Anemia

Question 1

Most of the iron in the body is in (1)

Answer 1

1. hemoglobin.

Question 2

What are the two forms of iron available in the diet?

Answer 2

heme iron (found in meat, fish & poultry), which has the greatest bioavailability and nonheme iron (found in vegetables & dietary supplements)

Question 3

Absorption of nonheme iron is affected by?

Answer 3

(a) phosphates which decrease absorption; and,

(b) ascorbic acid and meat which increase absorption.

Question 4

Iron is best absorbed in its (1) form, however, dietary iron is in the (2) form which is not absorbed. (2) is ionized by stomach acid and then reduced to the (1) form.

Answer 4

1. ferrous (Fe2+)

2. ferric (Fe3+)

Question 5

The ferrous form is actively taken up primarily in the (1) but absorptive processes of the mucosa limit the amount of iron absorbed.

Answer 5

1. duodenum

Question 6

Within the mucosal cells, ferrous iron is oxidized to ferric iron which forms a complex with (1), a ß1-glycoprotein with two binding sites for ferric iron.

Answer 6

1. transferrin

Question 7

This complex binds to specific receptors in the plasma membrane and is taken up by receptor-mediated endocytosis.

Answer 7

ferric iron and transferrin complex

Question 8

If iron is plentiful, then there are fewer (1) on the surface of cells. This prevents iron-replete cells from
receiving excess iron

Answer 8

1. transferrin receptors

Question 9

combination of ferric iron with apoferritin

Answer 9

ferritin

Question 10

aggregated ferritin

Answer 10

hemosiderin

Question 11

Sites of iron storage include:

Answer 11

(1) the reticuloendothelial system

(2) hepatocytes.

Question 12

Storage forms of iron include:

Answer 12

hemoglobin, myoglobin, enzymes, ferritin, hemosiderin

Question 13

Symptoms of iron deficiency anemia

Answer 13

a. Feelings of weakness and lassitude
b. Headache
c. Dizziness
d. Palpitations; chest pain
e. Decreased exercise tolerance; shortness of breath

Question 14

Iron deficiency diagnosis

Answer 14

quantitation of transferrin saturation,

and plasma ferritin

Question 15

Adverse effects of oral iron

Answer 15

(a) heartburn
(b) constipation or diarrhea
(c) nausea (more prevalent at higher doses)
(d) upper abdominal pain (more prevalent at higher doses)

Question 16

hemoglobin recovers in 1–2 months

Answer 16

ferrous sulfate

Question 17

Contraindications of oral iron

Answer 17

antacids, proton-pump inhibitors, H2-

receptor antagonists decrease absorption

Question 18

replenishment of iron stores may require many (3–6) months

Answer 18

ferrous sulfate

Question 19

can interfere with absorption of many drugs; Avoid

concurrent administration, separate doses by >2 hours.

Answer 19

ferrous sulfate

Question 20

Clinical uses of parenteral iron

Answer 20

(a) Patients in whom GI absorption is prevented by disease
(b) Patient who cannot tolerate orally administered iron
(c) Hemodialysis patients (Sodium ferric gluconate and iron
sucrose)

Question 21

complex of ferric oxyhydroxide with polymerized

dextran

Answer 21

Iron dextran

Question 22

The complex must be phagocytized by reticuloendothelial

cells before iron becomes available

Answer 22

Iron dextran

Question 23

Can cause anaphylaxis

Answer 23

Iron dextran

Question 24

Lower risk of anaphylactic reactions

Answer 24

Sodium Ferric gluconate and iron sucrose

Question 25

Delivered to transferrin more readily

Answer 25

Sodium Ferric gluconate and iron sucrose

Question 26

Signs and symptoms of iron poisoning

Answer 26

i) abdominal pain ii) diarrhea iii) vomiting brown or bloody stomach contents with pills iv) lassitude & drowsiness v) pallor or cyanosis vi) hyperventilation (due to acidosis) vii) cardiovascular collapse viii) Death can occur within 6 hours or be delayed 12-24 hours with a period of apparent recovery in between

Question 27

Iron poisoning treatment

Answer 27

Treatment includes emesis & lavage with sodium bicarbonate to precipitate iron

Question 28

If plasma concentration of iron > 3.5 mg/L, (1) (IM or IV) is indicated.

Answer 28

1. deferoxamine

Question 29

has a high affinity for ferric iron. Once bound with iron, excreted in the urine

Answer 29

Deferoxamine has a high affinity for ferric iron. Once bound with iron, feroxamine is excreted in the urine

Question 30

Deferoxamine contraindications

Answer 30

Contraindicated in renal insufficiency and anuria

Question 31

can cause allergic reactions (pruritus, wheals, | rash, anaphylaxis)

Answer 31

Deferoxamine

Question 32

Without vitamin B12, folate is trapped as (1), and subsequent steps in folate metabolism that require (2) are deprived of substrate. This provides the common basis for the development of (3) with deficiency of either vitamin B12 or folic acid

Answer 32

1. methylTHF 2. THF 3. megaloblastic anemia

Question 33

Deficiency in either of these substances results in defective synthesis of DNA in any cell attempting chromosomal repair or division.

Answer 33

Vitamin B12 and folic acid

Question 34

important for folate metabolism and for the formation of methionine and S-adenosylmethionine from homocysteine

Answer 34

Methylcobalamin (CH3B12) | one of the two active coenzyme forms of B12

Question 35

required for the isomerization of L-methylmalonyl CoA to succinyl CoA.

Answer 35

Deoxyadenosylcobalamin | one of the two active coenzyme forms of B12

Question 36

released from digested protein by the actions of gastric acid and pancreatic enzymes

Answer 36

B12

Question 37

Intrinsic factor, secreted from | (1) binds B12

Answer 37

1. parietal cells

Question 38

The complex interacts with specific receptors on (1) mucosal cells, is absorbed and enters the circulation

Answer 38

1. ileal | refers to IF-B12 complex

Question 39

Once absorbed, B12 binds with (1) for transport to tissues. The complex is preferentially distributed to the (2) (up to 90%)

Answer 39

1. transcobalamin II (TcII) | 2. liver

Question 40

Most circulating cobalamin is bound to ?

Answer 40

transcobalamin I and III

Question 41

An alternate pathway for absorption exists which does not require intrinsic factor or an intact terminal ileum. The pathway involves (1) and accounts for 1% of ingested B12.

Answer 41

1. passive diffusion

Question 42

Deficiency (takes several years to develop following vitamin deprivation due to enterohepatic circulation

Answer 42

vitamin B12

Question 43

Effects of B12 deficiency

Answer 43

a. Megaloblastic anemia b. Potentially irreversible nerve damage: parethesias of the hands and feet, decreased vibration and position senses with resultant unsteadiness, decreased deep tendon reflexes In later stages: confusion, moodiness, loss of memory, and loss of central vision.

Question 44

Diagnosis of B12 deficiency

Answer 44

a. Determination of the plasma concentration of B12 | b. Examination of blood smear for macrocytosis and hypersegmented polymorphonuclear leukocytes

Question 45

Clinical use: patients with pernicious anemia or ileal disease

Answer 45

Cyanocobalamin parenteral

Question 46

Clinical use: In patients with pernicious anemia high doses are used since it is absorbed via passive diffusion

Answer 46

Cyanocobalamin (oral)

Question 47

Plasma becomes normoblastic after 7 days

Answer 47

Cyanocobalamin

Question 48

Are neuropsychiatric signs of B12 deficiency reversible?

Answer 48

They can be reversible with cyanocobalamin treatment if they are LESS than 6 months duration. Will need to keep pt on Therapy for at least 6 months to see improvement

Question 49

Inadequate secretion of intrinsic factor

Answer 49

pernicious anemia

Question 50

reduced to tetrahydrofolic acid which acts as an acceptor of one-carbon units

Answer 50

folic acid

Question 51

``` Polyglutamates in food are hydrolyzed, reduced, & then methylated by (1). (2) is transported to tissues and is taken up by receptor-mediated endocytosis ```

Answer 51

1. dihydrofolate reductase | 2. methyl-THF

Question 52

acts as a methyl donor (for formation of CH3B12) and as a | source of THF

Answer 52

Methyl-THF

Question 53

The (1) reduces & methylates folic acid (PteGlu) and transports (2) into the bile for reabsorption by the gut

Answer 53

1. liver | 2. CH3THF

Question 54

Folate is stored within cells as (1)

Answer 54

1. polyglutamates

Question 55

The principal effect of folic acid deficiency is:

Answer 55

a. Megaloblastic anemia b. Unlike B12 deficiency, neurological abnormalities are NOT common c. Folate deficiency during pregnancy is associated with congenital neural tube defects

Question 56

Diagnosis of folic acid deficiency

Answer 56

a. Determining plasma concentration of folate | b. Examination of blood smear

Question 57

prophylactic administration when there is | increased utilization such as in pregnancy and lactation

Answer 57

folate

Question 58

circumvents the action of inhibitors of dihydrofolate reductase and potentiates the cytotoxic effects of 5- fluorouracil

Answer 58

Leucovorin (folinic acid)

Question 59

Folate deficiency during pregnancy is associated with ?

Answer 59

congenital | neural tube defects

Question 60

High doses counteract the effects of antiepileptic drugs

Answer 60

Folic acid

Question 61

Acute or chronic alcoholism

Answer 61

causes of folic acid deficiency

Question 62

Inhibitors of dihydrofolate reductase (methotrexate, trimethoprim)

Answer 62

causes of folic acid deficiency

Question 63

Drugs which interfere with absorption and storage of folate (certain anticonvulsants and oral contraceptives)

Answer 63

causes of folic acid deficiency