Overview

• Radiopaque or radiolucent calculi in the bile ducts, gallbladder (GB), or rarely bile ductules within the liver (hepatolithiasis). Gallbladder mucocele (GBM) is considered a form of cholelithiasis (see Gallbladder Mucocele).
• May be asymptomatic.
• Symptomatic-signs reflect sludged bile, EHBDO, cholecystitis, cholangiohepatitis, or bile peritonitis.
• Primary constituents of choleliths-mucin, glycoprotein, calcium carbonate, and bilirubin pigments; while dog bile is less lithogenic than human bile (lower cholesterol saturation); dog bile forms bilirubinate sludge with fasting; and provoked by a low-protein low-methionine diet.
• 50% feline choleliths mineralized; may be radiographically visible (calcium carbonate).
• Surgical/medical treatment-not recommended without clinical signs or clinico-pathologic abnormalities (current or historical).

Signalment

• Cat and dog
• Small-breed dogs may be predisposed
• Hyperlipidemic dogs-predisposed to GBM (see Gallbladder Mucocele)

Signs

• May be asymptomatic.
• When accompanied by infection or causing intermittent or complete EHBDO (with or without peritonitis)-vomiting; meal-related discomfort, abdominal pain; fever; ± jaundice.
• Episodic vague peri- or postprandial abdominal pain.

Causes & Risk Factors

• Predisposing factors-stasis of bile flow (GB dysmotility, choledochal cysts [cats]); lith nidus formation (inflammatory debris, infection, tumor, epithelial exfoliation, residual suture material); bile supersaturation (heme-bilirubin pigments, hemobilia, calcium, enhanced mucin production [inflammation, prostaglandins], cholesterol); fused feline pancreatic and bile duct (ampulla) predisposes to concurrent biliary /pancreatic cholelithiasis, choledochitis, and bile stasis progressing to EHBDO, and pancreatitis.
• Bile sludge and/or GB distention-enhances mucin production and coalescence of bile particulates.
• Inflammatory mediators and bacterial enzymes associated with cholecystitis-aggravate stone precipitation (mucin production, deconjugation, and dehydroxylation of bilirubin-yielding insoluble bili-pigments).
• Low-protein, low-taurine, and low-methionine diet in dogs-lithogenic.

Differential Diagnosis

• EHBDO-inflammatory, infectious, or neoplastic conditions involving liver or extrahepatic tissues adjacent to porta hepatis; suggested by marked increases in: ALP, GGT, bilirubin and cholesterol.
• Cholangiohepatitis.
• Cholecystitis/Choledochitis.
• Pancreatitis.
• Bile peritonitis.
• GBM.

CBC/Biochemistry/Urinalysis

• May have no clinicopathologic abnormalities.
• CBC-may be normal; abnormalities reflect bacterial infection, endotoxemia, biliary obstruction, or underlying causal factors; inflammatory leukogram in some cases.
• Biochemistry-if symptomatic: variable hyperbilirubinemia, increases in serum ALP, GGT, ALT, and AST activities.

Other Laboratory Tests

• Bacterial culture-bile: aerobic and anaerobic bacteria often confirmed in symptomatic patients.
• Cholelith nidus-culture may identify bacterial infection.
• Coagulation profile-bleeding may develop with chronic EHBDO (see Bile Duct Obstruction (Extrahepatic)) associated with prolonged clotting times (especially PIVKA and PT); responsive to parenteral vitamin K₁.
• Cholelith analysis: submit to laboratory equipped for cholelith analysis; usual composition-calcium carbonate complexed with mucin and bilirubinate pigments.

Imaging

• Abdominal radiography-limited value in delineating GB structure/content; choleliths often small, may be radiolucent; rarely mistaken for dystrophic biliary mineralization in animals with chronic cholangitis.
• Ultrasonography-can detect: choleliths 2 mm diameter, thickened GB wall, distended biliary tract, increased hepatic parenchymal echogenicity (inflammation, lipid, glycogen, or fibrosis), and extrahepatic ductal involvement; may facilitate specimen collection for culture, cytology, and histopathology; may detect evidence of EHBDO within 72hr; caution: a distended GB with bile “sludge” is common in anorectic or fasted patients: do not mistake for GB obstruction. Hepatolithiasis casts acoustic shadow in parenchyma. Imaging of choleliths in extrahepatic ducts may be difficult owing to enteric gas obstructing imaging “window.”

Diagnostic Procedures

Histopathologic evaluation of liver is necessary in patients undergoing surgical cholelith removal to detect comorbid conditions influencing treatment and prognosis.

Drug(s)

• Antibiotics-based on cultures of bile, tissue, and cholelith nidus or directed against enteric microbial opportunists; initial treatment with Timentin, metronidazole, combined with a fluoroquinolone is usually successful.
• Ursodeoxycholic acid-10–15 mg/kg/day PO, divided BID given with food; provides choleretic, hepatoprotectant, anti-endotoxic, antifibrotic effects, and may facilitate stone dissolution; therapy continued life-long if no cause for cholelithiasis identified.
• Vitamin K₁-parenterally; 0.5–1.5 mg/kg to a maximum of 3 doses in 36h in jaundiced patients; do not administer IV (anaphylaxis).

Contraindications/Possible Interactions

Ursodeoxycholic acid-contraindicated with EHBDO before biliary decompression.

Patient Monitoring

• Postoperatively: physical examination and pertinent diagnostic testing-every 2–4 weeks postoperatively until clinical signs and clinicopathologic abnormalities resolve.
• Periodic ultrasonography-assess cholelith status, integrity of biliary tract, hepatic parenchymal changes.

Possible Complications

Sudden onset of fever, abdominal pain, and malaise-may signify bile peritonitis and/or sepsis from a breakdown in bile containment, or recurrent cholelith lodged in sphincter of Oddi.

Expected Course and Prognosis

• May be asymptomatic
• Symptomatic disease-reflects existing infection, EHBDO, cholecystitis, or bile peritonitis.

Associated Conditions

• Bile Duct Obstruction (Extrahepatic)
• Cholecystitis
• Choledochitis
• Gallbladder Mucocele

Abbreviations

• ALP = alkaline phosphatase
• ALT = alanine aminotransferase
• AST = aspartate aminotransferase
• GBM = gallbladder mucocele
• GGT = γ –glutamyltransferase
• GSH = glutathione
• EHBDO = extrahepatic bile duct obstruction
• PIVKA = proteins invoked by vitamin K absence or antagonism
• PT = prothrombin time