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Basics ⬇

Basics

Overview

  • Accumulation of tenacious, thick, mucoid bile conglomerate in the gallbladder (GB), obstructing storage capacity and function.
  • Inspissated biliary sludge expands the GB, leading to necrotizing cholecystitis.
  • A canine syndrome, rare in cats.

Signalment

  • Dog
  • Shetland sheepdogs, miniature schnauzers, Cocker spaniels-overrepresented.
  • Middle-aged to older adults.
  • No sex predilection.
  • Associated with endocrinopathies.

Signs

General Comments

  • Symptomatic or asymptomatic
  • Asymptomatic discovered on abdominal ultrasonography for other health concerns

Historical Findings: symptomatic

  • Episodic abdominal discomfort
  • Anorexia
  • Vomiting
  • Polyuria/polydipsia
  • Lethargy
  • Collapse: vasovagal or bile peritonitis

Physical Examination Findings

  • May show no physical signs early in syndrome
  • Lethargy
  • Cranial abdominal discomfort
  • Jaundice late in syndrome
  • Dehydration
  • Fever

Causes & Risk Factors

  • Inborn errors of lipid metabolism may increase risk: miniature schnauzer, Shetland sheepdogs.
  • Medical conditions associated with hypercholesterolemia or promoting dyslipidemias: hypothyroidism, typical or atypical (sex hormone) adrenal hyperplasia, glucocorticoid therapy, diabetes mellitus, recurrent pancreatitis, feeding high fat diet to dog with a predisposing disorder.
  • GB dysmotility-may play a causal role.
  • Cystic hypertrophy of mucus-producing GB mucosa-common in older dogs; may play a causal or facilitatory role.

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

Conditions causing bile stasis-GB dysmotility; neoplasia; choleliths; pancreatitis

CBC/Biochemistry/Urinalysis

CBC

  • Inflammatory leukogram-variable
  • Non-regenerative anemia-if chronic inflammation or hypothyroidism

Biochemistry

  • High liver enzymes-only sign of illness in some dogs or may be noted on acute presentation; ALP, GGT, ALT, ± AST.
  • High ALP: early in syndrome development may indicate an underlying glycogen-type vacuolar hepatopathy (VH) and endocrinopathy (adrenal related).
  • Variable hyperbilirubinemia.
  • Low albumin if ruptured biliary tree and bile peritonitis.
  • Prerenal azotemia if ruptured GB, sepsis, or dehydration from postprandial vomiting.
  • Electrolyte abnormalities with fluid and acid-base disturbances-reflecting bile peritonitis or extensive vomiting.

Urinalysis

No specific features

Other Laboratory Tests

  • Triglyceride concentrations-high if inborn error of lipid metabolism: certain breeds, endocrinopathies, diabetes mellitus, hypothyroidism, or pancreatitis.
  • Coagulation tests-normal, unless chronic EHBDO, GB rupture, bile peritonitis, sepsis, or DIC.

Imaging

  • Abdominal radiography-normal or large liver; loss of detail in cranial abdomen if focal peritonitis (necrotizing cholecystitis, GB rupture); intrahepatic gas indicates septic inflammation with gas-producing bacteria (rare).
  • Abdominal ultrasonography-liver may be large, with rounded margins; diffuse to multifocal hyperechoic hepatic parenchyma common (associated with VH); typical US image is a GB lumen filled with amorphous echogenic debris appearing as a stellate or finely striated pattern, resembling a sliced kiwi fruit (“kiwi sign”); distended GB and sometimes distended common bile duct and cystic duct if EHBDO; fluid interface surrounding GB enhances wall image and suggests cholecystitis or GB rupture; diffusely thick GB wall with segmental hyperechogenicity and double-rimmed or laminated wall if necrotizing cholecystitis; edema may enhance GB wall imaging: may occur with hepatitis, cholangiohepatitis, or third-space fluid dispersal (hypoproteinemia, right heart failure, renal failure, pyelonephritis, abdominal effusion, iatrogenic fluid overload); GB rupture associated with discontinuous GB wall, or a difficult to image GB; GB mucocele (GBM) may be released into the abdominal cavity where a discrete free floating “mass” may be discovered; pericholecystic fluid or generalized effusion, and hyperechogenicity of surrounding tissues may indicate focal peritonitis and bile leakage; intrahepatic bile ducts may be difficult to visualize or may appear prominent (ascending cholangitis) or distended (EHBDO).
  • GB motility study-indicated if impending GBM recognized serendipitously and GB volume 1.2 mL/kg body weight; sequential GB volume measurements after meal ingestion (100 g), may include 1 mg/kg erythromycin as motilin agonist provoking GB contraction. Normal GB contracts 25% initial volume on one or more postprandial images: image GB at 0, 15, 30, 45, 60, 90, 120 minutes after feeding.

Diagnostic Procedures

  • Aspiration sampling-fluid adjacent to biliary structures or free in abdominal cavity; clarifies GB rupture and infection; caution: do not perform cholecystocentesis on a suspected GBM as this may cause bile peritonitis; GBM contents usually difficult to sample owing to their thick, tenacious character.
  • Laparotomy-for diagnosis, cholecystectomy and perhaps cholecystenterostomy.
  • Laparoscopy: only if technical excellence achieved for cholecystectomy by this method.
  • Liver biopsy-evaluates for coexistent or antecedent hepatobiliary disorders. Collect biopsy distant to the GB to avoid sampling peribiliary glands.
  • Bacterial culture /sensitivity-effusion, GB wall and contents, and liver; aerobic and anaerobic bacteria.
  • Cytology-impression smears of GB, liver, and bile for immediate determination of suppurative septic inflammation and neoplasia. Make smears of bile particulates where bacteria are “tangled.”

Pathologic Findings

  • Gross-GB distended, wall may be erythematous or hemorrhagic with focal areas of necrosis; focal peritonitis may be evident; liver and extrahepatic biliary structures usually appear normal; GB contents: dark green-black, tenacious, firm, or organized solid yellow-green on cut surface with a rubbery texture. Proliferative lesions on GB mucosa usually represent cystic mucosal hyperplasia or papillary proliferations.
  • Microscopic-variable mixed inflammatory infiltrate and fibrosis (chronic) in lamina propria of GB wall, focal areas of necrosis if necrotizing cholecystitis; GB mucosal hyperplasia-common; ascending cholangitis and cholangiohepatitis may develop as secondary complications; hepatocytes may demonstrate VH (glycogen and/or lipid inclusions) if underlying endocrinopathy (see associated conditions). Asymptomatic GBM removed preemptively may only demonstrate cystic mucosal hyperplasia.

Treatment ⬆ ⬇

Treatment

Medications ⬆ ⬇

Medications

Drug(s)

Antimicrobials

Initiate broad-spectrum antimicrobials before surgery: enteric Gram-negative and anaerobic organisms most likely opportunists; continue treatment 4–8 weeks if septic complications; adjust drugs based on culture and sensitivity test reports.

Vitamin K1

0.5–1.5 mg/kg IM or SC q12h for three doses-if jaundiced; oral route maybe ineffective if EHBDO: fat-soluble vitamin malabsorption.

Antiemetics/Antacids/Gastroprotectants

  • Metoclopramide 0.2–0.5 mg/kg PO, IV, or SC q6–8h or 1–2 mg/kg/day by CRI.
  • Ondasetron 0.5–1.0 mg/kg PO 30 min before feeding, maximum q8h or 0.1–0.2 mg/kg slow IV push q6–12h-if vomiting.
  • H2-receptor antagonists: famotidine 0.5 mg/kg PO, IV, SC q12–24h; may need to increase dose for efficacy.
  • Omeprazole or pantoprazole may induce p450 cytochrome associated drug interactions; 24–48 h delay onset of action.
  • Sucralfate 0.25–1.0 g PO q8–12h)-for upper gastrointestinal bleeding.

Choleresis

  • Maintain hydration status.
  • Ursodeoxycholic acid: choleretic, hepatoprotectant, anti-inflammatory, anti-endotoxic effects: (10–15 mg/kg PO divided BID daily with food), tablets provide best bioavailability); treat indefinitely
  • S-adenosyl-methionine (SAMe) provides GSH-dependent choleretic effect, dose may be higher than used as an antioxidant (see below); choleresis with 40 mg/kg PO per day.

Antioxidants

  • Vitamin E: -tocopherol 10 IU/kg PO daily with food); antioxidant, anti-inflammatory, antifibrotic effects.
  • S-adenosylmethionine (SAMe): 20 mg/kg PO daily 2h before feeding, use SAMe with proven bioavailability; give until liver enzymes normalize or indefinitely if chronic hepatitis.

Contraindications/Possible Interactions

N/A

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

  • Repeat sequential hematology, biochemistry, and imaging to monitor response.
  • Persistent clinicopathologic features may implicate underlying endocrinopathy requiring documentation and treatment, or an intrahepatic cholangiopathy.

Possible Complications

  • Cholangitis or cholangiohepatitis
  • Bile peritonitis
  • EHBDO

Expected Course and Prognosis

  • Good with successful surgery, chronic choleretic therapy, correction or management of comorbid conditions, diet modification.
  • Anticipate a protracted clinical course with ruptured biliary tract or peritonitis.
  • Recrudescence may occur even if mucocele removed and GB retained, with or without chronic medical therapy.

Miscellaneous ⬆

Miscellaneous

See Also

Abbreviations

  • ALP = alkaline phosphatase
  • ALT = alanine aminotransferase
  • AST = aspartate aminotransferase
  • BUN = blood urea nitrogen
  • CRI = constant rate infusion
  • DIC = disseminated intravascular coagulation
  • EHBDO = extrahepatic bile duct obstruction
  • GB = gallbladder
  • GBM = gallbladder mucocele
  • GGT = γ–glutamyltransferase
  • GSH = glutathione
  • VH = vacuolar hepatopathy

Suggested Reading

Aguirre AL, Center SA, Randolph JF. Gallbladder disease in Shetland Sheepdogs: 38 cases (1995–2005). J Am Vet Med Assoc 2007, 231:79–88.

Center SA. Diseases of the gallbladder and biliary tree. Vet Clin North Am Small Anim Pract 2009, 39(3):543–598.

Pike FS, Berg J, King NW, et al. Gallbladder mucocele in dogs: 30 cases (2000–2002). J Am Vet Med Assoc 2004, 224:1615–1622.

Worley DR, Hottinger HA, Lawrence HJ. Surgical management of gallbladder mucoceles in dogs: 22 cases (1999–2003). J Am Vet Med Assoc 2004, 225:1418–1422.

Author Sharon A. Center

Consulting Editor Sharon A. Center