"pancreatitis.Some people with sludge presenting with

abdominal pain have no clear underlying cause orillness.4 However, several groups of patients are atconsiderably increased risk of sludge formation.

Examples are recipients of total parenteral nutrition,5,6patients immediately after abdominal surgery, 7

pregnant women, and those who are critically ill inintensive care units.9 Bone marrow transplantationand AIDS likewise predispose to sludge."," Themain components of biliary sludge are bile

supersaturated with cholesterol, mucin glycoproteinin very high quantities, cholesterol monohydratecrystals, and calcium bilirubinate granules.12The evidence that biliary sludge leads to gallstones

is considerable. First, all groups of patients identifiedwith sludge who have been followed-up have a veryhigh incidence of subsequent gallstone formation, andgallstones can frequently be observed as developingwithin the biliary sludge.5-8.10,11 Second, bilirubin inbiliary sludge is predominantly unconjugated, a

pattern typical of that seen in the matrix of cholesterolgallstones, which is itself formed at the early stages ofgallstone development.12,13 By contrast, bilirubin innormal bile is predominantly conjugated.l4 Third,sludge contains cholesterol crystals, a criticaland essential early step in gallstone fonnation.12

Finally, the very high mucin glycoprotein contenthas also been noted in animal models of gallstoneformation such as cholesterol-fed prairie dogs.13Whether sludge is an essential intermediate step in

formation of all gallstones is unknown, although Leeet al, using ultrasound, observed that sludge is oftena recurrent event in subjects who have no clearpredisposing factor. The concept that gallstonescan form only at specific critical periods in the

gallbladder is an attractive but largely unexploredhypothesis.Many researchers now believe that gallstones

arise because of a triple hepatobiliary defect:

(a) cholesterol-supersaturated gallbladder bile;(b) increased rate of cholesterol crystal nucleation; and(c) reduced gallbladder contractility. Several factorsmay be important in controlling the rate of cholesterolnucleation, and considerable evidence suggests thatmucin glycoprotein is an important pronucleatingagent.15,16 It seems that the triple hepatobiliary defectassociated with gallstone formation may be present insubjects with biliary sludge. Sludge containssupersaturated bile and a very high concentration of

nucleating agent (mucin glycoprotein).12 We knowvery little about impairment of gallbladdercontractility in subjects with biliary sludge. The onlygroup of patients at risk of sludge formation to havebeen studied in this respect are recipients of totalparenteral nutrition, in whom contractility isreduced.17 Regular administration of cholecystokinin(CCK) stimulates gallbladder contractility and

prevents biliary sludge formation,18 which suggeststhat there is a contractility defect in some patients withsludge and that reversal of this defect will preventsludge formation and presumably gallstoneformation, as well.Two recent studies’9-20 have suggested that biliary

tract disease, and specifically biliary sludge, may beresponsible for most cases of "idiopathic"pancreatitis; many patients with this disorder

subsequently get gallstones. Treatment with bile salts,endoscopic sphincterotomy, or cholecystectomyseems to be effective in preventing further attacks ofpancreatitis in most cases.19,20

1. Conrad MR, Janes JO, Dietchy J. Significance of low level echoes withinthe gallbladder. Am J Roentgenol 1979; 132: 967-72.

2. Paumgartner G, Sauerbruch T. Gallstones: pathogenesis. Lancet 1991;338: 1117-21.

3. Editorial. Gallstones, bile acids, and the liver. Lancet 1989; ii: 249-51.4. Lee SP, Maher K, Nicholls JF. Origin and fate of biliary sludge.

Gastroenterology 1988; 94: 170-76.5. Roslyn JL, Pitt HA, Mann LL, Ament ME, DenBesten L. Gallbladder

disease in patients on long term parenteral nutrition. Gastroenterology1983; 84: 148-54.

6. Messing B, Bories C, Kunstlinger F, et al. Does total parenteral nutritioninduce gallbladder sludge formation and lithiasis? Gastroenterology1983; 84: 1012-19.

7. Bolondi L, Gaini S, Testa S, et al. Gallbladder sludge formation duringprolonged fasting after gastrointestinal surgery. Gut 1985; 26: 734-38.

8. Maringhini A, Marceno MP, Lanzarone F, et al. Sludge and stones ingallbladder after pregnancy. J Hepatol 1987; 5: 218-22.

9. Murray FE, Stinchcombe SJ, Hawkey CJ. High incidence of biliarysludge in patients on the intensive care unit. Clin Sci 1991; 81: 26S.

10. Frick MP, Snover DC, Feinberg SB, et al. Sonography of the gallbladderin bone marrow transplant patients. Am J Gastroenterol 1984; 79:122-27.

11. Grumbach K, Coleman BG, Gal AA, Arger PH, et al. Hepatic and biliarytract abnormalities in patients with AIDS. J Ultrasound Med 1989; 8:247-54.

12. Lee SP, Nicholls JF. Nature and composition of biliary sludge.Gastroenterology 1986; 90: 677-86.

13. Smith BF, LaMont JT. Identification of a mucin bilirubin complex in thematrix of cholesterol gallstones. J Clin Invest 1985; 76: 439-45.

14. Fevary J, Blanckaert N, Pol L, et al. Analysis of bilirubins in biologicalfluids by extraction and thin layer chromatography: applications topatients with haemolysis, Gilbert’s syndrome and cholelithiasis.

Hepatology 1983; 3: 177-83.15. Lee SP, LaMont JT, Carey MC. Role of gallbladder mucus

hypersecretion in the evolution of cholesterol gallstones. J Clin Invest1981; 67: 1712-23.

16. Levy P, Smith BF, LaMont JT. Human gallbladder mucin accelerates invitro nucleation of cholesterol in artificial bile. Gastroenterology 1984;87: 270-75.

17. Cano N, Cicero F, Ranier F, et al. Ultrasonographic study of gallbladdermotility during total parenteral nutrition. Gastroenterology 1983; 84:1012-19.

18. Sitzmann JV, Pitt HA, Steinborn PA, Pasha ZR, Sanders RC.

Cholecystokinin prevents parenteral nutrition induced biliary sludge inhumans. Surg Gynecol Obstet 1990; 170: 24-31.

19. Ros E, Navarro S, Bru C, Garcia-puges A, Valderrama R. Occultmicrolithiasis in ’idiopathic’ acute pancreatitis: prevention of relapsesby cholecystectomy or ursodeoxycholic acid therapy. Gastroenterology1991; 101: 1701-09.

20. Lee SP, Nicholls JF, Park HZ. Biliary sludge as a cause of acutepancreatitis. N Engl J Med 1992; 326: 589-93.