Megaloblastic Anemia and Vitamin B deficiency and Folic acid deficiency Hematology Pathology Lecture for Undergraduate Medical Student

1. Dept. of Pathology/
Hematology
MEGALOBLASTIC
ANEMIA

2. List of Contents:
 Objectives
 Contents
I. Definition
II. B12 forms, absorption and function
III. Folate forms, absorption and function
VI. Causes of B12 and folate deficiencies.
V. Clinical & lab. features, and treatment of
megaloblastic anemia
 Summary

3. Objectives:
 To define megaloblasic anemia
 To learn about the absorption and functions of
Vit. B12 and folate
 To explain the interaction of vit. B12 and
folate in the DNA synthesis.
 To know the clinical & lab features and mode
of treatment .

4. Definition
 Anaemias characterized by distinctive cytological and
functional abnormalities in blood and marrow due to
impaired DNA synthesis.
 It maybe due to Vitamin B12 (cobalamin), or folate
deficiencies or interference with DNA synthesis by
other mechanisms.

5. Forms of vitamin B12
 Methylcobalamin: main form in human plasma.
 Deoxyadenosylcobalamin: main form of B12 in
tissues.
 Cyanocobalamin: form used in studying B12
metabolism.
 Hydroxocobalamin: form used in treatment of B12
deficiency.

8.  B12 involved in two imp. biochemical
reactions:
 1. Co factor for the conversion of Homocysteine to
Methionine (methylcobalamin form), the later is essential
for maintaining the active form of folate inside the cells
and available for DNA synthesis.
 2. Co factor for the conversion of Methylmalonyl-Co A into
succinyl-Co A, (Deoxyadenosyl-cobalamin form), the later
is needed for the synthesis of myelin in the CNS..
Functions of vit. B12

9. This reaction is extremely
important for normal
Synthesis of DNA
This reaction is important
for normal myelination of
neurons.

10. Forms of folic acid
 Polyglutamates: 90% of the dietary folates and
the main form intracellularly.
 Monoglutamates: 10% of dietary folates. One
most important form is :
- Methyltetrahydrofolate monoglutamate (Methyl
THF): is the main form in body fluids.

11. Diatory folates
 Folates are present in Liver, kidney, fresh green
vegetables (especially leafy like Cabbage and
Spinach), and they are destroyed by cooking.
 Body stores are ~ 5-20 mg, mainly in liver.
 Minimal daily requirements are 100-200ug/day.

14. Causes of B12 Deficiency
Impaired Absorption
Reduced Intake
Gastric Intestinal
- Pernicious anemia.
- Gastrectomy.
-Ileal resection
-Blind loop Syndrome
-Crohn’s dis.
-Celiac Disease
- Unusual;
- Strict Vegetarians

15. Pernicious anaemia
• The best known of megaloblastic anemias due to
Cobalamin deficiency.
• Not common in Iraq.
• Mostly a disease of the elderly.
• Characterized by stomach atrophy, loss of intrinsic
factor and Hydrochloric acid.
• Mostly autoimmune in nature.
• Characterized classically by a combination of
Megaloblastic anemia, Glossitis and Neuropathy.

16. Causes of Folate Deficiency
Reduced Intake Excess
Utilization
Impaired
Absorption
Drugs
Frequent in
infants and elderly
Prematurity,
Pregnancy,
Lactation,
Hemolysis,
Malignancy
Malabsorption,
Celiac dis,
Lymphoma,
regional enteritis,
Jejunal resection
Methotrexate,
Anticonvulsants,
Hydroxyurea, ARA-c.

17. Blood Picture in Megaloblastic anaemia
 Variable degree of anemia.
 MCV increased >100 fl, may be up to
135.
 Low retics.
 Leucocytes maybe reduced, some
neutophils may be hypersegmented.
 platelets may be reduced.
Film Normochromic, Anisocytosis
poikilocytosis, macrocytosis, tear
drop cells The bone marrow is hypercellular
erythroblast are large with failure of
nuclear maturation

18. Hypersegmented Neutrophils
Blood Film in Megaloblastic anaemia

19.  symptoms and signs of anemia
 Mild jaundice
 Glossitis and angular stomatitis
 Intermittent infections
 Purpura due to thrombocytopenia
 Widespread melanin pigmentation
 Neuropathy and psychiatric symptoms (in B12
deficiency)
 Sterility
Clinical features

20. Clinical Features of Cobalamin Deficiency.
l
Pallor with mild of jaundice Glossitis

21. Further diagnostic evaluation of
Megaloblastic anemias
 Serum B12 and folate (should be done before
transfusions or initiating therapy).
 Search and exclude causes for B12 and folate, e.g.
gastrectomy, crohn’s disease, intake of certain
drugs, intestinal surgery, vegetarians, patients with
increase folate demands e.g. multiple pregnancy,
hemolysis etc.

22.  Schilling test: this is used in diagnosis of B12 def and
would help to differentiate between Pernicious anemia
and ileal malabsorption of B12. It is based on giving
radioactive B12 with and without IF and measuring the
urinary excretion of B12 in urine.
 Optional investigations: Check for antibodies against
intrinsic factor and parietal cells and check the
stomach by endoscopy.
Further Investigations of Megaloblastic
Anemia

23. Management :
- In cobalamin deficiency:
- Hydroxocobalamin by injection.
- Should never give folate on its own in cobalamin
deficients because although response will be seen,
aggravation or induction of neurological
complications may be induced.
- In folate deficiency :
- Folic acid orally
- The length of therapy is dependent on the
underlying pathology.

24. Assessment of response to therapy
 The patient will feel better rapidly after starting
therapy.
 Reticulocytes will increase within 3-5 days
reaching a peak in 7-10 days.
 Hb will increase at a rate of 1 g/dl per week.
 Leucocytes and platelets will return to normal
counts within days.
 The marrow will start changing from megaloblastic
to normoblastic within 12 hours, and this process
will be complete within 2-3 days.

25. Summary
 Megaloblasic anemia is caused by vit.B12 or
folate deficiency
 There is defective DNA maturation.
 The RBCs are normochromic macrocytic.
 Neutrophils can be hypersegmented.
 Platelet and WBC count are low
 B12 deficiency is associated with neurological
manifestations

26. Question
 How can you assess response to therapy in
megaloblastic anemia?