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Jaundice and cholestasis

Last updated: July 20, 2021

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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.

Unconjugated hyperbilirubinemia [1]

Increased hemoglobin breakdown

Impaired hepatic uptake of bilirubin

Defective conjugation of bilirubin

Conjugated hyperbilirubinemia [1]

Decreased excretion/impaired reuptake of bilirubin

Intrahepatic cholestasis

Extrahepatic cholestasis (biliary obstruction)

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.

Hepatitis and cirrhosis can cause both conjugated and unconjugated hyperbilirubinemia.

The most common causes of hyperbilirubinemia are “HOT Liver”: Hemolysis, Obstruction, Tumor, and Liver disease.

In addition to jaundice, the following signs may also indicate cholestasis: [7]

Liver function tests (LFTs) [6]

Imaging [6]

Types of jaundice [6]

Prehepatic jaundice Intrahepatic jaundice Extrahepatic jaundice
Stool color
  • Dark
  • Pale, clay-colored (rarely dark)
  • Pale, clay-colored
Indirect bilirubin
  • ↑↑
  • Normal
Direct bilirubin
  • Normal
  • ↑↑
Urinary bilirubin
  • Normal
  • ↑↑
Urinary urobilinogen
  • ↑↑
  • Normal or ↑
  • [9]
Urine color
Cholestatic enzymes (ALP, GGT)
  • Normal
  • ↑↑
  • Normal
  • Normal
  • Pseudojaundice [10]
    • 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.

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

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  2. Maxwell MJ, Wilson JA. Complications of blood transfusion. Contin Educ Anaesth Crit Care Pain. 2006; 6 (6): p.225-229. doi: 10.1093/bjaceaccp/mkl053 . | Open in Read by QxMD
  3. Mantri R, Bavdekar SB, Save SU. Congenital Hypothyroidism: An Unusual Combination of Biochemical Abnormalities. Case Reports in Pediatrics. 2016; 2016 : p.1-3. doi: 10.1155/2016/2678578 . | Open in Read by QxMD
  4. Sundaram V, Björnsson ES. Drug-induced cholestasis. Hepatology Communications. 2017; 1 (8): p.726-735. doi: 10.1002/hep4.1088 . | Open in Read by QxMD
  5. Drug-Induced Cholestatic Liver Disease. In: Madame Curie Bioscience Database [Internet].
  6. Roche SP, Kobos R. Jaundice in the adult patient.. Am Fam Physician. 2004; 69 (2): p.299-304.
  7. Schiff ER, Bergasa NV. Advances in Hepatology: Current Developments in the Treatment of Hepatitis and Hepatobiliary Disease. Gastroenterol Hepatol. 2009; 5 (8): p.550–552.
  8. Bassari R, Koea JB. Jaundice associated pruritis: a review of pathophysiology and treatment. World J Gastroenterol. 2015; 21 (5): p.1404-1413. doi: 10.3748/wjg.v21.i5.1404 . | Open in Read by QxMD
  9. Simerville et al.. Urinalysis: A Comprehensive Review. American Family Physician. undefined; 71 (6).
  10. Fletcher LL, Thomas DJ. The challenge of diagnosing the cause of jaundice.. Nurse Pract. 1999; 24 (10): p.98-102.