Vitamin B12 and folic acid are essential for DNA synthesis and the formation of red blood cells. Deficiencies can lead to megaloblastic anemia, where immature red blood cells are large with abnormal nuclei. Symptoms include pale skin, shortness of breath, sore mouth, and neurological issues. Diagnosis involves blood tests showing macrocytic anemia and bone marrow examination revealing large immature red blood cell precursors. Treatment involves replacing the deficient vitamin.

1. Folate and Vitamin B12
Metabolism and
Megaloblastic Anemia
Presented by
M Hamza Bangash
M Hassan
Shayan Shakeel

2.  Vitamin B12 Metabolism
 It water soluble vitamin
 Synthesized by microrgganisms like bacteria
 SOURCE
 LIVER
 MEAT
 FISH
 DAIRY PRODUCTS

3. Metabolism of vitamen B12

4. BIOCHEMICAL FUNCTION OF VITAMEN B12

5.  Folic acid sources
 Green leafy vegetables.
 Fortified foods (cereals ,grains)
 Nuts
 Brocholli
 Meats

6.  Metabolism of folic acid

7.  Biochemical reaction
 Conversion of homocysteine to methionine.
 Conversion of serine to glycine .
 Synthesis of thymidylic acid .
 Synthesis of purines .
 Histdine metabolism

8. Macrocytic Anemia
&
Megaloblastic Anemia

9.  MACROCYTIC ANEMIA
 Macrocytic anemia simply means anemia with Mcv>100.
 The macrocytic anemia can be divided into the megaloblastic and
non-megaloblastic anemia on bone marrow finding.

10. MEGALOBLASTIC ANEMIA:
 Megaloblastic Anemia is characterized by the
presence of erythroblast in bone marrow with
delayed nuclear maturation because of
defective DNA synthesis. Megaloblasts are
large and have large immature Nuclei.
CAUSE:
 • vitamin B12 deficiency or abnormal
Metabolism.
 Folic acid deficiency or abnormal Metabolism.

11. • Other defect of DNA synthesis such as congenital
enzymes deficiency in DNA synthesis or resulting from
therapy of Drug interfering with DNA synthesis.
BIOCHEMICAL BASIS:
The key biochemical problem common to both vitamin
B12 and Folate deficiency is block in DNA synthesis
owing inability to convert methylate Deoxyuridine
Monophosphate to deoxythimidine Monophosphate
which then use to build DNA.The methyl group is
supplied by folate coenzyme methyl tetrahydrofolate.

12. Folate Deficiency:
 Folate is obtained from green vegetables such as
spinach,and offal such as liver, kidney and some
fruits is absorbed in the jejunum.Folate deficiency
usually occur within a month because of body
stores are minimal.
Cooking cause a loss of 60-90% of the folate.The
minimal daily requirement is 100ug.
CAUSE:
 Poor intake
 Poor intake due to GIT disease or Crohn’s
disease.

13. Antifolate drugs , Pregnancy, lactation
,Hemolysis • Cancer
TREATMENT OF FOLATE DEFICIENCY:
Folate deficiency can be treated by giving 5mg
of Folic acid daily.
Treatment should be given for about 4 months
to replace body stores.
 Treating the underlying cause .i.e. Disease

14. B 12 DEFICIENCY:
 Dietary vitamin B12 is complexed is to animal
drive protein . Unlike Folate deficiency B12
deficiency takes year to develop due to large
hepatic store of B12 about 2 3 mg and daily loss
are small(1-2ug).
 CAUSE:
 Most common reason is Pernicious anemia.
Low dietary intake
Gastrectomy
 Congenital disease of Intrinsic factor.
 Bacterial overgrowth
 Pancreatic Insufficiency

15. PRENICIOUS ANEMIA:
is an autoimmune disorder characterized by
destruction of parietal cell which lead to intrinsic
factor deficiency and B12 malabsorption.
Prenicious anemia is more common in the elderly
above 60 years with female sex affected more the
male.
there is an association with autoimmune disease
particularly Thyroid disease, Addison
disease.There is also increase risk of gastric
carcinoma then the normal population.

16. Clinical Presentation Of
Megaloblastic Anemia

17.  Common symptoms of all types of Anemia
 Short breath.
 Pale (lemon yellow ).
 Muscles atrophy.
 Tachycardia.
 Symptoms of megaloblastic anemia
 Glossitis.
 angular cheilosis.
 Tingling in hands and feet .
 Purpura due to thromobocytopenia .
 Numbness in extermities .
 Mild symptoms of malabsorption with weight loss.
 Asymptomatic

18.  Vitamen B12 neuropathy (subacute
combined degeneration of cord )
 Caused by deficiency of vitamin B12.
 Affects the peripheral nerves and posterior and lateral
column.
 Optic atrophy .
 Parasthasia and balance disorder
 Dementia in several cases.
 Arteries and vein thrombosis due to raised level of
homocysteine.

19.  Neural tube defect
 Due to vitamin B12 and folate deficiency in maternal serum .
 impaired methylation of protein and lipid .
Sterlity in either sex.
Morphological abnormalities of buccal .bladder ,cervical and
other epithelia occur .
 Other tissues abnormalities

20.  Diagnosis of megaloblastic anemia
 Blood count / Blood CP
 Rbc Low
 Wbc Low
 Platelets Low
 Hb Low
 Mcv high
 Mch high
 Mchc normal
 Reticulocytes count Low

21.  Blood smear/peripheral film
 Anisocytosis and poikilocytosis.
 Cabot ring appearance
 Howel jolly bodies .
 Macro cytosis.
 Macro ovalo cytes with lack central palar.
 Basophilic stippling
 Hyper segmented neutrophil.

24.  Bone marrow findings
 Hyper cellularity .
 Erythropoiesis of megaloblastic type.
 Asynchrony of nucleus and cytoplasm.
 Biochemical tests
 Serum vitamin B12 .
 Serum folic acid
 Serum homocysteine
 Serum methyl malonic acid