CLINICAL LABORATORY DIAGNOSTICS OF LIVER PATHOLOGY

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• CLINICAL LABORATORY DIAGNOSTICS OF LIVER PATHOLOGY

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LIVER STRUCTURE
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• LIVER FUNCTIONS
• Metabolic
• Carbohydrate metabolism
• Lipid metabolism
• Protein metabolism
• Vitamin metabolism
• Mineral metabolism
• Excretory
• Biosynthesis of urea
• Synthesis of bile
• Detoxication

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Metabolism of carbohydrates in liver

• 1. Conversion of glucose-6-phosphate
• 2. Synthesis and decomposition of glycogen
• 3. Gluconeogenesis
• 4. Conversion of mannose, fructose and galactose
  to glucose

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Lipid metabolism in liver

• Synthesis and decomposition of triacylglycerols
• Synthesis and oxidation of fatty acids
• Synthesis and decomposition of phospholipids
• Synthesis and transformation of cholesterol
• Ketogenesis

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Protein metabolism in liver

• Deamination, transamination and decarboxilation
  of amino acids
• Synthesis of albumins of blood plasma
• Synthesis of majority of blood plasma globulins
• Synthesis of blood clotting factors

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Vitamin metabolism in liver

• Formation of active form of vitamin D
• Formation of vitamin A from carotins
• Depo of cyanocobalamine and folic acid
• Depo of vitamin E
• Phosphorilation of vitamins B, formation of
  coenzyme forms

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Detoxification in liver

• Substances detoxification in liver
• Xenobiotics
• Products of protein decay in the intestine
• The terminal products of metabolism

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• The decomposition of hemoglobin in tissues,
  bile pigments formation.
• After a life span of about 120 days the
  erythrocytes die. The dead erythrocytes are taken
  up by the phagocytes of the reticuloendothelial
  system of the body. About 7 gram of Hb is
  released daily from these phagocytosed
  erythrocytes. The Hb molecule is broken down into
  3 parts

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• (i) The protein (globin) part is utilized partly
  as such or along with other body proteins.
• (ii) The iron is stored in the reticuloendothelial
  cells and is reused for the synthesis of Hb and
  other iron containing substances of the body.
• (iii) The porphyrin part is converted to bile
  pigment, i.e. bilirubin which is excreted in
  bile.

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• Heme in the presence of the enzyme, heme
  oxygenase, loses one molecule of CO and one atom
  of iron in Fe3 form producing biliverdin.
• Biliverdin which is green in color is the first
  bile pigment to be produced it is reduced to the
  yellow-colored bilirubin, the main bile pigment,
  by the enzyme biliverdin reductase

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• Bilirubin is a very toxic compound. For example,
  it is known to inhibit RNA and protein synthesis
  and carbohydrate metabolism in brain. Bilirubin
  formed in reticuloendothelial cells then is
  associated with plasma protein albumin to protect
  cells from the toxic effects. As this bilirubin
  is in complex with plasma proteins, therefore it
  cannot pass into the glomerular filtrate in the
  kidney thus it does not appear in urine, even
  when its level in the blood plasma is very high.
  However, being lipid soluble, it readily gets
  deposited in lipid-rich tissues specially the
  brain.

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• This bilirubin is called indirect bilirubin or
  free bilirubin or unconjugated bilirubin.

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• The detoxication of indirect bilirubin takes
  place in the membranes of endoplasmatic reticulum
  of hepatocytes. Here bilirubin interact with
  UDP-glucuronic acid and is converted to the water
  soluble form -bilirubin mono- and diglucoronids.
• Another name of bilirubin mono- and
  diglucoronids is conjugated bilirubin or direct
  bilirubin or bound bilirubin.
• This reaction is catalized by UDP-glucoroniltransf
  erase.

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• Conjugated bilirubin is water soluble and is
  excreted by hepatocytes to the bile. Conjugated
  (bound) bilirubin undergoes degradation in the
  intestine through the action of intestinal
  microorganisms. Bilirubin is reduced and,
  mesobilirubin is formed. Then mesobilirubin is
  reduced again and mesobilinogen is formed. The
  reduction of mesobilinogen results in the
  formation of stercobilinogen (in a colon).
  Stercobilinogen is oxidized and the chief pigment
  (brown color) of feces stercobilin is formed.

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• A part of mesobilinogen is reabsorbed by the
  mucous of intestine and via the vessels of vena
  porta system enter liver. In hepatocytes
  mesobilinogen is splitted to pyrol compounds
  which are excreted from the organism with bile.
  If the liver has undergone degeneration
  mesobilinogen enter the blood and is excreted by
  the kidneys. This mesobilinogen in urine is
  called urobilin, or true urobilin. Thus, true
  urobilin can be detected in urine only in liver
  parenchyma disease.

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• Another bile pigment that can be reabsorbed in
  intestine is stercobolinogen. Stercobolinogen is
  partially reabsorbed in the lower part of colon
  into the haemorroidal veins. From the blood
  stercobolinogen pass via the kidneys into the
  urine where it is oxidized to stercobilin.
  Another name of urine stercobilin is false
  urobilin.

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• The total bilirubin content in the blood serum is
  1,7-20,5 micromol/l, indirect (unconjugated)
  bilirubin content is 1,7-17,1 micromol/l and
  direct (conjugated) bilirubin content is 0,86-4,3
  micromol/l.

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Differentiation between unconjugated and
conjugated bilirubin. Direct and indirect
bilirubin.

• Diazoreagent which is a mixture of sulfanilic
  acid, HCI and NaN02 is added to the serum. The
  conjugated bilirubin gives a reddish violet color
  with it and the maximum color intensity is
  obtained within 30 seconds this is called direct
  test.

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• The unconjugated bilirubin does not give the
  direct test however, it gives indirect test in
  which alcohol or caffeine is also added which
  sets free the bilirubin frum its complex with
  plasma proteins. Due to this difference in the
  type of diazo reaction given by these two forms
  of bilirubin, the term direct and indirect forms
  of bilirubin are also used

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• Jaundice or icterus is the orange-yellow
  discoloration of body tissues which is best seen
  in the skin and conjunctivae it is caused by the
  presence of an excess of bilirubin in the blood
  plasma and tissue fluids. Depending upon the
  cause of an increased plasma bilirubin level,
  jaundice can be classified as
• (i) pre-hepatic,
• (ii) hepatic and
• (iii) post-hepatic

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Pre-hepafic jaundice

• This type of jaundice is due to a raised plasma
  level of unconjugated bilirubin. It is due to an
  excessive breakdown of red cells which leads to
  an increased production of uncongugated
  bilirubin it is also called haemolytic jaundice.
  As the liver is not able to excrete into the bile
  all the bilirubin reaching it, the plasma
  bilirubin level rises and jaundice results.

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• Hemolytic jaundice is characterized by
• Increase mainly of unconjugated bilirubin in the
  blood serum.
• Increased excretion of urobilinogen with urine.
• Dark brown colour of feces due to high content of
  stercobilinogen.

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• Hepatic jaundice.This is typically seen in viral
  hepatitis. Several viruses are responsible for
  viral hepatitis and include hepatitis A, B, C and
  D viruses. The liver cells are damaged
  inflammation produces obstruction of bile
  canaliculi due to swelling around them. This
  cholestasis causes the bile to regurgitate into
  the blood through bile canaliculi. The blood
  contains abnormally raised amount both of
  conjugated and unconjugated bilirubin and bile
  salts which are excreted in the urine.

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• Hepatic jaundice is characterized by
• 1.Increased levels of conjugated and unconjugated
  bilirubin in serum.
• 2.Dark coloured urine due to the excessive
  excretion of bilirubin and urobilinogen.
• 3.Pale, clay coloured stools due to the absence
  of stercobilinogen.
• 4.Increased activities of alanine and aspartate
  transaminases.

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• Post hepatic jaundice.
• This results when there is extrahepatic
  cholestasis due to an obstruction in the biliary
  passages outside the liver. In this way, the bile
  cannot reach the small intestine and therefore
  the biliary passages outside as well as inside
  the liver are distended with bile. This leads to
  damage to the liver and bile regurgitates into
  the blood.

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• Liver function tests will vary according to the
  degree of obstruction, i.e complete or
  incomplete. If the obstruction is complete, the
  stools become pale or clay-colored and the urine
  does not have any stercobilin. The absorption of
  fat and fat soluble vitamins also suffers due to
  a lack of bile salts. Excess of bile salts in the
  plasma produces severe pruritus (itching).

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• Obstructive (post hepatic ) jaundice is
  characterized by
• 1.Increased concentration mainly of conjugated
  bilirubin in serum.
• 2.Dark coloured urine due to elevated excretion
  of bilirubin and clay coloured feces due to
  absence of stercobilinogen.

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FATTY LIVER
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Spider naevus in liver cirrhosis in the ventral
side of theleft shoulder
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Palmar erythema
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Mild jaundice
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Jaundiced patient