Causes of Elevated Bilirubin Levels
Bilirubin is a byproduct of normal hemoglobin breakdown. When old red blood cells are broken down, the hemoglobin within them is converted into bilirubin. The liver then degrades bilirubin into bile and either stores it in the gallbladder or excretes it through the stool. A small amount of bilirubin circulates in the bloodstream. Several diseases involving the liver, gallbladder or red blood cells may cause an increased bilirubin level. When bilirubin builds up in the blood, it may cause jaundice, a yellow discoloration of the whites of the eyes and skin.
The liver normally converts bilirubin to a more soluble form that can be excreted from the body in the stool. When the liver is not working properly, bilirubin is not converted into an excretable form and builds up in the body. Chronic liver conditions such as cirrhosis or viral hepatitis, which produce inflammation and liver scarring, commonly cause increased bilirubin. Inherited conditions, like Gilbert syndrome and Dubin-Johnson syndrome, interfere with normal bilirubin processing in the liver and commonly lead to high blood levels.
Bile Duct and Gallbladder Disease
Conditions that damage or block the bile ducts can cause elevated bilirubin levels. A condition called cholestasis -- with decreased bile flow caused by a blockage of the bile duct or reduced secretion of bile from the liver -- can lead to high bilirubin levels. Tumors of the gallbladder, liver, bile duct or pancreas can also cause high bilirubin levels by blocking the ducts used to excrete bilirubin. Gallstones can partially or completely obstruct bile flow, leading to high bilirubin levels.
Hemolytic anemia is a condition in which red blood cells are destroyed prematurely. Since bilirubin is produced during the breakdown process of red blood cells, increased destruction commonly leads to an elevated bilirubin level. Inherited conditions can lead to hemolytic anemia. For example, sickle cell anemia leads to crescent-shaped rather than normal disc-shaped red blood cells. The misshapen cells do not survive as long as normal red blood cells and are destroyed prematurely. Other conditions acquired during life can also cause hemolytic anemia 12. For example, with autoimmune hemolytic anemia, your body mistakenly produces antibodies against your red blood cells, targeting them for destruction. Lupus, certain types of leukemia or lymphoma, and infection with the Epstein-Barr virus -- which causes infectious mononucleosis -- can increase your risk for autoimmune hemolytic anemia.
Certain medications can cause increased bilirubin levels in some people. Some drugs decrease the uptake of bilirubin by the liver, which can lead to higher blood levels. Examples of drugs that have this effect include the antibiotic rifampin (Mycobutin) and probenecid, which is used to treat gout. Other medications can cause cholestasis and impede the secretion of bilirubin in the bile 4. Examples of medications that can cause cholestasis include the psychiatric drug chlorpromazine, the antibiotic erythromycin (Eryc, Ery-Tab), estrogens (Premarin, Prempro) used for hormone replacement therapy, and anabolic steroids such as: * nandrolone. Drugs such as acetaminophen (Tylenol, Excedrin), which can be toxic to the liver in high doses, can also increase bilirubin.
Warnings and Precautions
Talk with your doctor if you notice yellow discoloration of your skin, nail beds or the whites of your eyes, as this could be due to jaundice. Your bilirubin level can be checked with a simple blood test. Since many of the causes of a high bilirubin level are potentially serious, it's important to see your doctor if you are concerned about jaundice. Other possible warning signs that should prompt a visit to your doctor include: -- pain in the upper abdomen -- nausea and vomiting -- unintentional weight loss -- sudden swelling of the abdomen -- a change in bowel habits -- unusually light or dark stools -- unexplained fever or swollen glands
Reviewed by: Tina M. St. John, M.D.
- Robbins Pathologic Basis of Disease, 5th Edition; Ramzi Cotran, et al.
- Clinical Chemistry: Theory, Analysis, and Correlation, 5th Edition; Lawrence A. Kaplan and Amadeo J. Pesce
- Medical Biochemistry Page: Iron and Heme Metabolism
- Medical Biochemistry Page: Bile Acid Synthesis and Utilization
- Higuchi S, Kabeya Y, Uchida J, Kato K, Tsukada N. Low bilirubin levels indicate a high risk of cerebral deep white matter lesions in apparently healthy subjects. Sci Rep. 2018 Apr 24;8(1):6473. doi:10.1038/s41598-018-24917-8
- Ngashangva L, Bachu V, Goswami P. Development of new methods for determination of bilirubin. J Pharm Biomed Anal. 2018 Sep 18;162:272-285. doi:10.1016/j.jpba.2018.09.034
- Jovanmandic/iStock/Getty Images