Bilirubin is a substance produced by the liver from hemoglobin that is released after the destruction of red blood cells.
The bilirubin produced is naturally eliminated through feces and urine, however the amount of circulating bilirubin can increase in the case of diseases such as autoimmune hemolytic anemia, hepatitis or stones in the bile ducts, and the use of medications, such as some anti-inflammatories and antibiotics.
High bilirubin can be identified through symptoms such as yellowed skin and eyes and darker urine, and must be confirmed through a bilirubin test, also known as measuring total bilirubin and fractions. It is important that the cause of high bilirubin is identified by the doctor, so that the most appropriate treatment can be initiated.

Bilirubin test
The bilirubin test evaluates the following factors:
- Indirect bilirubin or unconjugated: it is the bilirubin that is formed when red blood cells are destroyed in the blood and is then transported to the liver;
- Direct bilirubin or conjugated: it is bilirubin that is produced in the liver from indirect bilirubin and is associated with a sugar. This bilirubin is directly acted upon by bile in the intestine and is eliminated in feces and urine;
- Total bilirubin: is the total amount of bilirubin levels in the blood, corresponding to the sum of indirect and direct bilirubin.
The bilirubin test is normally indicated to evaluate the functioning of the liver and bile ducts and when it is suspected that there are blood diseases that are causing the destruction of red blood cells. Find out about other tests to evaluate the liver.
Do you have questions about your exam results?
In general, it is not necessary to carry out any preparation for the bilirubin test, however in some cases the laboratory or doctor may recommend fasting for 4 hours. It is also important to inform the laboratory about the use of medications, such as propranolol or rifampicin, as they may interfere with the test results.
Reference values
The reference values for bilirubin in the blood are:
In the case of newborns, bilirubin values considered normal vary after birth. Higher levels are common in the first days of life, but tend to decrease after the 5th day of life. See the causes of high bilirubin in newborns and when treatment is indicated.
Symptoms of High Bilirubin
The main symptoms of high bilirubin are:
- Yellowish skin;
- Yellowish eye color;
- Dark urine, similar to Coca-Cola.
Other symptoms, such as pain or swelling in the abdomen, weakness, pale stools, nausea and vomiting, may also appear and indicate problems with the liver, bile ducts or even changes in the blood, for example. Know the main symptoms that may indicate liver problems.
What can be high bilirubin
High bilirubin in the blood usually occurs when there is increased production of bilirubin or when there is difficulty in eliminating bilirubin. Furthermore, the causes tend to vary according to the type of bilirubin affected:
High direct bilirubin
When direct bilirubin is high it may indicate diseases that affect its elimination, such as some types of hepatitis, stones in the bile ducts and primary sclerosing cholangitis. Furthermore, high direct bilirubin can also be caused by narrowing in the channels through which bile passes, due to tumors or surgery, for example.
The use of some medications, such as paracetamol, antibiotics and anti-inflammatories, especially when used without medical advice, can also cause an increase in direct bilirubin in some cases.
High indirect bilirubin
High indirect bilirubin can be caused by diseases that cause increased destruction of red blood cells in the blood, such as autoimmune hemolytic anemia, thalassemia or spherocytosis, or that are caused by genetic changes that impair the production of direct bilirubin, such as Gilbert’s syndrome and Crigler-Najjar syndrome.
In addition, the use of some medications, such as rifampicin, gentamicin and most antiretroviral drugs, large bruises on parts of the body and, sometimes, blood transfusions, can also cause high indirect bilirubin.
High total bilirubin
High total bilirubin is caused by increased direct, indirect, or both bilirubin. Thus, the causes vary and may include the use of medications that can harm the liver, hepatitis, cirrhosis and blood diseases, for example.
Low bilirubin
Low bilirubin is not typically considered a problem. Healthy people generally eliminate excess bilirubin from the body, keeping its levels within the reference values considered normal.
Bibliography
- PACE, Emma J; BROWN, Carina M; DEGEORGE, Katharine C. Neonatal hyperbilirubinemia: An evidence-based approach. J Fam Pract. Vol.68, n.1. 4-11, 2019
- FARGO, Matthew V; GROGAN, Scott P; SAGUIL, Araron. Evaluation of Jaundice in Adults. Am Fam Physician. Vol.95, n.3. 164-168, 2017
- MINE, Masataka et al. Association between Total Cholesterol and the Direct to Total Bilirubin Ratio in Serum. Vascular Failure. Vol.3, n.2. 51-58, 2020
- SULLIVAN, Jeremy I; ROCKEY, Don C. Diagnosis and evaluation of hyperbilirubinemia. Curr Opin Gastroenterol. Vol.33, n.3. 164-170, 2017
- STATPEARLS. Physiology, Bilirubin. 2022. Available at: <https://www.ncbi.nlm.nih.gov/books/NBK470290/>. Accessed on 09 Dec 2022
- STATPEARLS. Jaundice. 2022 Jaundice. Available at: <https://www.ncbi.nlm.nih.gov/books/NBK544252/>. Accessed on 09 Dec 2022
- STATPEARLS. Conjugated Hyperbilirubinemia. 2022. Available at: <https://www.ncbi.nlm.nih.gov/books/NBK562172/>. Accessed on 09 Dec 2022
- STATPEARLS. Unconjugated Hyperbilirubinemia. 2022. Available at: <https://www.ncbi.nlm.nih.gov/books/NBK549796/>. Accessed on 09 Dec 2022
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