2. Definition
• Defined as impairment of DNA synthesis that leads
to ineffective hematopoiesis and distinctive
morphological changes including abnormally large
erythroid precursors and red cells
3. Causes
1. Vit B 12 deficiency
2. Folic acid deficiency
3. Unresponsive to the B12 & folic acid therapy
4. Common form
• Pernicious anemia
• Folate deficiency
• Deficiency of these vitamins or impaired in their metabolism
• Defective nuclear maturation due to deranged or inadequate
DNA synthesis
5.
6. Functions of vit B12
1. Conversion of homocysteine to methionine
2. Isomerization of methylmalonyl co A to
succinyl co A
7. Pernicious anemia
• Specific form of megaloblastic anemia
• Caused by an autoimmune gastritis
• Impaired the production of intrinsic factor
• Required for vit B12 uptake from the gut
• Daily requirement – 2 to 3 μg
8. Incidence
• Autoimmune disorder
• Most common in older patients
• 60 years
• Rare in younger patient
• Genetic predisposition strongly suspected
9. Pathogenesis
• Result from autoimmune attack on gastric mucosa
• Formation of autoantibodies plays important role
• Type I – blocks the binding of B12 to IF
• Type II – prevent the B12 – IF complex binding to the ileal receptors
• Type III- non specific
• Associated with other autoimmune disorders
• Autoimmune thyroiditis
• Adrenalitis
10. Morphology
• Fundic gland atrophy
• Affecting both chief cells & parietal cells
• Intestinalization - Glandular epithelium is replaced by mucus secreting goblet cells-
gastric carcinoma
• Megaloblastic changes
• Tongue – shiny, glazed, beefy red
• Gastric atrophy and metaplastic changes due to autoimmunity not because of B 12
deficiency.
• Demyelination of the dorsal and lateral spinal tracts
• Spastic Para paresis, sensory ataxia, severe paresthesia in lower limbs.
11.
12.
13. Diagnosis
• Moderate to severe megaloblastic anemia
• Leukopenia with hyper segmented granulocyte
• Low serum vit B 12 level
• Elevated serum homocysteine and methyl malonic
acid - Atherosclerosis
