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Pathophysiology of Jaundice
by
Dr.Rahul
M.D Final Year
Department Of Physiology
SMS Medical College ,Jaipur
Introduction….
Jaundice (french: Jaune-Yellow) or icterus
Is a yellowish discolouration of tissue resulting
from the deposition of bilirubin .
Tissue deposition of bilirubin occurs only in the
presence of serum hyperbilirubinemia is a sign of
either liver disease or a hemolytic disease.
( Reference : Harrisons textbook of medicine/16th ed/vol.1 /238-240)
Carotenemia and use of the drug Quinacrine are few other
causes of yellow coloration of tissue .
Carotenemia can be distinguished from jaundice by sparing
of sclera.
In 4-37% patients treated with Quinacrine , yellowish
discolouration of skin is seen .
Unlike carotenemia ;quinacrine can cause discolouration of
sclera.
Slight increase in serum bilirubin are best detected by
examining the Sclera as sclera is rich in elastin and the
bilirubin has high affinity for the elastin .
The normal plasma concentration of bilirubin is less
than 21 μmol/L (1.2 mg/dL).
The presence of scleral icterus indicates a serum
bilirubin of atleast 3.0 mg/dl.
(Reference: Harrisons textbook of medicine/16thed/vol.1 /238-240)
Under steady state normal metabolic conditions
about 3.9 mg/kg or 250 to 350 mg of bilirubin is
produced each day from breakdown of Haem from
RBC in spleen and liver.
1gm of hemoglobin yields 36.2 mg of bilirubin .
Reference :API textbook of Medicine/7th ed/page-580.
Jaundice DR RAHUL PHYSIOLOGY SMS MC JAIPUR mobile no-8764324067
The breakdown of haeme produces bilirubin (an
insoluble waste product) Bilirubin must be made water
soluble to be excreted. This transformation can be
studied in 5 broad steps;-
1. Heme degradation & Formation of bilirubin
2. Plasma transport
3. Liver uptake & Conjugation
4. excretion of bilirubin
5. Formation and excretion of urobilinogen
Reference : Bilirubin metabolism: Applied physiology : X. Wang et al: Current
Paediatrics (2006) 16, 70–74
Heme degradation & Formation of bilirubin
Reference: Harrison’s Internal Medicine/17thed/fig:297-1:
Hepatocellular bilirubin transport : Albumin-bound bilirubin in sinusoidal blood passes
through endothelial cell fenestrae to reach the hepatocyte surface, entering the cell by both
facilitated and simple diffusional processes. Within the cell it is bound to glutathione-S-transferases
and conjugated by bilirubin-UDP-glucuronosyltransferase (UGT1A1) to mono- and diglucuronides,
which are actively transported across the canalicular membrane into the bile
ABBREVIATIONS :
ALB: albumin
UCB :unconjugated bilirubin
UGT1A1: bilirubin-UDP
glucuronosyltransferase
BMG: bilirubin monoglucuronide
GST: glutathione-S-transferase
MRP2: multidrug resistance–
associated protein 2
BDG : bilirubin diglucuronide
BT :proposed bilirubin transporter
BILIRUBIN IN THE GUT
A recap on catabolism of hemoglobin …
Van Den Berg test
It is helpful in determining the type of bilirubin present in
serum.
normal serum gives a negative van den berg test.
When diazo reagent is added to serum containing
conjugated bilirubin (water soluble) a purple coloration is
obtained within 30 seconds .This is called Direct positive
van den berg reaction.
It is performed using the diazo reagent (mixture of
sulphanilic acid , hydrochloric acid and sodium nitrite).
When diazo reagent is added to serum containing
mainly unconjugated biluruibin (water insoluble ), no
colour is obtained but with addition of solvent like
alcohol , purple colouration is obtained .This is
Indirect positive van den berg reaction .
If the serum contains both unconjugated and
conjugated bilirubin in high concentration the
purple color is produced immediately (direct
positive) which is further intensified by the
addition of alcohol (indirect positive).
This type of reaction is known as biphasic.
Reference for van den berg test : Biochemistry : U.Satyanarayan
:Elseveir: 4rth ed:chap 20/Pg 455
1. Hemolytic (Prehepatic) :
Intracorpuscular Defects:
- Hereditary spherocytosis
- Hemoglobinopathies : sickle cell anemia, β-thalassemia
Extra-corpuscular defects :
- Infections: Malaria
- Drugs : quinine ,sulphonamides
- Burns
- Poisons : snake venom
- Mismatched blood transfusion
ETIOLOGICAL CLASSIFICATION OF JAUNDICE
2. Hepatocellular (Hepatic ) :
a. Infections: viral hepatitis , malaria , typhoid ,septecemia
b. Toxic :
- Anaesthetic agents : Halothane , Chloroform
- Antitubercular drugs: Rifampicin ,Isoniazid ,P.A.S
- Metals : Arsenic ,Mercury ,Gold
c. Cirrhosis: 1. Portal 2. billiary .
3. Obstructive jaundice (post hepatic)
stones , stricture , parasites , ca head of pancreas ,
congenital biliary atresia
4. Congenital Hyperbilirubinemia :
A. Unconjugated :
1. Disturbance of bilirubin transport : Gilbert syndrome
2. Disturbance of bilirubin conjugation: Crigler Najjar
Syndrome.
B. Conjugated :
Distrubance in excretion of Bilirubin : Dubin Johnson
syndrome , Rotor’s Syndrome
Reference: Practical Medicine : P.J .Mehta /16th ed/18-19
Van den
berg test
Indirect positive
reaction
Biphasic reaction Direct positive
reaction
Mechanism
of Production
Excessive
breakdown of RBCs
producing
unconjugated
bilirubin in the
amounts more than
the healthy liver can
conjugate and
excrete.
Inability of liver to
efficiently
conjugate and
transport bilirubin
into the bile due to
liver cell damage .
Obstruction of the bile
ducts so conjugated
bilirubin can’t flow
through the biliary
tract freely resulting in
increased serum
conjugated bilirubin.
Type of
serum
bilirubin
accumulated
unconjugated
hyperbilirubenemia.
Both unconjugated
& conjugated
bilirubin is
increased in serum
conjugated
hyperbilirubenemia.
Hemolytic Jaundice
(Prehepatic)
Hepatic Jaundice Obstructive Jaundice
(Post hepatic)
Urine
urobilinogen
Increases
(liver excrete lot of
conjugated bilirubin in the
intestine with the bile so
more urobilinogen is
formed part of it is
reabsorbed and goes to
general circulation thus
urine urobilinogen is
increased.)
Decreases
(Damaged liver
cells produce &
excrete less of
conjugated
bilirubin so less
urobilinogen is
formed.)
Markedly
decreased/absent
(due to
obstruction,
conjugated
bilirubin is not
released into the
intestine thus no
urobilinogen is
formed.
Hemolytic Jaundice
(Prehepatic)
Hepatic Jaundice Obstructive
Jaundice
(Post hepatic)
Urine
Bilirubin
Absent
(Unconjugated bilirubin is
water insoluble
transported in plasma in
bound form with albumin
.Since albumin is not
filtered in urine
,unconjugated is too not
filtered into urine so this
is called Acholuric
Jaundice.)
Present
(conjugated
bilirubin is water
soluble and
present in plasma
in dissolved form
and gets filtered
in urine , such
jaundice is
called choluric
jaundice)
Present
(Since
conjugated
bilirubin is
filtered in urine)
Hemolytic
Jaundice
(Pre hepatic)
Hepatic
Jaundice
Obstructive
Jaundice
(Post hepatic)
Faecal
Fat level
normal
(as bile is
present in gut
for normal
digestion of fat )
Increased
(bile deficiency in the
intestine so
emulsification and
absorption of fat is
inadequate thus
producing bulky ,pale
greasy and foul smelling
faeces called
steatorrhoea )
Increased
Faecal
Stercobilinogen
markedly
increased
reduced Absent
Peripheral
blood film
Anemia
,reticulocytosis
Normal Normal
Hemolytic
Jaundice
(Pre hepatic)
Hepatic
Jaundice
Obstructive
Jaundice
(Post hepatic)
Serum
alkaline
phosphatase
normal
Because
excreted in bile
increased
Because less excretion
in bile
markedly
increased
Because not
excreted in bile
Plasma
albumin,
globulin and
A/G Ratio
normal albumin is decreased
due to less synthesis by
damaged .
Globulin increases
A/G Ratio decreases
Normal
Liver function
tests
normal
As liver is
healthy
Impaired
As liver is damaged
normal or
mildly impaired
Clinical
characterstics
Hemolytic
Jaundice
(Pre hepatic)
Hepatic
Jaundice
Obstructive
Jaundice
(Post hepatic)
Pruritis Absent Transient Marked
Tender Liver Absent May be present Absent
Spleen Present may be present Absent
Gall bladder Not Palpable Not Palpable May be Palpable
Urine colour Normal Deep yellow Deep yellow
stool colour Dark brown
coloured stool
Pale faeces Clay coloured
stool
Reference :PJ Mehta : Practical Medicine :16th ed : Page 20 & Indu
Khurana :Textbook of Physiology :Table 3.2-3 Page.161.
FIG.20.1 (A) Normal Bilirubin Metabolism (B) alterations in bilirubin
metabolism along with enzymes in 3 types of jaundice.
Note: RED-changes in hemolytic jaundice . Green – changes in hepatic
jaundice . Blue – changes in obstructive jaundice
Reference : Biochemistry :U.Satyanarayan:fig.20.1/chap20/457
Crigler-Najjar Syndrome (Type I)
Is a rare genetic disorder and is caused by complete
absence of UDP-glucuronyltransferase (UGT1A1)
It is inherited as an autosomal recessive trait.
Severe hyperbilirubenemia develops within the first 72
hours of life.
Serum bilirubin levels are >30 mg/dl resulting into
kernicterus .
Management is by repeated exchange transfusion
and phototherapy to keep the serum bilirubin <20
mg/dl .
There is no response to the treatment of
phenobarbitone
Liver transplantation is an efficacious therapy and it
requires life-long immune suppression .
Reference :Ghai essential pediatrics/6th ed/170-73
Crigler-Najjar Syndrome (Type II)
Is a rare autosomal dominant disorder.
It is characterized by partial deficiency of UDP-
glucuronyltransferase.
Unconjugated bilirubin is usually < 20 mg/dl.
Unlike Crigler-Najjar Type I, Type II responds
dramatically to Phenobarbital & a normal life can be
expected.
Jaundice DR RAHUL PHYSIOLOGY SMS MC JAIPUR mobile no-8764324067
Is benign, often familial condition characterized by recurrent
but asymptomatic mild unconjugated hyperbilirubinemia in the
absence of haemolysis or underlying liver disease.
If, it becomes apparent, it is not until adolescence and then
usually in association with stress such as intercurrent illness,
fasting or strenuous exercise.
There is decreased level of UDP Glucuronosyl transferase,
also there is evidence for a defect in hepatic uptake of bilirubin
Gilbert syndrome
Hyperbilirubinemia is mild .Serum bilirubin concentrations <3
mg/dL although both higher and lower values are frequent.
Diagnosis of Gilbert syndrome can be made in the
presence of :
1.Unconjugated hyperbilirubinemia noted on several occasions
2.Normal results on CBC, reticulocyte count, and blood smear
3.Normal liver function test results; and absence of other
disease processes.
Reference: A case report of Gilbert Syndrome:Manandhar SR:Kathmandu
University Medical Journal (2003) Vol. 1, No. 3, 187-189
Dubin Johnson Syndrome
Autosomal recessive
Defective excretion of conjugated bilirubin
Conjugated bilirubin in blood is increased
Mutation in MRP-2 protein responsible for transport
of conjugated bilirubin in bile.
Bilirubin deposits in liver and liver appears black
The condition is referred to as Black liver jaundice.
Reference:Textbook of Biochemistry:D.M Vasudevan:7th ed:Page279-280
Rotor Syndrome
Similar condition but the exact defect is not identified
Bilirubin excretion is defective
No staining of liver
Autosomal recessive
Reference:Textbook of Biochemistry:D.M Vasudevan:7th ed:Page279-280
Jaundice DR RAHUL PHYSIOLOGY SMS MC JAIPUR mobile no-8764324067
Summarize Congenital Hyperbilirubinemia …
Physiological jaundice of new born
Appears after 24 hours
Maximum intensity by 4th-5th day in term & 7th
day in preterm
Serum level less than 15 mg / dl
Clinically not detectable after 14 days
Note: Baby should, however, be watched for
worsening jaundice.
1.Excessive destruction of RBC occurs in first few days after
birth causing increase in serum bilirubin.
Mechanism of production of Physiological Jaundice
2. Hepatic immaturity in first few (7-10 ) days after birth also
contributes to increased serum bilirubin .
In the fetus bilirubin produced is cleared by the placenta
and eliminated by the maternal liver.
 Immediately after birth, the neonatal liver must assume
responsibility for bilirubin clearance and excretion but it
takes 7-10 days to mature.
 Levels of UGT1A1 are low, and alternative excretory
pathways allow passage of unconjugated bilirubin into the
gut.
The intestinal flora that convert bilirubin to urobilinogen are
also undeveloped, an enterohepatic circulation of
unconjugated bilirubin ensues.
As a consequence, most neonates develop mild
unconjugated hyperbilirubinemia .
Reference: Harrison's Internal Medicine /17th ed/Chapter 297 and Ghai essential
pediatrics/6th ed/170-71 and Indu Khurana Textbook of Physiology /section 3/162
It is presumed to be due to inhibitory substances in the
breastmilk that interfere with bilirubin conjugation like
preganaediol and free fatty acids.
Breastmilk Jaundice
Reference: Ghai essential pediatrics/6th ed/170-71
Temporary interruption of breastmilk feed reduces the
serum levels of bilirubin.
A bilirubin level of over 20 mg/dl may be attained.
Few babies exclusive breast feed develop jaundice in 2nd
week of life and may continue in 3rd month.
Pathological jaundice in newborns
Appears within 24 hours of age
 Increase of bilirubin > 5 mg / dl /24 hrs
 Total Serum bilirubin > 15 mg /dl
Direct bilirubin > 2 mg /dl
Reference: Ghai essential pediatrics/6th ed/170-71
Increased production
1.Fetomaternal blood group incompatibility :Rh ,ABO
2.Hereditary spherocytosis
3.G6PD deficiency , vitamin K induced hemolysis
4.Sepsis
5.Increased enterohepatic circulation : pyloric stenosis or
large bowel obstruction
Decreased clearance
Criggler-najjar syndrome type I and II
Causes of unconjugated hyperbilirubinemia
Reference: Ghai essential pediatrics/6th ed/170-71
This condition results from incompatibility betweeen
maternal and fetal blood groups.
Rh+ve fetus may produce antibodies in Rh -ve mother
In Rh incompatibility first child often escapes and
subsequent child would be affected .
Sometime the child is born with severe hemolytic disease
often referred to as erythroblastosis foetalis.
When blood level is more than 20 mg/dl the capacity of
albumin to bind bilirubin is exceded.
Hemolytic Jaundice in Newborn
In young children before the age of 1 year the blood brain
barrier is not fully matured and free bilirubin enters the
brain(kernicterus) deposited in brain leading to convulsions
, toxic encephalitis and spasticity.
Treatment :
 Exchange transfusion along with phototherapy and
barbiturates.
Phototherapy with blue light(440nm) isomerise insoluble
bilirubin to soluble isomers,can be excreted through urine
without conjugation.
THANK YOU FOR YOUR ATTENTION!!
AND HAVE A PLEASANT DAY!!
Jaundice DR RAHUL PHYSIOLOGY SMS MC JAIPUR mobile no-8764324067

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Jaundice DR RAHUL PHYSIOLOGY SMS MC JAIPUR mobile no-8764324067

  • 1. Pathophysiology of Jaundice by Dr.Rahul M.D Final Year Department Of Physiology SMS Medical College ,Jaipur
  • 2. Introduction…. Jaundice (french: Jaune-Yellow) or icterus Is a yellowish discolouration of tissue resulting from the deposition of bilirubin . Tissue deposition of bilirubin occurs only in the presence of serum hyperbilirubinemia is a sign of either liver disease or a hemolytic disease. ( Reference : Harrisons textbook of medicine/16th ed/vol.1 /238-240)
  • 3. Carotenemia and use of the drug Quinacrine are few other causes of yellow coloration of tissue . Carotenemia can be distinguished from jaundice by sparing of sclera. In 4-37% patients treated with Quinacrine , yellowish discolouration of skin is seen . Unlike carotenemia ;quinacrine can cause discolouration of sclera.
  • 4. Slight increase in serum bilirubin are best detected by examining the Sclera as sclera is rich in elastin and the bilirubin has high affinity for the elastin . The normal plasma concentration of bilirubin is less than 21 μmol/L (1.2 mg/dL). The presence of scleral icterus indicates a serum bilirubin of atleast 3.0 mg/dl. (Reference: Harrisons textbook of medicine/16thed/vol.1 /238-240)
  • 5. Under steady state normal metabolic conditions about 3.9 mg/kg or 250 to 350 mg of bilirubin is produced each day from breakdown of Haem from RBC in spleen and liver. 1gm of hemoglobin yields 36.2 mg of bilirubin . Reference :API textbook of Medicine/7th ed/page-580.
  • 7. The breakdown of haeme produces bilirubin (an insoluble waste product) Bilirubin must be made water soluble to be excreted. This transformation can be studied in 5 broad steps;- 1. Heme degradation & Formation of bilirubin 2. Plasma transport 3. Liver uptake & Conjugation 4. excretion of bilirubin 5. Formation and excretion of urobilinogen
  • 8. Reference : Bilirubin metabolism: Applied physiology : X. Wang et al: Current Paediatrics (2006) 16, 70–74 Heme degradation & Formation of bilirubin
  • 9. Reference: Harrison’s Internal Medicine/17thed/fig:297-1: Hepatocellular bilirubin transport : Albumin-bound bilirubin in sinusoidal blood passes through endothelial cell fenestrae to reach the hepatocyte surface, entering the cell by both facilitated and simple diffusional processes. Within the cell it is bound to glutathione-S-transferases and conjugated by bilirubin-UDP-glucuronosyltransferase (UGT1A1) to mono- and diglucuronides, which are actively transported across the canalicular membrane into the bile ABBREVIATIONS : ALB: albumin UCB :unconjugated bilirubin UGT1A1: bilirubin-UDP glucuronosyltransferase BMG: bilirubin monoglucuronide GST: glutathione-S-transferase MRP2: multidrug resistance– associated protein 2 BDG : bilirubin diglucuronide BT :proposed bilirubin transporter
  • 11. A recap on catabolism of hemoglobin …
  • 12. Van Den Berg test It is helpful in determining the type of bilirubin present in serum. normal serum gives a negative van den berg test. When diazo reagent is added to serum containing conjugated bilirubin (water soluble) a purple coloration is obtained within 30 seconds .This is called Direct positive van den berg reaction. It is performed using the diazo reagent (mixture of sulphanilic acid , hydrochloric acid and sodium nitrite).
  • 13. When diazo reagent is added to serum containing mainly unconjugated biluruibin (water insoluble ), no colour is obtained but with addition of solvent like alcohol , purple colouration is obtained .This is Indirect positive van den berg reaction .
  • 14. If the serum contains both unconjugated and conjugated bilirubin in high concentration the purple color is produced immediately (direct positive) which is further intensified by the addition of alcohol (indirect positive). This type of reaction is known as biphasic. Reference for van den berg test : Biochemistry : U.Satyanarayan :Elseveir: 4rth ed:chap 20/Pg 455
  • 15. 1. Hemolytic (Prehepatic) : Intracorpuscular Defects: - Hereditary spherocytosis - Hemoglobinopathies : sickle cell anemia, β-thalassemia Extra-corpuscular defects : - Infections: Malaria - Drugs : quinine ,sulphonamides - Burns - Poisons : snake venom - Mismatched blood transfusion ETIOLOGICAL CLASSIFICATION OF JAUNDICE
  • 16. 2. Hepatocellular (Hepatic ) : a. Infections: viral hepatitis , malaria , typhoid ,septecemia b. Toxic : - Anaesthetic agents : Halothane , Chloroform - Antitubercular drugs: Rifampicin ,Isoniazid ,P.A.S - Metals : Arsenic ,Mercury ,Gold c. Cirrhosis: 1. Portal 2. billiary . 3. Obstructive jaundice (post hepatic) stones , stricture , parasites , ca head of pancreas , congenital biliary atresia
  • 17. 4. Congenital Hyperbilirubinemia : A. Unconjugated : 1. Disturbance of bilirubin transport : Gilbert syndrome 2. Disturbance of bilirubin conjugation: Crigler Najjar Syndrome. B. Conjugated : Distrubance in excretion of Bilirubin : Dubin Johnson syndrome , Rotor’s Syndrome Reference: Practical Medicine : P.J .Mehta /16th ed/18-19
  • 18. Van den berg test Indirect positive reaction Biphasic reaction Direct positive reaction Mechanism of Production Excessive breakdown of RBCs producing unconjugated bilirubin in the amounts more than the healthy liver can conjugate and excrete. Inability of liver to efficiently conjugate and transport bilirubin into the bile due to liver cell damage . Obstruction of the bile ducts so conjugated bilirubin can’t flow through the biliary tract freely resulting in increased serum conjugated bilirubin. Type of serum bilirubin accumulated unconjugated hyperbilirubenemia. Both unconjugated & conjugated bilirubin is increased in serum conjugated hyperbilirubenemia. Hemolytic Jaundice (Prehepatic) Hepatic Jaundice Obstructive Jaundice (Post hepatic)
  • 19. Urine urobilinogen Increases (liver excrete lot of conjugated bilirubin in the intestine with the bile so more urobilinogen is formed part of it is reabsorbed and goes to general circulation thus urine urobilinogen is increased.) Decreases (Damaged liver cells produce & excrete less of conjugated bilirubin so less urobilinogen is formed.) Markedly decreased/absent (due to obstruction, conjugated bilirubin is not released into the intestine thus no urobilinogen is formed. Hemolytic Jaundice (Prehepatic) Hepatic Jaundice Obstructive Jaundice (Post hepatic) Urine Bilirubin Absent (Unconjugated bilirubin is water insoluble transported in plasma in bound form with albumin .Since albumin is not filtered in urine ,unconjugated is too not filtered into urine so this is called Acholuric Jaundice.) Present (conjugated bilirubin is water soluble and present in plasma in dissolved form and gets filtered in urine , such jaundice is called choluric jaundice) Present (Since conjugated bilirubin is filtered in urine)
  • 20. Hemolytic Jaundice (Pre hepatic) Hepatic Jaundice Obstructive Jaundice (Post hepatic) Faecal Fat level normal (as bile is present in gut for normal digestion of fat ) Increased (bile deficiency in the intestine so emulsification and absorption of fat is inadequate thus producing bulky ,pale greasy and foul smelling faeces called steatorrhoea ) Increased Faecal Stercobilinogen markedly increased reduced Absent Peripheral blood film Anemia ,reticulocytosis Normal Normal
  • 21. Hemolytic Jaundice (Pre hepatic) Hepatic Jaundice Obstructive Jaundice (Post hepatic) Serum alkaline phosphatase normal Because excreted in bile increased Because less excretion in bile markedly increased Because not excreted in bile Plasma albumin, globulin and A/G Ratio normal albumin is decreased due to less synthesis by damaged . Globulin increases A/G Ratio decreases Normal Liver function tests normal As liver is healthy Impaired As liver is damaged normal or mildly impaired
  • 22. Clinical characterstics Hemolytic Jaundice (Pre hepatic) Hepatic Jaundice Obstructive Jaundice (Post hepatic) Pruritis Absent Transient Marked Tender Liver Absent May be present Absent Spleen Present may be present Absent Gall bladder Not Palpable Not Palpable May be Palpable Urine colour Normal Deep yellow Deep yellow stool colour Dark brown coloured stool Pale faeces Clay coloured stool Reference :PJ Mehta : Practical Medicine :16th ed : Page 20 & Indu Khurana :Textbook of Physiology :Table 3.2-3 Page.161.
  • 23. FIG.20.1 (A) Normal Bilirubin Metabolism (B) alterations in bilirubin metabolism along with enzymes in 3 types of jaundice. Note: RED-changes in hemolytic jaundice . Green – changes in hepatic jaundice . Blue – changes in obstructive jaundice Reference : Biochemistry :U.Satyanarayan:fig.20.1/chap20/457
  • 24. Crigler-Najjar Syndrome (Type I) Is a rare genetic disorder and is caused by complete absence of UDP-glucuronyltransferase (UGT1A1) It is inherited as an autosomal recessive trait. Severe hyperbilirubenemia develops within the first 72 hours of life. Serum bilirubin levels are >30 mg/dl resulting into kernicterus .
  • 25. Management is by repeated exchange transfusion and phototherapy to keep the serum bilirubin <20 mg/dl . There is no response to the treatment of phenobarbitone Liver transplantation is an efficacious therapy and it requires life-long immune suppression . Reference :Ghai essential pediatrics/6th ed/170-73
  • 26. Crigler-Najjar Syndrome (Type II) Is a rare autosomal dominant disorder. It is characterized by partial deficiency of UDP- glucuronyltransferase. Unconjugated bilirubin is usually < 20 mg/dl. Unlike Crigler-Najjar Type I, Type II responds dramatically to Phenobarbital & a normal life can be expected.
  • 28. Is benign, often familial condition characterized by recurrent but asymptomatic mild unconjugated hyperbilirubinemia in the absence of haemolysis or underlying liver disease. If, it becomes apparent, it is not until adolescence and then usually in association with stress such as intercurrent illness, fasting or strenuous exercise. There is decreased level of UDP Glucuronosyl transferase, also there is evidence for a defect in hepatic uptake of bilirubin Gilbert syndrome
  • 29. Hyperbilirubinemia is mild .Serum bilirubin concentrations <3 mg/dL although both higher and lower values are frequent. Diagnosis of Gilbert syndrome can be made in the presence of : 1.Unconjugated hyperbilirubinemia noted on several occasions 2.Normal results on CBC, reticulocyte count, and blood smear 3.Normal liver function test results; and absence of other disease processes. Reference: A case report of Gilbert Syndrome:Manandhar SR:Kathmandu University Medical Journal (2003) Vol. 1, No. 3, 187-189
  • 30. Dubin Johnson Syndrome Autosomal recessive Defective excretion of conjugated bilirubin Conjugated bilirubin in blood is increased Mutation in MRP-2 protein responsible for transport of conjugated bilirubin in bile. Bilirubin deposits in liver and liver appears black The condition is referred to as Black liver jaundice. Reference:Textbook of Biochemistry:D.M Vasudevan:7th ed:Page279-280
  • 31. Rotor Syndrome Similar condition but the exact defect is not identified Bilirubin excretion is defective No staining of liver Autosomal recessive Reference:Textbook of Biochemistry:D.M Vasudevan:7th ed:Page279-280
  • 34. Physiological jaundice of new born Appears after 24 hours Maximum intensity by 4th-5th day in term & 7th day in preterm Serum level less than 15 mg / dl Clinically not detectable after 14 days Note: Baby should, however, be watched for worsening jaundice.
  • 35. 1.Excessive destruction of RBC occurs in first few days after birth causing increase in serum bilirubin. Mechanism of production of Physiological Jaundice 2. Hepatic immaturity in first few (7-10 ) days after birth also contributes to increased serum bilirubin . In the fetus bilirubin produced is cleared by the placenta and eliminated by the maternal liver.  Immediately after birth, the neonatal liver must assume responsibility for bilirubin clearance and excretion but it takes 7-10 days to mature.
  • 36.  Levels of UGT1A1 are low, and alternative excretory pathways allow passage of unconjugated bilirubin into the gut. The intestinal flora that convert bilirubin to urobilinogen are also undeveloped, an enterohepatic circulation of unconjugated bilirubin ensues. As a consequence, most neonates develop mild unconjugated hyperbilirubinemia . Reference: Harrison's Internal Medicine /17th ed/Chapter 297 and Ghai essential pediatrics/6th ed/170-71 and Indu Khurana Textbook of Physiology /section 3/162
  • 37. It is presumed to be due to inhibitory substances in the breastmilk that interfere with bilirubin conjugation like preganaediol and free fatty acids. Breastmilk Jaundice Reference: Ghai essential pediatrics/6th ed/170-71 Temporary interruption of breastmilk feed reduces the serum levels of bilirubin. A bilirubin level of over 20 mg/dl may be attained. Few babies exclusive breast feed develop jaundice in 2nd week of life and may continue in 3rd month.
  • 38. Pathological jaundice in newborns Appears within 24 hours of age  Increase of bilirubin > 5 mg / dl /24 hrs  Total Serum bilirubin > 15 mg /dl Direct bilirubin > 2 mg /dl Reference: Ghai essential pediatrics/6th ed/170-71
  • 39. Increased production 1.Fetomaternal blood group incompatibility :Rh ,ABO 2.Hereditary spherocytosis 3.G6PD deficiency , vitamin K induced hemolysis 4.Sepsis 5.Increased enterohepatic circulation : pyloric stenosis or large bowel obstruction Decreased clearance Criggler-najjar syndrome type I and II Causes of unconjugated hyperbilirubinemia Reference: Ghai essential pediatrics/6th ed/170-71
  • 40. This condition results from incompatibility betweeen maternal and fetal blood groups. Rh+ve fetus may produce antibodies in Rh -ve mother In Rh incompatibility first child often escapes and subsequent child would be affected . Sometime the child is born with severe hemolytic disease often referred to as erythroblastosis foetalis. When blood level is more than 20 mg/dl the capacity of albumin to bind bilirubin is exceded. Hemolytic Jaundice in Newborn
  • 41. In young children before the age of 1 year the blood brain barrier is not fully matured and free bilirubin enters the brain(kernicterus) deposited in brain leading to convulsions , toxic encephalitis and spasticity. Treatment :  Exchange transfusion along with phototherapy and barbiturates. Phototherapy with blue light(440nm) isomerise insoluble bilirubin to soluble isomers,can be excreted through urine without conjugation.
  • 42. THANK YOU FOR YOUR ATTENTION!! AND HAVE A PLEASANT DAY!!

Notes de l'éditeur

  1. Carotenemia and use of the drug Quinacrine are few other causes of yellow coloration of tissue .Carotenemia can be distinguished from jaundice by sparing of sclera. In 4-37% patients treated with Quinacrine , yellowish discolouration of skin is seen .Unlike carotenemia quinacrine can cause discolouration of sclera. Slight increase in serum bilirubin are best detected by examining the Sclera as Sclera is rich in ELASTIN and the bilirubin has high affinity for the elastin other organ rich in elastin is ear drum, which also is yellow during jaundince.. The normal plasma concentration of bilirubin is less than 21 μmol/L (1.2 mg/dL) The presence of scleral icterus indicates a serum bilirubin of atleast 3.0 mg/dl. (Harrisons textbook of medicine/16th ed/vol.1 /238-240)
  2. Under steady state normal metabolic conditions about 3.9 mg/kg or 250 to 350 mg of bilirubin is produced each day from breakdown of haem from rbc in spleen and liver. 1gm of hemoglobin yields 36.2 mg of bilirubin .(API textbook of Medicine/7th ed/page-580.)
  3. A. ETIOLOGICAL CLASSIFICATION OF JAUNDICE Hemolytic (Prehepatic) .a. Intracorpuscular Defects: 1.Hereditory spherocytosis 2. Hemoglobinopathies : sickle cell anemia , beta thalassemia .b. Extra-corpuscular defects : 1. Infections: Malaria 2.Drugs : quinine ,sulphonamides 3. Burns 4.poisons : snake venom 5. mismatched blood transfusion 2. Hepatocellular (Hepatic ) : a. Infections: viral hepatitis , malaria , typhoid ,septecemia b. toxic : Anaesthetic agents : Halothane , Chloroform Antitubercular drugs: Rifampicin ,Isoniazid ,P.A.S Metals : Arsenic ,Mercury ,Gold c. Cirrhosis: 1. Portal 2. biliary
  4. Prehepatic Jaundice(hemolytic jaundice)
  5. Harrison's Internal Medicine /17th ed/Chapter 297 and Ghai essential pediatrics/6th
  6. Lumibrin