2. Contents of the topic
Definition
Classification
Signs and symptoms
Diagnosis
Pathophysiology
Prevention
Treatment
3. Definition :
Jaundice, as in the French jaune, refers to the yellow
discoloration of the skin.
Also known as Icterus
Jaundice is a liver disease characterized by elevated
levels of bilirubin in the blood termed as
hyperbilirubinaemia.
Normal range of serum bilirubin concentration is 0.31.3mg/dl
Jaundice occurs when bilirubin levels exceeds 2mg/dl
4. Introduction to Bilirubin :
Bilirubin is a orange-yellow pigment formed in the liver
by the breakdown of hemoglobin and excreted in bile.
Two types of bilirubin :
Conjugated and Unconjugated bilirubin
Sources of Bilirubin :
• Catabolism of heme of hemoglobin (80-85%)
• Non-hemoglobin heme containing pigments such as
myoglobin, catalase and cytochromes
5. Conjugated Bilirubin
Unconjugated Bilirubin
Water soluble
Water Insoluble
It reacts quickly to produce
azobilirubin
It reacts slowly to produce
azobilirubin
It produces azobilirubin only in
the presence of dye
It produces azobilirubin in the
absence of dye
Known by Direct bilirubin
Known by Indirect bilirubin
8. Types of Jaundice
Prehepatic Jaundice
Intrahepatic jaundice
Post hepatic Jaundice
9.
10. Type of Jaundice
Pre-Hepatic
Intra-hepatic
Post-Hepatic
Other Name
Hemolytic
jaundice
Hepatocellular
Jaundice
Obstructive/
Regurgitation
Jaundice
Cause
Increased
hemolysis of
erythrocytes
Examples
Malaria, sickle cell
anemia,
incompatible
blood transfusion
Dysfunction of liver Obstruction of bile
due to damage to duct – prevents the
parenchymal cells passage of bile into
intestine
Viral
infection(hepatitis),
poisons and
toxins(chloroform,
carbon
tetrachloride,
phosphorus),
cirrhosis
Gallstones, cancer
of pancreas, gall
bladder and bile
duct
16. Etiopathogenesis
1.
2.
3.
4.
5.
Increased bilirubin
production
Reduced bilirubin uptake
by hepatic cells
Disrupted intracellular
conjugation
Disrupted secretion of
bilirubin into bile
canaliculi
Intra/extra-hepatic bile
duct obstruction
Lead to increases in
free (unconj.) bilirubin
Result in rise in conj.
bilirubin levels
17. 1. INCREASED BILIRUBIN PRODUCTION
(unconj. Hyperbilirubinemia)
Hemolysis
Increased destruction of RBCs
eg sickle cell anemia, thalassemia
Drastic increase in the amount of bilirubin produced
Unconj. bilirubin levels rise due to liver’s inability to catch up to the
increased rate of RBC destruction
Prolonged hemolysis may lead to precipitation of bilirubin salts in the
gall bladder and biliary network - result in formation of gallstones and
conditions such as cholecystitis and biliary obstruction
Other
Degradation of Hb originating from areas of tissue infarctions and
hematomas
Ineffective erythropoiesis
18. 2. DECREASED HEPATIC UPTAKE
(unconj. Hyperbilirubinemia)
Several drugs have been reported to inhibit
bilirubin uptake by the liver
e.g. novobiocin, flavopiridol
Hepatic cell
Plasma
Alb
Bile
B
B + GST
Alb
B :GST
B + UDPGA
CB
UGT1A1
sER
MRP2
19. 3) DISRUPTED INTRACELLULAR
CONJUGATION
(unconj. Hyperbilirubinemia)
Neonatal jaundice
occurs in 50% of newborns
fetal bilirubin is eliminated by mother’s liver
causes:
hepatic mechanisms are not fully developed resulting in
decreased ability to conjugate bilirubin
rate of bilirubin production is increased due to shorter
lifespan of RBCs
Acquired disorders
hepatitis, cirrhosis
impaired liver function
20.
21. Crigler-Najjar Syndrome, Type I (CN-I)
recessive allele; mutation-induced loss of
conjugating ability in the critical enzyme
glucuronosyltransferase
CN-II greatly reduced but detectable
glucuronosyltransferase activity due to mutation
(predominantly recessive); enzymatic activity can be
induced by drugs
Gilbert’s Syndrome
glucuronosyl transferase activity reduced to 1030% of normal; also accompanied by defective
bilirubin uptake mechanism
22. 4) DISRUPTED SECRETION OF BILIRUBIN INTO BILE
CANALICULI
(conj. Hyperbilirubinemia)
Dubin–Johnson Syndrome
mild conj. hyperbilirubinemia, but can increase with concurrent illness,
pregnancy, and use of oral contraceptives; otherwise asymptomatic
Inability of hepatocytes to secrete CB after it has formed
Due to mutation in the MRP2 gene (autosomal recessive trait)
Rotor Syndrome
Autosomal recessive condition characterized by increased total bilirubin
levels due to a rise in CB
Caused by a defect in transport of bilirubin into bile
23.
24. 5) Intra/extra-hepatic bile duct obstruction
Intra-hepatic
Obstruction of bile canaliculi, bile ductules or hepatic ducts
Extra-hepatic
Obstruction of cystic duct or common bile duct
Cholecystitis
Obstruction causes backup and reabsorption of CB which
results in increased blood levels of CB
25. Signs and Symptoms
Skin and sclerae - yellow
Stool - light colour, clay coloured
Dark urine
Pain in abdomen
Itching
Trouble with sleeping
Fatigue
Swelling
Ascites
Mental confusion
Coma
Bleeding
26. Diagnosis
Medical history and examination
Urine test
Liver function and blood tests
Imaging tests
Liver biopsy
27. Medical history and physical examination
Patient interview for
-
abdominal pain, itchy skin or weight loss
malaria or hepatitis A
change of colour in your urine and stools
history of prolonged alcohol misuse
Flu like symptoms
Medications
Occupation
Physical examination :
-
Yellowish discoloration of eye and skin
Swelling of legs, ankle and feet
Hepatomegaly
28. Urine test :
- to measure levels of a substance called urobilinogen
- more than normal urobilinogen levels : Pre and Intra hepatic
jaundice
- Less than normal urobilinogen level : Post hepatic jaundice
Liver function and blood tests :
Damage to liver releases liver enzymes like SGPT, SGOT and ALP
and proteins, this indicates
- Hepatitis
- Alcoholic liver disease
- cirrhosis
29. Imaging tests
- CT Scan
- MRI Scan
- Ultrasound Scan
- Endoscopic retrograde cholangiopancreatography (ERCP)
Used to check for abnormalities inside the liver or bile duct
systems.
Liver biopsy
Used to diagnosis Cirrhosis and liver cancer.
30.
31. Jaundice treatment
The treatment given to someone with jaundice will depend on what
type they have, how serious it is and what caused it.
It may include tackling an underlying condition such as malaria
and bothersome symptoms, such as itching.
For genetic conditions that don't get better, like sickle cell anaemia,
a blood transfusion may be given to replenish red blood cells in the
body.
If the bile duct system is blocked, an operation may be needed to
unblock it. During these procedures measures may be taken to
help prevent further problems, such as removal of the gallbladder.
If the liver is found to be seriously damaged, a transplant may be
an option
32. Treatment & Therapeutic Considerations
PHOTOTHERAPY
Through absorption of the wavelengths at the blue end of the spectrum
(blue, green and white light), bilirubin is converted into water-soluble
photoisomers. This transformation enhances the molecule’s excretion
into bile without conjugation.
33. PHENOBARBITAL
This drug is not approved by FDA for use in neither adult nor
pediatric hyperbilirubinemia patients, due to possibility of significant
systemic side-effects.
Exact pathway is not known, but it is believed to act as an inducing
agent on UDP-glucuronosyl transferase, thereby improving conjugation
of bilirubin and its excretion.
ALBUMIN
A 25% infusion can be used in treating hyperbilirubinemia (esp. due to
hemolytic disease).
It is used in conjunction with exchange transfusion to bind bilirubin,
enhancing its removal.
34. CLOFIBRATE (ATROMID-S)
This drug has been shown to reduce bilirubin levels via an unknown
mechanism.
Clofibrate is also associated with increased risk of developing
cholelithiasis, cholecystitis, as well as functional liver abnormalities,
which can worsen hyperbilirubinemia.
PERCUTANEOUS TRANSHEPATIC CHOLANGIOGRAPHY
Allows extraction of stones and thus removal of the source of
obstruction when present.
35. Prevention of Jaundice :
• Limit alcohol intake to not more than two drinks a day for
men or one drink a day for women.
• Avoid exposure to industrial chemicals.
• Do not use illegal drugs.
• Do not share needles or nasal snorting equipment.
• Vaccination : Hepatitis A and Hepatitis B
• Maintain healthy body weight.
