1. MEGALOBLASTIC ANEMIAS

2. MEGALOBLASTIC ANEMIAS Causes
1. Vit. B12 deficiency
2. Folic acid deficiency

3. VITAMIN B12 AND FOLIC ACID-PHYSIOLOGIC CONSIDERATIONS
Vitamin B Folic acid
Sources meat, fish green vegetables, yeast
Daily requirement ug ug
Body stores mg (liver) mg (liver)
Places of absorption ileum duodenum and proxymal
segment of small intestine

4. MEGALOBLASTIC ANEMIAS Causes of Vit.B12 deficiency(1)
1. Malabsorption
a) Inadequate production of intrinsic factor
- pernicious anemia
- gastrectomy, partial or total
b) Inadequate releasing vit. B12 from food
(partial gastrectomy, abnormality of stomach function,
chronic pancreatic insufficiency)
c) Terminal ileum disease (sprue, celiac disease, ilea resection, Crohn
disease, Imerslund syndrome)
d) Competition for intestinal B12 :
- bacterial overgrowth: jejunal diverticula, intestinal stasis and
obstruction due to strictures, blind-loop syndrome
- Fish tapeworm

5. MEGALOBLASTIC ANEMIAS Causes of Vit.B12 deficiency(2)
2. Inadequate intake
- vegetarians
3. Inadequate utylisation
Drugs: PAS, Neomycin, Colchicin, Nitrous oxide

6. MEGALOBLASTIC ANEMIAS- Causes of Folic acid deficiency
1. Inadequate intake
- diet lacking fresh, slightly cook food; chronic alcoholism, total parenteral nutrition,
2. Malabsorption
- small bowel disease (sprue, celiac disease,)
- alcoholism
3. Increased requirements:
- pregnancy and lactation
- infancy
- chronic hemolysis
- malignancy
- hemodialysis
4. Defective utilisation
Drugs:folate antagonists(methotrexate, trimethoprim, triamteren), purine analogs (azathioprine), primidine analogs (zidovudine), RNA reductase inhibitor (hydroxyurea), miscellaneous (phenytoin, N2)

7. MEGALOBLASTIC ANEMIAS clinical features
1. Symptoms of anemia
2. Symptoms associated with vit. B12 or Folic acid deficiency
neurologic manifestations (exclusivly in wit. B12 deficiency)
- megaloblastic madness or psychosis,
- subacute, combined degeneration of the spinal cord
( proprioceptive and vibratory sensation, spinal ataxia)
gastrointestinal compraints (vit.B12 and folic acid deficiency)
- loss of appetite
- glosstis (red, sore, smooth tongue)
- diarrhea or constipation

8. MEGALOBLASTIC ANEMIAS Diagnosis(1)
1. Blood cell count:
macrocytic anemia ( MCV>100fl )
thrombocytopenia
leucopenia (granulocytopenia)
low reticulocyte count
2. Blood smear:
macroovalocytosis , anisocytosis, poikilocytosis
hypersegmentation of granulocytes

9. MEGALOBLASTIC ANEMIAS Diagnosis(2)
3. Laboratory features
indirect hyperbilirubinemia
elevation of lactate dehrogenase (LDH)
serum iron concentration- normal or increased
4. Bone marrow smear
hypercellular
increased erythroid /myeloid ratio
erythroid cell changes (megaloblasts, RBC precursor a abnormally large with nuclear- cytoplasmic asynchrony)
myeloid cell changes (giant bands and metamyelocytes , hypertsegmentation)
megakariocytes are decreased and show abnormal morphology

10. MEGALOBLASTIC ANEMIAS Diagnosis
1. Diagnosis megaloblastic anemia
2. Establishing a type of deficiency (vit. B12 and/or folic acid)
3. Establishing a cause of deficiency

11. VIT B12 DEFICIENCY ANEMIA DIAGNOSIS
1. Establishing megaloblastic anemia
2. Clinical symptoms of vit. B 12 deficiency
3. Low serum vit. B 12

12. PERNICIOUS ANEMIA DIAGNOSIS
1. Establishing vit.B12 deficiency anemia
2. Absence of hydrogen ion secretion (achlorhydria) with maximal histamine stimulation
3. Radiolabeled vit. B12 absorption test (Schilling urinary excretion test) : very reduced absorption of the B12-isotope, corrected to normal only when coadministered with a source of gastric IF.
4. Intrinsic factor, parietal cell and IF-vit.B12 complex antibodies

13. FOLIC ACID DEFICIENCY ANEMIA DIAGNOSIS
1. Establishing megaloblastic anemia
2. History: causes of folate deficiency
3. Absence neurologic symptoms
4. Low serum and red blood cell folic acid

14. MEGALOBLASTIC ANEMIAS TREATMENT(1)
PERNICIOUS ANEMIA
1. Vitamin B12 administration intramuscular in dose 1000 (100) μg per day for a week , then 100 μg 2x per week for 2 weeks, 1 x per week 100μg for month
2. Reticulocytosis begins 2 or 3 days after therapy started and maximal number reached on day 5 to 8.
Serum iron monitoring, after 7-10 days of vit.B12 treatment,
if Fe deficiency is diagnosed we should start iron substitution
ug vit.B12 i.m. every month, regimen that must be mainted for the rest on the patients life.

15. MEGALOBLASTIC ANEMIAS TREATMENT(2)
FOLIC ACID DEFICIENCY ANEMIA
1. Oral administration of Ac. folicum 1 (5) mg per day, for
3 months, and maintance therapy if it’s necessary.
2. Reticulocytosis after 5-7 days
3. Correction of anemia is over after 1-2 months
therapy
4. Maintenance therapy if necessary