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Pathological Changes in Bile in Small Animals

(White Bile Syndrome, Inspissated Bile Syndrome, Bilirubin Deconjugation)


Sharon A. Center

, DVM, DACVIM, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University

Reviewed/Revised Aug 2023

In animals with bile stasis, nonabsorbable bile constituents (bile salts, phospholipids, glycoproteins, and cholesterol) are subject to concentration or dilution when water and inorganic electrolytes (sodium, chloride, bicarbonate) are resorbed or added by the biliary epithelium.

Extrahepatic bile duct obstruction Extrahepatic Bile Duct Obstruction in Small Animals Extrahepatic bile duct obstruction is the blockage of the normal flow of bile from the liver to the intestinal tract. Obstruction of the common bile duct is associated with a number of diverse... read more (EHBDO) can produce a gallbladder "white bile” syndrome reflecting exclusion of bilirubin pigments delivered from hepatic bile. This phenomenon coordinates with an obstructed gallbladder at the level of the cystic duct or hepatic ducts.

Stasis of bile flow also may lead to bile dehydration, culminating in development of pathologically sludged or inspissated bile. This physical change evolves dark green to black bile with a gritty texture in an unobstructed biliary tree.

Development of gallbladder mucocele (GBM) syndrome in dogs reflects gallbladder dysmotility as a primary pathogenic process. In this syndrome, retention and dehydration of gallbladder bile and local overproduction of mucin by the gallbladder epithelium is anchored to mucosal fronds and cystic mucosal lesions. The viscoelastic properties of entangled and entrapped mucin evolve a rubbery viscosity that various from dark and granular (early) to pale and rubbery (mature). Bile stasis in obstructed bile ducts can also lead to bilirubin deconjugation, a process reducing water solubility of bilirubin and favoring precipitation of calcium bilirubinate crystals.

Calcium bilirubinate contributes to the gritty consistency of retained bile. Choleresis (enhanced bile flow) produces watery, dilute bile and is a therapeutic goal in disorders associated with bile stasis. Animals treated with ursodeoxycholic acid (in the absence of bile duct obstruction) may demonstrate dark or light green liquid bile.

Syndromes Associated With Unusual Bile

White bile can be encountered in animals with extrahepatic biliary structures devoid of bilirubin-pigmented hepatic bile. Most often this occurs with disrupted or obstructed flow of pigmented hepatic bile into the common bile duct or gallbladder. Excessive mucin production by inflamed or irritated biliary epithelium importantly contributes to accumulated fluid.

In some cases, purulent inflammation contributes a white appearance to bile in the absence of complete bile flow obstruction. Accordingly, white bile should be cytologically examined as soon as possible to inform contemporary management considerations.

White bile also should be cultured for aerobic and anaerobic bacteria out of concern for possible complicating infection. Other less common causes of white bile are diffuse small bile duct ductopenia, most often encountered in cats in the terminal stages of lymphocytic cholangiohepatitis, and presentation of a choledochal cyst, mistaken for a major bile duct structure. Choledochal cysts are appendix-like malformations of the common bile duct that may be large and oriented lateral to the common bile duct. While these often become infected, they also may be filled with mucinous biliary secretions. Some dogs with GBM display a rubbery, nonpigmented gelatinous mucin-laden conglomerate filling the entirety of the gallbladder lumen, with only scant bilirubin pigments.

Black or dark green gallbladder bile represents inspissated bilirubin pigmented bile that often has a gritty feel due to calcium bilirubinate. This type of bile is most commonly encountered in dogs with gallbladder dysmotility before development of GBM and in dogs with chronic hemolytic anemia. Occasionally black or dark green inspissated biliary debris reflects intermittent hemobilia. Inspissated dark green to black gallbladder bile is also occasionally encountered in cats with cholangiohepatitis, presumably associated with deranged gallbladder motility and propensity for calcium bilirubinate precipitation.

Flushing the extrahepatic biliary tree free of such congealed dark bile is necessary in animals with this biliary change during a surgical intervention. Experimentally, feeding dogs a lithogenic, methionine-deficient, low-protein, high-cholesterol diet provoked development of dark green pigmented calcium bilirubinate choleliths. These associated with increased concentrations of unconjugated biliary bile acids. This diet was shown to provoke chronic taurine deficiency thought to compromise bile acid conjugation. However, taurine supplementation could not reverse the syndrome; only methionine supplementation corrected the disorder.

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