Rbc disorders-4
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Rbc disorders-4



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    Rbc disorders-4 Rbc disorders-4 Presentation Transcript

    • RBC Disorders Dr.CSBR.Prasad, M.D.,
    • Normal gastric epithelium
    • Atrophic gastritis Hyperplastic gastropathy
    • Perietal cell hyperplasia
    • Megaloblastic anemia
    • Megaloblastic anemia• Group of disorder characterized by impaired DNA synthesis & distinctive morphological changes in blood & BM• Erythroid precursor & erythrocytes – abnormally large• Defect in cell maturation & division• Deficiency of vit. B12 & folic acid
    • Megaloblastic anemia• Vit B12 & Folic acid are coenzyme in the DNA synthetic pathway• ↓ DNA synthesis – defective nuclear maturation• Synthesis of RNA & proteins are unaffected – cytoplasmic maturation is normal• Asynchronism bet. Cytoplasmic & nuclear maturation
    • Megaloblastic anemia• PBS – Anisopoikilocytosis – Macrocytes, ovalocytes – No central pallor – Retic count – low – Occasional nucleated RBC• MCV - ↑ 100 fl , MCHC – N• Neutrophils- Hypersegmented macropolys – larger in size – hypersegmented ( 5-6 or more lobes)
    • Elliptical macrocytes
    • Hypersegmented macropoly
    • Megaloblastic anemiaBone Marrow• Hypercellular with megaloblastic erythropoiesis• M:E ratio- 1:1• Granulocytic precursor – – N/C asynchrony – Giant metamyelocyte & band forms – Hypersegmented neutrophils• Megakaryocytes – – large with multilobated nuclei
    • D Megaloblastic anemia (BM aspirate)A,C-Megaloblasts. B-Intermediate Normoblast, D-Giant metamyelocyte
    • Megaloblastic anemia• Mechanisms of anemia – Ineffective erythropoiesis – Hemolytic destruction of RBC• Leukopenia• Thrombocytopenia
    • Vit B12 deficiency
    • Megaloblastic anemia – Vit B12 deficiency• Organometallic compound – cobalamin• Animal products – rich in Vit B12• Plants & vegetables- poor source• 2-3µg/day
    • FIGURE 14-18 Schematicillustration of vitaminB12 absorption.IF, intrinsic factor;R-binders,cobalophilins
    • Megaloblastic anemia – Vit B12 deficiency• Decreased intake – Inadequate diet – Veganism• Impaired absorption – Intrinsic factor deficiency • Pernicious anemia • Gastrectomy – Malabsorption syndrome – Diffuse intestinal disease – Ileal resection, ileitis – Competative parasite uptake – fish tape worm – Bacterial overgrowth in blind loop – Zollinger – Ellison syndrome – Imerslund syndrome – Drug induced Vit B12 malabsorption – Chronic disease of the pancreas• Increased requirement – Pregnancy , hyperthyroidism & disseminated cancers
    • Parasites causing Megaloblastic anemia• Diphillobothrium latum (Fish tape worm)• Fluke….. Cases have been reported from Puduchery1Ref: 1 vvvvvv
    • Megaloblastic anemia – Vit B12 deficiency1. Methyl cobalamin is essential cofactor for enzyme methionine synthase. Methionine is required for synthesis of folate polyglutamate2. Cobalamine is involved in isomerization of Methyl malonyl CoA to succinyl Co A
    • Relationship of N5-methyl FH4, methionine synthase, and thymidylate synthetase
    • Megaloblastic anemia – Vit B12 deficiency• Vit B12 deficiency - ↑ methyl malonate excretion in urine as methylmalonic acid• ↑ methyl malonate leads to formation of abnormal fatty acids that may incorporated into neuronal lipids – myelin breakdown – neurological complication
    • Pernicious Anemia
    • What is pernicious?
    • Pernicious Anemia• Autoimmune disorder• Destruction of gastric mucosa• Chronic atrophic gastritis – loss of parietal cells & inflammatory cell infiltrate
    • Pernicious Anemia3 types of Auto antibody• Type I – – 75% cases – Blocks binding of Vit B12 to IF – Present in gastric juice & plasma• Type II autoantibody – Prevent binding of Vit B12 + IF complex to ileal receptor• Type III autoantibody – 85- 90% cases – Ab against α & β subunits of gastric proton pump – Seen in 50% cases of idiopathic chronic gastritis without PA
    • FIGURE 14-18 Schematicillustration of vitaminB12 absorption.IF, intrinsic factor;R-binders,cobalophilins
    • Pernicious Anemia• Morphology• BM & blood• GIT – Atrophic glossitis – shiny, glazed & beefy tongue – Diffuse chronic gastritis – atrophy of fundic glands – Intestinalization of gastric mucosa – Some cells show megaloblastic change – Higher incidence of gastric cancer
    • Pernicious Anemia - CNS• 75 % of fulminant PA• Spinal cord – – Degeneration of myelin in dorsal & lateral tract – Degenerative changes in the ganglia of posterior roots & in peripheral nerve• Spastic paraperesis, sensory ataxia, severe paresthesias in lower limb• Subacute combined degeneration
    • Pernicious Anemia – C/F1. Moderate to severe megaloblastic anemia2. Leukopenia with hypersegmented granulocytes3. Mild to moderate thrombocytopenia4. Mild jaundice due to ineffective erythropoiesis5. Neurological changes – postero lateral spinal tract6. Achlorohydria even after histamine stimulation (Histamine fast achlorhydria)
    • Beefy red tongue
    • Vitiligo
    • Pernicious Anemia7. Schilling test – urinary excretion of radiolabelled cyanocobalamin8. ↓Serum B12 level9. ↑Homocysteine & methyl malonic acid in serum10. intra venous vit B12 – Reticulocytosis (after 5days of Tx)11. Serum Ab to IF
    • Folate deficiency
    • Folate• Folic acid or Tetrahydrofolate (FH4) derivatives act as biological Middle man in transfer of one carbon units (formyl / Methyl) groups to various compounds• Accepts 1 carbon unit from serine / Formiminoglutamic acid (FIGLU)
    • Role of folate derivatives in the transfer of one-carbon fragments for synthesis of biologic macromolecules
    • Folate - Functions1. Synthesis of purines2. Synthesis of Methionine from homocysteine3. Synthesis of deoxythymidine monophosphate (dTMP)
    • Role of folate derivatives in the transfer of one-carbon fragments for synthesis of biologic macromolecules
    • Relationship of N5-methyl FH4, methionine synthase, and thymidylate synthetase
    • Folate deficiency - Etiology• Daily requirement : 50 – 200 mg• Green veg – rich source• Fruits & animal protein – lesser amount1. ↓ intake – alcoholism, infancy2. Impaired absorption Malabsorption state Intrinsic intestinal disease Anticonvulsant, OCP3. ↑ loss - hemolysis4. ↑ requirement – pregnancy, infancy, cancer
    • Folate deficiency5. Impaired use – Folic acid antagonists – Mercaptopurines, methotrexate, flurouracil
    • Folate deficiencyDiagnosis – ↓ Folate levels in serum or red cells – ↑ Excretion of FIGLU after an administrated dose of histidine
    • END
    • Dr.CSBR.Prasad, M.D.,Associate Professor of Pathology,Sri Devaraj Urs Medical College, Kolar-563101, Karnataka, INDIA. csbrprasad@reiffmail.com