2. Definition: Macrocytic Anemia
MCV>100fL
Impaired DNA formation due to lack of vitamin B12
or folate in ultimately active form.
Therefore, maturation of nucleus is delayed relative
to that of cytoplasm.
3. Vitamin B12: Cobalamin
SOURCE:Meat and dairy products only
Minimum daily requirement 6-9 mcg/d
Total body store 2-5 mg.
Helps to synthesize thiamine, thus deficiency leads
to problems with DNA replication.
4. B12: Cobalamin absorption
Initially bound to protein in
diet, liberated by acid and
pepsin, then binds to R factors
in saliva and gastric acids
Freed from R factors by
pancreatic proteases then binds
to Intrinsic Factor secreted by
gastric parietal cells
Absorbed together (Cbl + IF) in
ileum
Released from IF in ileal cell
then exocytosed bound to
trans-Cbl II
Cbl bound to transcobalamin II
binds to cell surface receptors
and is endocytosed
6. Causes of B12 Deficiency:
Pernicious Anemia
Autoantibody to Intrinsic Factor detectable in <70%
cases.
Blocks attachment of Cbl to IF
Blocks attachment of Cbl-IF complex to ileal
receptors
Chronic atrophic gastritis
Autoantibody against parietal cells
7. Other Causes of B12 Deficiency:
Gastrectomy
Ileal resection
Ileal disease (TB, lymphoma, amyloid, Crohn’s)
Enteropathies (protein losing, chronic diarrhea, celiac sprue)
Bacterial overgrowth
HIV infection
Chronic alcoholism
Strict vegetarian diet
Inherited:
o Methylmalonic aciduria
o Homocystinuria
o Congenital intrinsic factor deficiency
Decreased absorption from medication:
Neomycin
Metformin (biguanides) up to 10-25%
PPI
Nitric oxide (inhibits methionine synthase)
9. B12 Symptoms: Neurologic
Memory loss
Numbness
Weakness
Symmetric neuropathy
legs>arms
Severe weakness,
spasticity, clonus,
paraplegia
Subacute combined
degeneration of the dorsal
(posterior) and lateral
spinal columns
Due to a defect in
myelination
11. B12 Lab findings
Macroovalocytic anemia
with elevated serum
bilirubin.
Increased red cell
breakdown due to
ineffective hematopoiesis
Reticulocytes, WBC &
platelets normal to low
Hypersegmented
neurophils
12. Bone Marrow
Hypercellular marrow
Megaloblastic erythroid
hyperplasia
Giant metamyelocytes
Due to slowing of DNA
synthesis and delayed
nuclear maturation
Methionine deficiency may
play a central role
17. Shilling Test
PART 1:
Oral labeled B12 and IM
unlabeled B12[ to saturate
tissue stores] are given at the
same time
24h urinary excretion is
detected to assess
absorption:
>5% normal
<5% impaired
PART 2:
Repeat with oral IF
if now normal =PA[due to
intrinsic factor deficiency]
if impaired = malabsorption
Part 1 test result Part 2 test result Diagnosis
Normal -
Normal
or vitamin B12
deficiency
Low Normal
Pernicious
anemia
Low Low Malabsorption
18. Diffferential diagnosis
Aplastic anaemia
Pure red cell aplasia
Transient erythroblastopenia of childhood
Congenital dyserythropoietic anemia
Chronic liver disease
Hypothyroidism
Myelodysplastic syndrome
19. Treatment
folate deficiency is treated with folate supplements:5
mg tablets are available.a dose of 1-5 mg/day for 3-4
weeks.
Vit.B12 is given parenterally at a dose of 1mg-
followup shows decrease in MCV,reticulocytosis and
improvement in platelet and neutrophil counts.
Lower doses are used in infants[250mcg].