Unconjugated Hyperbilirubinemia Clinical Presentation

  • Author: Sandeep Mukherjee, MB, BCh, MPH, FRCPC; Chief Editor: Julian Katz, MD   more...
 
Updated: Jan 5, 2012
 

History

  • Increased production of bilirubin: Ineffective erythropoiesis (ELB production) is characterized by the onset of asymptomatic jaundice.
  • Neonatal jaundice, physiologic: Physiologic jaundice is clinically obvious in 50% of neonates during the first 5 days of life.
  • Neonatal jaundice, nonphysiologic
    • Maternal milk jaundice: Bilirubin levels in breastfed babies can occasionally reach 15-24 mg/dL by 10-19 days of life.
    • Maternal serum jaundice (Lucey-Driscoll syndrome): Jaundice occurs during the first 4 days of life, with serum bilirubin concentrations reported at 8.9-65 mg/dL and reached within 7 days of birth.
  • Impaired conjugation of bilirubin
    • Crigler-Najjar syndrome type II (Arias syndrome): During surgery or intercurrent illnesses, the levels may increase to as much as 40 mg/dL.
    • Gilbert syndrome: Serum bilirubin fluctuates with time and increases during fasting, intercurrent illness, emotional stress, or menstruation. Apart from mild jaundice, physical examination findings in people with Gilbert syndrome are normal.
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Physical

  • Increased production of bilirubin
    • Ineffective erythropoiesis (ELB production): Patients with these diseases, which are characterized by abnormalities in heme biosynthesis within the developing normoblast, do not exhibit evidence of increased red blood cell destruction but they have significant increases in total bile pigment turnover. However, red blood cell destruction is increased, together with an absolute (but not relative) increase in erythroid ELB production in paroxysmal nocturnal hemoglobinuria and sickle cell anemia or following hemorrhage.
    • Hemolysis is characterized by unconjugated hyperbilirubinemia, although significant levels of conjugated bilirubin may be observed in the presence of underlying liver disease, sepsis, drugs, or when the amount of bilirubin generated and conjugated exceeds the biliary transport limit for conjugated bilirubin, as may occur in acute hemolytic crises or with multiple blood transfusions. Hemolysis due to hereditary abnormalities of erythrocytes (eg, hereditary spherocytosis/elliptocytosis, glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, sickle cell disease) generally produces a milder degree of jaundice, which may manifest within a few days of birth or as recurrent episodes during later life, and frequently in association with febrile illnesses.
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Causes

  • Increased bilirubin production
    • Hemolysis
    • Dyserythropoiesis
    • Hematoma
  • Impaired hepatic bilirubin uptake
    • Congestive heart failure
    • Portosystemic shunts
    • Drugs - Rifamycin, rifampin, probenecid, flavaspidic acid, bunamiodyl
  • Impaired bilirubin conjugation
    • Crigler-Najjar syndrome types I and II
    • Gilbert syndrome (decreased uptake and/or conjugation)
    • Neonatal physiologic jaundice
    • Breast milk jaundice
    • Maternal serum jaundice
    • Hypothyroidism/hyperthyroidism
    • Ethinyl estradiol
    • Liver diseases - Chronic hepatitis, cirrhosis, Wilson disease (decreased uptake and conjugation)
  • Fasting hyperbilirubinemia - Contributed to by increased enterohepatic circulation of bilirubin and genetic factors
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Contributor Information and Disclosures
Author

Sandeep Mukherjee, MB, BCh, MPH, FRCPC  Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center

Sandeep Mukherjee, MB, BCh, MPH, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Merck Honoraria Speaking and teaching; Ikaria Pharmaceuticals Honoraria Board membership

Coauthor(s)

Nuri Ozden, MD  Assistant Professor, Department of Internal Medicine, Meharry Medical College

Nuri Ozden, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Specialty Editor Board

Ann Ouyang, MBBS  Professor, Department of Internal Medicine, Pennsylvania State University College of Medicine; Attending Physician, Division of Gastroenterology and Hepatology, Milton S Hershey Medical Center

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Oscar S Brann, MD, FACP  Associate Clinical Professor, Department of Medicine, University of California at San Diego; Consulting Staff, Mecklenburg Medical Group

Oscar S Brann, MD, FACP is a member of the following medical societies: American Gastroenterological Association

Disclosure: Nothing to disclose.

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD  Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

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Production of bilirubin.
Enterohepatic circulation of bilirubin.
Conjugation of bilirubin.
 
 
 
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