Information about megaloblastic anemia and it's etiology and its classification. Vitmain b12 deficiencies Folic acid deficiencies Signs and symptoms of megaloblastic anemia Neural tube defects

1. Megaloblastic
Anemias,
Etiology And
Clinical Features
Nishkarsh Bansal
Roll No- 53

2. Megaloblastic Anemia
 Group of disorders in which erythroblasts in the bone marrow, show
delayed nuclear maturation relative to that of cytoplasm, due to
defective DNA synthesis.
 When DNA synthesis is impaired, the cell cycle cannot progress to
mitosis. This leads to continuing cell growth without division, which
presents as macrocytosis.

3. Morphology
 The presence of red cells that are macrocytic and oval
(macro-ovalocytes) is highly characteristic.
 Most macrocytes lack the central pallor of normal red cells
and even appear “hyperchromic”.
 Anisocytosis and poikilocytosis of red cells.
 Nuclear hypersegmentation of neutrophils.
 Marrow is usually markedly hypercellular as a result of
increased hematopoietic precursors, which often completely
replace the fatty marrow.

5. Etiology
1) Vitamin B12 deficiency OR abnormalities of
cobalamin metabolism.
2) Folate deficiency OR abnormalities of folate
metabolism.
3) Metabolic inhibitors of DNA synthesis OR Folate
metabolism.

7. Cobalamin (Vitamin B12)
 Vitamin B12 is a complex organometallic compound
also known as cobalamin.
 It is solely synthesized by microorganisms and the
only source for humans is food of animal origin like
meat, fish and dairy products.
 The daily requirement is 2-3 µg.

8. Absorption Of Vitamin B12
Absorption
Mechanism
Active
(75%)
Requires the presence of Intrinsic
Factor (a glycoprotein produced by
gastric mucosa)
Passive Absorption occurs by Diffusion and
works when pharmacological doses
of vitamin B12 are ingested.

9. (Haptocorrins)
(Cubilin)

10. Functions Of Vit B12

11. Causes Of Vit B12 Deficiency
Nutritional Low intake : vegans
Malabsorption Pernicious anemia
Gastric causes Congenital lack of IF
Total or partial gastrectomy
Intestinal
causes
Intestinal stricture, anatomic blind loop,
etc.
Ileal resection and Crohn’s disease
Tropical sprue
Fish tapeworm

12. Pernicious Anemia
 Pernicious anemia is an autoimmune disease that
affects the gastric mucosa and results in gastric atrophy.
 Antibodies are produced against cells of the stomach or
against IF (intrinsic factor).
 This leads to the destruction of parietal cells and failure to
produce intrinsic factor, resulting in vitamin B12
malabsorption .

13. Morphology
 The most characteristic alteration is fundic gland
atrophy.
 Parietal cells are virtually absent.
 The glandular epithelium is replaced by mucus-secreting
goblet cells that resemble those lining the large
intestine, a form of metaplasia referred to as
intestinalization.

14. Clinical Features

15. Pallor and mild icterus
(in a patient with a haemoglobin count of 7.0g/dL)

16. Other Findings
Glossitis
(The tongue is beefy-red, shiny
and painful)
Angular Cheilosis
(stomatitis)

17. Neurological Findings
 Demyelination of the dorsal and lateral spinal tracts, sometimes
followed by loss of axons.
 These changes give rise to spastic paraparesis, sensory ataxia,
and severe paresthesias in the lower limbs.
 Degenerative changes in the ganglia of the posterior roots and in
peripheral nerves. ( less frequent)
Present in about
3/4th of all cases of
pernicious anemia.
Can also be
seen in the
absence of other
hematologic
findings.

18. NOTE :-
 The gastric atrophy and metaplastic changes are
due to autoimmunity and not of vitamin B12
deficiency.
 Hence, parenteral administration of vitamin B12 corrects
the megaloblastic changes in the marrow and the
epithelial cells of the alimentary tract, but gastric
atrophy and achlorhydria persist.
 Persons with atrophy and metaplasia of the gastric
mucosa associated with pernicious anemia have an
increased risk of gastric carcinoma.

20. Folate
 Folic acid is parent compound of large family of natural
folate compounds.
Its highest concentration is found in liver, yeast, spinach,
other greens and nuts.
Total folate in adult is ~10mg with liver containing the
largest store.
Daily adult requirements are ~ 50-200 µg.

21. Functions Of Folic Acid
 Folic acid DHFA THFA (Active form)
 THFA mediates number of one-Carbon transfer reactions :-
∞ Conversion of homocysteine to methionine
∞ Generation of thymidylate
∞ Conversion of serine to glycine
∞ Purine synthesis
∞ Histidine metabolism
Folate
reductase
DHF
reductase

23. Causes Of Folic Acid Deficiency
Nutritional
(old age, poverty,
special diets)
Malabsorption
(Tropical sprue,
partial gastrectomy,
jejunal resection)
Increased
requirements
Pregnancy, infancy,
disseminated cancer,
increased
hematopoiesis
Excess urinary loss
(active liver disease,
congestive heart
failure)
Drugs
(anticonvulsants
eg. phenytoin)
Mixed
(liver disease,
alcoholism)

24. Clinical Features
 Signs & Symptoms :
 Similar to vitamin B12.
 No neurologic abnormalities, unlike vitamin B12 deficiency.
 Neural tube defects found.
 Vascular diseases.
(associated with high levels of homocysteine)