Bilirubin is a pigment that is produced in the liver as a byproduct of hemoglobin metabolism. After its production, the bilirubin is conjugated and excreted through the bile into the small intestine. From there, the bilirubin pigment gets excreted with the feces. The color of the bile and feces is mainly due to the presence of the bilirubin pigment.
An abnormally high concentration of bilirubin in the blood (technically referred to as hyperbilirubinemia) leads to jaundice. There is a prominent yellow discoloration of various tissues due to bilirubin accumulation. For example, jaundice causes the skin, sclera, and lining of the mouth to turn yellowish.
Bilirubin in the Blood
Hemoglobin present in the red blood cells (technically referred to as erythrocyte) is the primary carrier of oxygen in the blood. At the end of their lifespan (about 120 days), the red blood cells burst open and their contents (including hemoglobin) spill out into the bloodstream.
Red blood cells that become fragile due to some underlying disease (such as sickle cell anemia) also burst open when they pass through small capillaries. The hemoglobin released into the blood is rapidly engulfed by macrophages present in the liver, spleen and bone marrow.
The hemoglobin taken up by macrophages is separated into its iron and porphyrin components. The iron is released back into the blood in order to be stored as ferritin in the liver or to be used for new red blood cell production in the bone marrow.
The porphyrin component is converted into bilirubin before being released into the blood. This free bilirubin in the blood (also known as unconjugated bilirubin) is transported through the blood by albumin protein.
Read more on signs of anemia.
Bilirubin in the Liver
The unconjugated bilirubin present in the blood is taken up by the hepatocytes in the liver. With the help of glucuronyl transferase enzyme, these hepatocytes conjugate the bilirubin with glucuronic acid. The conjugated bilirubin is then released into the bile, which passes through the hepatic duct to enter the gallbladder. The bile stored in the gallbladder is then emptied into the duodenum (first part of the small intestine).
Various problems in the process of bilirubin handling by the liver can lead to different types of jaundice. For example, there is rapid breakdown of red blood cells in hemolytic conditions, which rapidly increases the amount of free bilirubin in the blood. This exceeds the uptake capacity of the liver, causing free bilirubin to remain in the blood. Such a condition is known as hemolytic jaundice.
Deficiency or absence of the bilirubin conjugating enzyme, glucuronyl transferase, in the hepatocytes can also lead to accumulation of free, unconjugated bilirubin in the blood. This condition is known as non-hemolytic jaundice. Hepatocellular jaundice is caused by damage to the hepatocytes, inability of the hepatocytes to take up bilirubin from the blood, or an inability to excrete bilirubin in the bile.
Obstructive or cholestatic jaundice is caused by an obstruction to the flow of bile due to accumulation of gallstones. This causes a backflow of bile and an increase in the amount of bilirubin in the blood.
Bilirubin in Urine and Stool
Conjugated bilirubin enters the first part of the small intestine (technically referred to as duodenum) via the bile. In the intestine, the resident bacterial flora converts the conjugated bilirubin into urobilinogen. Being a highly soluble form of bilirubin, urobilinogen gets absorbed by the intestinal cells and enters the bloodstream.
The majority of urobilinogen in the blood is taken up by the liver and passed back into the intestine. Within the intestine, urobilinogen gets oxidized into stercobilin, which is then passed out in the feces. The brown color of the feces is due to bilirubin, bile and decomposed food.
Some urobilinogen in the blood is taken up by the kidneys, which then oxidize it into urobilin. This oxidized form of urobilinogen is then passed out with the urine. Urobilin is responsible for the yellowish color of the urine.
Read more on pale stool.
Tests for Bilirubin
The amount of bilirubin present in the blood can be measured in a blood sample. Bilirubin exists in the blood in both free (unconjugated) and conjugated forms. Bilirubin tests can measure the total amount of bilirubin (sum of both conjugated and unconjugated forms) as well as the level of conjugated bilirubin in the blood.
Subtracting the amount of conjugated bilirubin from the amount of total bilirubin gives us the amount of unconjugated bilirubin in the blood. Due to these measurement and calculation methods, conjugated bilirubin is also known as direct bilirubin, and the unconjugated bilirubin is also referred to as indirect bilirubin.
Depending on the testing methodology and the laboratory, the concentration of bilirubin is expressed in units of either mg/dL or mmol/L.
Reference Ranges for Bilirubin Levels
To determine whether the measured bilirubin levels in the blood are normal or abnormal, one needs to compare the measured value with the known normal values. The range of normal values for bilirubin is known as the reference range. The reference range for normal bilirubin levels may vary slightly among different laboratories.
Bilirubin levels found to be lower or higher than the reference range of values is considered to be abnormal. However, not all cases of abnormal bilirubin levels require immediate treatment. Immediate treatment becomes imperative only when the abnormal values are persistent or reach a dangerously high level.
Reference ranges in adults
The following are the normal reference ranges for bilirubin in adults:
- Total bilirubin levels: The normal reference range for total bilirubin level in adults is 0.3-1.0 mg/dL (also expressed as 5.1-17 mmol/L)
- Conjugated (direct) bilirubin: The normal reference range for conjugated bilirubin level in adults is 0.1-0.3 mg/dL (also expressed as 1.7-5.1 mmol/L)
- Unconjugated (indirect) bilirubin: The normal reference range for unconjugated bilirubin level in adults is 0.2-0.8 mg/dL (also expressed as 3.4-12.0 mmol/L)
Jaundice is a result of elevated bilirubin level in the blood (also known as hyperbilirubinemia). Jaundice can be classified into different types based on the cause of hyperbilirubinemia. The causes may lie before the entry of bilirubin into the liver (pre-hepatic), within the liver (hepatocellular), or after exit from the liver (post-hepatic obstructive jaundice).
Reference ranges in newborns
The following are the normal reference ranges of bilirubin in full-term newborn infants:
- 1 day old (or less than 24 hour old): <6.0 mg/dL (or 103 mmol/L)
- 2 days old (or less than 48 hours old): <10.0 mg/dL (or 170 mmol/L)
- 3-5 days old: <12.0 mg/dL (or 205 mmol/L)
- 7 days and older: <10.0 mg/dL (or 170 mmol/L)
The following are the normal reference ranges of bilirubin in preterm infants:
- 1 day old (or less than 24 hour old): <8.0 mg/dL (or 137 mmol/L)
- 2 days old (or less than 48 hours old): <12.0 mg/dL (or 205 mmol/L)
- 3-5 days old: <15.0 mg/dL (or 256 mmol/L)