Definition and Epidemiology

Jaundice, or icterus, is a yellow or greenish discoloration of the skin, sclerae, and mucous membranes caused by bile pigments of conjugated or unconjugated bilirubin.¹ There are multiple causes of jaundice, necessitating determination of the underlying disorder.

Jaundice can be divided into three categories: prehepatic, hepatic, and posthepatic. Prehepatic jaundice is caused by conditions that produce excessive bilirubin. Examples include any condition that causes hemolysis. Hepatic jaundice is a result of hepatic injury, including infections, toxins, autoimmune disorders, and tumors. Posthepatic jaundice, also called obstructive jaundice, is a result of complete or partial obstruction of the bile ducts. Pancreatic tumors and gallstones are the most common causes of posthepatic jaundice.²

The causes of jaundice are categorized according to (1) symptoms (acute or chronic), (2) evidence of bile duct dilation, and (3) jaundice of the conjugated or unconjugated varieties.¹ Jaundice is common in newborns and occurs in 60% to 80% of term infants 4 to 14 days after birth.² In older children and young adults, common causes include viral hepatitis (accounts for 75% of jaundice in patients younger than 30 years), Gilbert syndrome, drug-induced hepatitis, pregnancy, cirrhosis, and alcoholic hepatitis. In older patients, the most common causes are cirrhosis (accounts for 30% of jaundice in the 30- to 60-year-old age group), pancreatic cancer, metastatic cancer to the liver, sepsis, common bile duct stone, and medication–induced hepatitis.³ Alcoholic liver disease, associated with loneliness and depression, is a common cause in older adults.³ Common causes of jaundice are presented in Box 140-1.

The liver plays a major role in the metabolism of bile pigments. This process is divided into three distinct phases: (1) hepatic uptake, (2) conjugation, and (3) excretion.¹ A byproduct of hemolysis is bilirubin, which is produced through the breakdown of hemoglobin in red blood cells (RBCs). There are two forms of bilirubin: indirect, or unconjugated, bilirubin (which is protein bound) and direct, or conjugated, bilirubin. The direct form circulates freely in the blood until it reaches the liver, where it is conjugated with glucuronide transferase and excreted into the bile.¹ An increase in unconjugated bilirubin is often associated with an increase in the destruction of RBCs. An increase in conjugated bilirubin is more likely seen with liver dysfunction or obstruction.¹ Disturbance in the passage of conjugated bilirubin from the liver to the intestine accounts for 60% of jaundice in patients older than 60 years. With bile duct obstruction, bilirubin is conjugated by the hepatocytes but cannot flow into the duodenum.¹ Therefore bilirubin accumulates in the liver and enters the bloodstream, causing hyperbilirubinemia.

Extrahepatic obstructive jaundice develops if the common bile duct is occluded by gallstones or tumors, especially pancreatic carcinoma or strictures.^1,2 Because conjugated bilirubin is water soluble, it is excreted in the urine. This produces the characteristic orange urine with elevated conjugated bilirubin produced by inflammation.

Intrahepatic obstructive jaundice involves disturbances in hepatocyte function or obstruction of bile canaliculi. The uptake, conjugation, and excretion of bilirubin are affected, resulting in increased levels of conjugated and unconjugated bilirubin.¹

Failure of liver cells to conjugate bilirubin causes hepatocellular damage, resulting in increased plasma concentrations of unconjugated bilirubin. In addition, bilirubin cannot pass from the liver to the intestine.¹ The causes of hepatocellular damage include infections, medications, toxins, and genetic defects causing decreased enzyme production.

Hemolytic jaundice is caused by excessive hemolysis of RBCs. An increased amount of unconjugated bilirubin is formed through metabolism of the heme component of destroyed RBCs and exceeds the conjugation ability of the liver.^1,4 This causes the blood levels of unconjugated bilirubin to rise. Hemolysis can occur with blood transfusion reactions, after cardiopulmonary bypass, with sickle cell anemia, and with marrow or splenic destruction of RBCs. In sickle cell anemia, abnormal hemoglobin and a fragile cell membrane lead to hemolysis and an increase in the amount of free, unconjugated bilirubin.¹ Bone marrow development problems and defective erythropoiesis are conditions in which poorly manufactured erythrocytes are fragile and have a short life span. The result is an excess of unconjugated bilirubin that reaches the liver for conjugation.¹ The most common causes of jaundice are hepatocellular destruction and mechanical obstruction of the biliary tracts.^1,2

Clinical Presentation

Jaundice is most commonly observed in the face, trunk, and sclera. Bilirubin is distributed uniformly in the sclera and is differentiated from the normal occurrence of the yellow subscleral fat that collects in the periphery.⁵ In African Americans, the hard palate or ventral surface of the tongue helps clinical jaundice to be observed.⁵ Jaundice caused by carotene does not stain the sclera but rather is seen in the forehead, around the alae nasi, and in the palms and soles. The patient with jaundice may have pruritus, which often accompanies obstructive jaundice. The pruritus is caused by nerve injury in the skin by the bile pigments.⁵ Cutaneous xanthomas may be seen in patients with jaundice from chronic cholestasis and suggest hypercholesterolemia. The presence of spider angiomas, palmar erythema, and ascites combined with malaise, anorexia, and right upper quadrant discomfort suggests chronic hepatocellular disease or cirrhosis. Colicky right upper quadrant pain, weight loss, and light-colored stools may be present in obstructive jaundice. Intermittent, colicky right upper quadrant pain before the onset of jaundice suggests choledocholithiasis.⁵ Fever and chills may accompany biliary obstruction and virus- or drug-induced hepatitis. Occult blood in the stools suggests cancer as a cause of jaundice.⁶

Appropriate history includes determining whether the jaundice is acute or chronic and ascertaining associated symptoms (e.g., fever, weight loss, anorexia, rash, pruritus, abdominal pain, or musculoskeletal aches and pains). In acute jaundice, inquiry focuses on hepatitis risks: recent travel; transfusions; tattoos; intravenous drug use; alcohol intake; medications (prescription drugs, herbals, or over-the-counter preparations); food, toxin, animal, or infected person exposures; unsafe sexual practices; and symptoms of biliary tract disease.² Chronic jaundice may suggest hepatitis (B, C, D, or autoimmune), biliary tract disease, pancreatitis, or chronic alcohol intake. Weight loss, anorexia, malaise, and other symptoms of cancer are noted. In addition, a list of medications (including over-the-counter medications) and a complete family history, including cancer, Wilson disease, Gilbert syndrome, hemochromatosis, and hereditary hemolytic anemias, provide vital information for an appropriate diagnosis. Exposure to toxins, including use of herbal products, and a surgical history should also be elicited.^2,7

Physical Examination

Acute jaundice requires a complete examination for the cause of the illness to be determined. Essential components are determination of vital signs (including temperature); evaluation of the skin (including the palms and soles), sclera, and mucous membranes; assessment of the cardiovascular system for congestive heart failure; and evaluation of the abdomen for ascites, organomegaly, guarding, and tenderness.^1,3 Fever and right upper quadrant tenderness are most often associated with choledocholithiasis, cholangitis, or cholecystitis. An enlarged, tender liver suggests acute hepatic inflammation or a rapidly growing hepatic tumor.² Splenomegaly suggests portal hypertension from acute or active chronic hepatitis as well as cirrhosis.⁵

Chronic jaundice mandates evaluation for chronic liver disease. Gynecomastia, testicular atrophy, and splenomegaly are strongly associated with cirrhosis.⁵ In addition, palmar erythema, facial telangiectasia, and Dupuytren contractures are associated with cirrhosis from chronic ethanol ingestion.⁸ Lymphadenopathy suggests malignant disease and can be related to a pancreatic tumor obstructing the splenic vein or to a metastatic lymphoma. When malignant disease is suspected, the investigation should concentrate on determining the location of the primary tumor as indicated by heme-positive stool, abdominal masses, breast masses, thyroid nodules, or supraclavicular lymphadenopathy.⁶ Physical findings associated with specific liver diseases include distended neck veins and hepatojugular reflux (right-sided heart failure), xanthomas (primary biliary cirrhosis), and Kayser-Fleischer rings (Wilson disease).⁵