ALL ABOUT VIT B12 DEFICIENCY ANAEMIA AND FOLIC ACID DEFICIENCY ANAEMIA BY STUDENTS OF IMS AND SH,BHUBANESWAR

1. *

2. * The Megaloblastic anemias are group of disorders characterised
by presence of distinctive morphological appearances of
developing red cells in bone marrow.
* The marrow : Hyper cellular & Anemia is based on ineffective
erythropoesis.
* The cause is usually deficiency of Cobalamin ( VIT B12) and/or
Folate.
* Folate is an important substrate and Vit B12 a cofactor for
generation of essential amino acids methionine from
homocystiene. This reaction produces Tetrahydrofolate which is
then converted to Thymidine monophosphate for DNA synthesis.
* So deficiency leads to impairement of DNA synthesis and
accumulation of homocysteine which predominantly are cause of
its clinical manifestations.
* What is Megaloblastic Anemia

3. Vit B12
* Sources: Meat, Fish, Egg , Milk
[ absent in foods of non animal origin ]
* Requirement : 1micro gram/ day
* Absorption :
FOLATE
Sources : Liver, Yeast, Spinach, GLV, Nuts
Requirement : 100 micro gram/ day
Absorption : Is rapidly absorbed from small intestine.
*

5. (1) Vit B12 ( cobalamin) deficiency
(2) Folate deficiency
(3) Therapy with antifolate drugs (Mtx)
(4) Idependent of deficiency
* AML, Myelodysplasis
* Therapy with drugs interfering with synthesis of DNA
( 6-Merccaptopurine, Azidothymidine etc )
*

6. * Causes of vit B12 deficiency
NUTRITIONAL Vegans
MALABSORTION Pernicious anemia
GASTRIC FACTORS • Cong. Absence of IF
• Total/partial gastrectomy
• Gastric bypass surgery
• Atrophic gastritis
• Use of PPI
INTESTINAL FACTORS • Obstruction
• Ileal resection
• Tropical sprue
• Transcobalamin II deficiency
• Severe pancreatitis
• Gluten induced enteropathy
• HIV
DRUGS • Colchicine, anticonvulsants,
cytotoxic drugs
Alcohol

7. *
DIETARY • Old age & infancy
• Poverty , alcoholism
MALABSORPTION * Tropical sprue, GIE
* Jejunal resection, Crohn’s ds,
systemic bact. Infection
EXCESSIVE UTILISATION OR LOSS * Physiological : Pregnancy
&lactation
• Pathological :
- CML, sickle cell ds
- Carcinoma, lymphomas
- TB, psoriasis, malaria
ANTIFOLATE DRUGS Anticonvulsants, Sulfasalazine,
Tetracyclins
MIXED Liver ds, Alcoholism, ICUs

8. *
SYMPTOMS
(1) Malaise -90%
(2) Paraesthesia – 80%
(3) Breathlessness -50%
(4) Sore mouth -20%
(5) Weight loss
(6) Altered skin
pigmentation
(7) Grey hair
(8) Impotence
(9) Poor memory
(10) Depression
(11) Personality change
(12) Hallucinations
(13) Visual disturbances

9. SIGNS
(1) Smooth tongue
(2) Angular cheilosis
(3) Vitiligo
(4) Skin pigmentation
(5) Heart failure
(6) pyrexia

10. NEUROLOGICAL FINDINGS D/T VIT B12 DEFICIENCY
(a) Peripheral nerves
* GLOVE AND STOCKING paraesthesia
* Loss of ankle reflexes
(b) Spinal cord
* Posterior columns – diminished vibration
sensation and proprioception.
* Corticospinal tracts – upper motor neuron signs.
(c) Cerebrum
* Dementia
* Optic atrophy
(d) Autonomic neuropathy

11. *PERIPHERAL BLOOD
*Oval macrocytes,usually with considerable
anisocytosis and poikilocytosis.
*MCV>100fL unless there is a cause of microcytosis
(E.g. Iron deficiency or Thalassaemia trait) is present.
*Some neutrophils are hypersegmented.
*Leukopenia due to a reduction in granulocytes &
lymphocytes,but this is usually >1.5x10^9/L

12. *Platelet count moderately reduced,rarely<40x10^9/L
*In a non anaemic patient,the presence of a few
macrocytes & hypersegmented neutrophils in the
peripheral blood may be the only indication of the
underlying disorder.

13. *BONE MARROW
*In a severely anaemic patient,the marrow is
hypercellular with an accumulation of primitive cells
due to selective death by apoptosis of mature forms.
*The erythroblast nucleus maintains a primitive
appearance despite maturation and
haemoglobinization of the cytoplasm.
*The cells are larger than normoblasts,and an
increased number of cells with eccentric lobulated
nuclei as nuclear fragments

14. *may be present.
*Giant and abnormally shaped metamyelocytes and
enlarged hyperpolyploid megakaryocytes are
characteristic.
*In severe cases,the accumulation of primitive cells
can mimic acute myeloid leukaemia,when in less
anaemic patients,the changes in the marrow may be
difficult to recognize.
*In megablastoid cells with both immature appearing
nuclei and defective haemoglbinization and is usually
seen in myelodysplasia.

15. *Bone marrow cells,transformed lymphocytes,and
other proliferating cells in the body show a variety of
changes,including random breaks,reduced
contraction,spreading of the centromere,and an
exaggeration of secondary chromosomal constrictions
and overprominent satellites.
*Drugs- Antimetabolite drugs (e.g. Cytosine
arabinoside,Hydroxyurea and Methotrexate) same
megaloblastic appearances.

16. *
*There is an accumulation of unconjugated bilirubin in
plasma due to the death of nucleated red cells in the
marrow ( Ineffective erythropoiesis)
*Raised Urine Urobilinogen
*Reduced Haptoglobins
*Positive urine hemosiderin
*A raised serum Lactate Dehydrogenase.
*False diagnosis of Autoimmune hemolytic anaemia- A
weakly positive direct antiglobulin test (cause- due to
complement)

17. *
*Severe megaloblastic anaemia- Vit B 12 + Folic Acid (
before Vit B12 & Red Cell folate results are available )
.
*Use of folic acid alone in the presence of Vit B12
deficiency may result in worsening of neurological
deficits.
*In severe angina/heart failure- Transfusion
*If cardiovascular system is adapted to chronic
anaemia- Exchange transfusion or slow administration
of 1 U of red cells with diuretic cover may be given
cautiously.

18. *
*Hydroxycobalamin 1000 microgram IM for 6 doses 2 or
3 days apart, followed by maintenance therapy 1000
microgram every 3 months for life.
*The reticulocyte count will peak by 5th-10th day of
replacement therapy .
*The Haemoglobin will rise by 10g/L every week until
normalized.
*The response of the marrow is associated with a fall
in plasma potassium levels & rapid depletion of iron
stores. If an initial response

19. *is not maintained and the blood film is dimorphic, the
patient may need additional iron therapy.
*A sensory neuropathy may take 6-12 months to
connect, long standing neurological damage may not
improve.

20. *
*Oral folic acid 5 mg daily for 3 weeks will treat acute
deficiency and 5 mg once weekly is adequate
maintenance therapy.
*Prophylactic Folic Acid in pregnancy prevents
megaloblastosis in women at risk, and reduces risk of
fetal neural tube defects.
*Prophylactic supplementation is also given in chronic
haematological disease associated with reduced red
cell lifespan.
*Supraphysiological supplementation (400
microgram/day) can reduce the risk of