Macrocytic anemias are characterized by large rbcs with a normal hemoglobin content



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Macrocytic anemias are characterized by large RBCs with a normal hemoglobin content.

  • Macrocytic anemias are characterized by large RBCs with a normal hemoglobin content.
  • Macrocytic anemias are classified as
  • Megaloblastic
  • Non-megaloblastic

Megaloblastic anemias are associated with defective DNA synthesis leading to abnormal RBC maturation in the bone marrow (a nuclear maturation defect).

  • Megaloblastic anemias are associated with defective DNA synthesis leading to abnormal RBC maturation in the bone marrow (a nuclear maturation defect).
  • Megaloblastic anaemia is due to Vitamin B12 deficiency & folic acid deficiency

Primary defect in DNA replication is due to depletion of thymidine triphosphate which leads to retarded mitosis, and therefore retarded nuclear maturation.

  • Primary defect in DNA replication is due to depletion of thymidine triphosphate which leads to retarded mitosis, and therefore retarded nuclear maturation.
  • The depletion of thymidine triphosphate is usually due to a deficiency of vitamin B12 or folic acid.
  • Cytoplasmic maturation proceeds ahead of nuclear maturation
  • Nuclear/cytoplasmic asynchrony
  • Granulocytic and megakaryocytic maturation are also affected leading to pancytopenia

Vitamin B12 (cyanocobalamine)

        • Vitamin B12 (cyanocobalamine)
          • Meats, eggs, dairy products, and liver.
          • Is absorbed in ileum via a binding protein called intrinsic factor (IF)
        • Folic acid (pteroyl glutamic acid)
          • Most foods, including eggs, milk, yeast, and liver.
          • Green, leafy vegetables and is synthesized by many microorganisms.
          • Is destroyed by heat
          • Absorption occurs in the duodenum & jejunum

Vitamin B12 deficiency

        • Vitamin B12 deficiency
        • Folic acid deficiency

Vitamin B12 deficiency

Folic acid deficiency

  • A. Inadequate diet
  • Poverty, elderly, alcoholics, teenagers, infants
  • B. Malabsorption
  • Tropical sprue, jejunal resection, Crohn’s disease, coeliac disease, partial gastrectomy
  • C. Excess demand
  • 1. Physiological: Pregnancy, lactation, infancy
  • 2. Pathological : Malignancy, increased haematopoesis, tuberculosis, rheumatoid siseases
  • D. Excess urinary folate loss
  • Active liver disease, congestive cardiac failure

Two categories

  • Two categories
  • In both types of deficiency
  • Pallor, weakness, lightheadedness
  • Smooth red tongue
  • Diarrhea alternating with constipation
  • 2. In vitamin B12 deficiency only
  • Neurological disturbances including
  • Numbness and tingling of extremities
  • Gait abnormalities
  • Mental disturbances.

Hemoglobin and RBC counts are decreased

  • Hemoglobin and RBC counts are decreased
  • Blood picture - Macrocytic anemia
  • MCV=100-140
  • MCH is increased (due to increased cell size)
  • MCHC is normal
  • WBC and platelet counts are decreased
  • Bone marrow – Megaloblasts
  • Biochemical changes – rise in serun unconjugated bilirubin & LDH

Special tests

  • Serum vitamin B12 assay
  • Schilling test
  • Urinary excretion of FIGLU
  • Serum folate essay
  • Red cell folate essay

Peripheral smear

  • Triad commonly seen:
  • 1. Oval macrocytes,
  • 2. Howell Jolly bodies (nuclear DNA fragments)
  • 3. Hypersegmented neutrophils (5 or more lobes).
  • In addition:
    • Anisocytosis is moderate
    • Poikilocytosis with nucleated RBCs, polychromatophilia, and cabot rings (spindle remnants).
    • RBC dimorphism is seen with concomitant IDA.
    • The absolute reticulocyte count is decreased because of ineffective erythropoiesis.
  • Progresses to pancytopenia

Hypercellular

  • Hypercellular
  • Megaloblasts
  • Mega band forms
  • Giant metamyelocytes
  • Abnormal megakaryocytes with multilobated nuclei

STAGE 1 – Hot Vit B 12 -0.5-2microgm (oral) Cold Vit B12-4mg (IV)

  • STAGE 1 – Hot Vit B 12 -0.5-2microgm (oral) Cold Vit B12-4mg (IV)
  • Cold Vit B12-4mg saturates serum & tissue binding sites
  • Normally more than 7% of 1 microgram of oral dose of hot Vit B12 is excreted
  • Intrinsic factor deficiency - Reduced excretion
  • STAGE 2 – if excretion is low then test is repeated with administration of intrinsic factor
  • STAGE 3- repeat test after antibiotic dose

Pernicious anemia (PA)

  • 85% of megaloblastic anaemia is due to lack of intrinsic factor (IF) secondary to gastric atrophy – Pernicious anemia (PA)
  • Gastric atrophy is due to Autoimmune reaction against the gastric parietal cells in the G.I. tract.
  • Older adults (over 40).
  • Individuals of Northern European descent.

C/F

  • Anaemia
  • Glossitis
  • Neurologic manifestation
  • Diarrhea, wt loss
  • Hepatospleenomegaly
  • Pathological changes
  • Gastric atrophy

Lab findings

  • Hypergastrinaemia
  • Blood & Bone marrow picture similar to megaloblastic anaemia
  • Schilling test abnormal
  • Rise in serum bilirubin, LDH, haptoglobin, ferritin & iron

Macrocytic anaemia -Non-megaloblastic

  • Haemolysis
  • Liver disease
  • Alcoholism
  • Hypothyroidism
  • Aplastic anaemia
  • Myeloproliferative disorders
  • Reticulocytosis
  • Thank you
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