From the Guidelines
Bilirubin is a yellow-orange pigment produced during the normal breakdown of red blood cells in the body, and its levels are crucial in evaluating liver function and identifying potential health issues related to bilirubin metabolism. When old red blood cells are destroyed, hemoglobin is broken down into bilirubin, which is then processed by the liver. The liver converts bilirubin into a water-soluble form that can be excreted in bile and ultimately eliminated through stool. Elevated levels of bilirubin in the blood can cause jaundice, a yellowing of the skin and whites of the eyes. This elevation may indicate various conditions such as liver disease, bile duct obstruction, or excessive red blood cell destruction (hemolysis) 1.
Key Points About Bilirubin
- Bilirubin exists in two forms, unconjugated and conjugated, and is transported to the liver in its insoluble unconjugated form, where it is converted into soluble conjugated bilirubin for excretion 1.
- Unconjugated hyperbilirubinaemia is usually due to haemolysis or impaired conjugation, whereas conjugated hyperbilirubinaemia is typically due to parenchymal liver disease or obstruction of the biliary system 1.
- Newborns commonly experience elevated bilirubin levels temporarily as their immature livers adjust to processing bilirubin after birth, a condition called neonatal jaundice 2, 3, 4, 5, 6.
- Blood tests measuring bilirubin levels are important diagnostic tools for evaluating liver function and identifying potential health issues related to bilirubin metabolism.
Clinical Considerations
- The management of hyperbilirubinemia in newborn infants involves promoting and supporting successful breastfeeding, performing a systematic assessment before discharge for the risk of severe hyperbilirubinemia, providing early and focused follow-up based on the risk assessment, and treating newborns with phototherapy or exchange transfusion to prevent the development of severe hyperbilirubinemia and, possibly, bilirubin encephalopathy (kernicterus) 3, 4, 5, 6.
- Phototherapy is an essential intervention for severe hyperbilirubinemia, especially in neonates at high risk, and its use reduces the risk of bilirubin neurotoxicity as well as the use of exchange transfusions 2, 6.
- The decision to initiate phototherapy or perform an exchange transfusion should be based on the total serum bilirubin (TSB) level, the age of the infant in hours, and the presence of neurotoxicity risk factors 6.
Recent Guidelines
- Recent guidelines recommend using TSB as the definitive diagnostic test to guide all interventions, measuring TSB if the transcutaneous bilirubin reading is within 3.0 mg/dL of the phototherapy treatment threshold, and using intensive phototherapy at thresholds based on gestational age, neurotoxicity risk factors, and age of the infant in hours 6.
- The guidelines also recommend evaluating the underlying cause or causes of hyperbilirubinemia in infants who require phototherapy, measuring glucose-6-phosphate dehydrogenase enzyme activity in any infant with jaundice of unknown cause whose TSB rises despite intensive phototherapy, and discontinuing phototherapy when the TSB has declined by 2 to 4 mg/dL below the hour-specific threshold at the initiation of phototherapy 6.
From the Research
Definition and Physiology of Bilirubin
- Bilirubin is the end product of heme catabolism formed during a process that involves oxidation-reduction reactions and conserves iron body stores 7.
- It exists in several isomeric forms that differ in their polarities and is considered a physiologically important antioxidant 7.
- The basic physiology of bilirubin metabolism, such as production, transport, and excretion, has been well described 7.
Clinical Significance of Bilirubin
- High plasma bilirubin levels are reflective of liver disease due to an injurious effect on hepatocytes 8.
- Low plasma bilirubin levels, defined as "hypobilirubinemia," are a possible new pathology analogous to the other end of the spectrum of extreme hyperbilirubinemia seen in patients with jaundice and liver dysfunction 9.
- Hypobilirubinemia is most commonly seen in patients with metabolic dysfunction, which may lead to cardiovascular complications and possibly stroke 9.
Diagnosis and Evaluation of Hyperbilirubinemia
- Jaundice, the physical finding associated with hyperbilirubinemia, results when the liver is unable to properly metabolize or excrete bilirubin 10.
- The best approach to evaluating a patient with jaundice is to start with a careful history and physical examination, followed by imaging assessment of the biliary tree and liver 10.
- Evaluation of patients with jaundice starts with a careful history and physical examination, followed by directed imaging of the biliary tree and liver 10.
Bilirubin as a Metabolic Hormone
- Recent research on bilirubin suggests an entirely new function as a metabolic hormone that drives gene transcription by nuclear receptors 9.
- A better understanding of bilirubin's hormonal function may explain why hypobilirubinemia might be deleterious 9.
- Bilirubin may be protective at mildly elevated levels, and research directions could generate treatment possibilities for patients with hypobilirubinemia 9.