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Basics ⬇

Outline

BASICS

Definition!!navigator!!

Icterus is caused by hyperbilirubinemia with bilirubin deposition in tissues and is characterized by yellow discoloration of the sclerae, nonpigmented skin, and mucous membranes.

Pathophysiology!!navigator!!

  • Bilirubin, from heme breakdown, is converted to biliverdin and then to unconjugated bilirubin, bound to plasma albumin for transfer to the liver, then conjugated by hepatocytes.
  • Conjugated bilirubin is secreted into bile and enters the intestine, where most is converted to urobilinogen.
  • Hyperbilirubinemia can result from increased bilirubin production, impaired hepatic uptake or conjugation, or impaired excretion

Systems Affected!!navigator!!

  • Skin—bilirubin has an affinity for elastic tissues; thus icterus is most evident in the sclerae and vulva.
  • Hepatobiliary—accumulated bilirubin may contribute to hepatocellular injury, cholestasis.
  • Renal—bile casts may cause tubular injury.
  • Nervous—bilirubin accumulation may cause degenerative lesions (e.g. kernicterus)

Signs!!navigator!!

  • Depression.
  • Anorexia.
  • Severely altered mentation—HE due to hypoglycemia, hyperammonemia, decreased BCAA:AAA ratio.
  • Weight loss—anorexia, failure of hepatic metabolic functions in chronic hepatic insufficiency.
  • Acute or recurrent subacute abdominal pain—hepatic swelling or biliary obstruction (e.g. cholelithiasis)

Less Frequent

  • Photodermatitis—phylloerythrin accumulation in skin.
  • Diarrhea—altered intestinal microflora, portal hypertension with chronic hepatic insufficiency.
  • Bleeding diathesis—inadequate hepatic synthesis of clotting factors.
  • Dependent edema—hypoalbuminemia or portal hypertension

Causes!!navigator!!

Prehepatic/Hemolytic Icterus

  • Intra- and/or extravascular hemolysis or massive intracorporeal hemorrhage; rate of bilirubin production exceeds hepatic conjugation and excretion.
  • Oxidative injury—red maple (Acer rubrum), wild onion (Allium spp.), phenothiazine toxicosis, nitrate poisoning.
  • Immune mediated—neonatal isoerythrolysis, IMHA (secondary to Clostridium perfringens septicemia, purpura haemorrhagica, lymphosarcoma, penicillin administration, etc.), disseminated intravascular coagulation.
  • Infectious—EIA, EVA, piroplasmosis, anaplasmosis, leptospirosis.
  • Iatrogenic—DMSO (>10%) IV, hypotonic/hypertonic fluids, blood transfusion.
  • Miscellaneous—snake venom, bee/wasp venom, erythrocytosis

Hepatic/Retention Icterus

Impaired hepatic uptake and/or conjugation of bilirubin.

Hepatic Causes—Hepatic Icterus

Acute Hepatic Diseases—Adults

  • Bacterial—cholangiohepatitis, endotoxemia, infectious necrotic hepatitis (Clostridium novyi type B).
  • Viral—EIA, EVA, serum hepatitis (Theiler's disease-associated virus).
  • Parasitic—migration of Strongylus equinus and Strongylus edentatus, S. equinus thromboembolic disease.
  • Toxic—arsenic, carbon tetrachloride, chlorinated hydrocarbons, monensin, pentachlorophenols, phenol, phosphorus, paraquat, aflatoxin, rubratoxin.
  • Drugs—anabolic steroids, erythromycin

Acute Hepatic Diseases—Foals

  • Bacterial—Tyzzer's disease (Clostridium piliforme), septicemia, endotoxemia.
  • Viral—equine herpesvirus 1.
  • Parasitic—Parascaris equorum, strongyles.
  • Toxic—ferrous fumarate, toxins listed for adults

Chronic Hepatic Diseases—Adults

  • Idiopathic—chronic active hepatitis.
  • Bacterial—hepatic abscessation.
  • Metabolic—hyperlipemia.
  • Neoplastic—primary (e.g. cholangiocarcinoma, hepatocellular carcinoma) or secondary (e.g. lymphosarcoma).
  • Immunologic—amyloidosis.
  • Toxic—chronic megalocytic hepatopathy due to pyrrolizidine alkaloids

Chronic Hepatic Diseases—Foals

  • Bacterial—hepatic abscessation secondary to septicemia or omphalophlebitis.
  • Neoplastic—mixed hamartoma

Extrahepatic Causes—Hepatic Icterus

  • Anorexia.
  • Heparin administration.
  • Prematurity

Posthepatic/Obstructive Icterus

Partial or complete obstruction of biliary tree that decreases excretion of conjugated bilirubin; usually accompanied by bilirubinuria.

  • Adults—cholelithiasis, large colon displacement, cholangitis, neoplastic infiltration, fibrosis or hyperplasia of biliary tract, hepatitis.
  • Foals—acquired biliary obstruction (e.g. healing duodenal ulcer adjacent to hepatopancreatic ampulla), congenital biliary atresia

Risk Factors!!navigator!!

  • Previous administration of equine-origin biologic.
  • Septicemia, omphalophlebitis (foals).
  • Duodenal ulceration.
  • Inadequate parasite control/vaccination.
  • Exposure to plant/environmental toxins.
  • Use of certain drugs.
  • Anorexic, obese pony/miniature horse/donkey

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

Prehepatic Icterus

  • Abrupt onset of exercise intolerance, weakness, fever, tachypnea, dyspnea, tachycardia, mucous membrane pallor, pigmenturia (some cases).
  • Hemolytic crisis that can occur with terminal liver failure resembles prehepatic icterus

Hepatic/Posthepatic Icterus

  • Chronic weight loss, diarrhea, abdominal pain, altered mentation, photodermatitis, pruritus; usually not observed in prehepatic icterus.
  • Icterus more marked in posthepatic than hepatic icterus—conjugated bilirubin causes more pronounced icterus.
  • Recurrent abdominal pain and pyrexia secondary to bacterial cholangitis are frequently found in posthepatic icterus

CBC/Biochemistry/Urinalysis!!navigator!!

Prehepatic Icterus

  • Severe anemia (usually regenerative), Heinz bodies, spherocytes.
  • Marked increase in unconjugated, some increase in conjugated bilirubin.
  • Mildly increased ALP, SDH.
  • Normal to low glucose.
  • Normal to high BUN.
  • Bilirubinuria

Hepatic Icterus

  • Mild nonregenerative anemia.
  • Moderate increase in unconjugated (rarely >25 mg/dL), mild to moderate increase in conjugated bilirubin (≤25% of total).
  • Mild to moderate increases in GGT, AST, SDH; mild increase in ALP.
  • Normal to low glucose, BUN, albumin.
  • Normal to slight bilirubinuria.
  • Normal to low urinary urobilinogen

Posthepatic Icterus

  • Mild nonregenerative anemia.
  • Normal to mild increase in unconjugated, marked increase in conjugated bilirubin (>25–50% of total).
  • Normal to mild increase in AST, SDH, moderate to marked increase in GGT and marked increase in ALP.
  • Marked bilirubinuria.
  • Urinary urobilinogen absent with complete bile duct obstruction

Other Laboratory Tests!!navigator!!

Prehepatic Icterus

  • Giemsa, new methylene blue stain for intraerythrocytic parasites.
  • Saline agglutination test.
  • Direct antiglobulin test.
  • Osmotic fragility test

Hepatic/Posthepatic Icterus

  • Serum bile acids—highest in obstructive liver disease, not discriminating.
  • Blood ammonia—not correlated with severity of HE, not discriminating.
  • Serum prothrombin time may be prolonged, not discriminating.
  • Serology for infectious diseases (hepatic icterus).
  • Serum triglycerides—marked increased in hyperlipemia

Imaging!!navigator!!

US

  • To determine liver size, presence of abscesses, cysts, choleliths, dilated bile ducts, neoplasms.
  • To demonstrate abnormal intra/extrahepatic blood flow.
  • To guide liver biopsy

Other Diagnostic Procedures!!navigator!!

Liver Biopsy

  • Yields diagnostic, prognostic, and therapeutic information.
  • Samples obtained using US-guided or blind techniques; placed in formalin for histopathology, transport media for microbiology.
  • Complications—hemorrhage, pneumothorax, spread of infectious hepatitis, peritonitis (due to bile or ingesta); minimized by performing hemostasis profile, using US guidance

Pathologic Findings!!navigator!!

  • Yellow discoloration of mucous membranes, body fat stores.
  • Other findings depend on the primary condition

Treatment ⬆ ⬇

Outline

TREATMENT

Appropriate Health Care!!navigator!!

Depends on primary disease.

Nursing Care!!navigator!!

  • In the first 24 h, use IV fluids (5% dextrose at 2 mL/kg/h) for hypoglycemic patients with signs of HE.
  • After 24 h, substitute 2.5–5% dextrose in LRS (60 mL/kg/day).
  • In anorexic patients, add potassium chloride (20–40 mEq/L) to fluids

Activity!!navigator!!

Restrict activity and avoid sunlight.

Diet!!navigator!!

For hepatic and posthepatic icterus, a diet with 40–50 kcal/kg in the form of low-protein, high-energy feeds rich in BCAAs (e.g. milo, Sorghum, beet pulp) is recommended.

Client Education!!navigator!!

Depends on primary disease.

Surgical Considerations!!navigator!!

  • Foals with acquired bile duct obstruction.
  • Horses with colonic displacement causing acute bile duct obstruction

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

Prehepatic Icterus

  • Treatment of IMHA (corticosteroids).
  • Whole-blood transfusion if indicated.
  • Fluid therapy (LRS 60 mL/kg/day) to promote diuresis

Hepatic/Posthepatic Icterus

  • Manage clinical signs of HE with sedation (e.g. xylazine, detomidine) if necessary, decrease production and absorption of toxic metabolites (mineral oil via nasogastric tube; lactulose 0.3 mL/kg PO every 6 h, neomycin 10–100 mg/kg PO every 6 h). Oral BCAA concentrates can be formulated, IV preparations are available.
  • Weekly supplementation with vitamin K1 (40–50 mg/450 kg), vitamin B1, and folic acid when cholestasis present.
  • Antimicrobial therapy based on results of culture and sensitivity. Empiric therapy for bacterial cholangitis includes potentiated sulfonamide or beta-lactam and aminoglycoside. Use metronidazole if anaerobic infection is suspected.
  • Chronic active hepatitis treated with corticosteroids—dexamethasone (0.05–0.1 mg/kg/day for 4–7 days, then gradually taper dose over 2–3 weeks) followed by prednisolone (1 mg/kg/day for several weeks)

Contraindications!!navigator!!

  • Hepatotoxic drugs—anticonvulsants, anabolic steroids, phenothiazines, macrolides.
  • Tetracyclines (suppress hepatic protein synthesis).
  • Drugs eliminated primarily by the liver—analgesics, anesthetics, barbiturates, chloramphenicol

Precautions!!navigator!!

  • Use reduced doses of sedatives metabolized by the liver.
  • Use corticosteroids cautiously—may exacerbate intercurrent infections

Possible Interactions!!navigator!!

Duration and intensity of action of many drugs may be increased in patients with hepatobiliary disease.

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

  • Recheck packed cell volume as needed.
  • Repeat transfusions as needed

Hepatic/Posthepatic Icterus

  • Monitor liver enzyme levels, serum bile acids, bilirubin concentration.
  • Repeat biopsies to monitor progression

Prevention/Avoidance!!navigator!!

Depends on primary disease.

Possible Complications!!navigator!!

Horses icteric due to anorexia or cholestatic drugs do not suffer long-term complications.

Expected Course and Prognosis!!navigator!!

Depends on primary disease.

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Associated Conditions!!navigator!!

Prehepatic Icterus

  • Hemoglobinemic nephrosis.
  • Hemic murmur

Hepatic/Posthepatic Icterus

See Causes.

Age-Related Factors!!navigator!!

See Differential Diagnosis.

Zoonotic Potential!!navigator!!

Leptospirosis may be transmitted to people.

Pregnancy/Fertility/Breeding!!navigator!!

Pregnant or lactating obese ponies/miniature horses/donkeys are predisposed to hyperlipemia.

Synonyms!!navigator!!

  • Hyperbilirubinemia.
  • Jaundice

Abbreviations!!navigator!!

  • AAA = aromatic amino acids
  • ALP = alkaline phosphatase
  • AST = aspartate aminotransferase
  • BCAA = branched-chain amino acid
  • BUN = blood urea nitrogen
  • DMSO = dimethyl sulfoxide
  • EIA = equine infectious anemia
  • EVA = equine viral arteritis
  • GGT = γ-glutamyltransferase
  • HE = hepatoencephalopathy
  • IMHA = immune-mediated hemolytic anemia
  • LRS = lactated Ringer's solution
  • SDH = sorbitol dehydrogenase
  • US = ultrasonography, ultrasound

Suggested Reading ⬆ ⬇

Barton MH. Disorders of the liver. In: Reed SM, Bayly WM, Sellon DC, eds. Equine Internal Medicine, 3e. St. Louis, MO: WB Saunders, 2010:939–975.

Divers TJ. The equine liver in health and disease. Proc Am Assoc Equine Pract 2015;61:66–103.

Author(s) ⬆

Authors: Emily E. John and Jeanne Lofstedt

Consulting Editors: Michel Levy and Heidi Banse