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Eric Niederhoffer SIU-SOM

A 4-year-old African boy is brought in by his adoptive parents who say that he has pain in his limbs and does not want to walk. What affects the normal functions of an erythrocyte?. Eric Niederhoffer SIU-SOM. RBC structure size, spectrin , channels Metabolism

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Eric Niederhoffer SIU-SOM

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  1. A 4-year-old African boy is brought in by his adoptive parents who say that he has pain in his limbs and does not want to walk What affects the normal functions of an erythrocyte? Eric Niederhoffer SIU-SOM

  2. RBC structure size, spectrin, channels Metabolism glycolysis (2,3-BPG), pentose phosphate pathway (G6PDH, NADPH), glutathione Hemoglobin genes, heme, Mb/Hb (normal), HbS (defect), fibers (sickling and inflammation) Red Blood Cell: Biochemistry and Sickle Cell Disease

  3. An Erythrocyte (RBC) Reference Ranges RBCs, male 4.3-5.9 x 106/µL female 3.5-5.5 x 106/µL Hb, male 13.5-17.5 g/dL female 12.0-16.0 g/dL Hct, male 41-53% female 36-46% MCH 25.4-34.6 pg MCV 80-100 fL MCHC 31-36 % Practical Values 65% of Fe in Hb 1 g Hb = 3.46 mg Fe 1 mL blood at 15 g/dL Hb = 0.5 mg Fe RBC x 3 = Hb Hb x 3 = Hct Microcytic < 80 fL Macrocytic > 100 fL

  4. Erythrocyte Membrane Composition http://www.ruf.rice.edu/~bioslabs/studies/sds-page/rbcmembrane.html

  5. H2O2 H2O GSH GP HK Glc G6P NADP+ + H+ GSSG PGI GR F6P Glycolysis NADPH PFK F16BP aldolase G6PDH lactonase 6PGDH G3P DHAP CO2 G3PDH BPG mutase 1,3-BPG 6PG PGK 2,3-BPG PPP 3PG PGM 2,3-BPG phosphatase 2PG 3-7 C metabolites (R5P, F6P, G3P) enolase PEP PK No O2 Lactate Pyr LDH RBC Metabolic Pathways

  6. Hemoglobin Genes and Gene Products http://www.mun.ca/biology/desmid/brian/BIOL3530/DB_Ch09/fig9_24.jpg

  7. Yolk sac Liver Spleen Bone marrow HbF: 2α and 2γ HbA1: 2α and 2β HbA2: 2α and 2δ HbE: 2ζ and 2ε Hemoglobin Gene Product Production Mehta, A. B., and A. V. Hoffbrand. 2000. Haematology at a glance, Blackwell Science, Malden, Mass.

  8. Glu6→Val6 oxyMb (MbO2) oxyHb (HbO2)   deoxyMb deoxyHb O2 O2 O2 O2  O2  Glu6→Val6 Myoglobin and Hemoglobin Structure

  9. Hemoglobin Structure Changes http://www.mfi.ku.dk/PPaulev/chapter8/images/8-3.jpg

  10. Sickle Cell Disease (>6 major genotypes) at least 1 sickle gene, hemoglobin S (HbS) ≥ 50% Hb present. homozygotic HbSS (sickle cell anemia) - HbS = 100% Hb present HbSbeta-0 thalassemia - Severe double heterozygote for HbS and beta-0 thalassemia; almost indistinguishable from sickle cell anemia phenotypically (MCV low) HbSC disease - Double heterozygote for HbS and HbC, with intermediate clinical severity HbS/hereditary persistence of fetal hemoglobin (S/HPHP) - Mild form or symptom free HbS/HbE syndrome - Rare and generally mild clinical course Rare combinations of HbS with HbD Los Angeles, HbO Arab, G-Philadelphia, among others http://www.emedicine.com/ped/TOPIC2096.HTM

  11. Homozygous HbS Heterozygous HbS Normal adult Normal neonate HbSC Hemoglobin Electrophoresis Relative protein charge http://themedicalbiochemistrypage.org/hemoglobin-myoglobin.html

  12. Heme Val Molecular Changes of HbS http://www.sicklecellinfo.net/fiberformation.htm. Daniel J. Harrington, D. J., K. Adachi, and W. E. Royer, Jr. 1997. J. Mol. Biol. 272(3):398-407

  13. Molecular and Cellular Changes of HbS Decreased PO2 Permanent damage to RBC Cell⟺endothelium interactions http://www.emedicine.com/ped/TOPIC2096.HTM

  14. Effects of Therapy with Hydroxyurea ★ ★ ★ http://www.emedicine.com/ped/TOPIC2096.HTM

  15. What proteins compose the membrane of erythrocytes? What metabolic pathways are used in erythrocytes? What is hemoglobin; what changes with sickle cell disease? What clinical observations would you make concerning patients with SCD? Review Questions

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