Bilirubin Production and Excretion

Bilirubin is a yellow-orange pigment that is formed from the breakdown of hemoglobin, the protein in red blood cells that carries oxygen throughout the body. The breakdown of hemoglobin occurs primarily in the spleen, liver, and bone marrow, and bilirubin is then transported in the bloodstream to the liver, where it is processed and eliminated from the body.

Bilirubin is formed from the breakdown of hemoglobin

As I mentioned earlier, bilirubin is produced from the breakdown of hemoglobin, which is the protein in red blood cells that carries oxygen throughout the body. When red blood cells reach the end of their lifespan, they are broken down in a process known as hemolysis. 

During hemolysis, the hemoglobin molecule is broken down into its constituent parts, including heme and globin. The heme molecule is further broken down by the enzyme heme oxygenase, which releases iron and converts the heme into biliverdin, a green pigment.

Biliverdin is then converted into bilirubin by the enzyme biliverdin reductase. Bilirubin is not water-soluble, so it must be transported in the bloodstream bound to a protein called albumin. 

Once it reaches the liver, bilirubin is taken up by liver cells, or hepatocytes. Inside the hepatocytes, bilirubin is conjugated, or chemically modified, with glucuronic acid by the enzyme UDP-glucuronosyltransferase. This forms bilirubin glucuronide, a water-soluble form of bilirubin.

Bilirubin glucuronide is then excreted in the bile, which is a fluid that is produced by the liver and stored in the gallbladder. Bile is released into the small intestine to aid in the digestion and absorption of fats. Bilirubin glucuronide is eliminated from the body through the feces.

In some cases, the production, transport, or elimination of bilirubin may be impaired. For example, certain liver diseases such as cirrhosis or hepatitis may interfere with the liver's ability to conjugate bilirubin. Infections such as hepatitis or malaria can cause increased hemolysis and therefore increased bilirubin production. Certain medications, such as some antibiotics or chemotherapy drugs, can also affect bilirubin production or elimination. In rare cases, genetic disorders such as Gilbert's syndrome or Crigler-Najjar syndrome may result in high levels of unconjugated bilirubin in the blood.

Elevated levels of bilirubin in the blood can lead to jaundice, which is a yellowing of the skin and whites of the eyes. Jaundice may be a sign of an underlying medical condition and should be evaluated by a healthcare professional.