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 characterized by large RBCs with a normal hemoglobin content.
- Macrocytic anemias are classified as
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
- 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
- Blood picture - Macrocytic anemia
- 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
- Serum vitamin B12 assay
- Schilling test
- Urinary excretion of FIGLU
- Serum folate essay
- Red cell folate essay
- 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
- 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.
- Neurologic manifestation
- Diarrhea, wt loss
- Pathological changes
- Gastric atrophy
- Blood & Bone marrow picture similar to megaloblastic anaemia
- Schilling test abnormal
- Rise in serum bilirubin, LDH, haptoglobin, ferritin & iron
Macrocytic anaemia -Non-megaloblastic
- Liver disease
- Aplastic anaemia
- Myeloproliferative disorders
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