Bilirubin is a yellowish pigment that forms as a natural byproduct when the body breaks down old red blood cells. Its presence in the body is a normal part of human metabolism, and it circulates in the bloodstream. The levels of bilirubin are routinely monitored as they can offer insights into various bodily processes, particularly those involving the liver and red blood cell turnover.
Where Bilirubin Begins
Bilirubin production primarily starts in the reticuloendothelial system, a network of cells involved in the body’s defense and waste removal. This system includes macrophages found in the spleen, liver (Kupffer cells), and bone marrow. Approximately 80% of daily bilirubin comes from the breakdown of hemoglobin, the oxygen-carrying protein within aged or damaged red blood cells.
The process begins with the degradation of heme, hemoglobin’s iron-containing component. Heme oxygenase converts heme into biliverdin, a green pigment. Then, biliverdin reductase reduces biliverdin into unconjugated bilirubin, which is yellow-orange. This initial form is not water-soluble, meaning it cannot dissolve easily in water or be readily excreted from the body.
The Liver’s Role in Processing Bilirubin
Once unconjugated bilirubin enters the bloodstream, its non-water-soluble nature requires it to bind to albumin for transport. This albumin-bilirubin complex travels to the liver. Upon reaching the liver, unconjugated bilirubin detaches from albumin and is taken up by liver cells, known as hepatocytes.
Inside hepatocytes, unconjugated bilirubin undergoes conjugation. An enzyme, UDP-glucuronosyltransferase (UGT1A1), attaches one or two molecules of glucuronic acid to the bilirubin. This makes the bilirubin water-soluble, converting it into conjugated (or direct) bilirubin. This water-soluble form is essential for its eventual excretion from the body.
How Bilirubin Leaves the Body
After conjugation, water-soluble conjugated bilirubin is secreted into bile, a digestive fluid produced by the liver. Bile flows from the liver through ducts and is typically stored in the gallbladder before release into the small intestine during digestion. This secretion into bile involves specific transport proteins.
Once in the small intestine, conjugated bilirubin is processed by gut bacteria. These bacteria break down bilirubin, converting it into various compounds, primarily urobilinogen. Most urobilinogen is then oxidized into stercobilin, which gives stool its brown color.
A smaller portion of urobilinogen is reabsorbed into the bloodstream. Some reabsorbed urobilinogen returns to the liver for recycling, while a small amount reaches the kidneys, where it is converted into urobilin and excreted in urine, contributing to urine’s yellow hue.
Understanding Elevated Bilirubin
When the balance of bilirubin processing is disrupted, levels in the blood can rise, a condition known as hyperbilirubinemia. The most noticeable sign of elevated bilirubin is jaundice, characterized by a yellow discoloration of the skin and eyes. Jaundice indicates an issue along the bilirubin pathway. This could involve excessive red blood cell breakdown, problems with the liver’s processing ability, or blockages preventing proper excretion.