Causes of Jaundice
Liver and Blood-Related Etiologies of Elevated Bilirubin
Jaundice is a symptom that usually warrants medical attention. What are the various ways the eyes and skin can turn a characteristic yellow color?
Jaundice is the condition of having yellow eyes and skin. It is not a typical symptom but one that should be alarming. There are many causes for jaundice, either related to the liver or to red blood cells.
Formation of Bilirubin
In order to understand jaundice, one must understand bilirubin. It all begins with red blood cells (RBCs). Once they reach the end of their lifespan, they are broken down in the spleen, releasing hemoglobin from within. Through a series of chemical reactions, the hemoglobin becomes a breakdown product called bilirubin. Bilirubin, which is initially unconjugated bilirubin, eventually reaches the liver where it is metabolized further. Through another conversion process, the bilirubin becomes conjugated bilirubin, which is water soluble compared to unconjugated bilirubin.
Conjugated bilirubin is secreted into the bile ducts from the liver cells, mixing with secreted bile salts to form bile. In between meals, bile travels through the bile ducts and ultimately stored in the gallbladder. During digestion, bile is released into the small intestine to aid in digestion of fats. Intestinal bacteria metabolize the bilirubin into urobilinogen, which gives stool its brown color. While some urobilinogen leaves the body in feces, some of it is reabsorbed into the bloodstream where it reenters the liver or leaves the body in urine.
Causes of Jaundice
The diseases that produce jaundice can be categorized by the major portion of the bilirubin pathway: before the liver (prehepatic), in the liver (hepatic), and after the liver (posthepatic). They can also be categorized by the type of bilirubin accumulating in the blood: unconjugated hyperbilirubinemia and conjugated hyperbilirubinemia.
Unconjugated hyperbilirubinemia can be caused by hemolytic anemia, because rapid bursting of RBCs leads to overproduction of bilirubin. Hemolytic anemia in turn has many causes, including autoimmune hemolytic anemia, sickle cell disease, and malaria just to name a few. Rarely, defects in liver uptake of bilirubin (Gilbert syndrome) and deficiency of the conjugating enzyme (Crigler-Najjar syndrome) cause unconjugated hyperbilirubinemia.
Conjugated hyperbilirubinemia tends to have hepatic and posthepatic causes. Conditions affecting the liver itself, including alcoholic hepatitis, viral hepatitis, and drug-induced hepatitis, impair liver function and excretion of bile. Obstructions of the bile ducts, such as with tumors and bile duct stones, cause conjugated bilirubin to back up into the liver and bloodstream.
Evaluation of Jaundice
When a physician evaluates a patient for jaundice, he or she orders lab tests that include total bilirubin, unconjugated bilirubin, and conjugated bilirubin. An elevated total bilirubin confirms it as the cause of jaundice, and an elevation in either unconjugated bilirubin or conjugated bilirubin narrows the list of possibilities. Further workup may include blood tests to evaluate the red blood cells and imaging studies to look for obstruction of the bile ducts.
Final Words
The take-home lesson from this overview of jaundice is that any concerns about yellowing of the eyes or skin should be evaluated. Whatever the cause may be, it should be treated promptly.
