MEGALOBLASTIC ANEMIAS

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

VITAMIN B12 AND FOLIC ACID-PHYSIOLOGIC CONSIDERATIONS Vitamin B12 Folic acid Sources meat, fish green vegetables, yeast Daily requirement 2-5 ug 50-100 ug Body stores 3-5 mg (liver) 10-12mg (liver) Places of absorption ileum duodenum and proxymal segment of small intestine

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

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

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)

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

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

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

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

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

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

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 3. 100 ug vit.B12 i.m. every month, regimen that must be mainted for the rest on the patients life.

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