95 Megaloblastic Anemia

Question 1

Causes of Megaloblastic anemia

Answer 1

B12 and Folate deficiency

Question 2

Enzymes where cobalamin is a co factor

Answer 2

L methylmamonyl Co Enzyme A mutase

Methionine synthase

Question 3

What is daily requirement for colabamin? How much are the body stores?

Answer 3

Daily requirements for cobalamin is 1-3 micrograms.

Body stores are at 1-3 mg sufficined to 3-4 years supply

Question 4

How is cobalamin absorbed and where? Which the normal physiologic mechanism? What mediates this mechanism

Answer 4

Passive: buccal, duodenal, ileal; inefficient only 1% absorbed
Active: normal physiologic mechanism; ileum and efficient; mediated by intrinsic factor

Question 5

Where is intrinsic factor produced?

Answer 5

Gastric parietal cell of the fundus and body of stomach

Question 6

Two amin cobalamin transport protein

Answer 6

One HC or TC I

Transcobalamin: TC II

Question 7

Food with the highest concentration of folate

Answer 7

Liver
Yeast
Spinach
Greens
Nut

Question 8

Largest store of Folate in the body

Answer 8

Liver

Question 9

Total body Folate store. Daily Folate requirement

Answer 9

Folate daily requirement 100 mcg

Body stores of Folate 10 mg, stores are only sufficient for 3-4 months

Question 10

How much of Folate is absorbed from food and where is it absorbed rapidly? Dietary Folate is converted to what? What pH?

Answer 10

Only 50% of Folate from food is absorbed rapidly in the upper small intestines
All dietary Folate is converted to 5 methyl tetrahydrofolate (5-MTHF)
Most absorbed happens at pH 5.5

Question 11

True or false. Pteroylglutamic acid at doses more than 400 mcg is largely absorbed unchanged and converted to natural Folates in liver

Answer 11

True.

Question 12

How much of Folate is bound and unbound?

Answer 12

1/3 loosely bound to albumin

2/3 is unbound

Question 13

3 types of Folate binding protein involved in Folate transport? Which is the major route of delivery to cells?

Answer 13

1. Reduced Folate transporter (RFC): major route
2. Folate receptor (FR2 and FR2)
3. PCFT

Question 14

Universal methyl donor

Answer 14

S adenosylmethionine (SAM)

Question 15

Common feature of all Megaloblastic anemia

Answer 15

Defect in DNA synthesis

Question 16

How does Folate or cobalamin affect DNA synthesis?

Answer 16

Either Folate or cobalamin deficiency leads failure to convert dUMP to dTMP.

Question 17

Two reactions in the body that require cobalamin

Answer 17

Methylmamonyl CoA isomerization

Methylation of homocysteine to methionine

Question 18

MTHF accumulates in the plasma and Folate concentrations fall because of failure in the formation of THF

Answer 18

THF starvation or methylfolate trap

Question 19

Reason for psychiatric disturbance in Folate deficiency

Answer 19

Attributed to failure to synthesize SAM which is needed in methylation of biogenic amines

Question 20

Most affected tissues with cobalamin and Folate deficiency

Answer 20

Epithelial surfaces of mouth, stomach, small intestines, Respiratory, urinary and female genital tracts

Question 21

When Folic acid supplementation given to reduce neural tube defects

Answer 21

Conception to first 12 weeks of pregnancy

Question 22

Protective dose of Folic acid to prevent neural tube defects in pregnancy

Answer 22

0. 4 mg daily

Question 23

Three enzymes defective in severe homocystinuria

Answer 23

Methionine synthase
MTHFR
Cystathionine synthase

Question 24

What type of leukemia is prevented with Folic acid supplementation

Answer 24

Acute lymphoblastic leukemia (ALL)

Question 25

What is the main feature of myeloblastic anemia on peripheral blood

Answer 25

Ovalocytes
MCV more than 100 fL
Hypersegmented neutrophils (more than 5 nuclear lobes)

Question 26

What is the bone marrow picture of Megaloblastic anemia

Answer 26

Hypercellular with an accumulation of primitive cells due to selective death by apoptosis of more mature forms

Question 27

Defined as severe lack of intrinsic favor due to gastric atrophy

Answer 27

Pernicious anemia

Question 28

How much of ileal removal leads to cobalamin Malabsorption

Answer 28

Removal of 1.2 M of terminal ileum leads to Malabsorption of cobalamin