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Disorders of hemoglobin ppt BIOCHEMISTRY

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Disorders of hemoglobin ppt BIOCHEMISTRY

  1. 1. Dr. Vijay Marakala, MBBS, MD. Assistant professor BIOCHEMISTRY SIMS & RC
  2. 2. Hemoglobinopathies are disorders of Hb resulting from changes in the amino acid sequence of one of the globin chains or lack /decreased production of globin chains
  3. 3. Hemoglobin S Hemoglobin C Methemoglobinemia Thalassemia
  4. 4. • Abnormal β-globin chains • GLUTAMIC ACID in the 6th position of β-globin chain is replaced by VALINE • Substitution due to point mutation
  5. 5. SICKLE CELL ANEMIA • Homozygous • Inherited 2 mutant β- globin genes • Polymerization of RBCs • Sickle shaped RBCs SICKLE CELL TRAIT • Heterozygous • One normal gene • Asymptomatic
  6. 6. Hemolytic anemia Tissue damage Pain Infection Protection against malaria
  7. 7. Microscopy • Microcytic hypochromic anemia • Sickling of RBCs Hb Electrophoresis • Presence of HbS • Decreased or absence of HbA & ↑HbF Molecular • RFLP
  8. 8. Blood transfusion For anemia Iron overload Cirrohosis Anti-sickling agents Hydroxyurea Sodium cyanate Aspirin
  9. 9. Substitution of glutamic acid by lysine in the 6th β-chain RBCs do not sickle Mild hemolytic anemia
  10. 10. • Substitution occurs in either proximal or distal histidine by tyrosine • Iron will be in ferric form forming methemoglobin • Oxygen binding is decreased • Cyanosis Alpha 58 His →Tyr [Hb M Boston] Beta 92 His → Tyr [Hb M Hyde Park]
  11. 11. Thalassemia are group of inherited disorders of Hb synthesis characterized by lack or decreased synthesis of α or β globin chains Absence or reduced output of one or more globin chains of Hb
  12. 12. • Found most frequently in the Mediterranean, Africa, Western and Southeast Asia, India and Burma • Distribution parallels that of Plasmodium falciparum
  13. 13. On the basis of Globin chains α- Thalassemia • Impaired α- chain production β- Thalassemia • Impaired β- chain production On the basis of Inheritance Homozygous • α- Thalassemia major • β- Thalassemia major Heterozygous • α- Thalassemia minor • β- Thalassemia minor
  14. 14. α-Thalassemia • Different types of gene deletions. • Rarer because alpha chain deficiency is incompatible with life
  15. 15. α- Thalassemia Silent carrier • - / • No effects Trait • - /- • --/ • Mild anemia Hb H disease • --/- • Moderate anemia Barts hydrops fetalis • --/-- • Severe • Fetal death /Normal
  16. 16. β Thalassemia Minor • / 0 • / + • Mild anemia Intermedia • 0/ + • Moderate anemia Major • 0/ 0 • +/ + • Severe anemia 0 = no production of the chain + = diminished production of the chain /Normal
  17. 17. 1- Anemia : Microcytic and hypochromic 2- Excessive hemolysis 3- Hyperplasia of the bone marrow and extramedullary erythropoiesis
  18. 18. In both thalassemia and hemoglobinopathy therapy is usually supportive rather than curative
  19. 19. • Time of presentation • Related to degree of severity • Usually in first few years of life • Untreated severe thalassemia • --/--: Prenatal or perinatal death • --/- & --/ : Normal life span with chronic hemolytic anemia
  20. 20. • Untreated thalassemia • Major: Death in first or second decade of life • Intermedia: Usually normal life span • Minor/Minima: Normal life span
  21. 21. 1- Palliative transfusion: It is just to keep patient surviving 2- Hypertransfusion: Maintain a hemoglobin level of 9 to 10 g/dl To reduce extramedullary erythropoiesis 3- Supertransfusion: Maintain a hemoglobin level >12 g/dl in an effort to suppress all erythropoiesis.
  22. 22. Chelation therapy with Deferoxamine
  23. 23. Alternative treatment • Activation of fetal hemoglobin genes • Bone marrow transplantation
  24. 24. Antenatal diagnosis. DNA diagnosis is based on PCR amplification of fetal DNA
  25. 25. HEMOGLOBIN DERIVATIVES Compounds that are formed by combinations of ligands with hemoglobin
  26. 26. HEMOGLOBIN DERIVATIVES Oxyhemoglobin Deoxyhemoglobin Carbaminohemoglobin Methemoglobin Carboxyhemoglobin Sulfhemoglobin
  27. 27. Mutation in the globin chain Deficiency of methemoglobin reductase Decreased supply of NADPH Combination of oxidizing chemicals
  28. 28. C A U S E S Smoking Exposure to coal mining Environmental pollution

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