Megaloblastic anaemia is a red blood cell disorder due to the inhibition of DNA synthesis during erythropioesis. Mitotically, the inhibition of the DNA synthesis impaires the progression of the cell cycle development from G2 to (M) stage.

1. MEGANOBLASTIC ANEMIA
PRESENTED
BY
ASOGWA UKAMAKA
DEPT. OF MEDICAL
LABORATORY SCIENCE
FEDERAL MEDICAL CENTRE
MAKURDI
15/09/2015
Asogwa Uka1

2. Megaloblastic Anemia
Outline
 Definition
 Etiology of megaloblastic anemia
 Pathophysiology
 Clinical presentation of megaloblastic
anemia
 Laboratory Diagnosis
 Sources of Vitamin B12 and Folic Acid
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3. Definition
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Megaloblastic anaemia is a red blood
cell disorder due to the inhibition of
DNA synthesis during erythropioesis.
 Mitotically, the inhibition of the DNA
synthesis impaires the progression of the
cell cycle development from G2 to (M)
stage.

4. Etiology of megaloblastic anemias
a. Vitamin B12 or Cobalamin deficiency.
b. Folic acid deficiency
c. a and b deficiency.
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5. VITAMIN B12 DEFICIENCY
 Inadequate intake: This is common among pure vegetarians,
old and bed ridden patients
 Inability to absorb vitamin B12: after gastric surgery, lack of
hydrochloric acid in gastric juice, lack of intrinsic factor due to
auto antibodies to parietal cells.
 Competition for intestinal vit.B12 : Competitive absorption
of the vitamin by fish tape worm (Diphyllobothrium latum)
and bacteria overgrowth in blind-loop syndrome, intestinal
stasis.
 Drugs Inhibition: Metformin, Proton pump inhibitors
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6. FOLATE DEFICIENCY
 Inadequate intake:
 a poor diet
 Old and bed ridden patients
 ICU patients.
 over cooked food especially vegetable
 Increased requirements
 pregnancy and lactating mothers.
 Growing infants
 Hemolytic anemic patients.
 Drugs
 Folic acid antagonists: Methotrexate
 Chronic alcoholism:
 It inhibits folic acid absorption.
 It increases folate excretion through the urine
 Inability to absorb folic acid:
 Following gastric surgery, chronic diarrhoea.
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7. Pathophysiology
When vitamin B12 or folate is deficient, thymidine synthase function is
impaired and DNA synthesis is interrupted but RNA synthesis remains
unimpaired. The inability to synthesize DNA leads to ineffectual
erythropoiesis resulting in excess hemoglobin and enlarged erythroid
precursors being produced. The developing red cell has difficulty in
undergoing cell division but RNA continues to be translated and
transcribed into protein leading to growth of the cytoplasm while the
nucleus lags behind. Often one or more cell division are skipped
leading to a larger than normal cell.
There is often erythroid hyperplasia in the marrow but most of these
immature cells die before reaching maturity leading to - elevated
Lactate Dehydrogenase (LDH) and hyperbilirunemia.
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8. Megaloblastic precursor cells versus
Normoblastic precursor
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Fig.1a. Megaloblastic precursors, showing
the asynchrony between the nucleus and the
chromatin; the cytoplasm of most cells is
extremely basophilic.
Fig.1b.Normoblastic erythropoiesis with a
polychromatophilic normoblast (arrow).

9. CLINICAL PRESENTATION
Anaemia symptoms
Neurological symptoms
Gastro- intestinal complain
Symptoms of Anemia
weakness, palpitation, fatigue, light-
headedness,,shortness of breath, premature graying
of hair, jaundice and pallor.
Severe pallor and slight jaundice combine to produce
a telltale lemon-yellow skin in patient with
megaloblastic anemia.
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Fig 2a,b “Lemon yellow”
pallor
Fg .2d Neura tube defects e.g. Spina Bifida
Clinical signs in pictures

11. Neurological symptoms
 The syndrome usually begins with paraesthesia
(numbness and tingling) in the feet and fingers,
difficulties in balance and walking.
 Vitamin B12 deficiency causes a demyelinization
of the peripheral nerves, the spinal cord, and the
brain, resulting in more severe neurological
symptoms.
 When it affects the spinal cord it causes spastic
ataxia( stiffness of the muscles with uncoordinated
movement). At the brain it results in dementia,
psychotic depression and paranoid schizophrenia.
This has been termed “megaloblastic madness.”
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12.  Gastro- intestinal complains : symptom include loss of
appetite, glossitis (red, sore, smooth tongue) and diarrhoea
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13. Laboratory diagnosis of megaloblastic anemias
 Full Blood Count ( FBC):
 ↓ Hb/Hct, ↑ MCV, ↓ retics, ↓WBC, ↓Plts,
macroovalocytosis , anisocytosis, poikilocytosis,
hypersegmentation of granulocytes. Also there may
be variable thrombocytopenia.
 Bone marrow smear: Bone marrow examination
reveals myeloid cell changes (giant bands,
metamyelocytes and hypertsegmentation) and
megakariocytes are decreased and show abnormal
morphology.
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14. Fig. 3a. Peripheral smear from a patient
with megaloblastic anemia. Note the
hypersegmented neutrophils and the
macro-ovalocytes.
Fig. 3b Megaloblastosis (Giant
Band Forms in Bone Marrow)
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15.  Biochemistry Test:
 hyperbilirubinemia
 ↑lactate dehrogenase (LDH)
Schilling test:
The Schilling test is used to
determine whether there is
faulty absorption of vitamin B12.
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17. Sources of Vitamin B12 and Folic Acid
Vitamin B12
• Meat, liver, kidney, clams, fish
• Eggs, cheese, and other dairy products
Folic Acid
• Green leafy vegetables
• Broccoli
• Fruit
• Whole grains
• Dairy products
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