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  1. What is the DNA-related biochemical abnormality that result from B12 and fotalte deficiency and what are the results of this abnormality?
    • Thymidine triphosphate (TTP) is needed for normal DNA synthesis
    • Decrease in TTP synthesis from uridine monophosphoate (UMP) results in abnormal DNA synthesis
    • Results
    • Defective nuclear maturation and megaloblastic morphology
    • immature nuclear proteins
    • *note-essentially DNA maturation lags behind cell development
    • early hemoglobinization of RBCs
    • fragmentation of nucleus and early destruction of RBCs (too big, broken apart in transit)
    • Macrocytic anemia
  2. What are the clinical features of macrocytic anemia (B12 deficiency, folate deficiency)
    • Fatigue
    • Weakness
    • Shortness of breath
    • Lightheadedness
    • Some jaundice in severe cases due to increased bilirubin
    • Congestive heart failure possible in severe cases
  3. Describe the bone marrow of a patient with macrocytic anemia
    • Ineffective hematopoiesis in RBCs, WBCs, and platelets
    • Hypercellular marrow (overcorrecting)
    • M:E ratio can be from 1:1 to 1:3
    • Asynchronous development between the nucleus and cytoplasm
  4. What are the stages of megaloblastic erythrocyte maturation?
    • Promegaloblast
    • Basophilic megaloblast
    • Polychromatic megaloblast
    • Orthochromatic megaloblast
    • Diffusely basophilic macrocyte
    • Macrocyte
  5. Describe the peripheral blood findings of a patient with macrocytic anemia (blood smear, standard RBC tests, morphology, other special tests)
    • Macrocytic, normochromic
    • RBC count: 1-3x106/μL
    • Hgb: 6-9 g/dL
    • Hct: 20-30%
    • MCV: 100-160fL
    • MCH: increased
    • MCHC: normal
    • morphology: macrocytes, macroovalocytes, anisocytosis, poikilocytosis, decreased reticulocyte count, RBC inclusion
    • Hypersegmented neutrophils (5+ segments)
    • Decreased platelets
    • Elevated Lactate dehydrogenase (LDH)
    • Bilirubin and urobilinogen
    • Decreased free haptoglobin
    • Increased free iron
    • Increased erythropoietin
  6. What are sources of B12? What are the nutritional requirements?
    • Produced by microorganisms and fungi
    • Liver, fish, poultry, meat, eggs
    • Intake 5-30μg/day, 1-5μg/day absorbed
    • dependent on body's needs
  7. Describe B12 absorption and transport
    • B12 enters stomach and couples with IF (intrinsic factor)
    • Decouples in/near the ileum, and B12 is absorbed (in the ileum)
    • TCII (transcobalamin II) (carrier protein) transmits B12 through the blood stream to final destination (marrow, liver, other)
  8. How much B12 does the body store?  What is the % loss each day?  How long might it take to become deficient?
    • 1-5mg Vit B12 is stored
    • ~.1%/day is lost (stool)
    • Takes years to become B12 deficient
  9. What is the etiology (various causes) of B12 deficiency?
    • Dietary
    • Poor diet
    • mothers who are strict vegetarian may have children who are deficient
    • Malabsorption
    • pernicious anemia (decreased IF due to parietal cell atrophy)
    • gastrectomy, ileal diseases
    • fish tapeworm
    • HIV and AIDS
    • Alcohol
  10. Clinical features of B12 deficiency?
    • Typical megaloblastic picture in bone marrow and blood
    • Neurological problems: degeneration of peripheral nerves, degeneration of spinal cord
  11. What are the sources of Folic Acid?
    • Water-soluble vitamin
    • Green, leafy vegetables
    • Fruits, dairy products, cereals
    • Liver, kidney
  12. What are the nutritional requirements for folic acid?
    • 400-600μg/day in the average diet
    • 50-100μg/day recommended intake
    • dependent on body's needs
    • *note-overcooking foods destroys folic acid and causes deficiency
  13. Describe folic acid absorption and transportation
    • Polyglutamic acid enters the stomach and is moved to the duodenum and jejunum
    • It is converted to monoglutamate then methyl tetrahydrofolate (CH3THF) in the duodenum and jejunum
    • CH3THF is coupled with a protein transporter and then delivered to the tissues
  14. How much folic acid is stored in the body? How long would it take to become deficient?
    • Body stores 5-10mg in many tissues
    • Takes only a few months to become deficient
  15. Describe the etiology (causes) of folate deficiency
    • Dietary
    • poverty
    • aging
    • alcoholism
    • Malabsorption
    • Tropical sprue syndrome
    • Increased requirement
    • pregnancy
    • infancy
    • cancer
    • Drugs
  16. What are the clinical features of folate deficiency
    • Typical megaloblastic picture in bone marrow and blood
    • Neurological problems: not as severe as B12 deficiency
    • Depression and dementia in some cases
  17. What laboratory tests differentiate between B12 and Folate deficiencies?
    • Serum B12 levels
    • Serum and RBC folate levels
    • Antibodies to intrinsic factor
    • Schillings test (evaluates B12 absorption from GI tract)
  18. Describe the treatments for B12 and for folate deficiencies
    • B12: oral therapy, injections
    • Folate: oral therapy
    • *note- Effectiveness monitored by increase in reticulocyte count and hematocrit
    • *note- may take only a few weeks to respond
  19. What are non-megaloblastic causes of macrocytosis?
    • Chronic liver disease
    • Alcoholism
    • Acute hemorrhage
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2014-03-19 06:09:08
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