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basic science Flashcards

1
Q

what transcription factor direct mesenchymal stem cells to be osteoblasts

A

Runx2

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2
Q

WNT effects on osteoblasts

A

promote osteoblast survival and proliferation

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3
Q

what does sclerostin do to osteoblasts?

A

produces DKK-1 which inhibits WNT/B-catenin which decreases stimulation of osteoblasts

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4
Q

nitrogen-containing bisphosphonate mechanism

A

inhibit protein prenylation within mevalonate pathway, blocking farnesyl pyrophosphate synthase. causes loss of GTP formation that’s needed for ruffle border

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5
Q

non-nitrogen containing bisphosphonate mechanism

A

metabolized into a non-functional ATP analogue inducing apoptosis

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6
Q

wolff’s law

A

remodeling occurs in response to mechanical stress

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7
Q

Hueter-Volkmann law

A

compression inhibits growth, tension stimulates growth

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8
Q

what zone of the physis do lysosomal storage diseases affect?

A

reserve zone

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9
Q

what is the precursor cell to osteoclasts?

A

hematopoietic cells in macrophage lineage

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10
Q

osteoblast precursor

A

undifferentiated mesenchymal stem cells

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11
Q

bone graft resorption rates, fastest to slowest

A

calcium sulfate -> tricalcium phosphate -> hydroxyapatite

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12
Q

what synthetic bone graft has the highest compressive strength?

A

calcium phosphate

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13
Q

what properties does DBM have as a bone graft?

A

osteoconductive, osteoinductive

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14
Q

what properties does autograft have as a bone graft?

A

osteoconductive, osteoinductive, osteogenic

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15
Q

what properties do synthetic allografts have as bone graft?

A

osteoconductive only

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16
Q

what properties do BMPs have as bone graft?

A

osteoinductive only

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17
Q

how does calcium affect PTH?

A

decreased calcium levels stimulate parathyroid chief cells to increase PTH, acts to increase resorption of calcium

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18
Q

defect in type 1 hereditary vitamin-D dependent rickets

A

defect in renal 25(OH)-vitamin D 1a-hydroxylase, inhibits conversion of vitamin D to active form

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19
Q

inheritance of type 1 and type 2 hereditary Vitamin-D dependent rickets

A

autosomal recessive

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20
Q

defect in type 2 hereditary Vitamin-D dependent rickets

A

defect in intracellular receptor for 1,25(OH)2-vitamin D3

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21
Q

inheritance of Vitamin D-resistant/familial hypophosphatemic rickets

A

x-linked dominant mutation in PHEX gene

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22
Q

labs in familial hypophosphatemic rickets/Vitamin-D resistant

A

low phosphate, normal calcium, vitamin D, and PTH, high alk phos

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23
Q

what lab value distinguishes type 1 from type 2 hereditary vitamin-D dependent rickets?

A

type 1 has low Vitamin D (can’t be converted to active form), type 2 has really high Vitamin D (receptor defect)

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23
Q

what type of collagen is the disc annulus?

A

type 1

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23
Q

what type of cartilage is the nucleus pulposus?

A

type 2

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23
Q

what disease causes black urine and black cartilage?

A

alkpatonuria, accumulation of homogentisic acid causes cartilage destruction

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23
Q

inheritance of alkaptonuria

A

autosomal recessive defect of homogentisic acid oxidase

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23
Q

most sensitive and specific lab test for RA

A

anti-CCP

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24
Q

mechanism of methotrexate

A

folate analogue, inhibits purine metabolism and T-cell activation

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25
Q

mechanism of leflunomide

A

inhibits pyrimidine synthesis

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26
Q

mechanism of hydroxychloroquine

A

blocks activation of toll-like receptors (TLR9) which decreases activity of dendritic cells

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27
Q

mechanism of etanercept

A

TNF-a receptor fusion protein that binds to TNF-a

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28
Q

mechanism of infliximab

A

anti TNF-a monocolonal antibody

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29
Q

mechanism of adalimumab

A

anti TNF-a monoclonal antibody

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30
Q

mechanism of golimumab

A

anti TNF-a monoclonal antibody

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31
Q

mechanism of anakinra

A

recombinant IL-1 receptor antagonist

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32
Q

mechanism of rituximab

A

monoclonal antibody to CD20 antigen (inhibits B cells)

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33
Q

mechanism of abatacept

A

selective co-stimulation modulator that binds to CD-80 and CD-86 (inhibits T cells)

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34
Q

mechanism of ustekinumab

A

monoclonal antibody targeting IL-12 and IL-23

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35
Q

mechanism of tocilizumab

A

IL-6 receptor inhibitor

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36
Q

what DMARDs target TNF-a?

A

etanercept, adalimumab, infliximab

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37
Q

lab in ankylosing spondylitis

A

HLA-B27

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38
Q

what kind of arthritis is DIP involvement associated with?

A

psoriatic

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39
Q

crystals seen in gout

A

monosodium urate, yellow needle-shaped, negatively birefringent

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40
Q

crystals seen in pseudogout

A

calcium pyrophosphate, rhomboid-shaped, blue, weakly positively birefringent

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41
Q

order of zones at direct bone-tendon insertion

A

tendon > fibrocartilage > mineralized fibrocartilage > bone

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42
Q

what changes on SSEPs are concerning?

A

50% decrease in amplitude, 10% increase in latency

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43
Q

characteristic of MRSA that makes it resistant

A

PBP2A (penicillin binding protein 2A) coded by mecA gene on SCCmecIV

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44
Q

GPCs in clusters

A

staph

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45
Q

GPCs in pairs/chains

A

strep

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46
Q

most common cause of septic arthritis after chickenpox/varicella

A

Group A strep (GPCs in chains)

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47
Q

p acnes

A

gram positive anaerobic rod

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48
Q

where is coccidiomycosis found

A

southwestern US to central America

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49
Q

where is histoplasmosis found

A

Ohio and Mississippi river valleys

50
Q

where is blastomyces found

A

africa and southeast/central US

51
Q

where is cryptococcus found

A

pacific northwest, british columbia, subtropics

52
Q

risk of HIV transmission from contaminated needlestick

A

0.3%

53
Q

risk of HIV transmission from blood transfusion

A

1/500,000

54
Q

risk of HCV transmission from needle stick

A

3%

55
Q

examples and mechanism of B-lactam antibiotics

A

penicillin, cephalosporin, vancomycin.
inhibit cross-linking of polysaccharides in the cell wall by blocking transpeptidase enzyme

56
Q

examples and mechanism of aminoglycosides

A

gentamycin, tobramycin
inhibit protein synthesis (30S-ribosomal subunit)

57
Q

examples and mechanism of clindamycin and macrolides

A

clinda, erythromycin, clarithromycin, azithromycin
inhibit dissociation of peptidyl-transfer RNA from ribosomes (50S-ribosomal subunit)

58
Q

mechanism of tetracylcines

A

inhibit protein synthesis (30S ribosomal subunit)

59
Q

mechanism of rifampin

A

inhibits DNA-dependent RNA polymerase F

60
Q

examples and mechanism of quinolones

A

ciprofloxacin, levofloxacin
inhibits DNA gyrase

61
Q

best measures of adequate resuscitation in shock

A

urine output > 30 ml/hr, lactate < 2.5

62
Q

mechanism of aspirin

A

irreversibly binds COX in platelets

63
Q

mechanism of warfarin

A

inhibits VitK-2,3-epoxide reductase to prevent vitamin-K carboxylation in liver, inhibits factors 2, 7, 9, 10, proteins C and S

64
Q

mechanism of heparin

A

activates antithrombin III which then inhibits factors 2a, 3, 10a

65
Q

mechanism of LMWH/lovenox

A

activates antithrombin III which then inhibits factors 2a, 3, 10a

66
Q

mechanism of fondaparinux

A

indirect Xa inhibitor (through AT3). fondaparINux - INdirect inhibition

67
Q

mechanism of rivaroxaban, apixaban

A

direct Xa inhibitor

68
Q

mechanism of dabigatran and argatroban

A

direct thrombin (IIa) inhibitor

69
Q

mechanism of TXA

A

synthetic lysine analogue, competitive inhibitor of plasminogen activation

70
Q

risk of HCV transmission from blood transfusion

A

1 in 2 million

71
Q

active form of Vitamin D

A

1,25-dihydroxycholecalciferol

72
Q

material with a linear stress-strain curve up to failure, little to no plastic deformation

A

brittle

73
Q

material that undergoes large plastic deformation before failure

A

ductile

74
Q

anisotropic material

A

mechanical properties vary with the direction of the applied load

75
Q

what metal is most susceptible to galvanic and crevice corrosion

A

stainless steel

76
Q

the risk of galvanic corrosion is highest between what two metals?

A

stainless steel and Co-Cr alloy

77
Q

what is Hooke’s law?

A

stress is proportional to strain when a material is loaded in the elastic zone

78
Q

galvanic corrosion

A

dissimilar metals leads to electrochemical destruction

79
Q

crevice corrosion

A

occurs in fatigue cracks due to differences in oxygen tension, titanium least prone

80
Q

fretting corrosion

A

mode of destruction at the contact site from relative micromotion of two materials/components

81
Q

what non-organic component gives bone its compressive strength?

A

hydroxyapatite (makes up 60% of dry weight). Ca10(PO4)6(OH)2

82
Q

which organic components of bone are made by osteoblasts?

A

collagen 1, osteocalcin, osteonectin, alk phos

83
Q

what conditions stimulate human mesenchymal stem cells to convert to osteoblasts?

A

low strain, high oxygen

84
Q

what conditions stimulate human mesenchymal stem cells to convert to fibroblasts?

A

high strain

85
Q

what conditions stimulate human mesenchymal stem cells to convert to chondroblasts?

A

med strain, low oxygen

86
Q

what molecules do osteoclasts use to break down bone?

A

MMP, cathepsin K, TRAP

87
Q

what inflammatory markers activate osteoclasts?

A

IL-1, IL-6, TNFa, PG-E2

88
Q

what indirectly stimulates osteoclasts via stimulating osteoblasts?

A

Vitamin D, PTH, PTHrP

89
Q

what directly inhibits osteoclasts?

A

calcitonin, TGF-B, IL-10. (OPG and estrogen indirectly via osteoblasts)

90
Q

what cell produces sclerostin?

A

osteocyte

91
Q

what does calcitonin do to osteocytes?

A

stimulates production of sclerostin

92
Q

what does PTH do to osteocytes?

A

inhibits (indirectly stimulates osteoblasts)

93
Q

inheritance of cleidocranial dysplasia

A

autosomal dominant mutation in CBFA-1/RUNx2

94
Q

what causes osteopetrosis?

A

osteoclast malfunction causing decreased osteoclast activity/remodeling (due to proton pump/Cl channel or carbonic anhydrase-2 malfunction, or OPG overexpression)

95
Q

what causes pyknodysostosis?

A

cathepsin K deficiency (causes acro-osteolysis of terminal phalanges)

96
Q

what is the treatment for paget’s disease?

A

bisphosphonates and calcitonin

97
Q

what is the treatment for paget’s disease secondary sarcoma?

A

chemo and wide resection

98
Q

labs in paget’s disease

A

high urine N- and C-telopeptides

99
Q

which bisphosphonates are non-nitrogen containing?

A

the low TEC ones (tiludronate, etidronate, clodronate)

100
Q

what condition is teriparatide contraindicated in?

A

paget’s, increases risk of secondary sarcoma

101
Q

what 2 receptors are on osteoblasts?

A

PTH receptor and Vitamin D receptor

102
Q

which growth factors promote cartilage/early tendon and ligament healing?

A

TIP - TGF-B, IGF-1, PDGF

103
Q

what type of collagen is present in initial tendon/ligament healing?

A

type 3

104
Q

what type of collagen is involved in ehlers-danlos?

A

type 5

105
Q

what type of collagen is involved in multiple epiphyseal dysplasia?

A

type 9

106
Q

what type of collagen is present in initial bone healing?

A

type 10

107
Q

what type of collagen is involved in schmid chondrodysplasia?

A

type 10

108
Q

what happens to water and collagen in OA?

A

water increases, collagen quantity, quality/cross linking, and proteoglycan synthesis decreases, no change in chondrocyte number

109
Q

what happens to cartilage in aging?

A

water decreases, collagen cross linking increases, keratan sulfate increases, chondroitin sulfate, proteoglycan synthesis, and chondrocyte number decrease

110
Q

what happens to collagen in a healed ligament?

A

increased number of fibers, lower cross linking, diameter, and mass

111
Q

which collagen type is increased in early OA?

A

type 10

112
Q

which conditions affect the reserve zone of the physis?

A

PKGD (packaged), pseudoachondroplasia (COMP), kniest syndrome (col 2A1 defect), gaucher (b-glucocerebrosidase), diastrophic dysplasia (AR mutation in DTDST sulfate transport gene)

113
Q

which conditions affect the proliferative zone of the physis?

A

MEGA - MHE (AD mutation in ext gene), gigantism, achondroplasia (AD mutation in FGFR3)

114
Q

which conditions affect the hypertrophic zone of the physis?

A

3S’s - SCFE, salter harris fx, Schmid

115
Q

what controls proximal to distal limb growth? what is the gene product?

A

AER, FGF

116
Q

what controls radial to ulnar limb growth? what is the gene product?

A

ZPA, sonic hedgehog

117
Q

what controls dorsal to ventral limb growth? what is the gene product?

A

WNT, wnt

118
Q

effects of PTH

A

activate osteoclasts, increase calcium (kidney resorption) and Vitamin D production, decrease phosphate (kidney resorption)

119
Q

effects of Vitamin D

A

activate osteoclasts, increase calcium and phosphate

120
Q

what zone of the physis is affected in nutritional Vitamin D deficient rickets?

A

hypertrophic/zone of provisional calcification

121
Q

labs in vitamin D deficient rickets

A

low Vitamin D, calcium, phosphate. high PTH (compensatory for low calcium) and alk phos

122
Q

treatment for x-linked hypophosphatemic rickets

A

phosphate and Vitamin D

123
Q

labs in renal osteodystrophy

A

low calcium, high phosphate (kidney malfunction leads to phosphate retention), high PTH and alk phos

124
Q

psoriatic arthritis HLA

A

HLA B27+

125
Q

what is overexpressed in psoriatic arthritis?

A

cathelicidin

126
Q

what gene is associated with CA-MRSA?

A

PVL gene

127
Q

mechanism of corticosteroids

A

inhibit phospholipase A2 (converts phospholipids to arachidonic acid which gets converted to prostaglandins)

128
Q

genetic hypercoagulable states

A

M35CS - MTHFR gene mutation, AT3 deficiency, Factor V Leiden, Protein C and S deficiency

129
Q

order of muscle fiber recruitment

A

slow-twitch fatigue resistant type 1, type IIa fast-twitch fatigue resistant, type IIb fast-twitch easily fatigable

Miller (12 decks)

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