Bilirubin

Definition

Bilirubin is a breakdown product of heme, derived primarily from senescent erythrocytes. It is carried by albumin to the liver, where it is detoxified by the glucuronic acid pathway, conjugated, and excreted into the bile. Biliverdin produced in reptiles and birds also undergoes this detoxification in the liver and is excreted into the bile.

Synonym

Bili

Physiology

Three forms of bilirubin have been identified: conjugated, unconjugated, and a fraction that is irreversibly bound to protein. Unconjugated bilirubin is the most clinically significant fraction because it is the form that is most likely to cause tissue damage.

Typical Normal Range

The typical normal range for this laboratory test varies greatly among species. The reader is referred to the following Elsevier publications for additional information:

Carpenter J: Exotic animal formulary, ed 4, St Louis, 2013, Saunders.

Mader D: Reptile medicine and surgery, ed 2, St Louis, 2006, Saunders.

Clinical Applications

Causes of Abnormally High Levels

• Prehepatic

image Hemolytic crisis

• Hepatic

image Hepatic disease (decreased ability to conjugate and excrete bilirubin)

image Intrahepatic cholestatic disease

• Post-hepatic

image Bile duct obstruction results in an accumulation of conjugated bilirubin.

Next Diagnostic Steps to Consider If Levels Are High

Complete blood count, chemistry panel, urinalysis, bile acids, radiographs ± abdominal ultrasound

Important Interspecies Differences

• Birds have an enzyme called heme oxygenase, which converts the protoporphyrin in heme to biliverdin. Both birds and reptiles have decreased hepatic production of biliverdin reductase, which converts biliverdin to bilirubin. Although decreased, biliverdin reductase is still present in some birds. Bacteria in the intestine may produce biliverdin reductase as well, and bilirubin can be absorbed from the gastrointestinal tract.

• Bilirubin is found only in small quantities in the avian and reptilian plasma, making it a relatively useless clinical parameter in these species.

• Rabbits also produce biliverdin as the primary heme metabolite, but in contrast to birds and reptiles, bilirubin is present in the blood of rabbits at measurable levels.

• Although the rabbit produces significantly more bile than a dog of equal size, rabbits have low activity of biliverdin reductase, and only about 30% is converted.

Specimen and Processing Considerations

Lab Artifacts That May Interfere with Readings of Levels of This Substance

• Hemolysis interferes with measurement. The value can be increased or decreased, depending on the method of analysis.

• Lipemia will artifactually increase bilirubin levels.

• Light will degrade bilirubin (up to 50% in 1 hour under fluorescent light).

Sample for Collection and Any Special Specimen Handling Notes

• Serum separator tube

• Protection from light

• Storage of sample in fridge

Pearls

• Yellow discolored urates in birds have been linked to excessive bilirubin due to a potential hepatopathy.

• In most cases where avian plasma is yellow, this is not due to an increased bilirubin level but rather to carotenoids in food.

References

Carpenter, JW. Exotic animal formulary, ed 3. St Louis: Elsevier; 2004.

Harrison, GJ, et al. Clinical avian medicine; vol 2. Spix Publishing, South Palm Beach, FL, 2006. [620–621].

Yin, SA. The small animal veterinary nerdbook, ed 2. Davis, CA: CattleDog Publishing; 1988. [4. 4–4. 7].

AUTHOR: CARRIE A. PHELPS

EDITOR: JÖRG MAYER