Hepatobiliary disease

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Hepatobiliary disease

• Prepared by Siti Norhaiza Binti Hadzir

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The anatomy of Biliary tract
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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.

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Production of bilirubin
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Hepatic transport and conjugation of bilirubin
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Hepatic uptake of bilirubin and production of bile
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Bilirubin Excretion in the human body
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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.

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Mechanism of jaundice

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

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Aetiology of jaundice
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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.

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Hepatic jaundice

• Defective hepatic uptake
• Abnormal conjugation
• Hepatocellular damage

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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.

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• Abnormal conjugation
• - Partial deficiency of glucoronyl transferase
• - drugs may interfere with this enzyme system
  e.g Novobiocin
• Hepatocellular damage
• - Acute or chronic hepatocellular injury

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Post hepatic jaundice

• 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 Rotors syndrome)
• b) Obstruction at the intra-hepatic level
• (cholestasis)
• Obtruction to the flow of bile in the
  intralobular biliary canaliculli

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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

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• 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.

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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

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Laboratory differential diagnosis of jaundice
Hemolytic Cholestatic Hepatocellular
Features Bilirubin usually lt75µmol/L No bilirubin in urine Reticulocytosis Hemoglobin ? Haptoglobin ? LDH may ? Bilirubin ? ? ? Bilirubin in urine ALP more than 3x normal range AST, ALT,LDH usually modestly ? AST, ALT ? ? Bilirubin ?later Bilirubin in urine ALP ? later
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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.

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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.

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Pathophysiology of neonatal jaundicecont

• 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

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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.

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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.

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• Plasma
• Tprot 64 g/L (60-80)
• Alb 35 g/L (30-50)
• ALP 725 U/L (30-120)
• ALT 78 U/L (lt35)
• Bili 72 µmol (lt20)
• -characteristic of cholestatic nature.
• -space occupying lesion due to secondary carcinoma

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• 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

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