Transcript Hepatobiliary disease

Hepatobiliary disease
Prepared by: Siti Norhaiza Binti Hadzir
The anatomy of Biliary tract
Bilirubin metabolism
• Major metabolite of heme
• Heme is found in hemoglobin, myoglobin and
cytocrome.
• Most of daily production (0.2 to 0.3g/dL) is
derived from breakdown of senescent
erythrocytes
• Rate of systemic bilirubin production is equal
to the rates of hepatic uptakes, conjugation,
and biliary excretion.
Production of bilirubin
Hepatic transport and conjugation of
bilirubin
Hepatic uptake of bilirubin and production
of bile
Bilirubin Excretion in the human body
Pathophysiology of jaundice
• Disturbance in bilirubin production or
clearance.
• It is characterized by yellow color of white of
the eyes (sclera) and skin
• Serum bilirubin levels rise above 2.0 to 2.5
mg/dL; level as high as 30-40mg/dL can occur
with severe disease
• ↑ also called as hyperbilirubinemia.
Mechanism of jaundice
•
•
•
•
•
Excessive production of bilirubin
Reduced hepatic uptake
Impaired conjugation
Decreased hepato-cellular excretion
Impaired bile flow (both intrahepatic and
extrahepatic)
Aetiology of jaundice
Jaundice
Pre-hepatic
Post-hepatic
Hepatic
Pre-hepatic jaundice
• Excessive production of bilirubin due to
excessive destruction of red blood cells.
• It is associated with increased hemolysis of
erythrocytes (e.g incompatible blood
transfusion, malaria, sickle cell anemia).
• This results in overproduction of bilirubin
beyond the capacity of the liver to conjugate
and excrete bilirubin.
Hepatic jaundice
• Defective hepatic uptake
• Abnormal conjugation
• Hepatocellular damage
Defective hepatic uptake
• Unconjugated bilirubin in the plasma is carried into
the liver by intracellular transport proteins.
• Absences of these proteins result in failure of
bilirubin uptake, leading to unconjugated
hyperbilirubinemia (e.g Gilbert Syndrome).
• Defective of blood supply to the liver also can cause
abnormality of bilirubin metabolism
• These problems happen in congestive heart failure,
pathway shunt due to surgery or congenital and
adverse effect from drug intake.
• Abnormal conjugation
- Partial deficiency of glucoronyl transferase
- drugs may interfere with this enzyme system
e.g Novobiocin
• Hepatocellular damage
- Acute or chronic hepatocellular injury
Post hepatic jaundice
a) Obstruction or impaired excretion of
bilirubin
Failure of transfer of bilirubin glucuronide from the liver cell
into the canaliculus (e.g Dubin-Johnson syndrome and
Rotor’s syndrome)
b) Obstruction at the intra-hepatic level
(cholestasis)
Obtruction to the flow of bile in the intralobular biliary
canaliculli
Post hepatic jaundice: cont;
 Intra-hepatic cholestasis occurs in:
- in viral hepatitis
- alcoholic liver disease
- as a toxic reaction to drugs, including andrigens
(methyltestosterone), anabolic steroids, oral
contraceptives, and phenothiazines
- in benign familial cholestatic jaundice, a rare
familial disease in which recurrent attacks of
cholestatic jaundice represent the only abnormality
 Extra-hepatic obstruction
Obtruction involve main hepatic ducts, the
common hepatic duct, or common bile
duct.
Complete obstructive jaundice prevents
entry of bilirubin into the intestine,
producing pale clay-colored or chalky
stools
Absence of fecal and urinary urobilinogen
dark brown (tea colored) urine containing
bilirubin.
Laboratory investigation
• Usually, the following examinations are taken:
- FBC (hemolysis)
-serum aminotransferase (AST,ALT)
- Serology for hepatitis including HCAb,HBsAg,
HBcAb
- ALP: if elevated or if an obstruction is suspected,
images of the bile ducts should be obtained.
- GGT
- Fractionated bilirubin
Laboratory differential diagnosis of
jaundice
Hemolytic
Features
Bilirubin usually
<75µmol/L
No bilirubin in
urine
Reticulocytosis
Hemoglobin ↓
Haptoglobin ↓
LDH may ↑
Cholestatic
Bilirubin ↑ ↑ ↑
Bilirubin in urine
ALP more than 3x
normal range
AST, ALT,LDH
usually modestly ↑
Hepatocellular
AST, ALT ↑ ↑
Bilirubin ↑later
Bilirubin in urine
ALP ↑ later
Neonatal jaundice
• Jaundice is the most common condition that requires
medical attention in newborns.
• In most infants, unconjugated hyperbilirubinemia
reflects a normal transitional phenomenon.
• However, in some infants, serum bilirubin levels may
excessively rise, cause death in newborns and lifelong
neurologic sequelae in infants who survive
(kernicterus).
• For these reasons, the presence of neonatal jaundice
frequently results in diagnostic evaluation.
Pathophysiology of neonatal jaundice
• Neonatal jaundice results the following
phenomena:
Increased breakdown of fetal erythrocytes. This is the result of
the shortened lifespan of fetal erythrocytes and the higher
erythrocyte mass in neonates.
Hepatic excretory capacity is low both because of low
concentrations of the binding protein ligandin in the hepatocytes
and because of low activity of glucuronyl transferase, the enzyme
responsible for binding bilirubin to glucuronic acid.
Pathophysiology of neonatal
jaundice:cont;



Certain factors present in the breast milk of some
mothers may contribute to increased
enterohepatic circulation of bilirubin (breast milk
jaundice).
Blood group incompatibilities (eg, Rh, ABO) may
increase bilirubin production through increased
hemolysis.
Nonimmune hemolytic disorders (spherocytosis,
G-6-PD deficiency) may also cause increased
jaundice
Laboratory investigation
• A total serum bilirubin level is the only testing
required in an infant with moderately jaundice.
• Blood type and Rh determination in mother and
infant
• Direct Coombs testing in the infant
• Hemoglobin and hematocrit values.
• Peripheral blood film for erythrocyte morphology
• Reticulocyte count
• Tests for viral and/or parasitic infection: These may
be indicated in infants with hepatosplenomegaly or
other evidence of hepatocellular disease.
Example
• The liver function tests shown below were
those of a 77 year old man with an
advanced carcinoma of the colon. The
physical examination revealed an enlarged,
hard, non-tender liver but there was no
evidence of jaundice.
• Plasma
Tprot 64 g/L (60-80)
Alb 35 g/L (30-50)
ALP 725 U/L (30-120)
ALT 78 U/L (<35)
Bili 72 µmol (<20)
-characteristic of cholestatic nature.
-space occupying lesion due to secondary
carcinoma
characteristic of cholestatic nature.
-space occupying lesion due to secondary
carcinoma
• Very high plasma ALP- obstruction of
intrahepatic bile ducts
• Modest increase in the plasma ALT-lesion
slowly expanding and destroying
hepatocytes
Thank you