L5 Megaloblastic anemia

Question 1

Production (source) of Vitamin B12?

Production (source) of Folate?

Answer 1

Vit B12: animal produced only

Folate: Vegetables, fruits, liver

Question 2

The daily requirement of Vitamin B12?

The daily requirement of Folate?

Answer 2

Vit B12: 1-2 ug

Folate: 100-150 ug

Question 3

Absorption site of Vitamin B12?

Absorption site of Folate?

Answer 3

Vit B12: Terminal ileum by IF-B12 complex

Folate: Duodenum and jejunum

Question 4

Transport of Vitmain B12 and folate (difference?)

Answer 4

Folate: weakly bound to albumin

Vit B12:

1. Transcobalamin (TC) is essential for cell uptake
   - Haptoccrin (TC1): inactive form 70-90%
   - Transcobalamin (TC2): an active form 10-30%

Question 5

Measurement/ confirmation assay of Vitamin B12?

Answer 5

Serum active B12 (TC2 bound Vitamin B12)

Question 6

Congenital TC2 deficiency cases? Serum VitB12?

Answer 6

Megaloblastic anemia;
Serum B12 is normal

(only active form is deficient)

Question 7

Measurement/ confirmation assay of folate?

Answer 7

Serum folate

Question 8

2 products of Vitamin B12 and their respective functions?

Answer 8

1. Methyl B12
   - cofactor for methionine synthase
   - methylation in DNA synthesis
2. Deoxyadenosyl B12 (Ado B12)
   - TCA cycle
   - Hb synthesis

• transfer folate from intestinal lumen into cells

Question 9

Elevated levels of MMA of homocysteine reflects?

Answer 9

B12 deficiency which causes Ado B12 deficiency

Question 10

Function of Folate?

Answer 10

DNA synthesis (dUMP > dTMP)

Question 11

Why willl B12 deficiency cause an elecation of folate?

Answer 11

False elevation of serum folate occurs due to reduced folate transfer from intestines to cells

Question 12

5 causes for B12 deficiency?

Answer 12

1. Diet - strict vegetarian
2. Stomach
   - pernicious anemia: autoimmune gastritis > impaired IF secretion
   - CA stomach
   - diagnosed by anti-IF Ab/ anti-parietal cell Ab
3. Pancreas - pancreatic insufficiency
4. Small bowel:
   - blind loops (bacterial overgrowth)
   - fish tapeworm infection
   - Crohn’s disease
5. Drugs
   - N2O (inhibit methionine synthase) (Anaes)
   - metformin
   - H2 receptor antagonists
   - PPI

Question 13

3 causes for folate deficiency?

Answer 13

1. Malabsorption
   - poor dietary intake
   - celiac disease
2. Excess utilization
   - pregnancy
   - hemolytic anemia
   = CA
3. Drugs
   - valporate
   - MTX (methotrexate, for cancer)

Question 14

Macrocytic anemia with nuclear-cytoplasmic maturation asynchrony =?

Answer 14

Megaoblastic anemia

Question 15

In megaloblastic anemia, nuclear maturation is faster/delayed compared to cytoplasmic maturation. Why?

Answer 15

Delayed;

due to defective DNA synthesis

Question 16

Why will patients with megaloblastic anemia have mild jaundice?

Answer 16

Excess breakdown of Hb (increase ineffective erythropoiesis > increase in intramedullary destruction)

Question 17

Other than jaundice, what are the clinical features of megaloblastic anemia?

Answer 17

1. Angular stomatitis, glossitis
2. Neurological:
   - memory loss
   - peripheral neuropathy: resersible with VitB12
   - Subacute combined cord degeneration: LL more affected, irreversible with B12 treatment
3. Subfertility

Question 18

MCV increases
reticulocytes decreases
WBC and O

Answer 18

Megaloblastic anemia

Question 19

Which of the following are true in megaloblastic anemia?
A. PB: Oval macrocytes
B. PB: hyposegmented neutrophils
C. Hypercellular BM
D. Nuclear maturation delayed compared to cytoplasmic
E. Serum Active B12 level

Answer 19

All except B

- Hypersegmented neutrophils

Question 20

Regarding the treatment for megaloblastic anemia,
A. no transfusion needed
B. folate deficiency - give oral folic acid daily only
C. B12 deficiency - monitor serum Na after treatment
D. B12 deficiency - IV hydroxocobalamin 1000ug

Answer 20

Only A
B: must not be given alone unless ruled out B12 deficiency

C: Serum K! hypokalemia due to resumption of erythropoiesis

D: Intramuscular

Question 21

What is non-megaloblastic macrocytic anemia?

Answer 21

Macrocytic anemia without impairment in DNA synthesis

Question 22

Reasons for non-megaloblastic macrocytic anemia? (7)

Answer 22

1. Alcohol (MC of raised MCV without anemia)
2. Liver disease
3. Hypothyroidism
4. Aplastic anemia
5. Myelodysplastic syndrome
6. Cold Agglutination disease
7. Others: smoking, hemolytic anemia (reticulocytes)

Question 23

What should you fo when you fonud macrocytes without megalaloblastic features like Howell Jelly bodies, hypersegmented neutrophils etc?

Answer 23

1. Check alcohol history, smoking etc
2. Red cell agglutination may cause falsely elevated MCV

>

3. LFT, TFT

Question 24

If retic >2%, suspect?

Answer 24

Hemolytic anemia