; Megaloblastic anaemia
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Megaloblastic anaemia


Common haematological conditions

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									    Macrocytic anaemia

* Red cells are larger than small
* Mean corpuscular volume is larger
than 98fl
     Causes of macrocytic anaemia
   Megaloblastic                 Normoblastic
    erythropoiesis                 erythropoiesis
   Any abnormality               Erythropoiesis is normal
    affecting DNA synthesis       Round macrocytes are
   Oval macrocytes are seen       seen
   Hypersegmented                No hypersegmented
    neutrophils seen               neutrophils seen
   Vit B12 and folate            Liver disease,
    deficiency are the             hypothyroidism,
    commonest causes               COAD, Scurvy
Normoblastic erythropoiesis   Megaloblastic erythropoiesis
     Megaloblastic anaemia
 Characterised by the distinctive cytological
  and functional abnormalities in peripheral
  blood and bone marrow cells due to
  impaired DNA synthesis
 Most commonly secondary to Vit B12 or
  folate deficiency
Metabolism of Vitamin B12
   Essential for normal haemopoiesis and integrety of
    nervous system
   Act as the co enzyme in chemical reactions
    affecting DNA synthesis
        Methylmalonyl co A          Succinyl co A
        Homocystine                 Methionine
   Cyanacobalamin / cobalmin family
   Sources: foods of animal origin; Kidney, liver, heart
   Absorbtion is via gastric intrinsic factor in the ileum
   Tissue stores in the liver 1.5 mg, adequate for about
    2 years
         Metabolism of Folate
   Essential for normal haemopoiesis
   Required for large number of reactions involving
    transfer of one carbon units from one compound
    to another
   Glutamates family
   Sources: plant & animal tissue eg: liver kidney
    yeast fresh green vegetables
   Minimal daily requirement is 100-200 g
   Absorption is at the duodenum and jejunum
   Tissue stores: liver 5-20 mg, and is adequate for 4
        Clinical manifestations

  Vitamin B12 deficiency         Folate deficiency
 Macrocytic                Macrocytic
  magaloblastic anaemia      megaloblastic anaemia
 Glossitis                 Glossitis

 Peripheral neuropathy
  and subacute combined
  degeneration of the
  spinal cord
         Causes of deficiency
       Vitamin B12                   Folate
  Decreased intake:           Decreased intake:
   Nutritional deficiency       Nutritional deficiency
 Impaired absorbtion:         Impaired absorbtion:
Gastric: Pernicious anaemia     Coeliac disease
          Gastrectomy          Increased demand
Intestinal: Ileal lesions       Pregnancy,
            Fish tape worm      haemolytic anaemia,
                                Myeloproliferative disorders
    Special tests in the diagnosis
        Vitamin B12                      Folate
 Serum B12 assay
                                    Serum folate assay
 Radioactive vit B12 absorbtion
                                    Red cell folate assay
  test: Schilling test
 Response to treatment             Response to treatment
  Reversion of erythropoiesis to     Reversion of
  normoblastic                       erythropoiesis to
  Healing of glossitis               normoblastic
  Cure of peripheral neuropathy      Healing of glossitis
  and arrest of SACD of spinal
  cord with some improvement
Laboratory tests in megaloblastic anaemia
  (findings common to both conditions)
   Low haemoglobin
   Low red cell count
   MCV increased (If over 125 fl almost always
    Vit B12 or Folate deficiency)
   MCH can be increased
   WBC can be low- Neutropenia
   Platelet count can be low-Symptom less
  *** One cause of pancytopenia
Peripheral blood film
              Oval macrocytic
              Hypersegmented
              Neutropenia
              thromboytopenia
Bone marrow aspiration
            Hypercellular bone marrow
            Very active megaloblastic
             Large erythroblasts
             Open chromatin network
             Basophillic cytoplasm
             Dissociation of cytoplasmic
             and nuclear maturation
            Giant metamyelocytes
      Treatment of megaloblasic
  Vitamin B12                     Folate deficiency
                             Folic acid 5mg daily
 Initial dosage: 1000
  micrograms of
  hydroxycobalamin IM
  injection for daily for
  one week
 Maintainance dosage
  1000g IM once every
  3 months
        Response to treatment
   Sense of well being in 2-3 days time
   Return of appetite
   Glossitis rapidly relieved
   Blood: Retic count starts to increase on the 2-3rd
    day, maximum on 6-8th day. MCV gradually falls,
    HSN disappear in 2 weeks
   If diagnosis of Vit B12 or Folate deficiency is
    doubtful always start treatment with Vit B12 and
    folate simultaneously. Never treat with folate
    alone as neurological symptoms of Vit B12
    deficiency will worsen if treated with folate alone.
        Pernicious Anaemia
 Chronic disorder of middle and old age
 Basic pathological lesion is failure of
  secretion of intrinsic factor with gastric
  atrophy results in Vit B12 deficiency.
 Genetic and autoimmune factors are
 Parietal cell Ab s and intrinsic antibodies
  play a role in the pathogenesis
           Clinical features
 Insidious onset
 Anaemia
 Glossitis
 Nervous system manifestations
  Mental disturbances
  Visual disturbances
 Gastrointestinal manifestations
 Clinical picture
 Macrocytic blood picture
 Megaloblastic bone marrow
 Low serum Vit B12
 Positive Shilling test
 Positive intrinsic factor Ab test

 Administration of Vitamin B12
 Symptomatic and supportive therapy
 Follow up and early detection of carcinoma
  of stomach
Other causes of megaloblastic anaemia
     due to vitamin B12 deficiency
   Gastrectomy
   Stricture, blind loop : leading to abnormal
    proliferation of organisms (binds IF-Vitamin
    B12 complex)
   Ileal resection, regional ileitis,
    gastrojejunocolic / ileocolic fistulae
   Fish tape worm:Diphyllobothrium latum
   Drugs: metformin, cimetidine, Slow release
    KCL, cholestyramin
     Other causes of Folate
 Tropical sprue
 Alcoholic patients
 Drugs:
     Uncertain mechanism: Phenytoin
     DHF reductase inhibitors: Methotrexate

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