Unit 16: Macrocytic anemias

Question 1

What is the main cause of megaloblastic anemia?

Answer 1

Impaired DNA synthesis; reduction in the number of cell divisions

Question 2

When B12 or folate is deficient, the production of what nucleotide is impaired?

Answer 2

Thymidine

Question 3

Which deficiency has more of a direct affect, folate or B12?

Answer 3

Folate, in preventing the methylation of dUMP

Question 4

Which deficiency has more of an indirect affect, folate of B12?

Answer 4

B12, preventing the production of THF from 5-methyl THF

Question 5

If there is no B12, what happens to the inactive folate that needs to be converted?

Answer 5

It is stuck in its inactive form, aka the folate trap

Question 6

Where is 5-methyl THF converted into THF?

Answer 6

The cytoplasm

Question 7

What happens to 5-methyl THF if it is not readily polyglutamated in the cell?

Answer 7

It will leak out of the cell, decreasing the intracellular folate

Question 8

What happens to homocysteine in the case of B12 or folate deficiency?

Answer 8

It accumulates because methionine synthase is unable to convert it to methionine without vitamin B12 as a cofactor

Question 9

What happens to the DNA in the case of a thymidine deficiency?

Answer 9

Uracil is incorporated into the DNA strand instead and is then removed in the replicated strand. This causes many single strand breaks

Question 10

What is the term for abnormal blood cell development?

Answer 10

Ineffective hematopoiesis

Question 11

What happens to most of the early erythroid progenitors and precursors in megaloblastic anemia?

Answer 11

They are destroyed when devision is halted via cell lysis or apoptosis

Question 12

What happens to the abnormal cells that do make it to the peripheral blood stream in megalobastic anemia?

Answer 12

They are increased in size, macrocytic

Question 13

Can RNA synthesis occur without thymidine?

Answer 13

Yes, it needs uracil instead

Question 14

As a result of RNA synthesis occurring and DNA synthesis halting, what happens to the cytoplasm development?

Answer 14

Cytoplasm is able to develop normally, in asynchrony with the nuclear development

Question 15

What is pancytopenia?

Answer 15

Ineffective hematopoiesis of all 3 blood cell lineages

Question 16

What are the general symptoms of anemia?

Answer 16

Fatigue, shortness of breath, and weakness

Question 17

What are some of the neurologic manifestations of B12 deficiency?

Answer 17

Memory loss, numbness, tingling, loss of balance

Question 18

What are some of the neuropsychiatric manifestations of B12 deficiency?

Answer 18

Personality changes and psychosis

Question 19

What are some of the specific manifestations of folate deficiency?

Answer 19

Depression, peripheral neuropathy, psychosis and neural tube defects (i.e. spina bifida)

Question 20

What is the most common cause of folate deficiency?

Answer 20

Inadequate intake

Question 21

What is the most common cause of B12 deficiency?

Answer 21

Impaired absorption

Question 22

What are the 5 causes of impaired absorption of B12?

Answer 22

Failure to separate, lack of intrinsic factor, malabsorption, inherited factors and competition

Question 23

What is it called to have a loss of epithelial cells on the tongue, resulting in a smooth surface and soreness?

Answer 23

Glossitis

Question 24

Which one takes longer to develop symptoms for, B12 deficiency or folate deficiency?

Answer 24

B12 - up to a few years, folate - up to a few months (this reflects the storage capacity of each vitamin)

Question 25

What is steatorrhea?

Answer 25

Fat in the feces

Question 26

What intestinal diseases may cause impaired absorption of folate?

Answer 26

Sprue and celiac disease

Question 27

Is folate heat labile or heat stable?

Answer 27

Labile

Question 28

Is B12 heat labile or heat stable?

Answer 28

Stable

Question 29

Binding carrier for B12 in the stomach?

Answer 29

Haptocorrin

Question 30

Binding carrier for B12 in the small intestine?

Answer 30

Intrinsic factor

Question 31

Binding carrier for B12 in enterocyte?

Answer 31

Transcobalamin

Question 32

What autoimmune disease is the result of lack of intrinsic factor?

Answer 32

Pernicious anemia

Question 33

What are two examples of competition for B12?

Answer 33

Fish tapeworm, and blind loops (portions of the intestine that are stenotic as a result of surgery and have an overgrowth of competing intestinal bacteria)

Question 34

What disease may cause a failure to separate B12 from haptocorrin due to the lack of gastric acidity or trypsin?

Answer 34

Chronic pancreatic disease

Question 35

What does H. pylori do to cause a lack of intrinsic factor?

Answer 35

Destroys parietal cells of the stomach and intestines

Question 36

What is achlorhydria?

Answer 36

A lack of hydrochloric acid in the gastric digestive fluids

Question 37

What are the most indicative clues of megaloblastic anemia from a blood smear?

Answer 37

Dacrocytes, oval macrocytes, hypersegmented neutophils and possibly Howell-Jolly bodies, occasional pronormoblasts

Question 38

Why is the MCHC usually within normal range for megaloblastic anemia?

Answer 38

Because the hgb production is not affected

Question 39

Why is the MCV usually high for megaloblastic anemia?

Answer 39

Because of the increase volume of the cells

Question 40

Is the retic count elevated for megaloblastic anemia?

Answer 40

No

Question 41

Is the RDW elevated for megaloblastic anemia?

Answer 41

Yes

Question 42

What happens to the H and H levels in megaloblastic anemia?

Answer 42

They are decreased

Question 43

When is a bone marrow exam done for megaloblastic anemia?

Answer 43

To confirm hypercellular marrow when there is pancytopenia in the blood

Question 44

What will you see in bone marrow exam for a patient with megaloblasic anemia?

Answer 44

Large banded neutrophils, many large immature blast cells and nuclear-cytoplasm asynchrony

Question 45

What happens to methylmalonic acid levels when B12 levels decrease? Why does this happen?

Answer 45

It increases due to the fact that B12 is a cofactor needed to convert methylmalonyl CoA to succinyl CoA (some of the accumulated methylmonyl CoA is hydrolyzed to methylmalonic acid)

Question 46

What happens to the levels of homocysteine when folate or B12 are decreased?

Answer 46

It is increased

Question 47

What sort of test is done to diagnose pernicious anemia?

Answer 47

Antibody assay to detect the development of antibodies to intrinsic and parietal cells

Question 48

When is a stool analysis done for B12 deficiency?

Answer 48

To detect the presence of D. latum (hookworm)

Question 49

What are the nonmegaloblastic macrocytic anemias?

Answer 49

Liver disease, chronic alcoholism and bone marrow failure (or aplastic anemia)

Question 50

Are retics increased in a patient with nonmegaloblastic macrocytic anemia?

Answer 50

Yes!

Question 51

Do you see hypersegmented neutrophils and oval macrocytes in nonmegaloblastic macrocytic anemia?

Answer 51

No