Megaloblastic Anemia

Question 1

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.

Answer 1

Megaloblastic Anemia

Question 2

Megaloblastic Anemia is a Macrocytic anemia (MCV more than 98fL), that results from defect in DNA synthesis in developing RBC due to deficiency

Answer 2

of B12 and folic acid

Question 3

Less common causes Megaloblastic Anemia

Answer 3

• Abnormalities of vit. B12 or folate metabolism.
• Other defects of DNA synthesis (congenital or acquired enzyme deficiency)

Question 4

Vitamin B12 is synthesized by

Answer 4

bacteria and found in foods of animal origin.

Question 5

The estimated average requirement for B12 in adults is

Answer 5

1–2 micrograms/day

Question 6

The main site of absorption of b12

Answer 6

the terminal ileum

Question 7

how is b12 stored

Answer 7

It is stored mainly in the liver (2-3 mg) which is sufficient for 2-4 years before it gets depleted

Question 8

Most of the B12 in food is protein-bound and is released when the protein is subjected

Answer 8

to acid peptic digestion in the stomach

Question 9

B12 -IF “Cbl-IF” complex bind to receptor (cubilin) at

Answer 9

distal ileum for mucosal absorption

Question 10

transport protein involved in delivering vit B12 to bone marrow and other tissues (functional B12)

Answer 10

Transcobalamine II

Question 11

storage protein (non functional B12)

Answer 11

TCI (haptocorrin)

Question 12

The total amount of B12 in the body

Answer 12

is 2–3 mg, mostly stored in liver

Question 13

The commonest cause for Cobalamine deficiency (due to impaired absorption)

Answer 13

Pernicious anemia

Question 14

what is The definitive test for the diagnosis of pernicious anemia

Answer 14

SCHILLING TEST

Question 15

Pernicious anemia CLINICAL FEATURES

Answer 15

• 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.

Question 16

Lab Findings Mild to severe anemia (7)

Answer 16

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

Question 17

BONE MARROW in Megaloblastic anemia

Answer 17

• Markedly hypercellular
• Myeloid : erythroid ratio decreased or reversed
• Erythropoiesis : MEGALOBLASTIC

Question 18

what is the normal M:E ratio

Answer 18

3:1

Question 19

Biochemical tests for assessing B12 status

Answer 19

• 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.

Question 20

Folates are found in foods

Answer 20

of both animal and vegetable origin.

Question 21

The estimated average requirement for folate in adults is

Answer 21

100–150 micrograms/day

Question 22

It can be easily destroyed by cooking

Answer 22

folic acid

Question 23

The main site of absorption of folic acid is

Answer 23

is the jejunum

Question 24

what happens in the jejunum

Answer 24

folic acid will be converted to methyl tetrahydrofolate ( methyl THF)

Question 25

Causes of Folate deficiency

Answer 25

A)Decreased intake B)Malabsorbtion C)Increased demands D) Drugs

Question 26

folate deficiency due to decreased intake

Answer 26

Alcoholism Hyperalimentation Hemodialysis Prematurity Synthetic diet feeding Goat’s milk feeding

Question 27

folate deficiency due to Malabsorbtion

Answer 27

Nontropical sprue Tropical sprue Intestinal resection Other intestinal diseases

Question 28

folate deficiency due to Increased demands

Answer 28

Pregnancy Chronic hemolytic diseases Myeloproliferative diseases Dermatitis(expholiat.) Hyperthyroidism

Question 29

folate deficiency due to Drugs

Answer 29

Oral contraseptive drugs Some anticonvulsant drugs Cholestyramine

Question 30

Clinical features of folate deficiency

Answer 30

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.

Question 31

Laboratory findings in Folate deficiency

Answer 31

* 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.