Medicine 5th year, 7th lecture/part two (Dr. Sabir)

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The lecture has been given on Mar. 27th, 2011 by Dr. Sabir.

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Medicine 5th year, 7th lecture/part two (Dr. Sabir)

  1. 1. MEGALOBLASTIC ANEMIAS Dr. Sabir
  2. 2. MARROW FAILURE <ul><li>Metabolically highly active, 2º to rapid cell turnover </li></ul><ul><ul><li>White cell life span 12-24 hours </li></ul></ul><ul><ul><li>Platelet life span 7 days </li></ul></ul><ul><ul><li>Red blood cell lifespan 120 days </li></ul></ul><ul><li>Any slowing of DNA production  marrow failure </li></ul>
  3. 3. MEGALOBLASTIC ANEMIA <ul><li>Hemoglobin production probably normal </li></ul><ul><li>Defect in nuclear replication & division </li></ul><ul><li>Affects all marrow elements </li></ul>
  4. 4. MEGALOBLASTIC ANEMIA <ul><li>Trademark cell: Oval macrocyte, (MCV > 100 fl) </li></ul><ul><li>Hypersegmented neutrophils - 98% </li></ul><ul><li>Pancytopenia, esp if anemia severe </li></ul><ul><li>Reticulocytopenia </li></ul><ul><li>LDH elevated (90%) </li></ul><ul><li>Serum Fe normal or elevated </li></ul><ul><li>Serum B 12 or folate low </li></ul><ul><li>Marrow  classic megaloblastic changes </li></ul>
  5. 8. MEGALOBLASTIC ANEMIAS Causes <ul><li>1. Vit . B 12 deficiency </li></ul><ul><li>2. Folic acid deficiency </li></ul>
  6. 9. VITAMIN B 12 AND FOLIC ACID-PHYSIOLOGIC CONSIDERATIONS <ul><li> V itamin B 12 F olic acid </li></ul><ul><li>Sources meat, fish green vegetables, yeast </li></ul><ul><li>Daily requirement 2-5 ug 50-100 ug </li></ul><ul><li>Body stores 3-5 mg (liver) 10-12mg (liver) </li></ul><ul><li>Places of absorption ileum duodenum and prox i mal </li></ul><ul><li>jejunum </li></ul>
  7. 10. MEGALOBLASTIC ANEMIAS Causes of Vit.B 12 deficiency(1) <ul><li>1. Malabsorption </li></ul><ul><li>a) Inadequate production of intrinsic factor </li></ul><ul><li>- pernicious anemia </li></ul><ul><li>- gastrectomy, partial or total </li></ul><ul><li>b) Inadequate releasing vit. B 12 from food </li></ul><ul><li> (partial gastrectomy, abnormality of stomach function, </li></ul><ul><li>chronic pancreatic insufficiency) </li></ul><ul><li>c) Terminal ileum disease (sprue, celiac disease, ilea l resection, Crohn ’s </li></ul><ul><li>disease) </li></ul><ul><li>d) Competition for intestinal B 12 : </li></ul><ul><li>- bacterial overgrowth: jejunal diverticula, intestinal stasis and </li></ul><ul><li>obstruction due to strictures, blind-loop syndrome </li></ul><ul><li>- Fish tapeworm </li></ul>
  8. 11. MEGALOBLASTIC ANEMIAS Causes of Vit.B 12 deficiency(2) <ul><li>2. Inadequate intake </li></ul><ul><li>- vegetarians </li></ul><ul><li>3. Inadequate ut i lisation </li></ul><ul><li>Drugs: PAS, Neomycin, Colchicin e , Nitrous oxide </li></ul>
  9. 12. MEGALOBLASTIC ANEMIAS- Causes of Folic acid deficiency <ul><li>1. Inadequate intake </li></ul><ul><li>- diet lacking fresh food; chronic alcoholism, total parenteral nutrition, </li></ul><ul><li>2. Malabsorption </li></ul><ul><li>- small bowel disease ( tropical sprue, celiac disease,) </li></ul><ul><li>- alcoholism </li></ul><ul><li>3. Increased requirements: </li></ul><ul><li>- pregnancy and lactation </li></ul><ul><li>- infancy </li></ul><ul><li>- chronic hemolysis </li></ul><ul><li>- malignancy </li></ul><ul><li>- hemodialysis </li></ul><ul><li>4. Defective utilisation </li></ul><ul><li>Drugs: folate antagonists (methotrexate, trimethoprim), purine analog ue s (azathioprine), p y rimidine analog ue s (zidovudine), RNA reductase inhibitor (hydroxyurea), miscellaneous (phenytoin) </li></ul>
  10. 13. MEGALOBLASTIC ANEMIAS clinical features <ul><li>1. Symptoms of anemia </li></ul><ul><li>2. Symptoms associated with vit. B 12 or Folic acid deficiency </li></ul><ul><li>neurologic manifestations (exclusiv e ly in v it. B 12 deficiency) </li></ul><ul><li>- megaloblastic madness or psychosis, </li></ul><ul><li>- subacute, combined degeneration of the spinal cord </li></ul><ul><li> ( proprioceptive and vibratory sensation, spinal ataxia) </li></ul><ul><li>gastrointestinal comp l aints (vit.B 12 and folic acid deficiency) </li></ul><ul><li>- loss of appetite </li></ul><ul><li>- gloss i tis (red, sore, smooth tongue) </li></ul><ul><li>- diarrhea or constipation </li></ul>
  11. 14. <ul><li>Combined degeneration refers to the combined </li></ul><ul><li>demyelination of both pyramidal (lateral </li></ul><ul><li>columns) and posterior (dorsal) columns, the </li></ul><ul><li>signs and symptoms being predominantly in the legs </li></ul>
  12. 15. Clinical features of SCD <ul><li>Sensory peripheral neuropathy with numbness </li></ul><ul><li>and paraesthesia in the feet are the usual presenting symptoms. </li></ul><ul><li>Less commonly, the disease presents as a spastic paraparesis. </li></ul><ul><li>The signs are of: </li></ul><ul><li>posterior column (loss of vibration and position senses, with positive Romberg); </li></ul><ul><li>upper motor neuron lesion (weakness, hypertonia and hyperreflexia, with absent abdominal reflexes and upgoing toes); </li></ul><ul><li>peripheral neuropathy (absence of all jerks), reduced touch sense and deep tenderness in the calves </li></ul>
  13. 17. MEGALOBLASTIC ANEMIAS Diagnosis(1) <ul><li>1. Blood cell count: </li></ul><ul><li>macrocytic anemia ( MCV>100fl ) </li></ul><ul><li>thrombocytopenia </li></ul><ul><li>leucopenia (granulocytopenia) </li></ul><ul><li>low reticulocyte count </li></ul><ul><li>2. Blood smear: </li></ul><ul><li>macroovalocytosis , anisocytosis, poikilocytosis </li></ul><ul><li>hypersegmentation of granulocytes </li></ul>
  14. 18. MEGALOBLASTIC ANEMIAS Diagnosis(2) <ul><li>3. Laboratory features </li></ul><ul><li>indirect hyperbilirubinemia </li></ul><ul><li>elevation of lactate dehrogenase (LDH) </li></ul><ul><li>serum iron concentration- normal or increased </li></ul><ul><li>4. Bone marrow smear </li></ul><ul><li>hypercellular </li></ul><ul><li>increased erythroid /myeloid ratio </li></ul><ul><li>erythroid cell changes (megaloblasts, RBC precursor abnormally large with nuclear- cytoplasmic asynchrony) </li></ul><ul><li>myeloid cell changes (giant bands and metamyelocytes , hypertsegmentation) </li></ul><ul><li>megakariocytes are decreased and show abnormal morphology </li></ul>
  15. 19. MEGALOBLASTIC ANEMIAS Diagnosis <ul><li>1. Diagnosis of megaloblastic anemia </li></ul><ul><li>2. Establishing a type of deficiency (vit. B 12 and/or folic acid) </li></ul><ul><li>3. Establishing a cause of deficiency </li></ul>
  16. 20. VIT B 12 DEFICIENCY ANEMIA DIAGNOSIS <ul><li>1. Establishing megaloblastic anemia </li></ul><ul><li>2. Clinical symptoms of vit. B 12 deficiency </li></ul><ul><li>3. Low serum vit. B 12 </li></ul>
  17. 21. PERNICIOUS ANEMIA DIAGNOSIS <ul><li>1. Establishing vit.B 12 deficiency anemia </li></ul><ul><li>2. Absence of [H +] secretion (achlorhydria) with maximal histamine stimulation </li></ul><ul><li>3. Radiolabeled vit. B 12 absorption test (Schilling test) : very reduced absorption of the B 12 -isotope, corrected to normal only when coadministered with a source of gastric IF. </li></ul><ul><li>4. Intrinsic factor, parietal cell and IF-vit.B 12 complex antibodies </li></ul>
  18. 22. SCHILLING TEST
  19. 23. FOLIC ACID DEFICIENCY ANEMIA DIAGNOSIS <ul><li>1. Establishing megaloblastic anemia </li></ul><ul><li>2. History: causes of folate deficiency </li></ul><ul><li>3. Absence neurologic symptoms </li></ul><ul><li>4. Low serum and red blood cell folic acid </li></ul>
  20. 24. MEGALOBLASTIC ANEMIAS TREATMENT(1) <ul><li>PERNICIOUS ANEMIA </li></ul><ul><li>1. Vitamin B 12 i m 1000 μg 3 times/ week for 2 weeks, then 100 0 μg every 3 month s (without neurological involvement) </li></ul><ul><li>With neurological signs: 1000 µg on alternate days until no further improvement, then 1000µg every 2 months </li></ul><ul><li>2. Reticulocytosis begins 2 or 3 days after therapy started and maximal number reached on day 5 to 8. </li></ul><ul><li>Serum iron monitoring, after 7-10 days of vit.B12 treatment, as it may fall, for which iron is indicated </li></ul>
  21. 25. MEGALOBLASTIC ANEMIAS TREATMENT(2) <ul><li>FOLIC ACID DEF . ANEMIA </li></ul><ul><li>1. Oral folic acid 5mg / day, for 3 months </li></ul><ul><li>2. Reticulocytosis after 5-7 days </li></ul><ul><li>3. Correction of anemia is over after 1-2 months </li></ul><ul><li>4. Maintenance therapy if necessary </li></ul>

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