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.

Normal metabolism of bilirubin:
I
n 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).

Types of jaundice:

Hemolytic jaundice (pre-hepatic jaundice)

Pathophysiology

Increased bilirubin load for hepatocytes

Causes

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

2. Ineffective erythropoiesis

Cholestatic jaundice :

Intra-hepatic cholestasis (hepatocellular jaundice)

Pathophysiology

Failure of bile secretion

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)

Extra-hepatic cholestasis (obstructive jaundice)

Pathophysiology

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

Causes

1. Gallstones

2. Pancreatic cancer

3. Gallbladder cancer or bile duct cancer

4. Pancreatitis (acute/ chronic)

Congenital (non-hemolytic) jaundice:

Unconjugated

Pathophysiology:

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

Crigler-Najjar syndrome:

Type I: autosomal recessive→ absence of UGT-1

Type II: autosomal dominant→ decreased UGT-1

Conjugated

Pathophysiology:

Dubin-Johnson syndrome

Rotor syndrome

 

Type of Jaundice

Pre-hepatic

Causes

  • Hemolysis

  • Ineffective erythropoiesis

  • Gilbert and Crigler Najjar syndrome

Hepatic

causes 

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

  • Leptosporiosis

  • Toxoplasmosis

  • Autoimmune hepatitis

  • Cirrhosis

  • Wilson’s disease

  • Rotor and Dubin Johnson syndrome

Post-hepatic:

causes 

  • 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

Web publisher:   Adel Yasky

                          Bayan Alzomaili

 

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

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