Hepatobiliary

Prepared by: Siti Norhaiza Binti

disease
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
Excessive production of bilirubin
jaundice
Reduced
hepatic uptake
Impaired conjugation
Decreased hepato-cellular excretion
Impaired bile flow (both intrahepatic and
extrahepatic)

Aetiology of
jaundiceJaundice

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
Unconjugated bilirubin in the plasma is carried into
theuptake
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

a)

Post
hepatic
Obstruction or impaired excretion of
bilirubin
jaundice

Failure of transfer of bilirubin glucuronide from the liver cell

into the canaliculus (e.g Dubin-Johnson syndrome and
Rotors 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
<75mol/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 mol (<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