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
RBCs Senecent RBCs Iron hemoglobin
Globin
Bilirubin Biliverdin heme
Hepatic Hemoproteins nonhemoglobin heme nonhemoglobin hemoprotein
Premature destruction of newly formed RBCs
C
MHO
R
CBR
1-5%
Chiefly
70+%
20%
Bilirubin formation
120ds
Transport of Bilirubin in Plasma
Albumin + UB UB ~ Albumin Complex
Molar
Ratio
Bilirubin
Bilirubin
Plasma protein
Albumin
H affinity binding sites
L affinity binding sites
can be replaced by
Other organic anions
PH? UB?
2:1
>2:1
CB
1,Hepatic uptake of Bilirubin
UCB~Albumin Complex Separated
Bilirubin Plasma membrane of the liver (be) taken up MTA (receptor?)
Transfer across
Microvillar membrane
3.Biliary Excretion of Bilirubin
Bile canaliculus
2.Conjugation of Bilirubin
UCB carrier protein ER
CBGA CB
(be) bound to transfer
Conjugation
(catalized by
UDPGT)
ligation (Y protein)
Hepatic Bilirubin Transport
(lipid soluble)
(water soluble)
? 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 B and I Urobilinogens (coloress) be degraded Bacterial Enzymes
feces (feceal urobilinogens)
Reabsorbed plasma
circulation kidneys
50-200 mg/d mostly
urine urobilinogen 4 mg/d
T
liver Bile feces re-excreted excreted 90%
trace
20%
?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
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?
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)
Obstructive Jaundice
symptoms
? Pruritus
? Jaundice may vary in intensity
? Chill+fever+gall bladder enlargement
?stone+cholangitis
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 ?
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 ?
Jaundice--- Diagnostic Procedures
? History
? P.E,
? Familiar occurrence of Jaundice
? Duodenal biliary drainage
? Imagine techniques
? Ultrasonography
? ERCP (Endoscopic Retrograde
cholangiopancratography )
? PTC
? X-ray (GI,Angiography)
? CT
Hepatocellular carcinoma
Primary sclerosing cholangitis in
childhood
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
CAUSES OF ISOLATED
HYPERBILIRUBIN
Indirect hyperbilirubinemia
A,Hemolytic disorders
? Inherited
? Acquired
B.Ineffective erythropoiesis
C.Drugs
D.Inherited conditions
CAUSES OF ISOLATED
HYPERBILIRUBIN
Indirect hyperbilirubinemia
Hemolytic disorders---------Inherited
? Spherocytosis,elliptocytosis
? Glucose-6phosphate dehydrogenase and
pyruvate kinase deficiencies
? Sickle cell anemia
CAUSES OF ISOLATED
HYPERBILIRUBINEMIA
Hemolytic disorders-----Acquired
? Microangiopathic
? Paroxysmal nocturnal hemoglobinuria
? Immune hemolysis
CAUSES OF ISOLATED
HYPERBILIRUBINEMIA
Indirect hyperbilirubinemia
Inherited conditions
? Crigler-Najjar types I and II
? Gilbert’s syndrome
CAUSES OF ISOLATED
HYPERBILIRUBINEMIA
Direct hyperbilirubinemia
? Viral hepatitis
? Alcohol
? Drug toxicity
? Environmental toxins
? Wilson’s disease
? Autoimmune hepatitis
? Inherited conditions
CAUSES OF ISOLATED
HYPERBILIRUBINEMIA
Direct hyperbilirubinemia
Inherited conditions
? Dubin-Johnson syndrome
? Rotor’s syndrome
HEPATOCELLULAR
CONDITIONS THAT MAY
PRODUCE JAUNDICE
CHOLESTATIC
CONDITIONS THAT MAY
PRODUCE JAUNDICE
? Intrahepatic
? Extrahepatic
CHOLESTATIC CONDITIONS THAT
MAY PRODUCE JAUNDICE
Intrahepatic
? Viral hepatitis
? Alcoholic hepatitis
? Drug toxicity
? Primary biliary cirrhosis
? Primary sclerosing cholangitis
? Vanishing bile duct syndrome
? Inherited
? Cholestasis of pregnancy
? Total parenteral nutrition
?,Nonhepatobiliary sepsis
? Benign postoperative cholestasis
? Paraneoplastic syndrome
? Venoocclusive disease
? Graft-versus-host disease
CHOLESCTATIC CONDITINS
THAT MAY PRODUCE
JAUNDICE
Vanishing bile duct syndrome
? Chronic rejection of liver transplants
? Sarcoidosis
? Drugs
CHOLESCTATIC
CONDITINS THAT MAY
PRODUCE JAUNDICE
Extrahepatic
?Malignant
?Benign
CHOLESCTATIC CONDITINS
THAT MAY PRODUCE
JAUNDICE
Extrahepatic------Malignant
? Cholangiocarcinoma
? Pancreatic cancer
? Gallbladder cancer
? Ampullary cancer
? Malignant involvement of the porta hepatis
lymph node
CHOLESCTATIC CONDITINS
THAT MAY PRODUCE
JAUNDICE
Extrahepatic------ Benign
? Choledocholithiasis
? Primary sclerosing cholangitis
? Chronic pancreatitis
? ALDS cholangiopathy
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?