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Iron Deficiency Anemia & Recent Advances In Iron Metabolism

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Iron Deficiency Anemia & Recent Advances In Iron Metabolism

Dept Of Lab Medicine
Basavatarakam Indo American Hospital And Research Institute

Published in: Health & Medicine

Iron Deficiency Anemia & Recent Advances In Iron Metabolism

  1. 1. Dr. Siddartha. K Moderator : Dr. Faiq Ahmed Dept Of Lab Medicine Basavatarakam Indo American Hospital And Research Institute
  2. 2.  Defined as an insufficient RBC mass to adequately deliver oxygen to peripheral tissues. -- Wintrobes  Defined as a decrease in the amount of red blood cells (RBCs) or the amount of hemoglobin in the blood. It can also be defined as a lowered ability of the blood to carry oxygen. -- Wikipedia  Anemia is defined as a reduction of the total circulating red cell mass below normal limits -- Robbins
  3. 3.  Iron deficiency is the most common nutritional deficiency in both developing and developed countries
  4. 4.  Full-term infants - 75 mg/kg body weight of Fe.  Adult male - 50 mg/kg body weight of Fe.  Adult women – 35 mg/kg body weight of Fe. Menstruation, Pregnancy, Parturition
  5. 5.  In the average subject, the plasma iron concentration is ∼18μmol/L (100 μg/dl), and the TIBC is ∼56 μmol/L (300 μg/dl).  Thus, only about one third of the available transferrin binding sites are occupied, leaving a large capacity to deal with excess iron.  Plasma iron concentration varies over the course of the day, with the highest values in the morning and the lowest in the evening.  Levels of serum transferrin are more constant
  6. 6.  Iron is not actively excreted from the body;  Eliminated only through the loss of ¶ Epithelial cells from the GIT, ¶ Epidermal cells of the skin, and, ¶ In menstruating women, red blood cells. ¶ Sweat ¶ Urine
  7. 7. https://www.inkling.com/read/robbins-cotran-pathologic-basis-of- disease-8th/chapter-14/figure-1422
  8. 8.  Ferroportin - also expressed in other tissues like • Macrophages recycling iron from old RBC, • Hepatocytes storing iron, and • Placental trophoblast delivering iron from mother to fetus  A small proportion of the heme iron may pass into the plasma heme exporter protein FLVCR (feline leukemia virus, subgroup C receptor), which transfers heme onto a heme-binding protein, hemopexin.
  9. 9.  Dietary heme iron – unaffected by diet  Dietary non-heme iron  Enhanced by Vit C, keto sugars, organic acids, and amino acids.  Decreased by phytates, polyphenols, calcium, tannates in tea, bran.
  10. 10.  Hepcidin, the liver-expressed antimicrobial peptide, (LEAP-1),  Type II acute-phase reactant produced in the liver that displays intrinsic antimicrobial activity  Acts as a systemic regulator of iron  Produced in the liver, secreted into the plasma, and excreted through the kidneys.
  11. 11. https://www.inkling.com/read/wintrobes-clinical-hematology- greer-13th/chapter-23/figure-23-3 Hemojuvelin (HJV), Matriptase-2 (MT-2) & Bone morphogenic protein(BMP).
  12. 12. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669438/fig ure/f1-0980845/
  13. 13.  Growth differentiation factor 15 (GDF15) and twisted-gastrulation 1 (TWSG1) are BMP family members that have been proposed as pathological suppressors of hepcidin in thalassemia.
  14. 14. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104984/
  15. 15.  Intracellular iron levels in enterocytes (and most other cells) are sensed by two iron- regulatory proteins (IRP1 and IRP2).
  16. 16.  Intracellular iron concentration is modulated by IRP binding to IREs ???  IRP1 contains a 4Fe•4S cluster ,when saturated with iron, converts IRP1 to a cytosolic aconitase .  In this enzyme form, IRP1 has low affinity for IREs in transferrin mRNAs.  When iron-poor, IRP1 loses its aconitase activity and greatly increases its affinity for IREs
  17. 17.  Transferrin – plasma iron binding protein  Synthesized in the liver, but lesser amounts are made in other tissues, including the central nervous system, the ovary, the testis, and helper T lymphocytes.  Transferrin keeps iron nonreactive in the circulation and extravascular fluid,  Delivers iron to cells bearing transferrin receptors.
  18. 18.  Transferrin binds 2 atoms of trivalent (ferric) iron.  Fe3+ binds to transferrin with very high affinity.  The affinity of iron–transferrin interaction is pH-dependent, decreasing as pH is lowered.  Metals like Cu,Cr,Mn,Ga,Al,Co also bind to transferrin but with less affinity than iron.
  19. 19.  2 receptors TfR1 and TfR2  TfR1- have more affinity for diferric transferrin  TfR2- binds transferrin with lower affinity  Max receptors are present in polychromatophilic erythroblasts.
  20. 20. https://www.inkling.com/read/wintrobes-clinical-hematology-greer-13th/chapter-23/figure-23-5 6-transmembrane epithelial antigen of the prostate 3 = steap3
  21. 21.  ∼80% to 90% of the Fe is incorporated into heme.  Rest is stored as ferritin.  Because excess heme is toxic to cells  Erythroblasts also express heme exporter FLVCR and iron exporter ferroportin.  FLVCR functions as a safety valve to prevent accumulation of excess heme early during erythroid differentiation feline leukemia virus subgroup C
  22. 22. Erythrophagocytosis RE system (macrophages) Membrane lysis  Hb  Heme Heme oxygenase Iron
  23. 23. 2 phases are seen  Early phase (with in hrs after Erythrophagocytosis )  Later phase (period of yrs)  The early phase - sequential induction of ferroportin mRNA expression  iron release  Later phase – in iron demand
  24. 24. Negative Fe balance
  25. 25.  Fatigue and Other Nonspecific Symptoms  Impaired muscular performance  Fingernails - brittle, fragile, or longitudinally ridged,. Koilonychia  Atrophy of the lingual papillae (filiform papillae 1st)  Angular stomatitis  Dysphagia  Plummer-Vinson syndrome http://byebyedoctor.com/wp- content/uploads/2011/04/koilon ychia-2.jpg
  26. 26.  Pica – craving to eat earth  Pagophagia - common form eating tray of rice daily
  27. 27. https://www.inkling.com/read/wintrobes-clinical-hematology-greer-13th/chapter-23/figure-23-9
  28. 28. RBC indices  MCV,MCH,MCHC are decreased  RDW is high
  29. 29. Iron indices  Serum ferritin ≤12 ng/ml (sensitivity -25%) and improved to 92%, by using a diagnostic cutoff value of ≤30 ng/ml.  Increased sTfR has been reported to be an indicator of iron deficiency - released by erythropoietic precursors in proportion to their expansion, and is not increased by inflammation.
  30. 30.  N = 15–300 μg/l in healthy men Detected by 1.Immunoradiometric assay 2.Immuno assay system  High concentrations of serum ferritin, may also be found in patients with liver disease, infection, inflammation, or malignant disease, aging, juvenile rheumatoid arthritis, leukemia, and Hodgkin's disease.
  31. 31.  N values in women 16.1 ± 7.4 μmol/l. in men 18.0 ± 6.3 μmol/l. Methods : - With protein precipitation With out protein precipitation Automated methods
  32. 32. The normal serum TIBC was  68.0 ± 12.6 μmol/l in women and  63.2 ± 9.1 μmol/l for men.  Increased in IDA and pregnancy.  Normal or decreased in anemia of chronic disease or sideroblastic anemia.  Decreased in pathological iron overload.
  33. 33.  Normal values – 0.63-1.80 g/l  1 mg of transferrin binds 1.4 μg of iron  Ratio of the serum iron conc. and the TIBC expressed as a percentage  Normal in men 29.1 ± 11.0%; in women 24.6 ± 11.8%
  34. 34.  Serum iron concentration (μmol/l) divided by the transferrin concentration (μmol/l).  Better precision than the TSAT and showed greater specificity for detecting iron overload than the transferrin saturation
  35. 35.  M=F  sTfR conc. are high in neonates and decline until adult conc. are reached at 17 years.  During pregnancy sTfR levels increase, returning to nonpregnant values 12 weeks after delivery.
  36. 36.  The “free” protoporphyrin conc.(Zn protoporphyrin) of RBC increases in iron deficiency.  Reticulocyte count will be low in IDA
  37. 37.  CHr – measures the Hb content of reticulocytes.  Directly reflects the recent Hb synthesis in bone marrow precursors.  Greater sensitivity(100%) and specificity(80%) for diagnosing Iron Deficiency Anemia.  Normal values – 24.5- 31.8 pg.
  38. 38. Normal iron stores with iron granules in erythroblasts Absence of iron stores in IDA
  39. 39.  Wintrobes-clinical-hematology-greer-13th/chapter- 23/chapter-23-introduction  Dacie and Lewis: PRACTICAL HAEMATOLOGY tenth editon.  Clinical laboratory hematology by McKenzie  Robbins and Cotran pathological basis of disease 9th edition  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104984/  http://www.ncbi.nlm.nih.gov/pubmed/23729726

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