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Metabolic Diseases Of Liver            

  1. Hemochromatosis

  1. Excessive body Fe
  2. Genetic / hereditary - AR condition Q
  3. Chromosome 6Q (HFE gene - regulates intestinal absorption of dietary iron)
  4. Linked to HLA - A3 halo type Cysteine Tyrosine at AA282 of HFE gene in H/C.
  5. - Secondary ­
    1. Parenteral Fe overload
    2. Ineffective erythropoiesis
    3. Increased oral Fe (Bantu disease)
    4. Congenital A atransferrinemia
    5. Chronic liver disease
B. Properties
  1. Total body Fe pool: 2-6 gm
  2. Liver: 0.5 gm (98% in hepatocytes)
  3. In genetic H/C: Fe> 50 gm (> 1/3 in liver)
  4. DM (75% - 80%)
  5. Defect in intestinal Fe absorption ... Fe accumulation of 0.5 - gm 1 year Q
  6. Disease manifestation' > 20 gm
  7. Male '" > Female        5 - 6 decade
  8. Micro nodular cirrhosis (all patients)
  9. Skin pigmentation (75%-80%) 

C. Excess Iron in the body leads to

  1. Lipid peroxidation (by Fe catalyzed free radical reactions)
  2. Stimulation of collagen formation
  3. Direct interaction of iron with DNA

D. Morphology

  1. Deposition of hemosiderin in Liver, pancreas, myocardium, pituitary, adrenal, thyroid, parathyroid, joints and skinQ
  2. Cirrhosis (Micro nodular)Q
  3. Pancreatic fibrosis

Liver: Periportal hepatocytes: golden yellow hemosiderin granules Pearls +ve reaction

- No inflammation

 

E. Hepatitic Fe content: Q

- (N): < 1000 g/gm dry weight of liver

Genetic hemochromatosis: > 10,000 g/gm weight of liver

Cirrhosis> 22,000 g/gm weight of liver

 

1. Pancreas:           

  1. Pigmented         
  2. Fibrosis in interstitial tissue
  3. Panchymal atrophy
  4. Hemosiderin' in acinar and islet cells 

2. Heart:     

  1. Hemosiderin in myocardial fibres
  2. Heart is enlarged 

3. Skin:       

  1. Hemosiderin in dermal macrophages and fibroblasts
  2. epidermal melanin production (results in pigmentation) Slate gray color Bronze diabetes
  3. Hemosiderin: in joint synovial lining tests pseudogout

4. Testes Small and atrophic

Screening technique for family members of pro bands ­

  1. S ferritin & iron     
  2. HLA gene molecular analysis                
  3. Liver biopsy
Wilson's Disease Q
  1. Accumulation of toxic levels of Cu in liver, brain, eye (Hepatolenticular degeneration)
  2. ARQ
  3. Excess of Ingested Cu absorbed In stomach/duodenum
F. Gene: ATP 7B, chromosome 13Q
  -   Encodes transmembrane Cu transporting ATPase
   -   Located at hepatocyte canalicular membrane
 
G.  Decrease Excretion => Cu accumulation in liver


 

Morphology
  1. Liver
    1. Fatty change                            
    2. Acute and chronic hepatitis
    3. Mallory bodies - Acute stage       
    4. Cirrhosis
    5. Massive liver necrosis – Rare
  1. Brain:  Q
    1. Toxic injury to basal ganglia: Putamen
    2. Neuropsychiatric I hepatic manifestations
  2. Eye:  Q
    1. Kayser Fleischer Rings (deposit in Descemet) Q
    2. Usually manifest after 6 years of age
  1. Lab diagnosis- Q
    1. ↓ Decrease serum ceruloplasmin
    2. ↑ Hepatic copper
    3. ↑ Urinary copper
    4. Excess Cu: Rhodamine / Orcein Stain
    5. Hepatic Cu> 250 g/gm dry weight of Liver.
    6. S. Ceruloplasmin < 20 mg/dl
    7. U. Cu> 30-50 g/ 24 hours




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