Christine, a 20-hour-old female infant presented with neonatal jaundice. She was born at term following an uncomplicated pregnancy. Physical examination shows she is alert, well-perfused, feeding normally, and afebrile. The skin is yellow in the face, trunk, and limbs, but there’s no organomegaly. Laboratory studies reveal high total bilirubin of 25mg/dL, normal liver function tests, and no evidence of hemolysis. On the other hand, a 17-year-old boy named Steven comes to his primary care physician because his sister has been telling him that periodically, he look a little yellow. Medical history is noncontributory, physical examination shows no abnormalities, but Steven mentions that he has recently started working out and dieting to prepare for prom. Laboratory studies show elevated total bilirubin concentration. A week later, his bilirubin concentration is normal.
Now, both Christine and Steven have jaundice, but the underlying cause of their problem is different. Jaundice, also called icterus, is the abnormal yellowish pigmentation of the skin, mucous membranes, and sclera due to the deposition of the bilirubin. The reference range for total bilirubin is 0.2 - 1.2 mg/dl; while jaundice typically occurs when total bilirubin levels exceed 2mg/dl. Now for your exam, it’s crucial to know the metabolism of bilirubin! When old red blood cells pass through the spleen, macrophages eat them up and break down the hemoglobin to heme and globin. Heme is then converted into biliverdin by an enzyme heme oxygenase. Biliverdin is further converted into unconjugated or indirect bilirubin by an enzyme biliverdin reductase.
Unconjugated bilirubin is the form of bilirubin that’s lipid-soluble.Since it’s not water soluble, this form of bilirubin binds tightly to albumin in the blood, therefore, it can’t be filtered by the kidneys and excreted in the urine. Instead, the unconjugated bilirubin undergoes hepatic metabolism of bilirubin, which consists of 3 main phases. The first phase is carrier-mediated uptake of bilirubin at the sinusoidal membrane of the hepatocyte. In the second phase two molecules of glucuronic acid are attached to bilirubin by an enzyme UDP glucuronyl transferase. The final product is bilirubin diglucuronide, which is also known as conjugated or direct bilirubin.