Jaundice

last authored: Aug 2009, David LaPierre

Introduction

Jaundice is the yellow pigmentation of the skin, sclerae, and mucous membranes caused by hyperbilirubinemia. It is often seen in liver disease, but can also occur with hematologic disorders causing hemolysis.

In most cases evaluation is not urgent, though in some - massive hemolysis, ascending cholangitis, or acute hepatic failure - jaundice can represent a medical emergency.

Normal serum bilirubin levels range from 0.5-1.0 mg/dL. Jaundice appears at levels higher than 2.5-3.0 mg/dL.

The Case of...

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Differential Diagnosis

Other conditions such as Addison's disease can cause skin yellowing, but scleral and mucous yellowing are specific to bilirubin accumulation.

The most important step is to determine whether bilrubin is unconjugated or conjugated. If unconjugated, assessment of hemolysis follows; if conjugated, the challenge is to determine whether hepatic excretion or biliary obstruction is the cause.

conjugated
unconjugated
neonatal

Conjugated Hyperbilirubinemia

Conjugated hyperbilirubinemia, or cholestasis, is generally associated with impaired formation or excretion of all components of bile. The two major mechanisms are a) a defect in excretion of bile from hepatocytes or b) mechanical obstruction through the bile ducts. In cholestatic jaundice, alkaline phosphatase levels are typically increased more than 3x, while serum transaminases are usually elevated less than 5-10x.

Cholestasis can also result in puritus and malabsorption of fat-soluble vitamins A, D, E, and K.

Intrahepatic cholestasis can result from impaired canalicular transport, by:

hepatitis, viral and drug-induced
hepatocellular disease
drugs, such as oral contraceptives, phenothiazines, and methyltestosterone
primary biliary cirrhosis occurs primarily in women and is characterized by progressive loss of lobular bile ducts
postoperative complications

Extrahepatic biliary obstruction can be due to many causes, including:

malignancy of the pancreas, gallbladder, bile duct, duodenum, Ampulla of Vater or metastatic tumours
gallstones
biliary strictures
infectious cholangiopathy - Ascaris lumbercoides, Fasciola hepatica, Clonorchis sinensis
pancreatitis

Unconjugated Hyperbilirubinemia

Unconjugated bilirubin can be caused by excess production of bilirubin (hemolysis), reduced hepatocyte uptake, and impaired congugation. These are not normally associated with significant liver disease.

Overproduction of bilirubin results from hemolysis.

malaria
sickle cell anemia
G6PD deficiency

Jaundice is characteristically mild, with serum levels rarely exceeding 5 mg/dL in the absence of co-existent hepatic disease. It can be investigated using peripheral blood smear, measuring reticulocyte count, LDH, erythrocyte fragility, and Coombs' test.

Impaired uptake of bilirubin can occur after administering certain drugs, such as rifampin, which competes for uptake. Gilbert's syndrome can also contribute to this in up to 7% of the male population.

Impaired conjugation can result from congenital problems in the UDP glucuronyl transferase system, or by drugs such as chloramphenicol.

Unconjugated bilirubin can build up all over the body, including the brain.

Neonatal Jaundice

Babies can have physiologic jaundice from uncongugated bilirubin due to increased production but decreased metabolic capacity. Mild to moderate jaundice may be present from the 2nd-5th days of life. Severe unconjugated hyperbilirubinemia is usually caused by blood group incompatibility coupled with defective conjugation. Kernicterus, or neurologic damage, is a possibility, and phototherapy is the treatment of choice. Breastmilk has an enzyme that ....

Jaundice can be pre-hepatic (unconjugated) or post-hepatic (conjugated). Conjugated bilirubin can be excreted in the urine, and therefore post-hepatic jaundice will produce dark urine. With pre-hepatic jaundice the bilirubin is not congugated and therefore cannot be excreted in the urine, causing normal color.