Q&A: Diagnosis Of Jaundice and Hyperbilirubinemia

The normal serum bilirubin concentration in children and adults is less than 1 mg/dL (17 micromol/liter), less than 5 percent of which is present in conjugated form. The measurement is usually made using diazo reagents and spectrophotometry. Conjugated bilirubin reacts rapidly ("directly") with the reagents. The measurement of unconjugated bilirubin requires the addition of an accelerator compound and is often referred to as the indirect bilirubin.

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In this article:
Jaundice and asymptomatic hyperbilirubinemia
MCQ exam: clinical scenario
MCQ exam: answer
MCQ exam: explanation

Jaundice and asymptomatic hyperbilirubinemia

Jaundice is often used interchangeably with hyperbilirubinemia. However, a careful clinical examination cannot detect jaundice until the serum bilirubin is greater than 2 mg/dL (34 micromol/liter), twice the normal upper limit. The yellow discoloration is best seen in the periphery of the ocular conjunctivae and in the oral mucous membranes (under the tongue, hard palate). Icterus may be the first or only sign of liver disease; thus its evaluation is of critical importance.

For clinical purposes, the predominant type of bile pigments in the plasma can be used to classify hyperbilirubinemia into two major categories.

• Plasma elevation of predominantly unconjugated bilirubin due to the overproduction of bilirubin, impaired bilirubin uptake by the liver, or abnormalities of bilirubin conjugation
• Plasma elevation of both unconjugated and conjugated bilirubin due to hepatocellular diseases, impaired canalicular excretion, defective reuptake of conjugated bilirubin and biliary obstruction

In some situations, both overproduction and reduced disposition contribute to the accumulation of bilirubin in plasma.

MCQ exam: clinical scenario

A 7 year old is noted to have mild icterus. On examination he is found to have moderate splenomegaly. Investigations reveal a conjugated hyperbilirubinemia. There are normal levels of AST, ALT, albumin, alkaline phosphatase. Tests on the urine reveal an elevated total coproporphyrin excretion of 5 times the normal with 25% being coproporphyrin I. A liver biopsy is normal.

A likely diagnosis is:

a) Pancreatic carcinoma
b) Hemochromatosis
c) Laennec's cirrhosis
d) Hepatitis A
e) Hepatocellular carcinoma
f) Rotor's Syndrome
g) Primary biliary cirrhosis
h) Gilbert's Syndrome
i) Hepatitis B
j) Hemolysis

MCQ exam: answer

The correct answer is F.

MCQ exam: explanation

Rotor's Syndrome is an inherited disorder characterized by a congenital defect in bilirubin uptake and storage resulting in chronic, benign jaundice. It is a rare autosomal recessive disorder characterized by various organic anions as well as bilirubin. The hyperbilirubinemia is conjugated and bile appears in the urine. Splenomegaly occurs in half of patients and jaundice may occur as early as age 5. It is usually intermittent in nature.

Rotor Syndrome and Dubin-Johnson Syndrome represent autosomal recessive disorders resulting in chronic, benign conjugated hyperbilirubinemia and jaundice. They are secondary to a genetic defect resulting in a deficiency of organic acid uptake and storage in the liver resulting in conjugated hyperbilirubinemia and jaundice. Clinical features include mild icterus and jaundice with no pruritis. The jaundice can be exacerbated by intercurrent infections.

Investigations reveal a conjugated hyperbilirubinemia, normal AST, ALT, albumin, alkaline phosphatase, PT, bile salts, a delayed plasma sulfobromophthalen excretion after IV injection, elevated total coproporphyrin excretion (2.5-5x normal) in the urine with 25% being coproporphyrin I. Biposy of the liver is normal since this is a benign condition with a normal life span.

Reference(s)
1). UpToDate: Classification and causes of jaundice or asymptomatic hyperbilirubinemia. Available online: https://www.uptodate.com/contents/classification-and-causes-of-jaundice-or-asymptomatic-hyperbilirubinemia