Jaundice comes from the French word “jaune,” meaning
yellow. Jaundice refers to the yellow staining of the sclera, mucous
membranes, and skin by bilirubin. It is not a disease by itself
but rather a manifestation that accompanies different diseases.
Jaundice is caused by elevated serum bilirubin levels with subsequent
tissue deposition. In infants, it is usually apparent with bilirubin levels
above 4–5 mg/dL (68–86 mmol/L).
In older children, jaundice can be noted at levels above 2–3
mg/dL (34–51 mmol/L). The color of the
sclera and skin varies depending on the serum bilirubin level. Jaundice
involves the head first and progresses caudally with higher levels.
Total serum bilirubin is the sum of the unconjugated (or indirect)
and conjugated (or direct) bilirubin fractions. The terms direct
and conjugated hyperbilirubinemia are often used interchangeably, but
this is not always accurate. Direct bilirubin is measured in the
laboratory using a diazo dye-binding assay, and, depending on the
method used, can include both conjugated bilirubin and delta bilirubin.
Delta bilirubin is formed by covalent bond formation between serum
conjugated bilirubin and albumin. Clearance of delta bilirubin can
therefore be prolonged, reflecting the half-life of albumin, and
may lag behind other signs of clinical improvement.
Cholestasis is defined as diminished bile formation or flow,
and is manifested by conjugated hyper-bilirubinemia. The guidelines
of the North American Society for Pediatric Gastroenterology, Hepatology
and Nutrition (NASPGHAN)1 define an abnormal conjugated
bilirubin level as:
- a conjugated bilirubin >1.0 mg/dL, if the total
bilirubin is <5 mg/dL, or
- a conjugated bilirubin level >20% of
the total bilirubin, if the total bilirubin is >5 mg/dL.
Neonatal jaundice is common, observed in the first week of life
in about 50% of term infants and 80% of
preterm infants. This is usually harmless, often related to physiological
jaundice or breastfeeding, and is characterized by unconjugated
hyperbilirubinemia. Rarely, however, severe unconjugated hyperbilirubinemia
can lead to bilirubin encephalopathy or kernicterus.2 On
the contrary, cholestasis (or conjugated hyperbilirubinemia) is
much less commonly seen but often results from conditions with serious
hepatobiliary dysfunction. Cholestatic jaundice affects approximately
1 in every 2500 infants.3 The challenge for physicians
is to identify infants with cholestasis who will need additional
evaluation and treatment. Early detection of cholestatic jaundice
and accurate diagnosis of its etiology are vital for successful
treatment and a favorable prognosis.
Bilirubin is the end product of heme moiety metabolism from hemoglobin
and other heme-containing proteins (Figure 7–1). After
unconjugated bilirubin is formed, it is transported with albumin
in blood to the liver. Inside hepatocytes, unconjugated bilirubin
is conjugated with glucuronic acid by uridine diphosphate glucuronosyltransferase
(UGT) to increase water solubility. Conjugated bilirubin, along
with cholesterol, bile acids, and phospholipids, is transported
through the bile canalicular system to the gallbladder and later
into the small intestine. Conjugated bilirubin cannot be reabsorbed
by enterocytes and is degraded by the intestinal flora into colorless
urobilinogen, which is excreted ...