• Clinical science

Jaundice and cholestasis

Abstract

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.

Definition

  • Jaundice: yellowish discoloration of the skin, sclerae, and mucous membranes due to the deposition of bilirubin
    • Scleral icterus: discoloration of the sclerae, starting at serum bilirubin levels > 2–3 mg/dL
    • Jaundice: discoloration of the skin; and mucous membranes, starting at serum bilirubin levels > 4–5 mg/dL
  • Cholestasis: : The term cholestasis refers to 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).

References:[1]

Etiology

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!

References:[2][3][4][5][6][7][8][9]

Pathophysiology

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
    • Increased hemoglobin breakdown
    • Defective hepatic uptake/conjugation of unconjugated bilirubin
  • Causes of conjugated (direct) serum bilirubin
    • Reduced drainage via biliary tract
    • Increased reuptake

References:[10][8]

Clinical features

References:[10][8][11][12]

Diagnostics

Liver function tests (LFTs)

Imaging

  • Ultrasound → high specificity and sensitivity for differentiating between different forms of cholestasis
  • Further imaging, if necessary (e.g., ERCP, MRCP, or CT)

Differentiating types of jaundice

Bilirubin Effects
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)

Hemolytic markers

Anemia

Intrahepatic jaundice Pale, clay-colored (rarely dark) ↑ (dark urine)

Normal or ↑

Transaminases

Cholestatic enzymes

Extrahepatic jaundice Pale, clay-colored Normal ↑↑ ↑↑ (very dark urine) Low

Dilated bile ducts

Cholestatic enzymes

References:[2][10]

Differential diagnoses

  • Pseudojaundice: deposition of carotene in the skin (carotenoderma) following excessive consumption of fruits and vegetables rich in carotene, such as carrots, sweet potatoes, kale, and oranges or multivitamin supplements. In contrast to jaundice, it does not lead to scleral icterus.

The differential diagnoses listed here are not exhaustive.

Treatment

Complications

References:[1]

We list the most important complications. The selection is not exhaustive.