Hemoglobin Metabolism

Hemoglobin is the protein in the red blood cells that binds to and carries oxygen from the lungs to the tissues of the body.  Red blood cells naturally live for about 120 days from the time they leave the bone marrow until they have lived their natural lifespan and are taken up by the reticulo-endothelial system in the liver and spleen and destroyed.  When they are destroyed the hemoglobin is released into the bloodstream.  The hemoglobin is broken down through a series of steps to unconjugated bilirubin.  This is then conjugated to sugar molecules in the liver to become what is referred to as conjugated bilirubin.

Unconjugated bilirubin is not filtered easily by the kidneys and is very slow to break down.  A second method of bilirubin conjugation is in the skin, where sunlight can facilitate the conjugation of bilirubin.  Conjugated bilirubin is easily cleared by the kidneys and excreted in the urine.

When laboratories measure bilirubin in the blood they measure total bilirubin, and also what is termed direct bilirubin.  Bilirubin that is unconjugated is not easily measured by the direct assay of bilirubin in laboratories.  To measure unconjugated bilirubin requires an extra step in the lab, and so it is referred to as indirect bilirubin.  Indirect bilirubin is another name for unconjugated bilirubin.

An elevated level of indirect bilirubin suggests either rapid red blood cell hemolysis or liver disease or dysfunction such that the hemoglobin from red blood cells that are broken down cannot be conjugated as fast as hemoglobin is metabolized into indirect bilifubin.  The most common time we see an elevated indirect bilirubin level is in neonatal jaundice.  In this case the normal rapid breakdown of red blood cells shortly after birth in infants leads to an overload of the immature liver and the unconjugated bilirubin accumulates.  Most babies become at least slightly jaundiced in their first few days of live in this normal phenomenon.  There are usually no jaundice symptoms of this physiologic phenomenon, but if the bilirubin levels get really high serious consequences can devevlop, so if your baby becomes jaundiced you should have this checked by your physician.