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Megaloblastic Anemias

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Megaloblastic Anemia:

Biochemical Abnormality 

  • Thymidine monophosphate (TMP) is needed for normal DNA synthesis
  • Decreases in TMP synthesis from uridine monophosphate (UMP) results in abnormal DNA synthesis
  • Defective nuclear maturation and megaloblastic morphology
    • im
Megaloblastic Anemia - Etiology
  • Vitamin B12 deficiency
  • Folicacid deficiency
Megaloblastic Anemia- Clinical features
  • fatigue
  • weakeness
  • shortness of breath
  • lightheadedness
  • some jaundice in severe cases due to increased bilirubin
  • congestive heart failure possible in severe cases
Megaloblastic Anemia: Bone marrow
  • ineffective hematopoiesis in RBC, WBC, platelets
  • hypercellular marrow: bone marrow making more because of lack of proper growth
  • M:E ratio can be from 1:1 to 1:3
  • Asynchronous development between nucleus and cytoplasm
Megaloblastic Anemia: Maturation
  • Promegaloblas
    • big hoff
    • stain more acid because bigger nucleus
  • Basophilic megaloblast
    • red, young nucleus lagging behind--> not making enough DNA (lack TMP)
  • polychromatic megal
Megaloblastic Anemia: Peripheral Blood
  • Erythrocyte
    • macrocytic, normochromic
    • RBC: 1-3 x10^6/ul; Hgb: 6-9 g/dl; Hct: 20-30%
    • MCV: 100-160 fL; MCH: increased; MCHC: normal
    • Morphology: macrocytes, macroovalocytes, A&P, decreased reticulocyte count, RB
Vitamin B12
  • produced by microorganisms and fungi
  • liver, fish, poultry, meat, eggs
  • Intake:
    • 5-30 ug/day
    • dependent on body's needs
    • 1-5 ug/day absorbed
  • Body stores 1-5 mg Vit B12
  • B12 loss is ab
Vitamin B12 deficiency- Etiology
  • Dietary
    • poor diet
    • mothers who are strict vegetarian may have children who are deficient
  • malabsorption
    • pernicious anemia
      • decreased Instrinsic Factor due to parietal cell atrophy
Vitamin B12 deficiency- Clinical features
  • typical megaloblastic picture in bone marrow and blood
  • Neurological problems
    • degeneration of peripheral nerves
    • degeneration of spinal cord
Folic Acid - Source
  • water-soluble vitamin
  • green, leafy veggies
  • fruits, dairy products, cereals,
  • liver, kidney
Folic Acid- Nutritional requirements
  • Intake
    • 400-600 ug/day in avg diet
    • 50-100 ug/day recommended
    • depend on body's needs
    • overcooking foods destroys folic acid and causes deficiency
  • Body stores 5-10 mg in many tissues
  • takes o
Folic Acid- Etiology
  • Dietary
    • poverty, agine
    • alcoholism
  • Malabsorption
    • tropical sprue
  • Increased requirement
    • pregnancy, infancy
    • cancer
  • Drugs
Folic Acid- Clinical features
  • typical megaloblastic picture in bone marrow and blood
  • neurological problems
    • not as severe as in B12
    • depressio, dementia in some
Lab findings for B12 and Folic Acid Deficiencies
  • serum B12 levels
  • serum and RBC folate levels
  • Antibodies to IF
  • Schilling's test evaluates B12 absorption from GI tract (radioactive test)
  • Vitamin B12 deficiency
    • oral therapy
    • injections
Non-Megaloblastic Causes of Macrocytosis
  • chronic liver disease
  • alcoholism
  • acute hemorrhage: lose B12 and folate in RBC, speed up RBC butr not right size

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