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PMCOL 344 > Hematopoietic System-B12 and Folate > Flashcards

Hematopoietic System-B12 and Folate Flashcards

1
Q

what is another name for megaloblastic anemias

A

macrocytic anemias

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2
Q

what are megaloblastic anemias

A

increase in number of large erythroblasts, many of which do not form like RBC (those formed are large)

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3
Q

what cases megaloblastic anemias

A

b12 or folic acid deficiency

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4
Q

why do cells grow large with these deficiencies

A

they grow large, accumulate hemoglobin, cant divide

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5
Q

what is B12 and folic acid essential for

A

DNA synthesis and cellular division

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6
Q

what happens once folic acid is absorbed in duodenum

A

reduced to methyl-FH4 by intestinal cells and then transported into blood stream

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7
Q

where is folic acid absorbed

A

duodenum

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8
Q

which bases is folic acid required for

A

both purine and pyrimidine

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9
Q

how does methyl FH4 enter erythroblasts

A

via folate receptor

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10
Q

what does methyl FH4 require for it to be able to synthesize DNA

A

it needs B12

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11
Q

which tissues are most affected by folic acid or b12 deficiency + what does this lead to

A

tissues with cells with rapid turnover (ex: bone marrow) which leads to macrocytic anemia

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12
Q

what 2 things happen with anemia progression with b12 and folic acid deficiency

A

neutropenia and thrombocytopenia

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13
Q

what is vitb12 essential for in the CNS

A

methylation reactions carried out by methionine synthase in the CNS

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14
Q

what is another name for vitamin b12

A

cobalamin

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15
Q

what solubility is b12

A

water

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16
Q

what is the main source of b12

A

meat and dairy products

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17
Q

what helps release b12 in the stomach

A

pepsin and acid

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18
Q

where does b12 absorb

A

in the ileum

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19
Q

how does b12 absorb in the ileum

A

by binding to glycoprotein (intrinsic factor IF)

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20
Q

how much b12 do you need daily

A

1-6ug

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21
Q

what is pernicious anemia

A

anemia caused by not enough b12

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22
Q

what is the most common cause of pernicious anemia

A

permanent deficiency of intrinsic factor in stomach

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23
Q

what is the most common cause of pernicious anemia in elderly

A

inability to release b12 from food cause low acid-pepsin secretion from gastric mucosa

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24
Q

how common is b12 dietary deficiency

A

rare

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25
Q

how is b12 taken up into ileal epithelial cell

A

when its bound to IF, it can enter via the IF receptor

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26
Q

what happens once b12 enters the bloodstream

A

it combines with transcobalamin

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27
Q

what happens once b12-IF enters the ileal epithelial cell

A

it dissociates with IF then b12 goes to leave cell

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28
Q

what is the main manifestation of b12 deficiency

A

anemia

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29
Q

what are 2 main types of b12 therapy

A

cyanocobalamin and hydroxycobalamin

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30
Q

what is cyanocobalamin

A

synthetic stable form of vit b12

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31
Q

what happens when cyanocobalamin enters the body

A

it loses the cyanide adduct then becomes active

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32
Q

how is cyanocobalamin administered

A

IM or deep SC

33
Q

how much cyanocobalamin is excreted in urine

A

50-90%

34
Q

what is the main difference of hydroxycobalamin vs cyanocobalamin

A

hydroxycobalamin has greater plasma protein (transcobalamin) binding than cyanocobalamin

35
Q

what is transcobalamin

A

b12 plasma protein

36
Q

what is the renal excretion of hydroxycobalamin

A

reduced renal excretion than cyanocobalamin

37
Q

what is the dosing of hydroxycobalamin vs cyanocobalamin

A

you can give lower doses of hydroxycobalamin at longer intervals

38
Q

how quick does b12 administration work in the bone marrow

A

rapid bone marrow response within 23 hours

39
Q

how quick does b12 administration work in the CNS

A

weeks/ months if the changes were not permanent

40
Q

what is another name for folic acid

A

vitamin b9

41
Q

what are sources of folic acid

A

green leafy vegetables, fruits, liver and kidneys

42
Q

what is folic acid converted into and how (step 1)

A

dihydrofolate (FH2) via dihydrofolate reductase (DHFR)

43
Q

what is dihydrofolate converted into and how (step 2)

A

tetrahydrofolate (FH4) via dihydrofolate reductase (DHFR)

44
Q

where does folic acid get converted into tetrahydrofolate

A

in cells of liver, intestines, bone marrow

45
Q

what does tetrahydrofolate do

A

mediates 1-carbon transfer reactions required for DNA synthesis

46
Q

how much folic acid is needed daily

A

50-200ug

47
Q

who needs more folic acid

A

pregnany, lactatin, chronic hemolytic anemia

48
Q

how do you administer folic acid

A

IM oral or IV

49
Q

where is erythropoietin produced

A

kidneys

50
Q

what can induce erythropoietin

A

hypoxia

51
Q

where does erythropoietin act

A

on receptors of committed erythroid progenitors in bone marrow

52
Q

what does erythropoietin cause (4)

A

increase hematopoietic growth, differentiation and maturation, increases RBC production

53
Q

what is recombinant human erythropoietin (r-huEPO) (epoietin) (2 things)

A

165aa, glycoprotein

54
Q

how is epoietin administered

A

IV or SC 3x or 1x a week

55
Q

how fast does epoietin onset occur

A

2 weeks

56
Q

how fast does epoietin desired effects occur

A

6-12 weeks

57
Q

what is essential for epoietin to work + why + how do you fix this

A

adequate supply of Fe, because you need Fe to make more RBC, so you can start supplementing Fe before starting epoietin

58
Q

what is darbopoeitin alpha

A

more stable form of epoietin that is hyperglycosylated

59
Q

what is the structure of darbopoeitin alpha vs epoietin

A

contains 5 instreat of 3 3N-linked oligosaccharide chains

60
Q

what is the half life of darbopoeitin alpha vs epoietin

A

increased more than 3x

61
Q

what is continuous erythropoietin receptor activator (CERA)

A

methoxy polyethylene glycol-epoetin beta (PEG-epoetin beta)

62
Q

what is the half life of continuous erythropoietin receptor activator (CERA)

A

130 days

63
Q

when do you use continuous erythropoietin receptor activator (CERA)

A

in anemia of chronic kidney disease

64
Q

what are 3 main treatments for EPO

A

darbopoeitin alpha, epoietin, continuous erythropoietin receptor activator (CERA),

65
Q

is darbopoeitin alpha or epoietin more stable

A

darbopoeitin alpha

66
Q

when do you not want to use darbopoeitin alpha or epoietin + why

A

with cancer related anemia because they increase RBC which can increase oxygen to tumor

67
Q

what are 3 types of anemia that you use darbopoeitin alpha or epoietin for

A

chronic renal failure, chronic disease and AIDS related

68
Q

what are 2 other things you use darbopoeitin alpha or epoietin for

A

bone marrow transplantation and autologous blood donation

69
Q

what are 4 adverse effects of darbopoeitin alpha or epoietin

A

flu like symptoms, headache, hypertension, thrombosis (CV event, if too much RBC)

70
Q

what is granulocyte colony stimulating factor (G-CSF) / granulocyte macrophage colony stimulating stimulating factor (GM-CSF)

A

recombinant technology drug that stimulates proliferation and differentiation of progenitor cells in bone marrow

71
Q

what do you use G-CSF and GM-CSF to treat for

A

drug-induced (chemo) neutropenia

72
Q

what are 2 drugs that can be used to treat drug-induced (chemo) neutropenia

A

G-CSF and GM-CSF

73
Q

what does G-CSF and GM-CSF stand for

A

granulocyte colony stimulating factor (G-CSF) / granulocyte macrophage colony stimulating stimulating factor (GM-CSF)

74
Q

what 2 drugs are used to stimulate proliferation and differentiation of progenitor cells in bone marrow

A

granulocyte colony stimulating factor (G-CSF) / granulocyte macrophage colony stimulating stimulating factor (GM-CSF)

75
Q

do you use recombinant thrombopoietin (TPO) clinically +why

A

no because repeated injections results in development of anti-TPO antibodies

76
Q

what are thrombopoietin (TPO) mimetics used clinically for

A

idiopathic/ immune thrombocytopenia purpura (ITP)

77
Q

which bases is b12 required for

A

both purine and pyrimidine

78
Q

what are both b12 and folic acid essential for

A

cellular division and DNA synthesis

PMCOL 344 (27 decks)

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