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Basics ⬇

Basics

Definition

Cholestasis caused by biliary tree obstruction at the level of the common bile duct (CBD) causing extrahepatic bile duct obstruction (EHBDO) or at the level of the hepatic ducts: may involve one, several, or all hepatic ducts.

Pathophysiology

  • Serious hepatobiliary injury-follows within weeks of duct obstruction secondary to accumulation of inflammatory mediators, neutrophils, noxious bile acids and other bile constituents accumulating in the periductal area, mechanical effect of duct distention (hydrostatic pressure), and oxidative injury.
  • Gallbladder (GB) bile-may become colorless (white bile) if cystic duct obstruction impairs influx of canalicular green hepatic bile (contains bilirubin pigments).
  • White bile-reflects increased mucin production, bilirubin exclusion, and sometimes, suppurative inflammation.
  • Bacterial infection of bile-increased risk with stasis of bile flow (normal clearance of splanchnic-derived bacteria in the portal circulation).

Systems Affected

Hepatobiliary

Signalment

Species

Dog and cat

Breed Predilection

  • Animals predisposed to pancreatitis and choleliths: e.g., GB mucocele (GBM)-hyperlipidemic breeds (e.g., miniature Schnauzer, Shetland sheepdog).
  • Animals with large duct ductal plate malformation (DPM) phenotype (Caroli's malformation) predisposed to infection and cholelithiasis.
  • Choleliths appear more common in small-breed dogs and cats.

Mean Age and Range

Middle-aged to old animals with acquired disease; younger animals with DPM.

Predominant Sex

None

Signs

Historical Findings

  • Depend on underlying disorder and “completeness” of EHBDO.
  • Progressive lethargy and vague illness.
  • Progressive jaundice.
  • Pale (acholic) stools: complete EHBDO.
  • Polyphagia: complete EHBDO causes nutrient malassimilation (fat).
  • Bleeding tendencies: within 10 days of complete EHBDO, more severe/overt in cats.

Physical Examination Findings

  • Depend on underlying cause
  • Weight loss
  • Severe jaundice
  • Hepatomegaly unless biliary cirrhosis
  • Cranial mass effect-extrahepatic biliary structures (small dogs and cats)
  • Vague cranial abdominal discomfort
  • Acholic feces-unless enteric bleeding (hemoglobin provides pigment)
  • Bleeding tendencies-chronic EHBDO
  • Orange urine: severe bilirubinuria

Causes

  • Diverse primary disorders
  • Cholelithiasis
  • Choledochitis
  • Neoplasia
  • Bile duct malformations: choledochal cysts, polycystic hepatobiliary disease, DPM, Caroli's malformation, cystadenoma encroaching on porta hepatis (cats)
  • Parasitic infestation: flukes (cats)
  • Extrinsic compression: lymph nodes, neoplasia, pancreatitis, CBD entrapment in diaphragmatic hernia; foreign body obstruction of sphincter of Oddi in duodenum
  • Duct fibrosis: trauma, peritonitis, pancreatitis; major duct involvement in feline cholangitis/cholangiohepatitis
  • Duct stricture: blunt trauma, iatrogenic surgical manipulations

Risk Factors

See “Causes”

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

  • Mass lesions-primary or metastatic hepatobiliary neoplasia; in adjacent viscera
  • Diffuse infiltrative liver disease-neoplastic, inflammatory, HL (cats, canalicular compression), amyloid (rare)
  • Infectious hepatitis-bacterial, viral, flukes
  • Decompensated chronic hepatitis
  • Copper-associated hepatopathy
  • Severe hepatic fibrosis/cirrhosis
  • Fulminant hepatic failure
  • Biliary cysts-choledochal (cats), cystadenoma, polycystic liver disease (cats) compressing CBD at porta hepatis; choledochal cyst (cats), DPM
  • Pancreatitis: CBD stenosis, stricture
  • Hepatic lipidosis (HL)-cats: canalicular collapse causes jaundice.
  • Cholangitis/cholangiohepatitis-cats, esp. sclerosing or destructive cholangitis form.

CBC/Biochemistry/Urinalysis

CBC

  • Anemia-mild non-regenerative (chronic disease) or regenerative (enteric bleeding due to hypertensive splanchnic vasculopathy, ulcerations, coagulopathy due to portal hypertension)
  • Microcytosis-uncommon
  • Leukogram-variable, neutrophilic leukocytosis, left-shifted leukogram with sepsis
  • Plasma-markedly jaundiced

Biochemistry

  • Liver enzymes-variable; marked increases in ALP and GGT reflect ductal injury; high ALT and AST reflect hepatocyte injury.
  • Total bilirubin-moderate to markedly high; less than observed with hemolysis or HL; bilirubin fractionation-overlaps with hemolytic and sepsis associated jaundice.
  • Albumin-variable, usually normal except when EHBDO >6 weeks (biliary cirrhosis); low albumin reflects synthetic failure.
  • Globulins-normal or increased.
  • Glucose-normal or low if biliary cirrhosis or sepsis; high if diabetes with pancreatitis.
  • Hypercholesterolemia-common.

Urinalysis

  • Bilirubinuria and bilirubin crystals.
  • Absence of urobilinogen-unless enteric bleeding; unreliable definitive test for EHBDO.

Other Laboratory Tests

  • Serum bile acids-always markedly increased; superfluous test if hepatobiliary jaundice already suspected.
  • Coagulation abnormalities-within 10 days of EHBDO develop vitamin K deficiency (PIVKA and PT clotting times most sensitive); may develop DIC; cats more dramatic effect.
  • Fecal examination-acholic stools suggest EHBDO; masked by small-volume melena; trematode eggs if fluke infestation.

Imaging

  • Abdominal radiography-hepatomegaly; variable mass lesion in area of gallbladder, pancreatitis pattern, mineralized cholelith(s).
  • Cholecystography-rarely provides additional practical information.
  • Abdominal ultrasonography-evidence of obstruction within 72–96h (distended, tortuous CBD, cystic duct, and intrahepatic bile ducts); may disclose underlying or primary disorder (e.g., pancreatitis, cystic lesions, mass lesions, choleliths). Caution: GB bile “sludge” and a full GB are common in anorectic or fasted patients-do not mistake for EHBDO.
  • Caution: Feline CBC is serpiginous compared to the dog-always inspect liver image for distended intrahepatic bile ducts and confirm “tubes” are ducts rather than vasculature with color flow Doppler.

Diagnostic Procedures

  • Hepatic aspiration cytology-used to rule in HL (cats) or sample mass lesions; avoid aspiration of obstructed biliary structures as this may cause bile leakage and peritonitis.
  • US guided-needle biopsy-strongly contraindicated; may cause iatrogenic bile peritonitis.
  • Laparotomy-best approach; allows tissue biopsy; biliary decompression; mass excision: cholelith or inspissated bile removal; creation of biliary-enteric anastomosis; stent insertion.

Pathologic Findings

  • Gross-distended, tortuous bile duct, distended GB: cause often grossly apparent; obstruction >2 weeks: large, dark green or mahogany-colored liver; chronic complete obstruction of cystic duct associates with white or clear GB bile.
  • Microscopic-early: biliary epithelial hyperplasia and bile ductule proliferation and dilation with intraluminal biliary debris (mucin, inflammatory cells, usually neutrophils) and periductular edema, and early fibrosis; chronic distention of biliary structures: leads to devitalized biliary epithelium with necrotic debris, intraluminal suppurative debris, mixed periportal inflammatory infiltrates, periductal edema with thick laminating circumferential fibrosis, multifocal parenchymal necrosis.

Treatment ⬆ ⬇

Treatment

Appropriate Health Care

Inpatient-surgical intervention for EHBDO unless the cause is pancreatitis with prospect for resolution with supportive care.

Nursing Care

  • Fluid therapy-depends on underlying conditions (see Pancreatitis); rehydrate and provide maintenance fluids before general anesthesia and surgical interventions; supplement polyionic fluids with potassium chloride and phosphate, judicious electrolyte adjustments based on electrolyte status.
  • Water-soluble vitamins-in intravenous fluids; B complex (2 mL/L polyionic fluids).
  • Initiate antibiotic therapy before surgery: see “Drugs of Choice.”
  • Vitamin K1: parenteral administration if EHBDO >5–7 days (see “Drugs of Choice”).

Activity

Depends on patient status and coagulopathy.

Nutritional Support

  • Maintain nitrogen balance-avoid protein restriction.
  • Restrict fat-if overt fat malassimilation caused by lack of enteric bile acids in chronic EHBDO-rare incidence.
  • Supplement fat-soluble vitamins: vitamins E and K most urgent; supplementing vitamins D and A can lead to toxicity.
  • Water-soluble vitamin E-necessary in chronic EHBDO (see “Drugs of Choice”).

Client Education

  • Inform client that surgical biliary decompression is essential (unless resolvable pancreatitis or cholelith obstruction); EHBDO progresses to biliary cirrhosis within 6 weeks; exception is pancreatitis causing EHBDO that may self-resolve within 2–3 weeks.
  • Warn client that surgical success is contingent on underlying cause, results of liver biopsy, infection, and individual variables.

Surgical Considerations

  • Surgical exploration-imperative for treating and determining underlying cause unless obvious pancreatitis.
  • Excise masses, remove choleliths and inspissated bile; ensure common duct patency.
  • Resect GB-if necrotizing cholecystitis or GB mucocele.
  • Biliary-enteric anastomosis-if irresolvable occlusion, fibrosing pancreatitis, or neoplasia; anastomotic stoma at least 2.5 cm wide. Chronic recurrent infection likely after biliary-enteric anastomosis. Temporary stent instead of biliary enteric anastomosis may be complicated by infection and stent obstruction, esp. in cats.
  • Hypotension and bradycardia (vasovagal reflex)-may develop during biliary tree manipulation; ensure availability of emergency drugs (anticholinergics) and ventilatory support for rescue endeavors.
  • Ensure IV catheter access and volume expansion-use colloids when necessary, plasma preferred; be prepared for hemorrhage (have blood available for transfusions).
  • Surgical biopsies-submit tissue and bile for aerobic and anaerobic bacterial culture; submit tissue for histology.
  • Cytology-make preps from tissue and bile; cytology may detect bacterial infections and fluke eggs not recognized in biopsy sections. Bile, biliary debris, and GB wall-more likely to culture organisms. Wright-Giemsa staining to detect bacteria, Gram stain to characterize bacterial morphology; may advise acute antimicrobial selection. Enteric opportunists are most common. Bacteroides may promote polymicrobial infection; may not culture all involved bacteria.
  • Sclerosing or destructive feline cholangitis

(intrahepatic ductopenia) may clinically emulate EHBDO; does not respond to biliary tree decompression; liver biopsy necessary.

Medications ⬆ ⬇

Medications

Drug(s) Of Choice

Vitamin K1

Provide 12–36h before surgery (0.5–1.5 mg/kg IM or SC), 3 doses at 12-h intervals. Caution: avoid IV, may cause anaphylaxis. If chronic EHBDO irresolvable, parenteral Vit. K1 given chronically with frequency titrated using PIVKA or PT, too much vit. K1 causes hemolytic (Heinz body) anemia in cats.

Vitamin E

  • If chronic EHBDO irresolvable (rare) use polyethylene glycol alpha tocopherol succinate (TPGS-vitamin E) 10 U/kg/day PO and injectable Vitamin K1 (see above).
  • Treat early to allow response before surgery.

Antibiotics

Before surgery-broad-spectrum antimicrobials for potential biliary infections as surgical manipulations may disseminate bacteremia; initially use antibiotics with wide spectrum as follows-triad of: ticarcillin 25 mg/kg IV q8h, metronidazole 7.5 mg/kg IV or PO q12h, enrofloxacin 5 mg/kg PO q12–24h (24h dose in cats no greater than 5 mg/kg/24h to avoid retinopathy).

Antioxidants

  • Vitamin E (-tocopherol acetate)-10–100 IU/kg; a larger-than-normal (normal = 10 IU/kg /day) oral dose needed in chronic EHBDO because of fat malabsorption (lack of enteric bile acids); use of TPGS-Vitamin E preferred (see previous).
  • S-Adenosylmethionine (SAMe) with proven bioavailability and efficacy as GSH donor-20 mg/kg/day PO enteric-coated tablet 1–2 hours before feeding; provides numerous additional metabolic benefits.

Ursodeoxycholic Acid

10–15 mg/kg PO per day-AFTER biliary decompression as a choleretic; ensure adequate hydration to achieve choleresis; inappropriate before biliary decompression: can accelerate liver injury in EHBDO. Does not facilitate fat assimilation in chronic EHBDO. Beneficial effects: antifibrotic, anti-endotoxic, hepato-protectant, anti-apoptotic, immunomodulator.

Bowl Preparation Before Surgery

  • May reduce endotoxemia potentiating perioperative hypotension.
  • Mechanical cleansing of colon with water or crystalloid fluids.
  • Acutely alter enteric flora to reduce enteric translocation of opportunistic pathogen with medications given either: PO or by high enema; neomycin: 22 mg/kg q8h, lactulose 1–2 mL/kg q8h; metronidazole 7.5 mg/kg q12h; rifaximin 5–10 mg/kg q12h; probiotic bacteria (empirical product dose); enrofloxacin 2.5 mg/kg q12h PO.

Gastrointestinal Protectants

Agents reducing gastric acidity-famotidine (H2-blocker) or omeprazole (pump inhibitor) combined with sucralfate for local cytoprotection if PO medications tolerated and enteric bleeding recognized; stagger sucralfate administration from other oral medications to avoid drug interactions.

Contraindications

  • Provide biliary decompression before institution of ursodeoxycholic acid.
  • Take care to reduce drug dosages for medications eliminated in bile if EHBDO.

Precautions

See “hypotension and bradycardia (vasovagal reflex)” under “Surgical Considerations.”

Alternative Drug(s)

N/A

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

  • Depends on underlying condition-special monitoring for underlying disorders causing EHBDO; see appropriate conditions.
  • Total bilirubin values acutely reflect biliary decompression; values normalize within days.
  • Liver enzyme activities-decline slowly.
  • CBC-repeat q2–3 days initially if septic.
  • Bile peritonitis-evaluate abdominal girth, body weight, and fluid accumulation (e.g., by palpation, ultrasonography preferred, abdominocentesis).
  • Determine necessity for pancreatic enzyme supplementation based on site of biliary-enteric anastomosis; patients with cholecystojejuno-stomies may benefit from enzyme supple-mentation; cannot rely on trypsin-like immunoreactive (TLI) substance to estimate pancreatic exocrine adequacy in this circumstance; evaluate body weight and condition; check feces for steatorrhea (fat malassimilation; suspend feces in water and microscopically examine for lipid globules-only relevant if animal is fed a normal fat-containing diet; if steatorrheic after biliary-enteric anastomosis and non-icteric, reduce dietary fat and supplement with pancreatic enzymes. Pancreatic enzymes can induce oral or esophageal ulcers especially in cats, must be mixed in food and followed by liquid or food to prevent mucosal injury.

Prevention/Avoidance

N/A

Possible Complications

  • Bile peritonitis
  • Restenosis of bile duct-if not bypassed
  • Stenosis of biliary-enteric anastomosis
  • Severe enteric hemorrhage with EHBDO-hypertensive enteric vasculopathy with coagulopathy (vitamin K deficiency)
  • Hemorrhage during surgery
  • Septic bacteremia or SIRS during or after surgery
  • Unresponsive hypotension during surgery
  • Vasovagal reflex-biliary tree manipulation

Expected Course and Prognosis

  • Depends on underlying disease.
  • Prognosis good if fibrosing pancreatitis and pancreatic inflammation resolves; bile duct patency may return.
  • Be aware: biliary tree may appear distended on subsequent ultrasounds.
  • Permanent peribiliary fibrosis from EHBDO.
  • Cats with sclerosing cholangitis can appear to have EHBDO; but show no response to biliary decompression; liver biopsy essential for diagnosis.

Considerations/Precautions

  • Anticipate bleeding tendencies and vasovagal reflex during surgical procedures.
  • Always submit liver and biliary tree biopsies for histology; all tissues and bile for bacterial culture (aerobic, anaerobic).

Miscellaneous ⬆

Miscellaneous

Associated Conditions

  • See “Causes”
  • Sclerosing or destructive cholangitis (cats) confused with EHBDO

Abbreviations

  • ALP = alkaline phosphatase
  • ALT = alanine aminotransferase
  • CBD = common bile duct
  • DIC = disseminated intravascular coagulation
  • EHBDO = extrahepatic bile duct obstruction
  • GB = gallbladder
  • GGT = gamma glutamyltransferase
  • GSH = glutathione
  • HL = hepatic lipidosis
  • PIVKA = proteins invoked by vitamin K absence or antagonism
  • PT = prothrombin time
  • TPGS-Vitamin E = d-∀-tocopheryl polyethylene glycol succinate

Author Sharon A. Center

Consulting Editor Sharon A. Center

Client Education Handout Available Online

Suggested Reading

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

Center SA. Interpretation of liver enzymes. Vet Clin North Am Small Anim Pract 2007, 37(2):297–333.