Ch5 - 3) Macrocytic anemia

Question 1

What is Macrocytic Anemia?

Answer 1

Anemia with MCV > 100 most commonly due to folate or vitamin B12 deficiency (megaloblastic anemia)

Question 2

What are folate and vitamin B12 are necessary for?

Answer 2

synthesis of DNA precursors,

Question 3

What does folate circulates in the serum as?

Answer 3

methyltetrahydrofolate (methyl THF);

Question 4

What happens to methyl-THF?

Answer 4

removal of the methyl group allows for participation in the synthesis of DNA precursors.

Question 5

What happens to the methyl group from methyl THF?

Answer 5

It is transferred to vitamin B12 (cobalamin),

Question 6

What does Vitamin B12 do with the methyl it receives from methyl THF?

Answer 6

B12 then transfers the methyl to homocysteine, producing methionine.

Question 7

Lack of folate or vitamin B12 does what?

Answer 7

impairs synthesis of DNA precursors,

Question 8

What does impaired division and enlargement of RBC precursors lead to?

Answer 8

Megaloblastic anemia

Question 9

What does impaired division of granulocytic precursors lead to?

Answer 9

hypersegmented neutrophils

Question 10

Where is megaloblastic change also seen?

Answer 10

in rapidly-dividing (e.g., intestinal) epithelial cells.

Question 11

What are some other causes of macrocytic anemia (without megaloblastic change)?

Answer 11

alcoholism, liver disease, and drugs (e.g., 5-FU).

Question 12

Where is dietary folate obtained?

Answer 12

from green vegetables and some fruits

Question 13

Where is dietary folate absorbed?

Answer 13

in the jejunum

Question 14

How fast does folate deficiency develop?

Answer 14

within months, as body stores are minimal

Question 15

What are some causes of folate deficiency?

Answer 15

1) poor diet. 2) increased demand 3) folate antagonists

Question 16

What are some examples of poor diet leading to folate deficiency?

Answer 16

Seen in alcoholics and elderly

Question 17

What are some examples of increased demand leading to folate deficiency?

Answer 17

pregnancy, cancer, and hemolytic anemia

Question 18

What are the clinical and laboratory findings?

Answer 18

1. Macrocytic RBCs and hypersegmented neutrophils (> 5 lobes. Fig. 5.5) 2. Glossitis 3. decreased serum folate 4. increased serum homocysteine (increases risk for thrombosis) 5. Normal methylmalonic acid

Question 19

What is dietary vitamin B12 complexed to?

Answer 19

animal-derived proteins

Question 20

What liberates Vitamin B12 that is complexed to animal derived protein?

Answer 20

salivary gland enzymes (e.g., amylase) liberate vitamin B12

Question 21

After Vit B12 reacts with salivary gland enzymes what happens?

Answer 21

It is bound by R-binder (also from the salivary gland) and carried through the stomach.

Question 22

What happens to Vit B12 after its bound to R binder?

Answer 22

Pancreatic proteases in the duodenum detach vitamin B12 from R-binder

Question 23

After Vitamin B12 is detached from R binder, what happens?

Answer 23

It binds intrinsic factor (made by gastric parietal cells) in the small bowel;

Question 24

Where is the intrinsic factor-vitamin B12 complex absorbed?

Answer 24

in the ileum

Question 25

How common is vitamin B12 deficiency?

Answer 25

it is less common than folate deficiency and takes years to develop due to large hepatic stores of vitamin B12

Question 26

Why does it take years for Vitamin B12 deficiency to develop?

Answer 26

Due to large hepatic stores of Vitamin B12

Question 27

What is the most common cause of vitamin B12 deficiency?

Answer 27

pernicious anemia

Question 28

What is pernicious anemia?

Answer 28

autoimmune destruction of parietal cells (body of stomach) leads to intrinsic factor deficiency

Question 29

What are some other causes of vitamin B12 deficiency?

Answer 29

include pancreatic insufficiency and damage to the terminal ileum (e.g., Crohn disease or Diphyllobothrium latum - fish tapeworm); dietary deficiency is rare, except in vegans.

Question 30

What are the clinical and laboratory findings for Vitamin B12 deficiency?

Answer 30

1. Macrocytic RBCs with hypersegmented neutrophils, 2. Glossitis, 3. Subacute combined degeneration of the spinal cord 4. decreased serum vitamin B12. 5. increased serum homocysteine 6. increased methylmalonic acid

Question 31

How does vitamin B12 relate to spinal cord degeneration?

Answer 31

Vitamin B12 is a cofactor for the conversion of methylmalonic acid to succinyl CoA (important in fatty acid metabolism) – build up of methylmalonic acid which impairs spinal myelinization

Question 32

How does Vitamin B12 deficiency relate to spinal cord degeneration?

Answer 32

Vit B deficiency results in increased levels of methylmalonic acid, which impairs spinal cord myelinization,

Question 33

What does damage to the spinal cord due to Vitamin B12 deficiency result in?

Answer 33

poor proprioception and vibratory sensation (posterior column) and spastic paresis (lateral corticospinal tract)

Question 34

How is Vitamin B12 deficiency similar to folate deficiency?

Answer 34

Increased serum homocysteine which is similar to folate deficiency and increases the risk for thrombosis and there is increased methylmalonic acid (unlike folate deficiency)