- Namita Roy-Chowdhury, PhD
Namita Roy-Chowdhury, PhD
- Professor of Medicine and Genetics
- Albert Einstein College of Medicine
- Jayanta Roy-Chowdhury, MD, MRCP
Jayanta Roy-Chowdhury, MD, MRCP
- Professor of Medicine and Genetics
- Albert Einstein College of Medicine
- Section Editors
- Sanjiv Chopra, MD, MACP
Sanjiv Chopra, MD, MACP
- Editor-in-Chief — Gastroenterology/Hepatology
- Section Editor — General Hepatology; Gallbladder and Biliary Tract Disease
- Professor of Medicine
- Harvard Medical School
- Senior Consultant in Hepatology
- James Tullis Firm Chief
- Beth Israel Deaconess Medical Center
- Elizabeth B Rand, MD
Elizabeth B Rand, MD
- Section Editor — Pediatric Hepatology
- Professor of Pediatrics
- University of Pennsylvania School of Medicine
Bilirubin is the potentially toxic catabolic product of heme metabolism. Fortunately, there are elaborate physiologic mechanisms for its detoxification and disposition. Understanding these mechanisms is necessary for interpretation of the clinical significance of high serum bilirubin concentrations. Furthermore, because bilirubin shares its metabolic pathway with various other sparingly water soluble substances that are excreted in bile, understanding bilirubin metabolism also provides insight into the mechanisms of transport, detoxification, and elimination of many other organic anions .
An overview of the major aspects of bilirubin formation and disposition will be reviewed here. The settings in which bilirubin disposition is impaired will also be discussed briefly. Clinical aspects of serum bilirubin determination, the evaluation of patients with hyperbilirubinemia, and the classification of causes of jaundice are presented separately. (See "Clinical aspects of serum bilirubin determination" and "Diagnostic approach to the adult with jaundice or asymptomatic hyperbilirubinemia" and "Classification and causes of jaundice or asymptomatic hyperbilirubinemia".)
FORMATION OF BILIRUBIN
Bilirubin is formed by breakdown of heme present in hemoglobin, myoglobin, cytochromes, catalase, peroxidase and tryptophan pyrrolase. Eighty percent of the daily bilirubin production (250 to 400 mg in adults) is derived from hemoglobin ; the remaining 20 percent being contributed by other hemoproteins and a rapidly turning-over small pool of free heme. Enhanced bilirubin formation is found in all conditions associated with increased red cell turnover such as intramedullary or intravascular hemolysis (eg, hemolytic, dyserythropoietic, and megaloblastic anemias).
Heme consists of a ring of four pyrroles joined by carbon bridges and a central iron atom (ferroprotoporphyrin IX). Bilirubin is generated by sequential catalytic degradation of heme mediated by two groups of enzymes:
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- FORMATION OF BILIRUBIN
- Measurement of serum bilirubin
- METABOLISM OF BILIRUBIN
- Albumin binding of bilirubin in plasma
- Uptake and storage of bilirubin by hepatocytes
- Conjugation of bilirubin
- Excretion of conjugated bilirubin
- Degradation of bilirubin in the digestive tract
- Alternative pathways of bilirubin elimination
- BILIRUBIN IN DISEASE STATES
- Potential beneficial effects of bilirubin
- Bilirubin toxicity
- SUMMARY AND RECOMMENDATIONS