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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
how is b12 taken up into ileal epithelial cell
when its bound to IF, it can enter via the IF receptor
26
what happens once b12 enters the bloodstream
it combines with transcobalamin
27
what happens once b12-IF enters the ileal epithelial cell
it dissociates with IF then b12 goes to leave cell
28
what is the main manifestation of b12 deficiency
anemia
29
what are 2 main types of b12 therapy
cyanocobalamin and hydroxycobalamin
30
what is cyanocobalamin
synthetic stable form of vit b12
31
what happens when cyanocobalamin enters the body
it loses the cyanide adduct then becomes active
32
how is cyanocobalamin administered
IM or deep SC
33
how much cyanocobalamin is excreted in urine
50-90%
34
what is the main difference of hydroxycobalamin vs cyanocobalamin
hydroxycobalamin has greater plasma protein (transcobalamin) binding than cyanocobalamin
35
what is transcobalamin
b12 plasma protein
36
what is the renal excretion of hydroxycobalamin
reduced renal excretion than cyanocobalamin
37
what is the dosing of hydroxycobalamin vs cyanocobalamin
you can give lower doses of hydroxycobalamin at longer intervals
38
how quick does b12 administration work in the bone marrow
rapid bone marrow response within 23 hours
39
how quick does b12 administration work in the CNS
weeks/ months if the changes were not permanent
40
what is another name for folic acid
vitamin b9
41
what are sources of folic acid
green leafy vegetables, fruits, liver and kidneys
42
what is folic acid converted into and how (step 1)
dihydrofolate (FH2) via dihydrofolate reductase (DHFR)
43
what is dihydrofolate converted into and how (step 2)
tetrahydrofolate (FH4) via dihydrofolate reductase (DHFR)
44
where does folic acid get converted into tetrahydrofolate
in cells of liver, intestines, bone marrow
45
what does tetrahydrofolate do
mediates 1-carbon transfer reactions required for DNA synthesis
46
how much folic acid is needed daily
50-200ug
47
who needs more folic acid
pregnany, lactatin, chronic hemolytic anemia
48
how do you administer folic acid
IM oral or IV
49
where is erythropoietin produced
kidneys
50
what can induce erythropoietin
hypoxia
51
where does erythropoietin act
on receptors of committed erythroid progenitors in bone marrow
52
what does erythropoietin cause (4)
increase hematopoietic growth, differentiation and maturation, increases RBC production
53
what is recombinant human erythropoietin (r-huEPO) (epoietin) (2 things)
165aa, glycoprotein
54
how is epoietin administered
IV or SC 3x or 1x a week
55
how fast does epoietin onset occur
2 weeks
56
how fast does epoietin desired effects occur
6-12 weeks
57
what is essential for epoietin to work + why + how do you fix this
adequate supply of Fe, because you need Fe to make more RBC, so you can start supplementing Fe before starting epoietin
58
what is darbopoeitin alpha
more stable form of epoietin that is hyperglycosylated
59
what is the structure of darbopoeitin alpha vs epoietin
contains 5 instreat of 3 3N-linked oligosaccharide chains
60
what is the half life of darbopoeitin alpha vs epoietin
increased more than 3x
61
what is continuous erythropoietin receptor activator (CERA)
methoxy polyethylene glycol-epoetin beta (PEG-epoetin beta)
62
what is the half life of continuous erythropoietin receptor activator (CERA)
130 days
63
when do you use continuous erythropoietin receptor activator (CERA)
in anemia of chronic kidney disease
64
what are 3 main treatments for EPO
darbopoeitin alpha, epoietin, continuous erythropoietin receptor activator (CERA),
65
is darbopoeitin alpha or epoietin more stable
darbopoeitin alpha
66
when do you not want to use darbopoeitin alpha or epoietin + why
with cancer related anemia because they increase RBC which can increase oxygen to tumor
67
what are 3 types of anemia that you use darbopoeitin alpha or epoietin for
chronic renal failure, chronic disease and AIDS related
68
what are 2 other things you use darbopoeitin alpha or epoietin for
bone marrow transplantation and autologous blood donation
69
what are 4 adverse effects of darbopoeitin alpha or epoietin
flu like symptoms, headache, hypertension, thrombosis (CV event, if too much RBC)
70
what is granulocyte colony stimulating factor (G-CSF) / granulocyte macrophage colony stimulating stimulating factor (GM-CSF)
recombinant technology drug that stimulates proliferation and differentiation of progenitor cells in bone marrow
71
what do you use G-CSF and GM-CSF to treat for
drug-induced (chemo) neutropenia
72
what are 2 drugs that can be used to treat drug-induced (chemo) neutropenia
G-CSF and GM-CSF
73
what does G-CSF and GM-CSF stand for
granulocyte colony stimulating factor (G-CSF) / granulocyte macrophage colony stimulating stimulating factor (GM-CSF)
74
what 2 drugs are used to stimulate proliferation and differentiation of progenitor cells in bone marrow
granulocyte colony stimulating factor (G-CSF) / granulocyte macrophage colony stimulating stimulating factor (GM-CSF)
75
do you use recombinant thrombopoietin (TPO) clinically +why
no because repeated injections results in development of anti-TPO antibodies
76
what are thrombopoietin (TPO) mimetics used clinically for
idiopathic/ immune thrombocytopenia purpura (ITP)
77
which bases is b12 required for
both purine and pyrimidine
78
what are both b12 and folic acid essential for
cellular division and DNA synthesis

PMCOL 344 (27 decks)

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