Jaundice (icterus) signifies the abnormal accumulation and distribution of bilirubin pigments into the systemic circulation, causing yellow discoloration of plasma and nonpigmented soft tissues (including skin, sclera, mucous membranes [eg, oral, vaginal, penile), and urine.
Jaundice is often the primary clinical sign in animals with disorders involving the gallbladder or extrahepatic biliary structures; abdominal effusion may reflect bile peritonitis. Finding a higher bilirubin concentration in an effusion relative to serum (> 10-fold difference) confirms leakage of bile into the abdominal cavity and constitutes a surgical emergency.
The differential diagnosis for jaundice is broad as it can reflect a multitude of hepatic and hematologic diseases, including diseases directly impacting or obstructing bile flow in the biliary tree, disorders causing hepatocellular dysfunction impairing elimination of bilirubin, or disorders involving hemolytic or hematopoietic abnormalities that escalate bilirubin formation such that it exceeds the rate of hepatic elimination.
Jaundice can be categorized according to localization of inciting cause as prehepatic, hepatic, or posthepatic.
Prehepatic jaundice reflects enhanced bilirubin formation. The most common cause is accelerated RBC turnover, usually due to hemolysis. Jaundice develops when released heme exceeds the hepatic capacity to process and excrete bilirubin. The most common cause is RBC hemolysis associated with an immune-mediated hemolytic anemia in dogs or Heinz body–related hemolytic anemia in cats. However, there are numerous additional causes.
Prehepatic jaundice may be aggravated by shortened RBC lifespan in transfused blood, especially in recipients of numerous repeated transfusions where immune reactions hasten RBC removal. This form of jaundice can also evolve in patients needing a large blood volume exchange transfusion. The least common cause of prehepatic jaundice is heme released from blood sequestered in large hematomas (bleeding disorders, trauma) or hemorrhagic effusions, such as intra-abdominal bleeding as encountered with a ruptured spleen (eg, hemangiosarcoma in dogs).
Hepatic jaundice reflects impaired hepatocyte bilirubin uptake, conjugation, or canalicular excretion, which are encountered in animals with critically decreased functional hepatic mass or disrupted sinusoidal circulation (eg, liver fibrosis, regenerative remodeling). However, impaired bilirubin conjugation and canalicular transport are also often encountered secondary to endotoxemia, sepsis, or other infections. Animals with impaired canalicular transport usually have canalicular cholestasis.
Jaundice associated with bacterial toxins, especially endotoxin—also known as lipopolysaccharide (LPS)—may not be associated with commensurate increases in liver enzyme activities. All potential pathological mechanisms causal to hepatic jaundice can emerge in animals with severe critical hepatocyte dysfunction (ie, fulminant hepatic failure, acute liver failure, acute-on-chronic liver failure, advanced-stage-liver disease [formerly categorized as cirrhosis]).
Posthepatic jaundice reflects cholestatic disorders involving larger ductal elements, notably the extrahepatic or common bile duct or gallbladder or rupture of the biliary tree, causing bile peritonitis.
Although cholestasis can occur at the canalicular level due to disrupted canalicular bile flow (canalicular cholestasis), associated jaundice is better considered as hepatic jaundice.
The least common cause of posthepatic jaundice is bile-induced chemical peritonitis (ie, bile peritonitis), in which there is spillage of bile from the biliary tree (eg, ruptured common bile duct or gallbladder), typically associated with abdominal effusion.
