1. No category

Jaundice
Definition
Accumulation of yellow pigment in
the skin and other tissues (Bilirubin)
Bilirubin Metabolism

Bilirubin formation

Transport of bilirubin in plasma

Hepatic bilirubin transport


Hepatic uptake

Conjugation

Biliary excretion
Enterohepatic circulation
Bilirubin formation
RBCs
Chiefly
70+%
Bilirubin
120ds
Senecent RBCs
Iron
hemoglobin
Globin
R
C
Bilirubin CBR
Biliverdin MHO
heme
20%
nonhemoglobin heme
Hepatic Hemoproteins nonhemoglobin hemoprotein
1-5%
Premature destruction of newly formed RBCs
Transport of Bilirubin in Plasma
Albumin + UB
UB ~ Albumin Complex
H affinity binding sites
2:1
Bilirubin
Molar
Ratio
L affinity binding sites
>2:1
Plasma protein
Albumin
Bilirubin
Other organic anions
can be replaced by
PH
UB
Hepatic Bilirubin Transport
1. Hepatic uptake of Bilirubin
UCB~Albumin Complex Separated
(be) taken up
Bilirubin MTA (receptor ?) Plasma membrane of the liver
2.Conjugation of Bilirubin
ligation (Y protein)
UCB
(be) bound to
(lipid soluble)
3.Biliary Excretion of Bilirubin
CB
Transfer across
Microvillar membrane
transfer
carrier
protein
ER
Conjugation
(catalized by
UDPGT)
CB
CBGA
(water soluble)
Bile canaliculus
• UDPGT: Uridine Diphosphate Glucuronyl
Transferase
• UCB: because of its tight albumin binding
and lipid solubility, it is not excreted in
urine.
• CB: is less tightly bound to albumin and is
water soluble, so it is filtered at the
glomerulus and appears in the urine.
Entero-hepatic circulation
CB
mostly
T
B and I
be degraded
Bacterial Enzymes
feces (feceal urobilinogens)
90%
20%
Urobilinogens (coloress)
Reabsorbed
50-200 mg/d
liver
re-excreted
Bile
excreted
feces
plasma
trace
4 mg/d
circulation
kidneys
urine urobilinogen
•The serum of normal adults contains 1 mg of bilirubin per 100 ml.
•In healthy adults
The direct fraction is usually <0.2 mg/100 ml
The indirect fraction is usually <0.8 mg/100 ml
Pathophysiologic classification of
Jaundice

Hemolytic Jaundice

Hepatic Jaundice

Obstructive Jaundice(Cholestasis)

Congenital Jaundice
Jaundice classification
predominantly unconjugated
hyperbilirubinaemia
predominantly conjugated
hyperbilirubinaemia
Hemolytic Jaundice
Pathogenesis
Overproduction
Hemolysis (intra and extra vascular)
inherited or genetic disorders
 acquired immune hemolytic anemia
(Autoimmune hemolytic anemia)
 nonimmune hemolytic anemia
(paroxysmal nocturna Hemoglobinruia)


Ineffective erythropoiesis
Overproduction may overload the liver with UB
Hemolytic Jaundice
Symptoms
weakness, Dark urine, anemia,
Icterus, splenomegaly
Lab





UB without bilirubinuria
fecal and urine urobilinogen
hemolytic anemia
hemoglobinuria (in acute intravascular
hemolysis)
Reticulocyte counts
Hemolytic Jaundice
(pre-hepatic)
•
•
•
•
•
•
•
Serum / blood:
bilirubin (micormoles/l) 50-150; normal
range 3-17
AST I.U. < 35; normal range <35
ALP I.U. <250; normal range <250
gamma GT I.U. 15-40; normal range
15-40
albumin g/l 40-50; normal range 40-50
reticulocytes(%) 10-30; normal range
<1
prothrombin time (seconds) 13-15;
normal range 13-15
Hemolytic Jaundice
(pre-hepatic)
urinary changes:
• bilirubin: absent
• urobilinogen: increased or
normal
faecal changes:
stercobilinogen: normal
Obstructive Jaundice
Pathogenesis
it is due to intra- and extra hepatic
obstruction of bile ducts
• intrahepatic Jaundice: Hepatitis, PBC,
Drugs
• Extra Hepatic Biliary Obstruction:
Stones, Stricture, Inflammation, Tumors,
(Ampulla of Vater)
Etiology of Obstructive
Jaundice
Intrahepatic-Liver cell Damage/Blockage
of Bile Canaliculi
•
•
•
•
•
•
•
Drugs or chemical toxins
Dubin-Johnson syndrome
Estrogens or Pregnancy
Hepatitis-viral,chemical
Infiltrative tumors
Intrahepatic biliary hypoplasia or atresia
Primary biliary cirrhosis
Etiology of Obstructive
Jaundice
Extrahepatic-Obstructive of bile Ducts
• Compression obstruction from tumors
• Congenital choledochal cyst
• Extrahepatic biliary atresia
• Intraluminal gallstones
• Stenosis-postoperative or inflammary
cholestasis
clinical features
• pain, due to gallbladder disease,
malignancy, or stretching of the
liver capsule
• fever, due to ascending
cholangitis
• palpable and / or tender
gallbladder
• enlarged liver, usually smooth
General signs of cholestasis
• xanthomas: palmar creases, below the
breast, on the neck. They indicate
raised serum cholesterol of several
months. Xanthomas on the tendon
sheaths are uncommonly associated
with cholestasis.
• xanthelasma on the eyelids
• scratch marks: excoriation
• finger clubbing
• loose, pale, bulky, offensive stools
• dark orange urine
Obstructive Jaundice
Lab Findings
• Serum Bilirubin
• Feceal urobilinogen (incomplete obstruction)
• Feceal urobilinogen absence (complete
obstruction)
• urobilinogenuria is absent in complete
obstructive jaundice
• bilirubinuria 
• ALP 
• cholesterol 
Obstructive Jaundice
extrahepatic
•
•
•
•
•
•
•
•
serum / blood
bilirubin (micromoles/l) 100-500;
normal range 3-17
AST I.U. 35-400; normal range <35
ALP I.U. >500; normal range <250
gamma GT I.U. 30-50; normal range
15-40
albumin g/l 30-50; normal range 40-50
reticulocytes(%) <1; normal range <1
prothrombin time (secs) 15-45; normal
range 13-15
( " + parenteral vitamin K) falls
Obstructive Jaundice
extrahepatic
urinary changes
• bilirubin: increased
• urobilinogen: reduced or absent
faecal changes
stercobilinogen: reduced or
absent
Hepatic Jaundice
Due to a disease affective hepatic
tissue either congenital or acquired
diffuse hepatocellular injury
Hepatic Jaundice
Pathogenesis
• Impaired or absent hepatic conjugation of bilirubin


decreased GT activity (Gilbert‘s syndrome)
hereditary absence or deficiency of UDPGT (Grigler-Najjar
Syndrome)
• Familiar or hereditary disorders


Dubin-Johnson Syndrome
Rotor syndrome
• Acquired disorders


hepatocellular necrosis
intrahepatic cholestasis
(Hepatitis, Cirrhosis, Drug-related)
Gross specimen of cirrhosis of
the liver
Hepatic Jaundice
Symptoms
weakness, loss appetite, hepatomegaly, palmar
erythema, spider
Lab Findings
• liver function tests are abnormal
• both CB and UCB
• Bilirubinuria 
Hepatic Jaundice
•
•
•
•
•
•
•
•
serum / blood
bilirubin (micromoles/l) 50-250; normal
range 3-17
AST I.U. 300-3000; normal range <35
ALP I.U. <250-700; normal range <250
gamma GT I.U. 15-200; normal range
15-40
albumin g/l 20-50; normal range 40-50
reticulocytes(%) <1; normal range <1
prothrombin time (secs) 15-45; normal
range 13-15
( " + parenteral vit. K) 15-45
Hepatic Jaundice
urinary changes
• bilirubin: normal or increased
• urobilinogen: normal or reduced
faecal changes
stercobilinogen: normal or
reduced
Jaundice
diagnosis(1)
history and examination
urine, stools
serum biochemistry
• bilirubin
• transaminases - AST, ALT
• albumin
• alkaline phosphatase
Jaundice
diagnosis(2)
haematology
• haemoglobin
• WCC
• platelets
• prothrombin time +/- parenteral
vitamin K
abdominal ultrasound and chest X-ray
further investigations - determined by
the basis of the jaundice, e.g. prehepatic, hepatic, extra-hepatic
conjugated hyperbilirubinaemia
the liver is able to conjugate bilirubin, but
the excretion is impaired.
failure of bilirubin excretion by
hepatocytes:
• Dubin-Johnson syndrome
• Rotor's syndrome
obstruction to biliary flow i.e.
cholestasis, both intra-hepatic and
extra-hepatic
The proportion of conjugated
bilirubin to the total raised
bilirubin
• 20-40% of total: more suggestive of
hepatic than posthepatic jaundice
• 40-60% of total: occurs in either hepatic
or posthepatic causes
• > 50% of total: more suggestive of
posthepatic than hepatic jaundice
• less than 20% :secondary to haemolysis
or constitutional e.g. Gilbert's disease,
Crigler-Najjar syndrome
unconjugated
hyperbilirubinaemia
• increased bilirubin formation
• failure of bilirubin
uptake(Gilbert's disease)
• failure of bilirubin
conjugation
unconjugated
hyperbilirubinaemia
increased bilirubin formation
haemolysis
ineffective erythropoiesis:
• megaloblastic anaemia
• iron deficiency
• haemoglobinopathies
unconjugated
hyperbilirubinaemia
failure of bilirubin conjugation
• neonatal jaundice
• Crigler Najjar syndrome
• drug inhibition e.g.
chloramphenicol
• extensive hepatocellular
disease e.g. hepatitis,
cirrhosis
Cholestasis
diagnosis
• elevated serum bilirubin - in proportion
to duration of cholestasis; returns to
normal once cholestasis is relieved
• raised serum alkaline phosphatase - to
more than 3X upper limit of normal;
• LFTs - aminotransferases mildly raised;
raised gamma GT
• increased urinary bilirubin
• urinary urinobilinogen is excreted in
proportion to amount of bile reaching the
duodenum i.e. absence of urinobilinogen
indicates complete biliary obstruction
Identification of cause
• dilated ducts on ultrasound percutaneous transhepatic
cholangiograpy
• undilated ducts on ultrasound endoscopic retrograde cholangiopancreatography
• needle biopsy of the liver
Hepatocellular carcinoma
Primary sclerosing cholangitis in
childhood
Accompanied Symptoms
•
•
•
•
•
•
•
Fever
Pain,Charcot syndrome
Hepatomegaly
Spleenmegaly
Ascites
GI bleeding
itch
Jaundice- Differential diagnosis
1. Once Jaundice is recognized, it is important to
determine whether hyperbilirubinemia is
predominantly CB or UCB?
2. Differentiation of hemolitic from other type of
Jaundice is usually not difficult.
3. The laboratory findings are in constant in partial
biliary obstruction and differentiation from
intrahepatic cholestesis is particularly difficult.
Jaundice- Differential diagnosis
Differential Diagnosis




UCB or CB
Exclude UCB (e.g. hemolysis or Gilbert Synd.)
Distinguish hepatocellular from obstructive
Distinguish intrahepatic from extra hepatic
cholestasis
Case Study1
• History: 68-year-old,jaundice,stomach pain,
“dark urine”,itching of the
skin,rapid weight loss of 21lb
• Lab data
 CBC within narmal limits
 Total bilirubin:238μmol/l
 GGT:300U/l
 ALP:360U/l
 AST:80u/l
 ALT:75u/l
 Urinalysis:positive bilirubin,normal urobilinogen
 Serum amylase:elevated
Case Study1
Question:
• What is the most probable diagnosis for this
patient?
• Which labtory tests provided the most
information,and which provided the least?
Case Study2
• History:38-year-old white
female,jaundice,right upper
quadrant abdominal
pain,nausea,vomiting,itching
skin.She has a history of
intravenous drug use and alcohol
abuse.
Case Study2
• Lab data
 elevated total bilirubin(136 μmol/l)
 elevated conjugated bilirubin(102μmol/l)
 Urine:orange-brown,3+bilirubin,normal
urobilinogen
 elevated
ALP(1.5ULT),GGT(3ULT),ALT,AST(5ULT)
 Modest increase:Serum cholesterol and
triglyceride
Case Study2
Question
• What is the probable diagnosis for this
patient?Why?
• What other laboratory test would
recommend to confirm this diagnosis?
• Which laboratory tests ordered provided the
most information?Why?
SUMMARY
• Have the patient had an isolated elevation of
serum bilirubin?
SUMMARY
• Is the bilirubin elevation due to an increased
unconjucated or conjucated fraction?
SUMMARY
• Is the hyperbilirubinemia hepatocellular or
cholestatic?
SUMMARY
• If cholestatic,is it intra-or extrahepatic?