- Clinical science
Jaundice, or icterus, is a yellowish discoloration of tissue caused by the accumulation of bilirubin deposits. Bilirubin deposition most commonly occurs in the skin and the sclerae and becomes apparent on physical exam when bilirubin levels reach > 2 mg/dL. Hyperbilirubinemia may be of prehepatic, intrahepatic, or posthepatic origin. Prehepatic jaundice is caused by the accumulation of unconjugated bilirubin due to increased hemoglobin breakdown or impaired hepatic uptake/conjugation of bilirubin. Intrahepatic and posthepatic jaundice may be due to decreased excretion/impaired reuptake of bilirubin by the liver or cholestasis, which can result from either reduced formation/secretion of bile (nonobstructive cholestasis) or biliary obstruction (obstructive cholestasis). In addition to skin and sclerae discoloration, jaundice is also characterized by pruritus, darkening of urine, and pale stools (in case of intrahepatic or posthepatic cholestasis). Diagnosis is based on the laboratory markers of 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 used.
- Jaundice: yellowish discoloration of the skin, sclerae, and mucous membranes due to the deposition of bilirubin
- Hyperbilirubinemia: an increased serum concentration of bilirubin
Increased hemoglobin breakdown
- Resolving hematoma or internal hemorrhage (e.g., in trauma patients or postoperatively)
Impaired hepatic uptake of bilirubin
Defective conjugation of bilirubin
- Liver disease
- Thyroid disease
Decreased excretion/impaired reuptake of bilirubin
- Liver disease
Biliary tract disorders
- Postoperative cholestasis
- Infiltrative disorders
- Other causes
Extrahepatic cholestasis (biliary obstruction)
- Biliary tract disorders
- Inflammatory processes
- Infectious diseases
Jaundice is not always a confirmatory 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.
- 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. Any pathology that impairs the process could increase serum bilirubin level: 
Liver function tests (LFTs) 
- Elevated transaminases: alanine aminotransferase (ALT), aspartate aminotransferase (AST)
- Hepatitis serology, autoantibodies
- Hemolysis markers
- Albumin and PT/INR
- Inflammatory markers
Ultrasound: high specificity and sensitivity for differentiating between different forms of cholestasis
Obstructive cholestasis findings
- Extrahepatic obstruction: dilated common bile duct with possible (also visible on CT scan)
- Intrahepatic obstruction: double-barrel shotgun sign (due to obstructive cholestasis and consequent intrahepatic bile ducts dilation that allows the two bile ducts to be seen side-by-side, similar to a double-barrel shotgun )
- Cause of biliary obstruction, if present (e.g., stones, tumors, cysts, cholangitis)
- Nonobstructive cholestasis findings
- Obstructive cholestasis findings
- Other tests (if necessary): e.g., ERCP, MRCP, or CT
Types of jaundice 
|Prehepatic jaundice||Intrahepatic jaundice||Extrahepatic jaundice|
|Stool color|| || || |
|Indirect bilirubin|| || || |
|Direct bilirubin|| || || |
|Urinary bilirubin|| || || |
|Urinary urobilinogen|| || || |
|Urine color|| || || |
|Cholestatic enzymes (ALP, GGT)|| || || |
|Transaminases|| || || |
- Deposition of carotene in the skin (carotenoderma) can also cause yellow discoloration of the skin.
- Usually occurs after excessive consumption of 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.
- See “Etiology” above.
The differential diagnoses listed here are not exhaustive.
- Management of the underlying condition 
- Management of cholestasis-associated pruritus