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Jaundice

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Definition:​

  • Jaundice (icterus):

    • Refers to the yellow coloring of the skin and sclera due to elevated levels of bilirubin in plasma.

    • It is detectable clinically when serum bilirubin is >3 mg/dL.

  • Bilirubin:

    • An orange-yellow pigment formed in the liver by the breakdown of hemoglobin and excreted in bile.

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Normal metabolism of bilirubin:
In the spleen:

  • RBCs are broken down (by macrophages) into Heme & globin.

    • Globin is converted to → amino acids.

    • Heme is further broken down into:

      • Iron → recirculates to bone marrow.

      • Unconjugated bilirubin (water insoluble) → binds to albumin & travels to the liver.

In the liver:         

  • Unconjugated bilirubin + glucuronic acid → conjugated bilirubin (glucuronides) → excreted via bile into duodenum.

In the intestines:

  • Bilirubin converted to → stercobilinogin & stercobilin (brownish color of stool)

    • Stercobilinogin & stercobilin are partly reabsorbed and execreted in urine as urobilinogen & urobilin (yellowish color of the urine).

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Types of jaundice:

Hemolytic jaundice (pre-hepatic jaundice)

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Pathophysiology

Increased bilirubin load for hepatocytes

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Causes

1. Hemolysis: Hemolytic anemia caused by: genetics, immune disorders, infections, hypersplenism, and reaction to drugs or blood transfusion.

2. Ineffective erythropoiesis

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Cholestatic jaundice :

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Intra-hepatic cholestasis (hepatocellular jaundice)

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Pathophysiology

Failure of bile secretion

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Causes

1. Hepatitis viruses (A, B, C, E, EBV, cytomegalovirus, HSV)

2. Leptospirosis/ toxoplasmosis

3. Liver cancer

4. Liver damage or liver cirrhosis of any cause (e.g. drugs*, alcohol)

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Extra-hepatic cholestasis (obstructive jaundice)

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Pathophysiology

Obstruction of bile flow at any point in the biliary tract distal to bile canaliculi

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Causes

1. Gallstones

2. Pancreatic cancer

3. Gallbladder cancer or bile duct cancer

4. Pancreatitis (acute/ chronic)

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Congenital (non-hemolytic) jaundice:

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Unconjugated

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Pathophysiology:

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Gilbert’s syndrome: reduced activity levels of UDP-glucuronosyl transferase (UGT-1) due to a gene mutation.

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Crigler-Najjar syndrome:

Type I: autosomal recessive→ absence of UGT-1

Type II: autosomal dominant→ decreased UGT-1

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Conjugated

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Pathophysiology:

Dubin-Johnson syndrome

Rotor syndrome

 

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Type of Jaundice

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Pre-hepatic

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Causes

  • Hemolysis

  • Ineffective erythropoiesis

  • Gilbert and Crigler Najjar syndrome

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Hepatic

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causes 

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  • Viruses: Hep A,B,C,E, EBV,HSV, VZV, and CMV

  • Leptosporiosis

  • Toxoplasmosis

  • Autoimmune hepatitis

  • Cirrhosis

  • Wilson’s disease

  • Rotor and Dubin Johnson syndrome

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Post-hepatic:

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causes 

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  • Intrahepatic:

  • Primary biliary cirrhosis

  • Primary sclerosing cholangitis

  • Cholangiocarcinoma

  • Extrahepatic:

  • Head of pancreas carcinoma

  • Gallstones 

Notes:

  • Drugs that can cause jaundice are Isoniazid, paracetamol excess, chlorpromazine and drugs that cause cholestasis.

  • Gilbert’s syndrome is the most common familial hyperbilirubinaemia:

    • Features: Asymptomatic, is usually detected incidentally, & treatment is not necessary. 

    • Lab workup: normal LFTs, slightly raised unconjugated bilirubin (1-6 mg/dL).

  • Crigler-Najjar syndrome:

    • Very rare.

    • Only effective treatment is: Liver transplantation.

  • Prognosis of Dubin-Johnson syndrome and Rotor syndrome is good. 

References:

  1. Hoffbrand A, Moss P, Pettit J. Essential haematology. Malden, Mass.: Wiley-Blackwell; 2011.

  2. Collins P, Fox C. Gastroenterology. Edinburgh: Mosby; 2008.

  3. Kumar P, Clark M. Kumar & Clark's clinical medicine.

  4. 1. Agabegi S, Agabegi E, Ring A. Step-up to medicine. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins; 2013.

  5. Walker B, Colledge N, Ralston S, Penman I. Davidson's principles and practice of medicine.

  6. Rahatdawakhana.com. Kidney Stone Treatment [Internet]. 2015 [cited 12 December 2015]. Available from: http://rahatdawakhana.com/jaundice.php (Figure1).

  7. Ole.bris.ac.uk. Part 1 - Bilirubin Metabolism [Internet]. 2015 [cited 12 December 2015]. Available from: https://www.ole.bris.ac.uk/bbcswebdav/institution/Faculty%20of%20Health%20Sciences/MB%20ChB/Hippocrates%20Year%203%20Medicine%20and%20Surgery/Abdomen%20-%20Jaundice%20core%20topic/part_1__bilirubin_metabolism.html (Figure2).

  8. Web.b.ebscohost.com. Jaundice: DynaMed [Internet]. 2016 [cited 1 February 2016]. Available from: http://web.b.ebscohost.com/dynamed/detail?vid=3&sid=8f8518dd-d58e-4ff3-b223-73786a0bff57%40sessionmgr112&hid=102&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d

 

 

Written by:         Haifa Al-Issa.


Reviewed by:      Roaa Amer
                          Lama Al Luhidan

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Web publisher:   Adel Yasky

                          Bayan Alzomaili

 

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Audio recording:
- Read by: Bayan Alzomaili
- Audio production: Bayan Alzomaili

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