Jaundice
• Definitions:
o Jaundice (icterus):
§ Refers to the yellow coloring of the skin and sclerae due to elevated levels of bilirubin
in plasma.
§ It is detectable clinically when serum bilirubin is >3 mg/dL.
o Bilirubin:
§ An orange-yellow pigment formed in the liver by the breakdown of hemoglobin and
excreted in bile.
• Normal metabolism of bilirubin: Figure 1:Jaundice.

o In the spleen:
§ RBCs are broken down (by macrophages) into Heme & globin.
ü Globin is converted to à amino acids.
ü Heme is further broken down into:
Ø Iron à recirculates to bone marrow.
Ø Unconjugated bilirubin (water insoluble) à binds to albumin & travels to the liver.
o In the liver:
§ Unconjugated bilirubin + glucuronic acid à conjugated
bilirubin (glucuronides) à excreted via bile into
duodenum.
o In the intestines:
§ Bilirubin converted to à stercobilinogin & stercobilin
(brownish color of stool)
§ Stercobilinogin & stercobilin are partly reabsorbed and
execreted in urine as urobilinogen & urobilin (yellowish
color of the urine).

Figure 2:Normal Metabolism of Bilirubin.

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• Types of jaundice:

Hemolytic Cholestatic jaundice Congenital (non-hemolytic) jaundice

jaundice (pre- Intra-hepatic Extra-hepatic Unconjugated Conjugated
hepatic cholestasis cholestasis
jaundice) (hepatocellular (obstructive
jaundice) jaundice)
Pathophysiology Increased Failure of bile Obstruction of Gilbert’s syndrome: reduced Syndromes:
bilirubin load secretion bile flow at activity levels of UDP- Dubin-
for hepatocytes any point in glucuronosyl transferase (UGT- Johnson
the biliary 1) due to a gene mutation. syndrome
tract distal to Crigler-Najjar syndrome: Rotor
bile canaliculi Type I: autosomal recessive→ syndrome
absence of UGT-1
Type II: autosomal dominant→
decreased UGT-1

Causes 1. Hemolysis: 1. Hepatitis viruses 1. Gallstones Syndromes: * Syndromes: *

Hemolytic (A, B, C, E, EBV, 2. Pancreatic Gilbert’s syndrome Dubin-
anemia caused cytomegalovirus, cancer Crigler-Najjar syndrome Johnson
by: genetics, HSV) 3. Gallbladder syndrome
immune 2. Leptospirosis/ cancer or bile Rotor
disorders, toxoplasmosis duct cancer syndrome
infections, 3. Liver cancer 4. Pancreatitis
hypersplenism, 4. Liver damage or (acute/
and reaction to liver cirrhosis of any chronic)
drugs or blood cause (e.g. drugs*,
transfusion. alcohol)
2. Ineffective
erythropoiesis

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Type of Jaundice Causes Drugs

Pre-hepatic o Hemolysis ____________________
o Ineffective erythropoiesis
o Gilbert and Crigler Najjar
syndrome
Hepatic o Viruses: Hep A,B,C,E, EBV,HSV, o Isoniazid
VZV, and CMV o Paracetamol toxicity
o Leptosporiosis
o Toxoplasmosis
o Autoimmune hepatitis
o Cirrhosis
o Wilson’s disease
o Rotor and Dubin Johnson
syndrome
Post-hepatic o Intrahepatic: o Oral contraceptive pills
ü Primary biliary cirrhosis o Steroids
ü Primary sclerosing
cholangitis
ü Cholangiocarcinoma
o Extrahepatic:
ü Head of pancreas
carcinoma
ü Gallstones

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

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o Crigler-Najjar syndrome:
§ Very rare.
§ Only effective treatment is: Liver transplantation.
o Prognosis of Dubin-Johnson syndrome and Rotor syndrome is good.

Jaundice

Normal urine & Dark urine & pale

normal stool stool

Measure conjugated
and unconjugated Liver ultrasound No dilated ducts
bilirubin +
reticulocyte count+
Liver function tests
(usually normal)

viral hepatitis, drugs,

Dilated ducts toxins, infiltrative
disease
Specialized
investigations

gallstones,bile duct Autoantibodies,

stricture, pancreatic immunoglobulins and
carcinoma etc. hepatitis serology.

Liver biopsy

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%20M
edicine%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.
Format Editor: Roaa Amer. Lama AlLuhidan.
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