Biology of Disease

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N

N

N

N

H

N

C

H 2

C

O

H 2 N

OH

H

N C

CH 2

CH 2

COO-

COO-

H

B)

Figure 13.18 Structures of (A) vitamin B 12 (cobalamin) and (B) folic acid.

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The deoxyuridine suppression test for megaloblastic anemia is performed by

adding tritiated thymidine (^3 H-thymidine) to a sample of bone marrow. Bone

marrow samples may be obtained by aspiration or by trephine. Aspiration,

using a specialized needle, is usually carried out at the iliac crest with a local

anesthetic. In normal marrow less than 5% of the^3 H-thymidine is usually

taken up, but in megaloblastic marrow up to 50% of it may be used. The

microscopic picture of the bone marrow can be investigated by using the

aspirate to make a smear on a microscopy slide. If a larger sample of bone

marrow is required, the posterior iliac crest is used but a longer and wider

needle is used to obtain a ‘core’ of bone. This core is fixed and decalcified

over several days and then stained for microscopy.

It is important to distinguish pernicious anemia from other causes of

megaloblastic anemia, such as folate deficiency, because this will affect

treatment. However, this is usually clear from the blood concentrations of

these two vitamins. Also, the ability to absorb vitamin B 12 can be measured

using the Schilling test in which patients are given vitamin B 12 radioactively-

labeled with^58 Co. The urine is collected over a period of 24 h and the amount

of radioactivity measured.

Vitamin B 12 deficiency is treated by intramuscular injection of 1 mg of

the pure vitamin, to a total of 6 mg over a period of three weeks. Oral

administration is obviously unsuccessful in pernicious anemia because of the

lack of intrinsic factor. A maintenance dose of 1 mg every three months is

then given for the rest of the patient’s life. Clinical improvement may occur

within a few days (provided that the neuropathy has not been long-standing)

and a reticulocytosis is observed a few days later. Folate deficiency can be

corrected by giving 5 mg of folic acid daily, and this usually produces a rapid

hematological response. Prophylactic folate is recommended for all women

during pregnancy and especially for women who have had a previous child

with a neural tube defect.

N

H

H

H

H

N N

N

N

N

Co

O

O

O

O

HO

• O P

CH 2

CH 2

C O

NH

NH 2

NH 2

CH 2

HOH 2 C

CH 3

CH 3

CH 3

CH (^3) CH 3
CH 3
CH 3
C
O
O
A)
H
H
H
H
H 3 C
H 3 C
H 3 C
H 3 C
H 3 C
H 2 N
O
O
H 2 N
O
H 2 N
H 2 N