Degradation of Hemoglobin and Metabolism of Bile Pigments
- When red blood cells reach the end of their lifespan (around 120 days), they are removed mainly by macrophages in the spleen, liver and bone marrow. The hemoglobin inside them is released and broken down.
- Hemoglobin splits into heme and globin.
Globin is simply broken into amino acids and reused in protein synthesis.
- Heme metabolism begins with the removal of iron. Iron is recycled and stored in the body (ferritin, hemosiderin, transferrin transport) so almost no iron is wasted.
- The remaining structure after iron removal is converted into biliverdin by the enzyme heme oxygenase. This step releases carbon monoxide. Biliverdin is a green pigment.
- Biliverdin is then reduced to bilirubin by biliverdin reductase. Bilirubin is yellow-orange. This is the pigment responsible for the yellow color of bruises as they heal.
- Bilirubin formed here is unconjugated and is not water soluble. It circulates in the blood bound tightly to albumin to prevent it from entering tissues (if free it is toxic).
Hepatic Metabolism of Bilirubin
- The liver takes up unconjugated bilirubin from the blood.
Inside hepatocytes, bilirubin is conjugated mainly to glucuronic acid by UDP-glucuronyl transferase, forming bilirubin diglucuronide.
This conjugated bilirubin is now water soluble.
- Conjugated bilirubin is excreted into bile and sent to the intestines.
Intestinal Conversion and Excretion
- In the intestine, gut bacteria convert bilirubin to urobilinogen.
- Most urobilinogen remains in the gut and is oxidized to stercobilin, which gives feces its brown color.
- A small portion of urobilinogen is reabsorbed, enters the portal circulation (enterohepatic circulation). Some is excreted by kidneys as urobilin, giving urine its yellow color.
Jaundice (Hyperbilirubinemia)
- Jaundice appears when bilirubin accumulates in the blood and tissues.
The sclera of the eyes is usually the first place you notice yellowing.
Types based on where the problem occurs:
- Pre-hepatic (Hemolytic) Jaundice
- Excess RBC destruction produces more bilirubin than the liver can conjugate.
- Unconjugated bilirubin rises.
- Urine is normal color (unconjugated bilirubin is not water-soluble), but urobilinogen increases.
- Hepatic Jaundice (Problem inside the liver)
- Seen in hepatitis, liver failure, cirrhosis.
- Both conjugated and unconjugated bilirubin may rise.
- Damage to hepatocytes reduces uptake, conjugation or excretion.
- Urine becomes dark (due to conjugated bilirubin leaking into blood and filtered by kidneys).
- Post-hepatic (Obstructive) Jaundice
- Bile flow is blocked (gallstones, tumors).
- Conjugated bilirubin builds up and enters bloodstream.
- Stool becomes pale (lack of stercobilin).
- Urine is dark (increased conjugated bilirubin excreted by kidneys).