Haemopoietic system

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Haemopoietic system

  1. 1. HAEMOPOIETIC SYSTEM
  2. 2. HAEMOPOIETIC SYSTEMBLOODPlasma Coagulation factorsCells White blood cells/Leukocytes (WBCs) Red blood cells/Erythrocytes (RBCs) Platelets/Thrombocytes
  3. 3. HAEMOPOIETIC SYSTEMHaemopoiesis yolk sac Liver Spleen Bone marrow long bones (children) Axial skeleton (adults)
  4. 4. HAEMOPOIETIC SYSTEMDISEASES OF HAEMOPOIETIC SYSTEMCytopenia ↓ production ↑ destruction / poolingCytosis reactive malignant
  5. 5. HAEMOPOIETIC SYSTEMRBCs AnaemiasWBCs  Leukaemias  myeloproliferative disorders  Lymphomas  plasma cell disordersPlatelets  Thrombocytopenia  function defectsCoagulation disorders factor deficiency
  6. 6. HAEMOPOIETIC SYSTEMANAEMIA:Reduction below the normal limits of thetotal circulating red cell mass.Reduction in Hb, HCT/PCV below thenormal limit for that age, sex andenvironment
  7. 7. HAEMOPOIETIC SYSTEMERYTHROPOIESIS:Formation of RBCsErythropoietinMinerals, vitamins etc: iron, Mn, Co vit B12, folic acid, B6, vit C, E, B1 amino acids hormones
  8. 8. HAEMOPOIETIC SYSTEMCLASSIFICATION OF ANAEMIAS:Morphological Size Shape ColourPathogenetic blood loss Reduced production increased destruction
  9. 9. HAEMOPOIETIC SYSTEMMorphological classification:1. Normocytic Normochromic blood loss aplastic anaemia ACD hemolytic anameia
  10. 10. HAEMOPOIETIC SYSTEM2. Microcytic Hypochromic Iron deficiency anaemia Thalassaemias Sidroblastic anaemia ACD
  11. 11. HAEMOPOIETIC SYSTEM3. Macrocytic Megaloblastic anaemia hemolytic anaemia
  12. 12. HAEMOPOIETIC SYSTEMPathogenetic classification:1. Blood loss Acute Chronic2. Increased destruction (hemolytic) Hereditary membrane defects Spherocytosis Elliptocytosis
  13. 13. HAEMOPOIETIC SYSTEM Metabolic defects G6PD deficiency PK deficiency Hb defects quantitaive defects Thalassaemias qualitative defects sickle cell anaemia HbC, D, E unstable Hb
  14. 14. HAEMOPOIETIC SYSTEM Acquired Immune hemolytic anaemias Non immune MAHAs (mechanical) PNH malaria & other infections mechanical trauma Hypersplenism DIC Drugs
  15. 15. HAEMOPOIETIC SYSTEM3. Impaired production: Nutritional deficiencies megaloblastic anaemia iron deficiency anaemia Aplastic anaemia Pure red cell aplasia sideroblastic anaemia anaemia of chronic disease
  16. 16. HAEMOPOIETIC SYSTEMParameter Males FemalesHb 15+/-2 gm/dl 13+/-1.5RBC count 5+/-0.5x10 /l 12 4.5+/-0.5PCV 0.45+/- 0.05l/l 0.4+/- 0.5 l/lMCV 92 +/- 9 flMCH 29.5+/-2.5 pgMCHC 33 +/- 1.5 g/dlCell diameter 6.7 – 7.7 umReticulocyte 0.5-2.5%count 50 – 100x10 /l 12
  17. 17. HAEMOPOIETIC SYSTEMHEMOLYTIC ANAEMIAS:Normal red cell life span = 120 daysSplenic reticuloendothelial cellsDegradation of Hb  bilirubin
  18. 18. HAEMOPOIETIC SYSTEMHemolysis  shortened red cell life spanStimulated erythropoiesis  intra &extramedullary↑ Hb breakdown  ↑ bilirubin jaundice  gall stones
  19. 19. HAEMOPOIETIC SYSTEMExtravascular IntravascularPhysiologic PathologicRE cells spleen In blood vesselsFc receptor mediated Complement mediatedLess deformable RBC Mechanical injurySplenomegaly ++ Splenomegaly +/-Indirect Hbaemia, Hburia,hyperbilirubinaemia hemosidrinuriaJanudice ++ Jandice +Normal ↓ plasma Haptoglobin
  20. 20. HAEMOPOIETIC SYSTEMAnaemia  ↑ EPO  erythroid hyperplasia Marrow expansion  reticulocytosis  Leukoerythroblastic blood picture Gall stones haemosiderosis
  21. 21. Never look down on anybody unless youre helping him up
  22. 22. HAEMOPOIETIC SYSTEM HEREDITARY SPHEROCYTOSIS:
  23. 23. HAEMOPOIETIC SYSTEMAutosomal dominantIntrinsic membrane defectDeformability of RBC due to cytoskeletalProteinsSpectrinActinAnkyrinBand 4.2 & 3
  24. 24. HAEMOPOIETIC SYSTEMReduced membrane stabilityReduced deformability  spheroidalTrapped in spleen  lactic acid ++ Intracellular Na+ ↑  osmotic injuryPhagocytosis by RE cellsSplenomegaly
  25. 25. HAEMOPOIETIC SYSTEMVariable severityChronic hemolytic anaemiaAplastic crisisHemolytic crisis
  26. 26. HAEMOPOIETIC SYSTEMDIAGNOSIS:HistoryExaminationBlood filmOsmotic Fragility test
  27. 27. HAEMOPOIETIC SYSTEMGLUCOSE 6 PO4 DEHYDROGENASEDEFICIENCY
  28. 28. HAEMOPOIETIC SYSTEMX linkedOxidant damage to RBCs Heinz bodies  Bite cellsOxidant stress: Drugs (antimalarials, sulfonamides) Foods (Fava beans) Infections
  29. 29. HAEMOPOIETIC SYSTEMVariants  G6PD-A (Mediterranian)  G6PD-B (commonest)  G6PD A- (African, mild)Neonatal jaundiceAcute hemolysisChronic low grade hemolysisIntravascular hemolysisExtravascular hemolysis
  30. 30. HAEMOPOIETIC SYSTEM5 years boyProgressive pallorPainful swelling of fingers & toesJaundice twiceO/E pallor ++Jaundice +Spleen +Leg ulcersShort right middle finger
  31. 31. HAEMOPOIETIC SYSTEMHb = 5.5 gm/dlMCV = 74 flMCH = 26 l/lTLC = 18.6Plt = 110Retics = 12 %Leucoerythroblastic blood picture
  32. 32. HAEMOPOIETIC SYSTEMHAEMOGLOBIN ELECTROPHORESIS: Band of HbS
  33. 33. HAEMOPOIETIC SYSTEM SICKLING TEST
  34. 34. HAEMOPOIETIC SYSTEMSICKLE CELL DISEASE:Autosomal recessiveStructural variant of Hb6th position β globin chainValine  Glutamic acid  HbS
  35. 35. HAEMOPOIETIC SYSTEM Deoxy Hb ↓ Crystallization/polymerization HbS ↓ Tactoid formation (reversible) ↓ Repeated sickling de-sickling ↓ Irreversibly sickled ↓ Vascular occlusion
  36. 36. HAEMOPOIETIC SYSTEM Membrane damage  ↑ Ca  ↓ K+ ↓ Intracellular dehydration ↓ Sticky RBCs ↓ Vascular occlusion
  37. 37. HAEMOPOIETIC SYSTEMHomozygous  SCDHeterozygous  SC traitHbF inhibits polymerization of HbSIntracellular dehydration  ↑ MCHC  Sickling ++↓ pH  deoxy Hb  sickling
  38. 38. HAEMOPOIETIC SYSTEMCLINICAL PRESENTATION:Chronic hemolysis (extravascular)AnaemiaJaundiceInfections by encapsulated organisms osteomyelitis (salmonella)H-Influenza, PneumococciLeg ulcers
  39. 39. HAEMOPOIETIC SYSTEMVaso occlusive crisis  painful crisis bones  hand – foot syndrome lungs  acute chest syndrome brain  seizures / stroke liver  hepatic sequestration  pain spleen  sequestration syndrome penis
  40. 40. HAEMOPOIETIC SYSTEMMarrow expansion  hair on ends (x-ray skull)Prominent cheek bonesExtramedullary haemopoiesisGall stonesAplastic crisis (parvo virus)Autosplenetomy
  41. 41. HAEMOPOIETIC SYSTEMDIAGNOSIS:HistoryExaminationPeripheral smear ISC leucoerythroblastic blood picture reticulocytosis
  42. 42. HAEMOPOIETIC SYSTEMHb electrophoresis HbS bandSickling testPCR
  43. 43. HAEMOPOIETIC SYSTEMMANAGEMENT:Blood transfusion (RCC)PreventionBone marrow transplant
  44. 44. A man who is "of sound mind" is one who keeps the inner madman under lock and key
  45. 45. HAEMOPOIETIC SYSTEMHAEMOGLOBIN:Heme + 4 Globin chainsHbA  2a/2βHbA2  2a/2δHbF  2a/2γξ and ζ embryonic chains
  46. 46. HAEMOPOIETIC SYSTEMSynthesis of globin chains: Haemopoietic GF ↓ Gene activation ↓ Transcription ↓ Translation ↓ Post translation stability
  47. 47. HAEMOPOIETIC SYSTEM1.5 year girlFailure to thrivepallor and abdominal distensionCousin died at 3 years with similar problemsOne transfusion 2 months backO/E pallor +++Spleen 4 cmLiver edge
  48. 48. HAEMOPOIETIC SYSTEMTLC : 24.6Hb : 6.2Plt : 130MCV : 72MCH : 21NRBC 43/100 WBCLeft shift in neutrophils
  49. 49. HAEMOPOIETIC SYSTEMHbF : 97%DIAGNOSIS:Clinical, blood and electrophoresis findings are consistent with β - THALASSAEMIA MAJOR(β°)
  50. 50. HAEMOPOIETIC SYSTEMTHALASSAEMIAS:Reduced or no synthesis of one or moreglobin chains of Hb.Autosomal recessiveα chain deficiency  α thalassaemiaβ chain deficiency  β thalassaemia
  51. 51. HAEMOPOIETIC SYSTEMCLASSIFICATION:ClinicalGeneticThalassaemia major homozygous β + (β+/ β+) homozygous β o (βo / βo) β / Hb Lepore β / HbE
  52. 52. HAEMOPOIETIC SYSTEMThalassaemia Intermedia: β+/β+ β with α thalassaemia HbH disease β/δ compound heterozygotes HbE/ β
  53. 53. HAEMOPOIETIC SYSTEMThalassaemia minor:Silent carriers α + thalassaemia trait rare β thalassaemia traitMild anaemia α o thalassaemia trait α+/α+ thalassaemia β o trait β + trait δβ trait
  54. 54. HAEMOPOIETIC SYSTEMBETA THALASSAEMIA:Mutations in β globin gene Transcription promoter region mutations chain terminator mutations Processing of mRNA splicing mutations splice site in exon IVS CAP site
  55. 55. HAEMOPOIETIC SYSTEM Translation nonsense frameshift initiation site Post translational stability Exon 3
  56. 56. HAEMOPOIETIC SYSTEMDIAGNOSIS:HistoryExaminationBlood filmHb electrophoresisPCRFamily studies
  57. 57. HAEMOPOIETIC SYSTEMTREATMENT:Regular blood transfusionsIron chelation injectable oralSupportive treatmentBone marrow transplant
  58. 58. HAEMOPOIETIC SYSTEMPREVENTION*** genetic counseling antenatal diagnosisCOMPLICATIONS: growth retardation iron overload endocrine abnormalities CCF hepatic failure transfusion mediated infections (HBV,HCV)
  59. 59. "Sometimes the best helping hand you can get is a good, firm push”
  60. 60. HAEMOPOIETIC SYSTEMACQUIRED HEMOLYTIC ANAEMIAS:Immune hemolytic anaemia:Autoimmune HA warm antibody type idiopathic autoimmune diseases LPD infections cancers drugs
  61. 61. HAEMOPOIETIC SYSTEM cold antibody type cold agglutinin syndrome CHAD (idiopathic) infections LPD PCH
  62. 62. HAEMOPOIETIC SYSTEMAlloimmune HA transfusion reactions HDN allograft associated drug induced macrophage mediated complement mediated
  63. 63. HAEMOPOIETIC SYSTEMWarm antibody HA Cold antibody HACommonest (45-70%) 15-30%50% idiopathic Secondary >IgG, IgA IgMExtravascular Intravascular ++hemolysis Extravascular <Fc receptor mediated Complementmcrophage activation, C3b macro
  64. 64. HAEMOPOIETIC SYSTEMSpherocytosis RBC agglutinatesSplenomegaly Raynauds phenomena
  65. 65. HAEMOPOIETIC SYSTEMParoxysmal Cold Haemoglobinuria:Acute intermittent severe intravascularHemolysisP blood groupDonath – Landsteiner antibodyIgG  biphasic antibodyComplement mediated
  66. 66. HAEMOPOIETIC SYSTEM35 yrs femaleMother of 5 children (LCB 1.5 yrs)H/O menorrhagia 1 yearIncreasing weakness & fatiguabilityHusband is a labourer
  67. 67. HAEMOPOIETIC SYSTEMBlood CP:Hb : 7.6 gm/dlTLC : 6.5Plt : 460MCV : 66MCH : 19DLC : normalRetics 1.0 %
  68. 68. HAEMOPOIETIC SYSTEMSerum iron: 23 ug/dl (60-180)TIBC : 650 ug/dl (250-400)Serum Ferritin 6 ng/ml (15-150)DIAGNOSIS:IRON DEFICIENCY ANAEMIA.
  69. 69. HAEMOPOIETIC SYSTEMIRON METABOLISM:Diet / sourceAbsorptionTransportUtilization & excretionStoragedeficiency
  70. 70. HAEMOPOIETIC SYSTEMIron conc in males = 50 mg/kg females = 40 mg/kgTotal body iron = 3-5 gm7-8 yrs for depletion6 months-2 yrs physiological iron def
  71. 71. HAEMOPOIETIC SYSTEMAbsorption increased absorption decreasedHeme iron, animal food OppositeFerrous salts Ferric saltsAcid gastric pH AlkalisVit C, amino acids, sugars Phytates, tannates, teaIron deficiency Iron overload↑ eryhthropoiesis ↓ erythropoiesisPregnancy Inflammatory disordersHypoxia ------
  72. 72. HAEMOPOIETIC SYSTEMCauses of iron deficiency:Dietary lack poverty old age vegetariansIncreased demand pregnancy & lactation infants & children puberty
  73. 73. HAEMOPOIETIC SYSTEMImpaired absorption malaborption syndromes achlorhydria gastrectomy atrophic gastritisChronic blood loss GIT, genitourinary, respiratory hook worm infestation
  74. 74. HAEMOPOIETIC SYSTEMClinical presentation: symptoms of anaemia symptoms related to causeExamination: pallor angular cheilosis koilonychiaAbsence of certain features
  75. 75. HAEMOPOIETIC SYSTEMDiagnosis:HistoryExaminationRoutine investigationsSerum ferritinSerum iron TIBCBone marrow examination.
  76. 76. HAEMOPOIETIC SYSTEMTreatment:Treatment of causeIron supplements oral injectable
  77. 77. Ability is of little account without opportunity
  78. 78. HAEMOPOIETIC SYSTEMMEGALOBLASTIC ANAEMIA:A group of disorders characterized bypresence of MEGALOBLASTS in the bonemarrow.Impaired DNA synthesis
  79. 79. HAEMOPOIETIC SYSTEMCauses:Cobalamine deficiency or defect in metabolismFolate deficiency or defect in metabolismMDS, AMLAntifolate drugs, drugs interfering with DNA synthesisOrotic aciduriaLesh-Nyhan syndrome
  80. 80. HAEMOPOIETIC SYSTEMDNA synthesisRapidly proliferating cells haemopoietic cells …. GIT …. diarrhoea can be cause or effect GUT …. respiratory ….. prematurity neural tube defects
  81. 81. HAEMOPOIETIC SYSTEMMethylation of biogenic amines(dopamine) psychitric symptomsOf myelin proteins, phospholipids Neurologic symptoms bilateral peripheral neuropathy degeneration of dorsal columns & pyramidal tracts optic atrophy mental abnormalities (poor brain dev)
  82. 82. HAEMOPOIETIC SYSTEMHaematological findings: oval macrocytosis MCV > 100 fl pancytopenia hypersegmented neutrophils
  83. 83. HAEMOPOIETIC SYSTEMBone marrow findings:HypercellularDyserythropoiesisIneffective erythropoiesisMegaloblastsGiant myeloid precursorsHyperlobated megakaryocytesAbnormal mitotic figures
  84. 84. MEGALOBLAST:Large abnormal erythroid precursorsnuclear cytoplasmic asynchrony
  85. 85. HAEMOPOIETIC SYSTEMCOBALAMINE (VITAMIN B12)Only source animal foodBody stores = 2-3 mgSufficient for 3-4 yearsAbsorption (ileum, IF)Transport (transcobalamines)
  86. 86. HAEMOPOIETIC SYSTEMCauses of Cobalamine deficiency:1. Vegans2. Malabsorption Pernicious anaemia gastric causes IF def gastrectomy
  87. 87. HAEMOPOIETIC SYSTEM intestinal causes stagnant loop syndromes ileal resection crohn’s disease tropical sprue fish tape worms TC deficiency
  88. 88. HAEMOPOIETIC SYSTEMPERNICIOUS ANAEMIASpecific type of MBASevere lack of Intrinsic factor due togastric atrophyAutoimmune disorderAnti IF antibodiesAnti Parietal cell antibodies
  89. 89. HAEMOPOIETIC SYSTEMDiagnosis:HistoryExaminationBlood CPBone marrow examinationSerum B12 levelsSchillings testIF & PC antibodiesElevated homocystine & CH3-malonic acidTherapeutic response
  90. 90. HAEMOPOIETIC SYSTEMFOLIC ACID (Pteroylglutamic acid)Liver, yeast, spinach, greens, nutsTotal store = 10 mgFor 4-6 monthsAbsorbed from upper small intestinePolyglutamates  monoglutamatesTransported by albumin
  91. 91. HAEMOPOIETIC SYSTEMCauses of deficiency:1. Dietary: old age, poverty, infancy, alcoholism, psychiatrics2. Malabsorption tropical sprue celiac disease intestinal resection crohns disease
  92. 92. HAEMOPOIETIC SYSTEM3. Excess demand: physiological pregnancy, prematurity, lactation pathological hemolytic anaemias, malignancies inflammatory conditions homocystinuria hemodialysis patients
  93. 93. HAEMOPOIETIC SYSTEM4. Anti-folate drugs: anticonvulsants antiTB tetracyclins5. Liver disease, alcoholism
  94. 94. HAEMOPOIETIC SYSTEMTreatment:1. Of cause2. Cobalamine injections3. Folic acid tablets
  95. 95. HAEMOPOIETIC SYSTEMAPLASTIC ANAEMIA:“Presence of pancytopenia in theperipheral blood & a hypocellularmarrow in which normal haemopoieticmarrow is replaced by fat cells.”
  96. 96. HAEMOPOIETIC SYSTEMHaemopoietic stem cell defectDefect in microenvironmentCytotoxic T cell mediated suppression ofStem cellsIFN gamma, TNFAbsence of abnormal cells or fibrosis inBone marrow
  97. 97. HAEMOPOIETIC SYSTEMCauses:Idiopathic primary stem cell defect immune mediatedChemical agents dose related alkylating agents & antimetabolites benzene, arsenic chloramphenicol
  98. 98. HAEMOPOIETIC SYSTEM idiosyncratic chloramphenicol phenylbutazone arsenic, streptomycin insecticides & pesticidesPhysical agents radiation
  99. 99. HAEMOPOIETIC SYSTEMInfections hepatitis CMV, EBV, herpes VInherited Fanconi’s anaemia
  100. 100. HAEMOPOIETIC SYSTEMClinical presentation:Anaemia Thrombocytopenia Neutropenia 
  101. 101. HAEMOPOIETIC SYSTEMDiagnosis:HistoryExaminationBlood CPBone marrow aspiration & trephine
  102. 102. The purpose of life is to live a life of purpose.
  103. 103. HAEMOPOIETIC SYSTEM
  104. 104. HAEMOPOIETIC SYSTEM
  105. 105. HAEMOPOIETIC SYSTEM
  106. 106. HAEMOPOIETIC SYSTEM
  107. 107. HAEMOPOIETIC SYSTEM
  108. 108. "You make the world a better place by making yourself a better person."
  109. 109. HAEMOPOIETIC SYSTEM

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