Approach to jaundice (Proceedings)
Aug 01, 2010
CVC IN KANSAS CITY PROCEEDINGS
Jaundice: Jaundice (or icterus), broadly defined, refers to the accumulation of excessive amounts of bilirubin in either the circulation or the tissues.
Normal Bilirubin Metabolism (see Figure 1)
Jaundice is classified as prehepatic, hepatic or posthepatic, a classification based on the phase in bilirubin metabolism that is affected by the causative disease process.
Prehepatic jaundice is usually caused by the release of hemoglobin associated with RBC lysis. High plasma levels of unconjugated (free) bilirubin derived from massive hemoglobin breakdown can overwhelm hepatic bilirubin metabolism. Since the liver is usually very effective at conjugating free bilirubin, hemolysis must be acute and severe to cause jaundice. Patients with prehepatic jaundice are therefore invariably severely anemic. Jaundice is typically transient, since ongoing hemolysis of sufficient magnitude to cause persistent jaundice would cause death due to anemia. Hemolytic anemia in dogs and cats is most commonly subacute or chronic, and therefore usually does not cause detectable jaundice.
Theoretically, prehepatic jaundice should cause high unconjugated bilirubin and normal conjugated bilirubin levels. However, the increased hepatic production of conjugated bilirubin in response to high levels of unconjugated bilirubin can overwhelm hepatocyte excretion mechanisms, particular if liver function is impaired by hypoxia secondary to severe anemia. Prehepatic jaundice is therefore often a mixture of unconjugated and conjugated hyperbilirubinemia.
Common Causes of Prehepatic Jaundice
Immune-mediated hemolytic anemia Zinc toxicity
Cats: Mycoplasma hemofelis infections Dogs: Heartworm (caval syndrome)
2. Hepatic Jaundice
Hepatic jaundice is caused by dysfunction of either hepatocytes or the intrahepatic biliary tree. Hepatocyte uptake and conjugation of free bilirubin is impaired, as is hepatocyte and biliary excretion of conjugated bilirubin. Since the healthy liver has a large functional reserve, most normal hepatic functions (including bilirubin metabolism) are not impaired unless liver disease is severe. Mild hepatic diseases such as steroid or diabetic hepatopathy do not typically cause jaundice. Theoretically, any cause of severe liver dysfunction could cause hepatic jaundice. However, despite causing profound hepatic dysfunction, some diseases (portosystemic shunts in particular) rarely cause jaundice. Since hepatocyte excretion of conjugated bilirubin is the rate-limiting step in bilirubin metabolism, hepatic jaundice would be expected to be associated with elevated plasma levels of conjugated bilirubin and normal unconjugated bilirubin levels. Usually, however, the intracellular build up of conjugated bilirubin in the failing liver then causes unconjugated bilirubin to also bank up within hepatocytes, following which both forms of bilirubin spill over into the circulation. Like prehepatic jaundice, hepatic jaundice is therefore usually a mix of unconjugated and conjugated hyperbilirubinemia.