- Clinical science
Jaundice, or icterus, refers to the yellowish discoloration of tissue caused by accumulated deposits of bilirubin. Bilirubin deposition most commonly occurs in the skin and the sclerae. It results from elevated bilirubin, starting at levels > 2 mg/dL. Hyperbilirubinemia may be of prehepatic, intrahepatic, or posthepatic origin. Prehepatic causes include an accumulation of unconjugated bilirubin; intrahepatic and posthepatic jaundice may be due to cholestasis (i.e., the reduced formation or secretion of bile or extrahepatic biliary obstruction). In addition to jaundice, clinical features can include pruritus, pale stool in cases of intrahepatic or posthepatic cholestasis, and darkening of urine. Diagnosis relies on the analysis of laboratory values for cholestasis, liver function, and hemolysis, as well as ultrasound of the biliary tract. Management of jaundice involves treatment of the underlying condition. In cases of moderate to severe pruritus, medication such as cholestyramine, rifampin, opioid antagonists, or ursodeoxycholic acid may be administered.
- Jaundice: yellowish discoloration of the skin, sclerae, and mucous membranes due to the deposition of bilirubin
- Cholestasis: any condition affecting bile formation or secretion ; (nonobstructive intrahepatic cholestasis), or leading to biliary obstruction within the liver; (obstructive intrahepatic cholestasis) or in the biliary ducts between the liver and the duodenum (obstructive extrahepatic or posthepatic cholestasis)
Increased hemoglobin breakdown
- Hemolysis; (e.g., glucose-6-phosphate dehydrogenase deficiency, , spherocytosis, , and blood transfusions )
- Dyserythropoiesis (e.g., thalassemia, pernicious anemia, erythropoietic porphyria, and sideroblastic anemia)
- Resolving hematoma or internal hemorrhage (e.g., in trauma patients or postoperatively)
- Impaired hepatic uptake of bilirubin
- Defective conjugation of bilirubin
- Increased hemoglobin breakdown
Decreased excretion/reuptake of bilirubin
- Inherited disorders: , ; , and progressive familial intrahepatic cholestasis )
- Intrahepatic cholestasis
Extrahepatic cholestasis (biliary obstruction)
- Tumors (pancreatic cancer, cholangiocellular carcinoma, gallbladder cancer)
- Inflammatory processes (e.g., , acute and chronic pancreatitis, and abscesses)
- Malformations of the bile ducts; (e.g., postoperative/inflammatory strictures, and biliary cysts)
- Parasitic infection (e.g., liver flukes)
- Postoperative bile leaks or biliary duct strictures
- Decreased excretion/reuptake of bilirubin
Jaundice is not always a sure sign of cholestasis; it may also indicate prehepatic causes. Conversely, cholestasis may be present in the absence of jaundice, particularly during the early stages of cholestasis!
Common causes of hyperbilirubinemia can be remembered with HOT Liver: Hemolysis, Obstruction, Tumor, and Liver disease!
Jaundice is due to an elevated level of serum bilirubin, which may be caused by prehepatic, intrahepatic, or posthepatic defects. Serum bilirubin concentration depends on the rate of formation and hepatobiliary elimination of bilirubin.
- Causes of ↑ unconjugated (indirect) serum bilirubin
Causes of ↑ conjugated (direct) serum bilirubin
- Reduced drainage via biliary tract
- Increased reuptake
- Elevated liver enzymes: alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
- See .
- Albumin and PT/INR
- Other liver tests: e.g., hepatitis serology, markers of hemolysis (LDH, haptoglobin, indirect bilirubin), autoantibodies
- Inflammatory markers
Ultrasound → high specificity and sensitivity for differentiating between different forms of cholestasis
- Obstructive cholestasis
- Nonobstructive cholestasis
- Further imaging, if necessary (e.g., ERCP, MRCP, or CT)
Differentiating types of jaundice
|Cause||Color of stool||Indirect bilirubin||Direct bilirubin||Bilirubin in urine||Urinary urobilinogen|| |
Other significant findings
|Prehepatic jaundice||Dark||↑↑||Normal||Normal||↑↑ (no darkening of urine , but dark urine may occur in the case of hemoglobinuria)|| |
|Intrahepatic jaundice||Pale, clay-colored (rarely dark)||↑||↑||↑ (dark urine)|| |
Normal or ↑
|Extrahepatic jaundice||Pale, clay-colored||Normal||↑↑||↑↑ (very dark urine)||Low|| |
Dilated bile ducts
- Deposition of carotene in the skin (carotenoderma) can also cause yellowing and usually occurs following excessive consumption multivitamin supplements or fruits and vegetables rich in carotenes, such as carrots, sweet potatoes, kale, and oranges.
- In contrast to jaundice, it does not lead to scleral icterus.
The differential diagnoses listed here are not exhaustive.