Megaloblastic Anemia

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.

4. Etiology Vitamin B 12 deficiency OR abnormalities of cobalamin metabolism. Folate deficiency OR abnormalities of folate metabolism. Metabolic inhibitors of DNA synthesis OR Folate metabolism.

5. Vitamin B 12 Deficiency

6. Cobalamin (Vitamin B 12 ) Vitamin B 12 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.

7. Absorption Of Vitamin B 12

8. ( Haptocorrins ) ( Cubilin )

9. Functions Of Vit B 12

10. Causes Of Vit B 12 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

11. 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 B 12 malabsorption .

12. 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.

13. Clinical Features

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

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

16. 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)

17. NOTE :- The  gastric  atrophy and metaplastic changes are due to autoimmunity  and  not  of vitamin B 12  deficiency. Hence, parenteral administration of vitamin B 12  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 .

18. Folate Deficiency

19. 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.

20. 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

21. Causes Of Folic Acid Deficiency

22. Clinical Features Signs & Symptoms : Similar to vitamin B 12. No neurologic abnormalities, unlike vitamin B 12 deficiency. Neural tube defects found. Vascular diseases. (associated with high levels of homocysteine )

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