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IRON DEFICIENCY ANEMIA/ ANEMIA OF CHRONIC DISEASE

IRON DEFICIENCY ANEMIA/ ANEMIA OF CHRONIC DISEASE. Maj Gen Muhammad Ayyub MBBS (Pesh), Ph.D (London), FRC Path (UK), Army Medical College, Rawalpindi. ANEMIA Definition. Decrease in the number of circulating red blood cells Most common hematologic disorder by far. ANEMIA Causes.

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IRON DEFICIENCY ANEMIA/ ANEMIA OF CHRONIC DISEASE

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  1. IRON DEFICIENCY ANEMIA/ ANEMIA OF CHRONIC DISEASE Maj Gen Muhammad Ayyub MBBS (Pesh), Ph.D (London), FRC Path (UK), Army Medical College, Rawalpindi

  2. ANEMIADefinition • Decrease in the number of circulating red blood cells • Most common hematologic disorder by far

  3. ANEMIACauses • Blood loss • Decreased production of red blood cells (Marrow failure) • Increased destruction of red blood cells • Hemolysis • Distinguished by reticulocyte count • Decreased in states of decreased production • Increased in destruction of red blood cells

  4. ANEMIACauses - Decreased Production • Cytoplasmic production of protein • Usually normocytic (MCV 80-100 fl) or microcytic (MCV < 80) • Nuclear division/maturation • Usually macrocytic (MCV > 100 fl)

  5. ANEMIACauses - Cytoplasmic Protein Production • Decreased hemoglobin synthesis • Disorders of globin synthesis • Disorders of heme synthesis • Heme synthesis • Decreased Iron • Iron not in utilizable form • Decreased heme synthesis

  6. IRON DEFICIENCY ANEMIAPrevalence

  7. IRON • Functions as electron transporter; vital for life • Must be in ferrous (Fe+2) state for activity • In anaerobic conditions, easy to maintain ferrous state • Iron readily donates electrons to oxygen,  superoxide radicals, H2O2, OH• radicals • Ferric (Fe+3) ions cannot transport electrons or O2 • Organisms able to limit exposure to iron had major survival advantage

  8. Stores1000mg Tissue500 mg Red Cells2300 mg IRONBody Compartments - 75 kg man Absorption < 1 mg/dayExcretion < 1 mg/day 3 mg

  9. CIRCULATING RBCs MONONUCLEARPHAGOCYTES Fe Fe Fe Fe Fe Fe Transferrin Receptor Ferritin Fe Fe Fe Fe Ferritin Fe Ferritin Fe slow Hemosiderin Fe Fe RBC PRECURSOR Fe Fe TRANSFERRIN IRON CYCLE

  10. INTRACELLULAR IRON TRANSPORT Fe+2 Transferrin Transferrin receptor H+ H+ Lysosome Fe+2 H+ H+

  11. IRONCauses of Iron Deficiency • Blood Loss • Gastrointestinal Tract • Menstrual Blood Loss • Urinary Blood Loss (Rare) • Blood in Sputum (Rarer) • Increased Iron Utilization • Pregnancy • Infancy • Adolescence • Polycythemia Vera • Malabsorption • Tropical Sprue • Gastrectomy • Chronic atrophic gastritis • Dietary inadequacy (almost never sole cause) • Combinations of above

  12. DAILY IRON REQUIREMENTS Pregnancies

  13. IRON ABSORPTION

  14. Fe Fe Fe Fe Fe Fe Fe TRANSFERRIN GI ABSORPTION OF IRON Fe Fe Fe Fe Fe Fe Fe Ferritin Fe Fe Fe Fe Fe Fe Fe Fe

  15. IRE Ferritin HIGH IRON IREBindingProtein Fe Fe Fe + Fe Fe Fe Fe Fe IRE FerritinMessage LOW IRON Fe Fe IREBindingProtein Ribosome Fe FERRITIN REGULATION

  16. IRE Transferrin LOW IRON IREBindingProtein Fe Fe Fe + Fe Fe Fe Fe Fe Transferrin Message IRE HIGH IRON Fe Fe IREBindingProtein Ribosome Fe TRANSFERRIN REGULATION Fe

  17. IRON ABSORPTION

  18. IRON DEFICIENCY ANEMIAProgression of Findings • Stainable Iron, Bone Marrow Aspirate • Serum Ferritin - Low in Iron Deficiency • Desaturation of transferrin • Serum Iron drops • Transferrin (Iron Binding Capacity) Increases • Blood Smear - Microcytic, Hypochromic; Aniso- & Poikilocytosis • Anemia

  19. Tissue500 mg Red Cells1500 mg IRON STORESIron Deficiency Anemia Stores0 mg Absorption 2-10 mg/dayExcretion Dependent on Cause 3 mg

  20. IRON DEFICIENCYSymptoms • Fatigue - Sometimes out of proportion to anemia • Atrophic glossitis • Pica • Koilonychia (Nail spooning) • Esophageal Web

  21. IRONCauses of Iron Deficiency • Blood Loss • Gastrointestinal Tract • Menstrual Blood Loss • Urinary Blood Loss (Rare) • Blood in Sputum (Rarer) • Increased Iron Utilization • Pregnancy • Infancy • Adolescence • Polycythemia Vera • Malabsorption • Tropical Sprue • Gastrectomy • Chronic atrophic gastritis • Dietary inadequacy (almost never sole cause) • Combinations of above

  22. IRON REPLACEMENT THERAPYResponse • Usually oral; usually 300-900 mg/day • Requires acid environment for absorption • Poorly absorbed

  23. IRON THERAPYResponse • Initial response takes 7-14 days • Modest reticulocytosis (7-10%) • Correction of anemia requires 2-3 months • 6 months of therapy beyond correction of anemia needed to replete stores, assuming no further loss of blood/iron • Parenteral iron possible, but problematic

  24. ANEMIA OF CHRONIC DISEASEFindings • Mild, non-progressive anemia (Hgb c. 10, Hct c. 30% • Other counts normal • Normochromic/normocytic (30% hypochromic/microcytic) • Mild aniso- & poikilocytosis • Somewhat shortened RBC survival • Normal reticulocyte count (Inappropriately low for anemia) • Normal bilirubin • EPO levels increased but blunted

  25. ANEMIA OF CHRONIC DISEASECauses • Thyroid disease • Collagen Vascular Disease • Rheumatoid Arthritis • Systemic Lupus Erythematosus • Polymyositis • Polyarteritis Nodosa • Inflammatory Bowel Disease • Ulcerative Colitis • Crohn’s Disease • Malignancy • Chronic Infectious Diseases • Osteomyelitis • Tuberculosis • Familial Mediterranean Fever • Renal Failure

  26. Stores2500 mg Tissue500 mg IRON STORESAnemia of Chronic Disease Absorption < 1 mg/dayExcretion < 1 mg/day 1 mg Red Cells1100 mg

  27. CIRCULATING RBCs MONONUCLEARPHAGOCYTES Fe Fe Ferritin Fe Fe Fe Fe Fe Fe Transferrin Receptor Ferritin Ferritin Fe slow Fe Hemosiderin RBC PRECURSOR Fe Fe IL-1/TNF TRANSFERRIN IRON CYCLEAnemia of Chronic Disease

  28. IRON DEFICIENCY versus ACD Serum Iron Transferrin Ferritin Iron Deficiency ACD

  29. SUMMARYIron-Related Anemias • Most common anemia • Symptom of pathologic process • Primary manifestation is hematologic • Treatment requires: • Replacement therapy • Correction of underlying cause (if possible)

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