haemopoietic system
TRANSCRIPT
CLASSIFICATION OF ANAEMIAS:Morphological
SizeShapeColour
Pathogeneticblood lossReduced productionincreased destruction
HAEMOPOIETIC SYSTEM
Morphological classification:1. Normocytic Normochromic
blood lossaplastic anaemiaACDhemolytic anameia
HAEMOPOIETIC SYSTEM
2. Microcytic HypochromicIron deficiency anaemiaThalassaemiasSidroblastic anaemiaACD
HAEMOPOIETIC SYSTEM
3. MacrocyticMegaloblastic anaemiahemolytic anaemia
HAEMOPOIETIC SYSTEM
Pathogenetic classification:1. Blood loss
AcuteChronic
2. Increased destruction (hemolytic)Hereditary
membrane defectsSpherocytosisElliptocytosis
HAEMOPOIETIC SYSTEM
Metabolic defectsG6PD deficiencyPK deficiency
Hb defectsquantitaive defects
Thalassaemiasqualitative defects
sickle cell anaemiaHbC, D, Eunstable Hb
HAEMOPOIETIC SYSTEM
AcquiredImmune hemolytic anaemiasNon immune
MAHAs (mechanical)PNHmalaria & other infectionsmechanical trauma
HypersplenismDICDrugs
HAEMOPOIETIC SYSTEM
3. Impaired production:Nutritional deficiencies
megaloblastic anaemiairon deficiency anaemia
Aplastic anaemiaPure red cell aplasiasideroblastic anaemiaanaemia of chronic disease
HAEMOPOIETIC SYSTEM
HAEMOPOIETIC SYSTEM
Parameter Males Females
Hb 15+/-2 gm/dl 13+/-1.5
RBC count 5+/-0.5x1012/l 4.5+/-0.5
PCV 0.45+/- 0.05l/l 0.4+/- 0.5 l/l
MCV 92 +/- 9 fl
MCH 29.5+/-2.5 pg
MCHC 33 +/- 1.5 g/dl
Cell diameter 6.7 – 7.7 um
Reticulocyte count
0.5-2.5%50 – 100x1012/l
HEMOLYTIC ANAEMIAS:Normal red cell life span = 120 days
Splenic reticuloendothelial cells
Degradation of Hb bilirubin
HAEMOPOIETIC SYSTEM
Hemolysis shortened red cell life span
Stimulated erythropoiesis intra &extramedullary
↑ Hb breakdown ↑ bilirubin jaundice gall stones
HAEMOPOIETIC SYSTEM
HAEMOPOIETIC SYSTEM
Extravascular IntravascularPhysiologic PathologicRE cells spleen In blood vesselsFc receptor mediated Complement mediatedLess deformable RBC Mechanical injurySplenomegaly ++ Splenomegaly +/-Indirect hyperbilirubinaemia
Hbaemia, Hburia, hemosidrinuria
Janudice ++ Jandice +
Normal ↓ plasma Haptoglobin
Anaemia ↑ EPO erythroid hyperplasia Marrow expansion reticulocytosis
Leukoerythroblastic blood picture Gall stones haemosiderosis
HAEMOPOIETIC SYSTEM
Never look down on anybody unless you're helping him up
HEREDITARYSPHEROCYTOSIS:
HAEMOPOIETIC SYSTEM
Autosomal dominantIntrinsic membrane defectDeformability of RBC due to cytoskeletalProteinsSpectrinActinAnkyrinBand 4.2 & 3
HAEMOPOIETIC SYSTEM
Reduced membrane stabilityReduced deformability spheroidalTrapped in spleen lactic acid ++Intracellular Na+ ↑ osmotic injury Phagocytosis by RE cellsSplenomegaly
HAEMOPOIETIC SYSTEM
Variable severityChronic hemolytic anaemiaAplastic crisisHemolytic crisis
HAEMOPOIETIC SYSTEM
DIAGNOSIS:HistoryExaminationBlood filmOsmotic Fragility test
HAEMOPOIETIC SYSTEM
GLUCOSE 6 PO4 DEHYDROGENASEDEFICIENCY
HAEMOPOIETIC SYSTEM
X linkedOxidant damage to RBCs Heinz bodies Bite cellsOxidant stress:
Drugs (antimalarials, sulfonamides)Foods (Fava beans)Infections
HAEMOPOIETIC SYSTEM
Variants G6PD-A (Mediterranian) G6PD-B (commonest) G6PD A- (African, mild)
Neonatal jaundiceAcute hemolysisChronic low grade hemolysis
Intravascular hemolysisExtravascular hemolysis
HAEMOPOIETIC SYSTEM
5 years boyProgressive pallorPainful swelling of fingers & toesJaundice twiceO/E pallor ++Jaundice +Spleen +Leg ulcersShort right middle finger
HAEMOPOIETIC SYSTEM
Hb = 5.5 gm/dlMCV = 74 flMCH = 26 l/lTLC = 18.6Plt = 110Retics = 12 %Leucoerythroblastic blood picture
HAEMOPOIETIC SYSTEM
HAEMOGLOBIN ELECTROPHORESIS:
Band of HbS
HAEMOPOIETIC SYSTEM
SICKLING TEST
HAEMOPOIETIC SYSTEM
SICKLE CELL DISEASE:Autosomal recessiveStructural variant of Hb
6th position β globin chainValine Glutamic acid HbS
HAEMOPOIETIC SYSTEM
Deoxy Hb↓
Crystallization/polymerization HbS↓
Tactoid formation (reversible)↓
Repeated sickling de-sickling↓
Irreversibly sickled↓
Vascular occlusion
HAEMOPOIETIC SYSTEM
Membrane damage ↑ Ca ↓ K+↓
Intracellular dehydration↓
Sticky RBCs↓
Vascular occlusion
HAEMOPOIETIC SYSTEM
Homozygous SCDHeterozygous SC traitHbF inhibits polymerization of HbSIntracellular dehydration ↑ MCHC
Sickling ++↓ pH deoxy Hb sickling
HAEMOPOIETIC SYSTEM
CLINICAL PRESENTATION:Chronic hemolysis (extravascular)AnaemiaJaundiceInfections by encapsulated organismsosteomyelitis (salmonella)H-Influenza, PneumococciLeg ulcers
HAEMOPOIETIC SYSTEM
Vaso occlusive crisis painful crisisbones hand – foot syndrome lungs acute chest syndromebrain seizures / strokeliver hepatic sequestration painspleen sequestration syndromepenis
HAEMOPOIETIC SYSTEM
Marrow expansion hair on ends (x-ray skull)
Prominent cheek bonesExtramedullary haemopoiesisGall stonesAplastic crisis (parvo virus)Autosplenetomy
HAEMOPOIETIC SYSTEM
DIAGNOSIS:HistoryExaminationPeripheral smear
ISCleucoerythroblastic blood picturereticulocytosis
HAEMOPOIETIC SYSTEM
Hb electrophoresisHbS band
Sickling testPCR
HAEMOPOIETIC SYSTEM
MANAGEMENT:Blood transfusion (RCC)PreventionBone marrow transplant
HAEMOPOIETIC SYSTEM
A man who is "of sound mind" is one who keeps the inner madman under lock and key
HAEMOGLOBIN:Heme + 4 Globin chains
HbA 2a/2βHbA2 2a/2δHbF 2a/2γ
ξ and ζ embryonic chains
HAEMOPOIETIC SYSTEM
Synthesis of globin chains:Haemopoietic GF
↓Gene activation
↓Transcription
↓Translation
↓Post translation stability
HAEMOPOIETIC SYSTEM
1.5 year girlFailure to thrivepallor and abdominal distensionCousin died at 3 years with similar problemsOne transfusion 2 months back
O/E pallor +++Spleen 4 cmLiver edge
HAEMOPOIETIC SYSTEM
TLC : 24.6Hb : 6.2Plt : 130MCV : 72MCH : 21NRBC 43/100 WBCLeft shift in neutrophils
HAEMOPOIETIC SYSTEM
HbF : 97%
DIAGNOSIS:Clinical, blood and electrophoresis findings
are consistent with β - THALASSAEMIA MAJOR(β°)
HAEMOPOIETIC SYSTEM
THALASSAEMIAS:Reduced or no synthesis of one or moreglobin chains of Hb.Autosomal recessiveα chain deficiency α thalassaemiaβ chain deficiency β thalassaemia
HAEMOPOIETIC SYSTEM
CLASSIFICATION:ClinicalGeneticThalassaemia major
homozygous β + (β+/ β+)homozygous β o (βo / βo) β / Hb Lepore β / HbE
HAEMOPOIETIC SYSTEM
Thalassaemia Intermedia: β+/β+ β with α thalassaemiaHbH disease β/δ compound heterozygotesHbE/ β
HAEMOPOIETIC SYSTEM
Thalassaemia minor:Silent carriers
α + thalassaemia traitrare β thalassaemia trait
Mild anaemia α o thalassaemia trait α+/α+ thalassaemia β o trait β + trait δβ trait
HAEMOPOIETIC SYSTEM
BETA THALASSAEMIA:Mutations in β globin gene
Transcriptionpromoter region mutationschain terminator mutations
Processing of mRNAsplicing mutationssplice site in exonIVSCAP site
HAEMOPOIETIC SYSTEM
Translationnonsenseframeshiftinitiation site
Post translational stabilityExon 3
HAEMOPOIETIC SYSTEM
DIAGNOSIS:HistoryExaminationBlood filmHb electrophoresisPCRFamily studies
HAEMOPOIETIC SYSTEM
TREATMENT:Regular blood transfusionsIron chelation
injectableoral
Supportive treatmentBone marrow transplant
HAEMOPOIETIC SYSTEM
PREVENTION***genetic counselingantenatal diagnosis
COMPLICATIONS:growth retardationiron overload
endocrine abnormalitiesCCFhepatic failure
transfusion mediated infections (HBV,HCV)
HAEMOPOIETIC SYSTEM
"Sometimes the best helping hand you can get is a good, firm push”
ACQUIRED HEMOLYTIC ANAEMIAS:Immune hemolytic anaemia:Autoimmune HA
warm antibody typeidiopathicautoimmune diseasesLPDinfectionscancersdrugs
HAEMOPOIETIC SYSTEM
cold antibody typecold agglutinin syndromeCHAD (idiopathic)infectionsLPDPCH
HAEMOPOIETIC SYSTEM
Alloimmune HAtransfusion reactionsHDNallograft associateddrug induced
macrophage mediatedcomplement mediated
HAEMOPOIETIC SYSTEM
HAEMOPOIETIC SYSTEM
Warm antibody HA Cold antibody HA
Commonest (45-70%) 15-30%
50% idiopathic Secondary >
IgG, IgA IgM
Extravascular hemolysis
Intravascular ++Extravascular <
Fc receptor mediated mcrophage
Complement activation, C3b macro
HAEMOPOIETIC SYSTEM
Spherocytosis RBC agglutinates
Splenomegaly Raynauds phenomena
Paroxysmal Cold Haemoglobinuria:Acute intermittent severe intravascularHemolysisP blood groupDonath – Landsteiner antibodyIgG biphasic antibodyComplement mediated
HAEMOPOIETIC SYSTEM
35 yrs femaleMother of 5 children (LCB 1.5 yrs)H/O menorrhagia 1 yearIncreasing weakness & fatiguabilityHusband is a labourer
HAEMOPOIETIC SYSTEM
Blood CP:Hb : 7.6 gm/dlTLC : 6.5Plt : 460MCV : 66MCH : 19DLC : normalRetics 1.0 %
HAEMOPOIETIC SYSTEM
Serum iron: 23 ug/dl (60-180)TIBC : 650 ug/dl (250-400)Serum Ferritin 6 ng/ml (15-150)DIAGNOSIS:
IRON DEFICIENCY ANAEMIA.
HAEMOPOIETIC SYSTEM
IRON METABOLISM:Diet / sourceAbsorptionTransportUtilization & excretionStoragedeficiency
HAEMOPOIETIC SYSTEM
Iron conc in males = 50 mg/kg females = 40 mg/kg
Total body iron = 3-5 gm7-8 yrs for depletion6 months-2 yrs physiological iron def
HAEMOPOIETIC SYSTEM
HAEMOPOIETIC SYSTEM
Absorption increased absorption decreased
Heme iron, animal food Opposite
Ferrous salts Ferric salts
Acid gastric pH Alkalis
Vit C, amino acids, sugars Phytates, tannates, tea
Iron deficiency Iron overload
↑ eryhthropoiesis ↓ erythropoiesis
Pregnancy Inflammatory disorders
Hypoxia ------
Causes of iron deficiency:Dietary lack
povertyold agevegetarians
Increased demandpregnancy & lactationinfants & childrenpuberty
HAEMOPOIETIC SYSTEM
Impaired absorptionmalaborption syndromesachlorhydriagastrectomyatrophic gastritis
Chronic blood lossGIT, genitourinary, respiratoryhook worm infestation
HAEMOPOIETIC SYSTEM
Clinical presentation:symptoms of anaemiasymptoms related to cause
Examination:pallorangular cheilosiskoilonychia
Absence of certain features
HAEMOPOIETIC SYSTEM
Diagnosis:HistoryExaminationRoutine investigationsSerum ferritinSerum iron TIBCBone marrow examination.
HAEMOPOIETIC SYSTEM
Treatment:Treatment of causeIron supplements
oralinjectable
HAEMOPOIETIC SYSTEM
Ability is of little account without opportunity
MEGALOBLASTIC ANAEMIA:A group of disorders characterized bypresence of MEGALOBLASTS in the bonemarrow.Impaired DNA synthesis
HAEMOPOIETIC SYSTEM
Causes:Cobalamine deficiency or defect in metabolismFolate deficiency or defect in metabolismMDS, AMLAntifolate drugs, drugs interfering with DNA
synthesisOrotic aciduriaLesh-Nyhan syndrome
HAEMOPOIETIC SYSTEM
DNA synthesisRapidly proliferating cells
haemopoietic cells ….GIT ….
diarrhoea can be cause or effectGUT ….respiratory …..prematurityneural tube defects
HAEMOPOIETIC SYSTEM
Methylation of biogenic amines(dopamine)
psychitric symptomsOf myelin proteins, phospholipids
Neurologic symptomsbilateral peripheral neuropathydegeneration of dorsal columns &
pyramidal tractsoptic atrophymental abnormalities (poor brain dev)
HAEMOPOIETIC SYSTEM
Haematological findings:oval macrocytosisMCV > 100 flpancytopeniahypersegmented neutrophils
HAEMOPOIETIC SYSTEM
Bone marrow findings:HypercellularDyserythropoiesisIneffective erythropoiesisMegaloblastsGiant myeloid precursorsHyperlobated megakaryocytesAbnormal mitotic figures
HAEMOPOIETIC SYSTEM
MEGALOBLAST:
Large abnormal erythroid precursorsnuclear cytoplasmic asynchrony
COBALAMINE (VITAMIN B12)Only source animal foodBody stores = 2-3 mgSufficient for 3-4 yearsAbsorption (ileum, IF) Transport (transcobalamines)
HAEMOPOIETIC SYSTEM
Causes of Cobalamine deficiency:1. Vegans2. Malabsorption
Pernicious anaemiagastric causes
IF defgastrectomy
HAEMOPOIETIC SYSTEM
intestinal causesstagnant loop syndromesileal resectioncrohn’s diseasetropical spruefish tape wormsTC deficiency
HAEMOPOIETIC SYSTEM
PERNICIOUS ANAEMIASpecific type of MBASevere lack of Intrinsic factor due togastric atrophyAutoimmune disorderAnti IF antibodiesAnti Parietal cell antibodies
HAEMOPOIETIC SYSTEM
Diagnosis:HistoryExaminationBlood CPBone marrow examinationSerum B12 levelsSchillings testIF & PC antibodiesElevated homocystine & CH3-malonic acidTherapeutic response
HAEMOPOIETIC SYSTEM
FOLIC ACID (Pteroylglutamic acid)Liver, yeast, spinach, greens, nutsTotal store = 10 mgFor 4-6 monthsAbsorbed from upper small intestinePolyglutamates monoglutamatesTransported by albumin
HAEMOPOIETIC SYSTEM
Causes of deficiency:1. Dietary:
old age, poverty, infancy, alcoholism,psychiatrics
2. Malabsorptiontropical sprueceliac diseaseintestinal resectioncrohns disease
HAEMOPOIETIC SYSTEM
3. Excess demand:physiological
pregnancy, prematurity, lactationpathological
hemolytic anaemias, malignanciesinflammatory conditionshomocystinuriahemodialysis patients
HAEMOPOIETIC SYSTEM
4. Anti-folate drugs:anticonvulsantsantiTBtetracyclins
5. Liver disease, alcoholism
HAEMOPOIETIC SYSTEM
Treatment:1. Of cause2. Cobalamine injections3. Folic acid tablets
HAEMOPOIETIC SYSTEM
APLASTIC ANAEMIA:“Presence of pancytopenia in theperipheral blood & a hypocellularmarrow in which normal haemopoieticmarrow is replaced by fat cells.”
HAEMOPOIETIC SYSTEM
Haemopoietic stem cell defectDefect in microenvironmentCytotoxic T cell mediated suppression ofStem cellsIFN gamma, TNFAbsence of abnormal cells or fibrosis in Bone marrow
HAEMOPOIETIC SYSTEM
Causes:Idiopathic
primary stem cell defectimmune mediated
Chemical agentsdose related
alkylating agents & antimetabolitesbenzene, arsenicchloramphenicol
HAEMOPOIETIC SYSTEM
idiosyncraticchloramphenicolphenylbutazonearsenic, streptomycininsecticides & pesticides
Physical agentsradiation
HAEMOPOIETIC SYSTEM
InfectionshepatitisCMV, EBV, herpes V
InheritedFanconi’s anaemia
HAEMOPOIETIC SYSTEM
Clinical presentation:Anaemia Thrombocytopenia Neutropenia
HAEMOPOIETIC SYSTEM
Diagnosis:HistoryExaminationBlood CPBone marrow aspiration & trephine
HAEMOPOIETIC SYSTEM
The purpose of life is to live a life of purpose.