basic science Flashcards
(134 cards)
1
Q
what transcription factor direct mesenchymal stem cells to be osteoblasts
A
Runx2
2
Q
WNT effects on osteoblasts
A
promote osteoblast survival and proliferation
3
Q
what does sclerostin do to osteoblasts?
A
produces DKK-1 which inhibits WNT/B-catenin which decreases stimulation of osteoblasts
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
5
Q
non-nitrogen containing bisphosphonate mechanism
A
metabolized into a non-functional ATP analogue inducing apoptosis
6
Q
wolff’s law
A
remodeling occurs in response to mechanical stress
7
Q
Hueter-Volkmann law
A
compression inhibits growth, tension stimulates growth
8
Q
what zone of the physis do lysosomal storage diseases affect?
A
reserve zone
9
Q
what is the precursor cell to osteoclasts?
A
hematopoietic cells in macrophage lineage
10
Q
osteoblast precursor
A
undifferentiated mesenchymal stem cells
11
Q
bone graft resorption rates, fastest to slowest
A
calcium sulfate -> tricalcium phosphate -> hydroxyapatite
12
Q
what synthetic bone graft has the highest compressive strength?
A
calcium phosphate
13
Q
what properties does DBM have as a bone graft?
A
osteoconductive, osteoinductive
14
Q
what properties does autograft have as a bone graft?
A
osteoconductive, osteoinductive, osteogenic
15
Q
what properties do synthetic allografts have as bone graft?
A
osteoconductive only
16
Q
what properties do BMPs have as bone graft?
A
osteoinductive only
17
Q
how does calcium affect PTH?
A
decreased calcium levels stimulate parathyroid chief cells to increase PTH, acts to increase resorption of calcium
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
19
Q
inheritance of type 1 and type 2 hereditary Vitamin-D dependent rickets
A
autosomal recessive
20
Q
defect in type 2 hereditary Vitamin-D dependent rickets
A
defect in intracellular receptor for 1,25(OH)2-vitamin D3
21
Q
inheritance of Vitamin D-resistant/familial hypophosphatemic rickets
A
x-linked dominant mutation in PHEX gene
22
Q
labs in familial hypophosphatemic rickets/Vitamin-D resistant
A
low phosphate, normal calcium, vitamin D, and PTH, high alk phos
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)
23
Q
what type of collagen is the disc annulus?
A
type 1
23
what type of cartilage is the nucleus pulposus?
type 2
23
what disease causes black urine and black cartilage?
alkpatonuria, accumulation of homogentisic acid causes cartilage destruction
23
inheritance of alkaptonuria
autosomal recessive defect of homogentisic acid oxidase
23
most sensitive and specific lab test for RA
anti-CCP
24
mechanism of methotrexate
folate analogue, inhibits purine metabolism and T-cell activation
25
mechanism of leflunomide
inhibits pyrimidine synthesis
26
mechanism of hydroxychloroquine
blocks activation of toll-like receptors (TLR9) which decreases activity of dendritic cells
27
mechanism of etanercept
TNF-a receptor fusion protein that binds to TNF-a
28
mechanism of infliximab
anti TNF-a monocolonal antibody
29
mechanism of adalimumab
anti TNF-a monoclonal antibody
30
mechanism of golimumab
anti TNF-a monoclonal antibody
31
mechanism of anakinra
recombinant IL-1 receptor antagonist
32
mechanism of rituximab
monoclonal antibody to CD20 antigen (inhibits B cells)
33
mechanism of abatacept
selective co-stimulation modulator that binds to CD-80 and CD-86 (inhibits T cells)
34
mechanism of ustekinumab
monoclonal antibody targeting IL-12 and IL-23
35
mechanism of tocilizumab
IL-6 receptor inhibitor
36
what DMARDs target TNF-a?
etanercept, adalimumab, infliximab
37
lab in ankylosing spondylitis
HLA-B27
38
what kind of arthritis is DIP involvement associated with?
psoriatic
39
crystals seen in gout
monosodium urate, yellow needle-shaped, negatively birefringent
40
crystals seen in pseudogout
calcium pyrophosphate, rhomboid-shaped, blue, weakly positively birefringent
41
order of zones at direct bone-tendon insertion
tendon > fibrocartilage > mineralized fibrocartilage > bone
42
what changes on SSEPs are concerning?
50% decrease in amplitude, 10% increase in latency
43
characteristic of MRSA that makes it resistant
PBP2A (penicillin binding protein 2A) coded by mecA gene on SCCmecIV
44
GPCs in clusters
staph
45
GPCs in pairs/chains
strep
46
most common cause of septic arthritis after chickenpox/varicella
Group A strep (GPCs in chains)
47
p acnes
gram positive anaerobic rod
48
where is coccidiomycosis found
southwestern US to central America
49
where is histoplasmosis found
Ohio and Mississippi river valleys
50
where is blastomyces found
africa and southeast/central US
51
where is cryptococcus found
pacific northwest, british columbia, subtropics
52
risk of HIV transmission from contaminated needlestick
0.3%
53
risk of HIV transmission from blood transfusion
1/500,000
54
risk of HCV transmission from needle stick
3%
55
examples and mechanism of B-lactam antibiotics
penicillin, cephalosporin, vancomycin.
inhibit cross-linking of polysaccharides in the cell wall by blocking transpeptidase enzyme
56
examples and mechanism of aminoglycosides
gentamycin, tobramycin
inhibit protein synthesis (30S-ribosomal subunit)
57
examples and mechanism of clindamycin and macrolides
clinda, erythromycin, clarithromycin, azithromycin
inhibit dissociation of peptidyl-transfer RNA from ribosomes (50S-ribosomal subunit)
58
mechanism of tetracylcines
inhibit protein synthesis (30S ribosomal subunit)
59
mechanism of rifampin
inhibits DNA-dependent RNA polymerase F
60
examples and mechanism of quinolones
ciprofloxacin, levofloxacin
inhibits DNA gyrase
61
best measures of adequate resuscitation in shock
urine output > 30 ml/hr, lactate < 2.5
62
mechanism of aspirin
irreversibly binds COX in platelets
63
mechanism of warfarin
inhibits VitK-2,3-epoxide reductase to prevent vitamin-K carboxylation in liver, inhibits factors 2, 7, 9, 10, proteins C and S
64
mechanism of heparin
activates antithrombin III which then inhibits factors 2a, 3, 10a
65
mechanism of LMWH/lovenox
activates antithrombin III which then inhibits factors 2a, 3, 10a
66
mechanism of fondaparinux
indirect Xa inhibitor (through AT3). fondaparINux - INdirect inhibition
67
mechanism of rivaroxaban, apixaban
direct Xa inhibitor
68
mechanism of dabigatran and argatroban
direct thrombin (IIa) inhibitor
69
mechanism of TXA
synthetic lysine analogue, competitive inhibitor of plasminogen activation
70
risk of HCV transmission from blood transfusion
1 in 2 million
71
active form of Vitamin D
1,25-dihydroxycholecalciferol
72
material with a linear stress-strain curve up to failure, little to no plastic deformation
brittle
73
material that undergoes large plastic deformation before failure
ductile
74
anisotropic material
mechanical properties vary with the direction of the applied load
75
what metal is most susceptible to galvanic and crevice corrosion
stainless steel
76
the risk of galvanic corrosion is highest between what two metals?
stainless steel and Co-Cr alloy
77
what is Hooke's law?
stress is proportional to strain when a material is loaded in the elastic zone
78
galvanic corrosion
dissimilar metals leads to electrochemical destruction
79
crevice corrosion
occurs in fatigue cracks due to differences in oxygen tension, titanium least prone
80
fretting corrosion
mode of destruction at the contact site from relative micromotion of two materials/components
81
what non-organic component gives bone its compressive strength?
hydroxyapatite (makes up 60% of dry weight). Ca10(PO4)6(OH)2
82
which organic components of bone are made by osteoblasts?
collagen 1, osteocalcin, osteonectin, alk phos
83
what conditions stimulate human mesenchymal stem cells to convert to osteoblasts?
low strain, high oxygen
84
what conditions stimulate human mesenchymal stem cells to convert to fibroblasts?
high strain
85
what conditions stimulate human mesenchymal stem cells to convert to chondroblasts?
med strain, low oxygen
86
what molecules do osteoclasts use to break down bone?
MMP, cathepsin K, TRAP
87
what inflammatory markers activate osteoclasts?
IL-1, IL-6, TNFa, PG-E2
88
what indirectly stimulates osteoclasts via stimulating osteoblasts?
Vitamin D, PTH, PTHrP
89
what directly inhibits osteoclasts?
calcitonin, TGF-B, IL-10. (OPG and estrogen indirectly via osteoblasts)
90
what cell produces sclerostin?
osteocyte
91
what does calcitonin do to osteocytes?
stimulates production of sclerostin
92
what does PTH do to osteocytes?
inhibits (indirectly stimulates osteoblasts)
93
inheritance of cleidocranial dysplasia
autosomal dominant mutation in CBFA-1/RUNx2
94
what causes osteopetrosis?
osteoclast malfunction causing decreased osteoclast activity/remodeling (due to proton pump/Cl channel or carbonic anhydrase-2 malfunction, or OPG overexpression)
95
what causes pyknodysostosis?
cathepsin K deficiency (causes acro-osteolysis of terminal phalanges)
96
what is the treatment for paget's disease?
bisphosphonates and calcitonin
97
what is the treatment for paget's disease secondary sarcoma?
chemo and wide resection
98
labs in paget's disease
high urine N- and C-telopeptides
99
which bisphosphonates are non-nitrogen containing?
the low TEC ones (tiludronate, etidronate, clodronate)
100
what condition is teriparatide contraindicated in?
paget's, increases risk of secondary sarcoma
101
what 2 receptors are on osteoblasts?
PTH receptor and Vitamin D receptor
102
which growth factors promote cartilage/early tendon and ligament healing?
TIP - TGF-B, IGF-1, PDGF
103
what type of collagen is present in initial tendon/ligament healing?
type 3
104
what type of collagen is involved in ehlers-danlos?
type 5
105
what type of collagen is involved in multiple epiphyseal dysplasia?
type 9
106
what type of collagen is present in initial bone healing?
type 10
107
what type of collagen is involved in schmid chondrodysplasia?
type 10
108
what happens to water and collagen in OA?
water increases, collagen quantity, quality/cross linking, and proteoglycan synthesis decreases, no change in chondrocyte number
109
what happens to cartilage in aging?
water decreases, collagen cross linking increases, keratan sulfate increases, chondroitin sulfate, proteoglycan synthesis, and chondrocyte number decrease
110
what happens to collagen in a healed ligament?
increased number of fibers, lower cross linking, diameter, and mass
111
which collagen type is increased in early OA?
type 10
112
which conditions affect the reserve zone of the physis?
PKGD (packaged), pseudoachondroplasia (COMP), kniest syndrome (col 2A1 defect), gaucher (b-glucocerebrosidase), diastrophic dysplasia (AR mutation in DTDST sulfate transport gene)
113
which conditions affect the proliferative zone of the physis?
MEGA - MHE (AD mutation in ext gene), gigantism, achondroplasia (AD mutation in FGFR3)
114
which conditions affect the hypertrophic zone of the physis?
3S's - SCFE, salter harris fx, Schmid
115
what controls proximal to distal limb growth? what is the gene product?
AER, FGF
116
what controls radial to ulnar limb growth? what is the gene product?
ZPA, sonic hedgehog
117
what controls dorsal to ventral limb growth? what is the gene product?
WNT, wnt
118
effects of PTH
activate osteoclasts, increase calcium (kidney resorption) and Vitamin D production, decrease phosphate (kidney resorption)
119
effects of Vitamin D
activate osteoclasts, increase calcium and phosphate
120
what zone of the physis is affected in nutritional Vitamin D deficient rickets?
hypertrophic/zone of provisional calcification
121
labs in vitamin D deficient rickets
low Vitamin D, calcium, phosphate. high PTH (compensatory for low calcium) and alk phos
122
treatment for x-linked hypophosphatemic rickets
phosphate and Vitamin D
123
labs in renal osteodystrophy
low calcium, high phosphate (kidney malfunction leads to phosphate retention), high PTH and alk phos
124
psoriatic arthritis HLA
HLA B27+
125
what is overexpressed in psoriatic arthritis?
cathelicidin
126
what gene is associated with CA-MRSA?
PVL gene
127
mechanism of corticosteroids
inhibit phospholipase A2 (converts phospholipids to arachidonic acid which gets converted to prostaglandins)
128
genetic hypercoagulable states
M35CS - MTHFR gene mutation, AT3 deficiency, Factor V Leiden, Protein C and S deficiency
129
order of muscle fiber recruitment
slow-twitch fatigue resistant type 1, type IIa fast-twitch fatigue resistant, type IIb fast-twitch easily fatigable
