Megaloblastic Anemia Flashcards
a group of anemia’s in which the erythroblasts in the bone marrow show a characteristic abnormality- maturation of the nucleus being delayed relative to that of the cytoplasm.
Megaloblastic Anemia
Megaloblastic Anemia is a Macrocytic anemia (MCV more than 98fL), that results from defect in DNA synthesis in developing RBC due to deficiency
of B12 and folic acid
Less common causes Megaloblastic Anemia
- Abnormalities of vit. B12 or folate metabolism.
- Other defects of DNA synthesis (congenital or acquired enzyme deficiency)
Vitamin B12 is synthesized by
bacteria and found in foods of animal origin.
The estimated average requirement for B12 in adults is
1–2 micrograms/day
The main site of absorption of b12
the terminal ileum
how is b12 stored
It is stored mainly in the liver (2-3 mg) which is sufficient for 2-4 years before it gets depleted
Most of the B12 in food is protein-bound and is released when the protein is subjected
to acid peptic digestion in the stomach
B12 -IF “Cbl-IF” complex bind to receptor (cubilin) at
distal ileum for mucosal absorption
transport protein involved in delivering vit B12 to bone marrow and other tissues (functional B12)
Transcobalamine II
storage protein (non functional B12)
TCI (haptocorrin)
The total amount of B12 in the body
is 2–3 mg, mostly stored in liver
The commonest cause for Cobalamine deficiency (due to impaired absorption)
Pernicious anemia
what is The definitive test for the diagnosis of pernicious anemia
SCHILLING TEST
Pernicious anemia CLINICAL FEATURES
- Mild jaundice.
- Angular stomatitis and mild symptoms of Malabsorption with loss of weight due to epithelial abnormality.
- Atrophic glossitis- “beefy” tongue.
- Neurological disorders due to defective methylation of myelin.
Lab Findings Mild to severe anemia (7)
1- Increased MCV & MCH, normal MCHC
2- Low RBC, HGB, WBC and PLT counts (fragile cells) due to ineffective hematopoiesis.
3- Low reticulocytes count
4- Macrocytic ovalocytes and teardrops.
5- Marked anisocytosis and poikilocytosis.
6- Schistocytes due to RBC breakage upon leaving the BM
7- Hypersegmented Neutrophils
BONE MARROW in Megaloblastic anemia
- Markedly hypercellular
- Myeloid : erythroid ratio decreased or reversed
- Erythropoiesis : MEGALOBLASTIC
what is the normal M:E ratio
3:1
Biochemical tests for assessing B12 status
- High unconjugated bilirubin.
- High LDH.
- Low total serum B12.
- High methylmalonic acid (MMA), which is highly specific for B12 deficiency, being more specific than a low serum B12.
- High plasma total homocysteine (poor specificity).
- Auto antibodies screening (IF and Parietal cells AB).
- Schilling test.
- 60% of B12 -deficient patients have low red cell folate levels.
Folates are found in foods
of both animal and vegetable origin.
The estimated average requirement for folate in adults is
100–150 micrograms/day
It can be easily destroyed by cooking
folic acid
The main site of absorption of folic acid is
is the jejunum
what happens in the jejunum
folic acid will be converted to methyl tetrahydrofolate ( methyl THF)
Causes of Folate deficiency
A)Decreased intake
B)Malabsorbtion
C)Increased demands
D) Drugs
folate deficiency due to decreased intake
Alcoholism
Hyperalimentation
Hemodialysis
Prematurity
Synthetic diet feeding Goat’s milk feeding
folate deficiency due to Malabsorbtion
Nontropical sprue
Tropical sprue
Intestinal resection
Other intestinal diseases
folate deficiency due to Increased demands
Pregnancy
Chronic hemolytic diseases
Myeloproliferative diseases
Dermatitis(expholiat.)
Hyperthyroidism
folate deficiency due to Drugs
Oral contraseptive drugs
Some anticonvulsant drugs
Cholestyramine
Clinical features of folate deficiency
Very similar to B12 deficiency.
* Differs from B12 deficiency in that it does not cause the sub acute combined degeneration of the spinal cord.
* Treatment with folic acid to patients with Megaloblastic anemia and neuropathy due to B12 deficiency will improve the degree of anemia but not the neuropathy.
Laboratory findings in Folate deficiency
- Lab and BM findings are identical to B12 deficiency.
- In biochemical tests: Low Serum folate. Low RBC folate
- Homocysteine level is elevated in both folate and B12 deficiency
- Methylmalonic acid level is normal in folate deficiency.
