Liver

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Liver
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• All are Autosomal Recessive
• 1. Hemochromatosis excessive accumulation of
  iron in the parenchymal cells of various organs
  (liver and pancreas, heart etc.,)
• Types 1. Genetic (autosomal recessive, HFE gene
  on chr-6) ,2. Secondary (with underlying cause of
  excess iron ?Hemolytic anemia, ß Thalassemia
• Common in Northern European descent
• MC mutation cysteine -to-tyrosine substitution
  at 282
• Fundamental defect unregulated intestinal
  absorption of iron
• Tissue damage direct iron toxicity to host
  tissues
• Mechanisms Free radical formation iron acts on
  DNA
• Clinical more common in males (61)
• Abdominal pain, hepatomegaly, skin pigmentation
  (due to melanin), DM, cardiac dysfunction,
  arthritis and Hypogonadism and infertility
• Clinical course Almost all patients develop
  cirrhosis 30 develop and die of HCC
• Lab Diagnosis Prussian blue reaction for
  Hemosiderin
• Best hepatic iron content in unfixed tissue
• lt 1000 µg/gm Normal
• gt 10,000 µg/gm Early genetic Hemochromatosis
• gt 22,000 µg/gm Fibrosis and cirrhosis
• Treatment Deferuxamine or phlebotomy treatment

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Prussian Blue
? Site of accumulation of iron
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• 2. Wilson Disease Disorder of copper metabolism
• Toxic levels of copper in liver, brain and eye
• Also called Hepatolenticular degeneration
• Gene is ATP7B (chromosome 13), located at
  Hepatocyte canalicular membrane
• Defect Diminished export from the liver into
  the circulation due to defective secretion of
  copper into bile
• Mechanisms of tissue damage poisoning of hepatic
  enzymes, abnormal binding of copper to serum
  proteins, free radical formation
• Morphology KF rings in cornea of eye (highly
  diagnostic),
• Liver? Fatty change, hepatitis with Mallory
  bodies, cirrhosis
• Brain Neuropsychiatric disorders ( due to
  involvement of Basal Ganglia or Lenticulate
  nucleus)
• Diagnosis ? serum Ceruloplasmin (a
  copper-binding serum protein), ? hepatic copper,
  ? urinary copper

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• 3. Alpha 1-Antitrypsin Deficiency protease
  inhibitor (Pi) (chromosome 14)
• Genetics Homozygotes PiZZ have only 10 of
  Normal circulating alpha1-AT levels (substitution
  of Glu to Lys at 342 position )
• Normal Alpha 1-Antitrypsin genotype is PiMM
• Mechanism mis-folding of protein
• Clinical Features Neonatal hepatitis
  (cholestatic jaundice), Childhood and adult
  cirrhosis HCC
• Clinical course Leads to Emphysema and
  Cholestasis or Cirrhosis
• Treatment Liver transplantation Avoidance of
  smoking
• 4. Neonatal Cholestasis hepatic disorders from
  many possible causes in the neonate
• Cause not known in 50 of cases
• Features prolonged Conjugated hyperbilirubinemia
  (neonatal cholestasis), Hepatomegaly, hepatic
  dysfunction (Hypoprothrombinemia)
• Pathology giant cell transformation
  (multinucleate hepatocytes)
• Hepatocytes necrosis and lobular disarray
• Cholestasis, inflammation of portal tracts,
  Kupffer cell reaction, Extramedullary
  hematopoiesis

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Alpha 1-Antitrypsin Deficiency

• PAS ve Diastase resistant

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Case -1

• A 45-year-old man has become increasingly short
  of breath over the past year. He has also noted a
  darker color to his skin, even though he has a
  job in a bank and does not go out in the sun
  much. He has worsening joint pain, but no joint
  deformity. His physician notes a firm liver edge
  on physical examination, but no abdominal pain or
  masses. A stool sample is negative for occult
  blood. Laboratory findings include sodium 148
  mmol/L, potassium 4.2 mmol/L, chloride 97 mmol/L,
  CO2 24 mmol/L, urea nitrogen 19 mg/dL, creatinine
  1.2 mg/dL, glucose 178 mg/dL, total protein 5.9
  g/dL, albumin 3.4 g/dL, alkaline phosphatase 30
  U/L, AST 43 U/L, ALT 40 U/L, and total bilirubin
  0.8 mg/dL. The gross appearance of organs of a
  patient at autopsy with the same underlying
  condition are shown in image 9.1.

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Case -1
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Case -1
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Case -1
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Case -1