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Bilirubin is a tetrapyrrole pigment formed from the heme groups of hemoglobin molecules. This chemical, normally present in dog erythrocytes, and produced by the liver, is responsible for the yellow color of bruises and the background yellow color of urine (via its reduced breakdown product, urobilin).

As erythrocytes age, macrophages phagocytose senescent cells and release hemoglobin, which is subsequently metabolized in the reticulo-endothelial system to heme and globulin. Iron is removed from the heme molecule, and after a number of biochemical degradations, bilirubin is formed from biliverdin and becomes bound to albumin for transport to the liver, where it is conjugated with glucuronic acid, forming a water-soluble conjugated bilirubin. This is secreted into bile.

Gastrointestinal bacteria degrade the water-soluble bilirubin to urobilinogen, which is then reabsorbed and excreted in the urine. The remaining urobilinogen is further degraded to stercobilin, a brown pigment which contributes to the color of feces.

In dogs with cholestasis, urobilinogen is absent from the urine and the feces have a grey color due to the absence of stercobilin.

Elevation in levels of serum bilirubin (hyperbilirubinemia; normal range 0.1 - 0.6 mEq/dL) are associated with icterus and causes include:

  • Pre-hepatic causes
- Immune-mediated hemolytic anemia
- Leptospira spp
- Babesia spp
- Mycoplasma spp
  • Hepatic causes
- Hepatitis
- Cholangiohepatitis
- Portosystemic shunt
- Infectious canine hepatitis
- Biliary Cirrhosis
- Hepatic lipidosis
- Cholangitis
- Hepatic carcinoma
- Bile duct carcinoma
  • Post-hepatic causes
- Cholelithiasis

Bilirubin increases when the production of bilirubin exceeds the ability of the liver to recover unconjugated bilirubin from the bloodstream and process it, or when clearance of the conjugated form is altered by impaired hepatocyte processes or obstruction to the discharge of bilirubin into the intestines. Clinically, this means that hyperbilirubinaemia can be caused by heamolysis or choleostasis - the next step diagnostically is to establish if the inciting cause is prehepatic, hepatic or posthepatic.