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CLINICAL CHEMISTRY-2 (MLT 302) LIVER FUNCTION AND THE BILIARY TRACT LECTURE FOUR

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CLINICAL CHEMISTRY-2 (MLT 302) LIVER FUNCTION AND THE BILIARY TRACT LECTURE FOUR Dr. Essam H. Aljiffri * * JAUNDICE Neonatal Jaundice The major enzyme which ... – PowerPoint PPT presentation

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Title: CLINICAL CHEMISTRY-2 (MLT 302) LIVER FUNCTION AND THE BILIARY TRACT LECTURE FOUR


1
CLINICAL CHEMISTRY-2 (MLT 302) LIVER FUNCTION AND
THE BILIARY TRACT LECTURE FOUR
  • Dr. Essam H. Aljiffri

2
JAUNDICE
  • Neonatal Jaundice
  • The major enzyme which conjugates bilirubin in
    the liver (UDP glucuronyl transferase) is not
    fully mature at birth
  • - unconjugated hyperbilirubinaemia
  • and jaundice are common.
  • This is usually physiological causes of neonatal
    jaundice.

3
Neonatal Jaundice
  • Physiological jaundice is maximal within 2-5 days
    of delivery it is more severe in premature
    infants.
  • Unconjugated bilirubin is toxic to the nervous
    system
  • Jaundice has no effect on the central nervous
    system in adults, since bilirubin does not cross
    the blood brain barrier.

4
Neonatal Jaundice
  • The blood brain barrier is immature in neonates
    and unconjugated bilirubin can enter brain
    tissue.
  • One of the methods of treating physiological
    jaundice include
  • phototherapy.

5
Congenital Defects in Bilirubin Transport
  • Gilbert's Disease
  • Gilbert's disease is a common congenital disorder
    of bilirubin transport
  • - affecting approximately 2 of
  • the population,
  • - males more than females.

6
Gilbert's Disease
  • The activity of UDPglucuronyl transferase is
    reduced and defects in the uptake of bilirubin by
    hepatocytes also occur.
  • Gilbert's disease characteristically causes mild
    jaundice, serum bilirubin concentrations usually
    being 20-85 µmol/L.

7
Other Congenital Transport Syndromes
  • A severe congenital deficiency in UDPglucuronyl
    transferase occurs in Crigler-Najjar syndrome,
  • Most patients dying in infancy from high
    unconjugated bilirubin which is toxic to the
    nervous system.

8
ASSESSMENT OF HEPATIC FUNCTIONS
It is possible to investigate many of the
functions of the liver in detail.
9
ASSESSMENT OF LIVER FUNCTIONS
  • Hepatic carbohydrate metabolism can be assessed
    by measuring blood galactose removal following
    injection, and glucose output can be quantified.
  • The assessment of liver function in daily
    clinical practice is usually performed by
    measuring serum levels of bilirubin, hepatic
    enzymes and proteins.

10
ASSESSMENT OF LIVER FUNCTION
  • Serum enzymes in liver disease
  • Small amounts of enzymes leak from their
    intracellular location into serum and cellular
    dysfunction often causes increased leakage.
  • The measurement of enzyme activity in serum may
    be useful in the investigation of organ
    dysfunction to differentiate patterns of disease.

11
Serum enzymes in liver disease
  • Abnormal mainly in hepatocellular disease
  • Alanine aminotransferase (transaminase) (ALT)
  • Aspartate aminotransferase (transaminase) (AST)
  • Lactate dehydrogenase (LDH)
  • Abnormal mainly in cholestasis
  • Alkaline phosphatase (ALP)
  • y-Glutamyl transferase (transpeptiase) (GGT)

12
Aminotransferases
  • Aminotransferases are involved in amino acid
    metabolism.
  • Aspartate aminotransferase (AST) occurs in both
    the cytosol and mitochondria of cells
  • Alanine aminotransferase (ALT) is a cytosolic
    enzyme.
  • Increased amounts of both transaminases leak
    from
  • - inflamed or damaged hepatocytes

13
Aminotransferases
  • Measurement of one of these enzymes is included
    in liver function tests.
  • ALT is more specific for liver disease than AST,
  • AST is more sensitive because the liver contains
    larger amounts.

14
Lactate Dehydrogenase
  • Lactate dehydrogenase (LDH) is often raised in
    hepatocellular dysfunction
  • It is rarely measured for this purpose since it
    lacks specificity because of wide distribution of
    LDH in the body.

15
Alkaline Phosphatase
  • Levels of alkaline phosphatase increase in
    cholestasis, mainly because of increased
    synthesis of the enzyme.

16
Gama-glutamyl Transferase
  • Increased serum activities of GGT are found in
    both
  • - hepatocellular and
  • - cholestatic disease.
  • Higher activities are found in cholestasis, when
    levels greater than 50 times the upper limit of
    normal.
  • Increased synthesis of GGT is induced by
    excessive ethanol intake.

17
KEY POINTS
Transaminase (ALT and AST) levels are raised
mainly in hepatocellular disease
Alkaline phosphatase levels is raised mainly in
obstructive disease
Increased in serum GGT levels are modest in
hepatocellular and marked in obstructive disease
18
Proteins measured in the investigation of disease
19
Plasma Proteins in Liver Disease
  • Albumin has a half-life in serum of about 20 days
    and levels fall slowly if no synthesis occurs.
  • Serum albumin is usually normal/decrease in
    hepatic failure and chronic liver diseases such
    as cirrhosis, impaired synthesis may lead to low
    serum levels.

20
Plasma Proteins in Liver Disease
  • Serum globulins are often increased in cirrhosis
  • alpha1-Antitrypsin deficiency
  • - neonatal jaundice and
  • - cirrhosis in children and young
    adults.

21
Plasma Proteins in Liver Disease
  • Alpha-fetoprotein
  • - modest levels are found,
  • e.g during acute viral
    hepatitis,
  • - very high values occur
  • in hepatocellular carcinoma.

22
Investigation of Liver Disease
  • Biochemical liver function tests are an essential
  • part of assessment of liver disease.
  • Tests must be interpreted with knowledge of
  • the clinical details of the patient, and
  • the results of other investigations.

23
Investigation of Liver Disease
  • These often include
  • ultrasound examination,
  • radiological procedures, and
  • liver biopsy.
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