Equis ISSN 2398-2977

Liver: icterus

Synonym(s): Hyperbilirubinemia, jaundice

Contributor(s): Imogen Johns, Janice Sojka, Han van der Kolk

Introduction

  • Icterus is the yellow discoloration that occurs in the tissues of animals with increased blood levels of bilirubin.
  • Within the hepatocyte the bilirubin is conjugated with glucuronide and this conjugated bilirubin is water soluble and is excreted into the bile canaliculi.
  • Microflora in the digestive tract reduce conjugated bilirubin to urobilinogen, which is found concentrated in the alkaline urine of the equine species.
  • Following fasting in the equine species, the normal uptake by the liver of bilirubin originating from hemoglobin and myoglobin (also referred to as indirect reacting or unconjugated bilirubin) is reduced and as a consequence its concentration in blood increases resulting in (moderate) yellow coloration of sclera.
  • Under normal circumstances, little conjugated bilirubin escapes into the general blood circulation. 
  • Cause: this can occur due to two main mechanisms:
    • Increased production of bilirubin occurs in instances of hemolytic anemia that overwhelms the livers capacity to remove it from the circulation. 
    • Alternately, decreased removal of bilirubin due to liver insufficiency causes blood concentrations to increase. 
    • Clinical icterus is usually present when serum bilirubin concentrations increase to above 4 mg/dl.
  • Signs: yellow discoloration to the mucous membranes and sclera; discoloration to carcass.
  • Diagnosis: complete blood count and clinical chemistry.
  • Treatment: icterus per se does not require treatment depends on underlying cause.
  • Prognosis: depends on cause.

Pathogenesis

Etiology

  • Icterus occurs when bilirubin is deposited in body tissues. 
  • This occurs when blood bilirubin concentrations exceed 4 mg/dl; it can be seen because it is a distinctive yellow pigment.

Predisposing factors

General
  • Hemolysis.
  • Anorexia.
  • Hepatic disease or failure.
  • Post-hepatic bile duct obstruction.

Specific

  • Bilirubin is the normal breakdown product of red blood cells and is constantly being produced. In the normal state, the liver is able to remove the bilirubin and excrete it via the bile into the intestine.
  • Hemolysis is lysis of the red blood cells within the circulation. It can be caused by oxidative insult such as wild onion or red maple leaves, anti-RBC antibodies in the case of immune-mediated anemia   Vagina: vaginitis  and neonatal isoerythrolysis   Immunology: neonatal isoerythrolysis  , blood borne parasites such asBabesiaspp   Babesia spp  , or other factors.
  • Prolonged anorexia results in mobilization of free fatty acids from adipose stores and the production of triglycerides by the liver. The enzyme systems involved with gluconeogenesis, lipid transport and metabolism become saturated and become less efficient at removing bilirubin from the circulation.
  • Liver insufficiency occurs with a host of insults, common ones include toxic hepatopathy such as pyrrolizidine alkaloid toxicity   Liver: hepatotoxicosis  , infections such as Tyzzers disease   Liver disease: overview  or EIA   Equine infectious anemia (EIA)  , or idiopathic such as Theilers disease   Liver disease: overview  . 
  • Post-hepatic or biliary obstruction may occur secondary to gastrointestinal disease such as colonic displacement   Colon: displacement - left dorsal    Colon: displacement - right dorsal  or small intestinal disease   Intestine: neoplasia - overview  . It may also occur due to cholangitis   Liver: cholangiohepatitis  and/or the formation of stones within the biliary tree.
  • Icterus occurs when blood bilirubin concentrations get above 4 mg/dl.

Pathophysiology

  • When hemoglobin is broken down the iron is scavenged and the remaining heme molecule is converted to biliverdin. This is then converted into free or unconjugated bilirubin and transported to the liver. 
  • In the liver the bilirubin is modified and converted into conjugated bilirubin; a small fraction of that escapes back into the circulation, but most is excreted into the biliary system and then into the small intestine via the common bile duct. 
  • In instances of increased RBC destruction, the amount of free bilirubin exceeds the livers ability to transport unconjugated bilirubin into the hepatocyte and excrete it. 
  • In instances of liver failure, the amount of bilirubin being produced by destroyed RBCs is not increased, but the liver can not efficiently transport free bilirubin into the hepatocyte, nor excrete the conjugated bilirubin into the bile cannuliculi. 
  • The excretion of bile into the biliary system is an energy dependent process and is the rate-limiting step in normal bilirubin metabolism. Thus, in most instances of hepatic disease, there is an excess amount of unconjugated bilirubin in the circulation rather than conjugated. In instances of biliary obstruction either post-hepatic or intrahepatic the hepatocyte can remove free bilirubin from the circulation and conjugate it, but can not excrete it through the biliary system in a normal fashion. In these instances, conjugated bilirubin may represent up to 40% of the total bilirubin concentration in the blood. 
  • The accumulation of bilirubin in the hepatocyte results in hepatocyte dysfunction, further compounding the problem. The excess bilirubin in the blood will deposit in peripheral tissues, leading to icterus.

Timecourse

  • The time between increased blood bilirubin levels and detectible icterus is quite short, usually it is apparent no more than 24 h after bilirubin levels increase. It can be several days, however, for the opposite to occur. 
  • Once an animal is clinically icteric, mucous membrane color will remain yellow for several days after normal blood bilirubin levels have returned.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Loynachan A T, Williams N M & Freestone J F (2007)Kernicterus in a neonatal foal.J Vet Diagn Invest19, 209-212 PubMed.
  • Boyle A G, Magdesian K G & Ruby R E (2005)Neonatal isoerythrolysis in horse foals and a mule foal: 18 cases (1988-2003).JAVMA227, 1276-1283 PubMed.
  • Johnston J K, Divers T J & Reef V B (1989)Cholelithiasis in horses: ten cases (1982-1986).JAVMA194(3), 405-409 PubMed.
  • Pearson E G (1982)Clinical management of the icteric horse.Comp Cont Ed Vet Prac3, S114-S122 VetMedResource.


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