Jaundice
Study guide:
Definition:
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Jaundice (icterus):
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Refers to the yellow coloring of the skin and sclera due to elevated levels of bilirubin in plasma.
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It is detectable clinically when serum bilirubin is >3 mg/dL.
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Bilirubin:
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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:
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RBCs are broken down (by macrophages) into Heme & globin.
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Globin is converted to → amino acids.
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Heme is further broken down into:
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Iron → recirculates to bone marrow.
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Unconjugated bilirubin (water insoluble) → binds to albumin & travels to the liver.
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In the liver:
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Unconjugated bilirubin + glucuronic acid → conjugated bilirubin (glucuronides) → excreted via bile into duodenum.
In the intestines:
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Bilirubin converted to → stercobilinogin & stercobilin (brownish color of stool)
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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)
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
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Hemolysis
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Ineffective erythropoiesis
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Gilbert and Crigler Najjar syndrome
Hepatic
causes
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Viruses: Hep A,B,C,E, EBV,HSV, VZV, and CMV
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Leptosporiosis
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Toxoplasmosis
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Autoimmune hepatitis
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Cirrhosis
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Wilson’s disease
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Rotor and Dubin Johnson syndrome
Post-hepatic:
causes
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Intrahepatic:
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Primary biliary cirrhosis
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Primary sclerosing cholangitis
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Cholangiocarcinoma
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Extrahepatic:
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Head of pancreas carcinoma
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Gallstones
Notes:
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Drugs that can cause jaundice are Isoniazid, paracetamol excess, chlorpromazine and drugs that cause cholestasis.
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Gilbert’s syndrome is the most common familial hyperbilirubinaemia:
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Features: Asymptomatic, is usually detected incidentally, & treatment is not necessary.
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Lab workup: normal LFTs, slightly raised unconjugated bilirubin (1-6 mg/dL).
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Crigler-Najjar syndrome:
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Very rare.
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Only effective treatment is: Liver transplantation.
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Prognosis of Dubin-Johnson syndrome and Rotor syndrome is good.

References:
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Hoffbrand A, Moss P, Pettit J. Essential haematology. Malden, Mass.: Wiley-Blackwell; 2011.
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Collins P, Fox C. Gastroenterology. Edinburgh: Mosby; 2008.
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Kumar P, Clark M. Kumar & Clark's clinical medicine.
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1. Agabegi S, Agabegi E, Ring A. Step-up to medicine. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins; 2013.
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Walker B, Colledge N, Ralston S, Penman I. Davidson's principles and practice of medicine.
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Rahatdawakhana.com. Kidney Stone Treatment [Internet]. 2015 [cited 12 December 2015]. Available from: http://rahatdawakhana.com/jaundice.php (Figure1).
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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).
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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