Causes of Icterus

Icterus or jaundice is the yellowish discolouration of tissues, due to increased levels of bilirubin. Typically, we see bilirubin deposition in tissues with a high elastic content, like the aorta. Bilirubin is normally processed by the liver, so we often think about three major classifications of hyperbilirubinemia: pre-hepatic, hepatic and post-hepatic.

Pre-Hepatic

To understand pre-hepatic icterus, we need to think about where bilirubin comes from. Bilirubin is a breakdown product of erythocytes, which is normally taken up by the liver and processed, before being excreted in the bile. When there is excessive breakdown of erythrocytes, like in hemolysis, the amount of bilirubin present overwhelms the liver’s ability to process it, resulting in hyperbilirubinemia. This type of icterus is considered pre-hepatic because it happens before the liver gets involved.

We most classically associate hemolysis with immune-mediated hemolytic anemia (IMHA), where the erythrocytes are targeted by the immune system due to the body thinking that they are foreign. However, lots of other things can cause hemolysis too. Some other conditions to consider:

1. Neonatal isoerythrolysis, where the neonate gains antibodies against its own blood antigens from the mother’s colostrum
2. Blood-borne pathogens stimulating the immune system against the blood cells
3. Excess copper in the bloodstream in copper toxicity
4. Certain toxic compounds like gallic acid in red maple leaves
5. Administration of excessive hypotonic IV fluids

Hepatic

Hepatic icterus is pretty easy to understand. As mentioned, one of the main jobs of the liver is to process bilirubin in the bloodstream, and excrete it as bile. If the hepatocytes’ ability to process bilirubin is impaired, it will stay in the bloodstream and cause hyperbilirubinemia.

There are about a million things (citation needed) that can cause hepatic icterus, because hepatocytes are pretty easily injured! So listing them all would not be very helpful for this post.

Instead, I will remind you of something you’ve probably heard in your travels: DAMNIT. Pretty much any condition can be attributed to something in this fun acronym, and in the case of the liver, pretty much all of these disease processes affecting the liver could lead to icterus.

• D: Degenerative, developmental
• A: Autoimmune, anomalous
• M: Metabolic, mechanical injury
• N: Nutritional, neoplastic
• I: Inflammatory, infectious, ischemic, immune-mediated, inherited, iatrogenic, idiopathic
• T: Traumatic, toxic

Post-Hepatic

Once the bilirubin is processed, it has to go somewhere! Typically, it gets excreted into the bile. However, if this excretion pathway is compromised in some way, it can back up the production chain and cause hyperbilirubinemia. This process is called cholestasis (literally stasis of the bile). Typically, post-hepatic icterus is broken down into two categories: intrahepatic and extrahepatic cholestasis.

Intrahepatic cholestasis occurs at the level of the hepatocytes. If there is some kind of inherited or metabolic abnormality that prevents normal excretion of bile, intrahepatic icterus can develop. For example, some sheep breeds have genetic diseases that affect bilirubin excretion, leading to hyperbilirubinemia. Typically though, these diseases do not lead to gross icterus, as not enough bilirubin accumulates to produce the yellow tinge.

Extrahepatic cholestasis is far more common, and occurs when there is some type of obstruction in the bile ducts. We most commonly think of this obstruction as being caused by bile calculi, choleliths, however it can also be caused by some types of parasites, or even neoplasia or inflammation compressing the bile ducts. Regardless, the obstruction prevents the bile from making it out into the intestine for removal, and causes the biliary excretion system to back up.

Comparison Table

Check Your Understanding

Zachary JF. Pathologic Basis of Veterinary Disease, Sixth Edition.