From the Guidelines
Elevated bilirubin levels are primarily caused by the breakdown of red blood cells, liver dysfunction, or bile duct obstruction, and require prompt medical evaluation to determine the underlying cause and appropriate treatment. Bilirubin is a yellow compound that exists in two forms: unconjugated and conjugated. Unconjugated hyperbilirubinemia is usually due to hemolysis or impaired conjugation, whereas conjugated hyperbilirubinemia is typically due to parenchymal liver disease or obstruction of the biliary system 1. The most common cause of an isolated elevated bilirubin concentration is Gilbert’s syndrome, an inherited disorder of metabolism that leads to impaired conjugation via reduced activity of the enzyme glucuronyltransferase 1.
Some key points to consider when evaluating elevated bilirubin levels include:
- Normal total bilirubin ranges from 0.3-1.2 mg/dL; levels above this are considered elevated
- Treatment depends entirely on the underlying cause, which can range from benign conditions like Gilbert's syndrome to more serious conditions like hepatitis, bile duct obstructions, or hemolytic disorders
- Symptoms like yellowing of skin or eyes (jaundice), dark urine, light-colored stools, abdominal pain, or fever alongside elevated bilirubin warrant immediate medical attention
- The liver processes bilirubin by converting it from an insoluble form (unconjugated) to a soluble form (conjugated) for excretion, so disruption anywhere in this pathway can lead to elevated levels 2.
In terms of diagnosis, a detailed history, targeted physical examination, and pertinent laboratory studies (e.g., a hepatic profile, conjugated versus unconjugated bilirubinemia, complete blood count) are necessary to differentiate between the various potential etiologies of jaundice 2. While waiting for medical evaluation, it is recommended to avoid alcohol, stay hydrated, and discontinue any non-essential medications that could stress the liver.
It is essential to note that the most common causes of jaundice can vary depending on geographical location, demographics, and other factors, but generally include hepatitis, alcoholic liver disease, blockage of the common bile duct, and toxic reactions to drugs or medicinal herbs 2. Therefore, a thorough medical evaluation is necessary to determine the underlying cause of elevated bilirubin levels and provide appropriate treatment.
From the Research
Causes of Elevated Bilirubin (Hyperbilirubinemia)
- Hyperbilirubinemia can be caused by various factors, including hemolysis, which is the breakdown of red blood cells, leading to an increased production of bilirubin 3
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency is another common cause of severe hyperbilirubinemia in neonates, as it can lead to hemolysis and increased bilirubin production 4
- Hepatocellular dysfunction and biliary obstruction can also cause jaundice and hyperbilirubinemia, as they can lead to a buildup of bilirubin in the blood 5
- Physiologic jaundice is a common cause of hyperbilirubinemia in newborns, occurring in over 80% of infants, but persistent and extreme elevations can lead to serious complications 6
Mechanisms of Hyperbilirubinemia
- The degree of hyperbilirubinemia depends on two major processes: bilirubin production and elimination 3
- Bilirubin production can be increased due to hemolysis, while elimination can be decreased due to hepatocellular dysfunction or biliary obstruction 5
- The ability to identify infants with hemolytic disease is important in assessing those at risk for developing bilirubin-induced neurologic dysfunction (BIND) 3
Clinical Detection and Evaluation
- Clinical signs of jaundice occur when the serum bilirubin level exceeds 2.5 to 3 mg/dL 5
- Evaluation of hyperbilirubinemia begins with liver chemistry tests, including bilirubin, alkaline phosphatase, and liver enzymes 5
- A stepwise approach to evaluation, combining serologic evaluation with hepatobiliary imaging, can help elucidate the underlying mechanism of disease and improve patient outcomes 5