Basic Science Flashcards

1
Q

A southern blot detects….

A

DNA.

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2
Q

A western blot detects…

A

protein.

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3
Q

A northern blot detects…

A

RNA.

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4
Q

siRNA blocks…

A

mRNA translation.

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5
Q

RT-PCR converts…

A

RNA to DNA.

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6
Q

Diseases that show anticipation (more severe form of disease at earlier age)

A

Huntington, myotonic dystrophy, Friedreich ataxia

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7
Q

Imprinting

A

gene expression (phenotype) occurs from one allele only

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8
Q

Examples of imprinting

A

Prader-Willi (paternal inheritance)

Angelman (maternal inheritance)

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9
Q

Epigenetics

A

inheritance by modifying gene expression rather than altering the genetic code

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10
Q

Examples of epigenetics

A

DNA methylation, histone acetylation/deacetylation

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11
Q

Rheumatoid pathway

A

T cells produce RANKL causing bone erosion

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12
Q

Cancer cells produce…

A

RANKL which leads to osteoclastogenesis which is responsible for lytic lesions.

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13
Q

What is responsible for osteolysis around ortho implants?

A

RANK/RANKL

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14
Q

What molecule is responsible for osteoclast differentiation from monocyte/macrophage lineage?

A

RANKL

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15
Q

Sclerostin blocks…

A

the Wnt/BMP pathway which inhibits osteoblastogenesis leading to decreased bone formation.

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16
Q

Gene expression for adipose lineage

A

PPARy2

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17
Q

Gene expression for cartilage lineage

A

SOX9

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18
Q

Gene expression for osteoblast lineage

A

Cbfa1/Runx2

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19
Q

What factor stimulates cartilage regeneration in vitro?

A

TFG-beta

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20
Q

What factor stimulates tendon and ligament formation?

A

scleraxis

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21
Q

What factor causes osteolysis around implants?

A

IL-6

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22
Q

Sunlight helps to synthesize…

A

VitD3 (cholecalciferol) on the skin surface which leads to hydroxylation in the liver to 25-OH VitD3 (25-hydroxyvitaminD3) whith then gets hydroxylated again in the kidney to 1-25(OH) or calcitrol

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23
Q

Active form of vitamin D

A

1,25-dihydroxyvitaim D3

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24
Q

Lab test for vitamin D deficiency is…

A

25-hydroxyvitamin D3.

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25
Q

Vitamin D increases serum…

A

calcium and phosphate while PTH (from chief cells of parathyroid glands) increases calcium and decreases phosphate.

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26
Q

Limb buds are first seen at…

A

8 weeks of gestation

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27
Q

what gene regulates limb bud formation/development?

A

sonic hedge-hog

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28
Q

the zone of polarizing activity controls…

A

AP axis (radioulnar axis, or thumb to SF, great toe to small toe)

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29
Q

The apical ectodermal ridge controls…

A

longitudinal limb growth.

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30
Q

Wnt controls…

A

dorsoventral axis development.

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31
Q

Wolff law

A

bone remodels in response to mechanical stress applied to it

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32
Q

Intramembranous bone formation

A

the no cartilage model

flat bones, physeal growth, primary bone healing (haversian remodeling), with absolute stability

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33
Q

Primary bone healing involves…

A

cutting cones, osteoclasts and osteoblasts remodeling lamellar bone

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34
Q

Cleidocrainal dysplasia is caused by…

A

Cbfa1/Runx2 mutation leading to dysfunction of intramembranous ossification.

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35
Q

Endochondral bone formation

A

cartilage model

long bones, 2ndary bone healing with relative stability. Callus formation

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36
Q

What initiates the SMAD signaling pathway?

A

BMP binds to serine/threonine kinase receptor

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37
Q

BMPs induce…

A

host progenitor cell migration and differentiation at fracture sites (inflammatory stage of fx healing).

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38
Q

BMP2 is FDA approved for…

A

acute open tibia fractures after IMN and ALIF.

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39
Q

BMP2 is the best alternative to…

A

iliac crest autograft.

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40
Q

BMP2 is involved in…

A

chondrogenic differentiation from mesenchymal cells.

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41
Q

BMPs 5, 6, and 7 are involved in…

A

osteoinduction and osteogenesis.

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42
Q

BMP7 is FDA approved for…

A

long bone nonunion and posterolateral lumbar fusion.

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43
Q

Which BMP has no osteoinductive potential?

A

BMP3

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44
Q

What factor is important in the apoptosis of interdigital web spaces during development?

A

BMP

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45
Q

Osteoclasts are derived from…

A

monocyte/macrophage lineage.

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46
Q

When PTH binds to a PTH receptor on an osteoblast, then…

A

the osteoblast secretes RANKL which leads to RANKL binding RANK on an osteoclast leading to bone resorption.

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47
Q

What secretes osteoprotegerin?

A

osteoblasts

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48
Q

OPG binds…

A

RANKL which inhibits osteoclast activity.

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49
Q

Bone resorption at Howship’s lacunae

A

ruffled border of osteoclast attaches to the bone surface –> integrin on osteoclast binds to vibronectin on bone surface

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50
Q

Vibronectin contains…

A

Arg-Gly-Asp (RGD) sequence, which is an integrin recognition sequence.

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51
Q

Carbonic anhydrase acts to…

A

lower pH of Howship’s lacunae and cathepsin K breaks down organic bone matrix.

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52
Q

Bone gets its compressive strength from…

A

proteoglycans and calcium hydroxyapatite.

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53
Q

Bone gets its tensile strength from…

A

type I collagen.

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54
Q

What supplies the outer 1/3 of the diaphysis blood supply?

A

periosteal arterioles

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55
Q

What blood sources supplies the inner 2/3 of bone (60% of cortical bone of a long bone)?

A

nutrient artery

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56
Q

What supplies the growth plate?

A

Perichondral artery

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57
Q

Cancellous chips properties

A

osteoconductive

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58
Q

DBM properties

A

osteoconductive and osteoinductive

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59
Q

MOA of bone stimulator

A

electrical stimulation –> upregulation of TGF-beta and BMPs

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60
Q

What is the relevance of the proliferative zone?

A

Chrondrocyte proliferation

**Achondroplasia is affected by this zone.

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61
Q

The hypertrophic zone is made up of…

A

zones of maturation, degeneration, and provisional calcification.

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62
Q

What is the importance of the zone of provisional calcification?

A

chondrocyte death, matrix calcification (type X collagen is important)

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63
Q

Which growth plate zone is affected in SCFE and salter harris fractures?

A

hypertrophic zone

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64
Q

What growth plate zone is affected in rickets?

A

zone of provisional calcification

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65
Q

What zone of the growth plate is affected in scurvy?

A

primary spongiosa (metaphysis)

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66
Q

The groove of ranvier is important for….

A

appositional growth of the long bone.

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67
Q

Collagen restrains the swelling pressure of…

A

aggrecan in articular cartilage.

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68
Q

Which structures are predominantly type I collagen?

A
  • bone
  • tendon
  • ligament
  • meniscus
  • fibrocartilage
  • annulus fibrosis
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69
Q

What structures are predominantly type II collagen?

A
  • articular cartilage

- nucleus pulposus

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70
Q

The superficial zone of articular cartilage has…

A

high collagen and low proteoglycan. The chondrocytes are flat and collagen fibers oriented parallel to the joint surface.

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71
Q

What zone of cartilage are the chondrocyte progenitor cells located in?

A

superficial zone

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72
Q

In the deep zone of articular cartilage, the chondrocytes are…

A

round. Collagen fibers are oriented perpendicular to the joint surface. This layer has highest proteoglycan content.

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73
Q

The tidemark separates…

A

articular cartilage form subchondral bone.

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74
Q

Articular cartilage only heals if…

A

injury crosses the tidemark into the subchondral bone.

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75
Q

With advanced age, articular cartilage becomes…

A

more brittle bc of increase in glycation end products.

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76
Q

in the spine, aging leads to conversion of…

A

disc to fibrocartilage and an increase keratin sulfate to chondroitin sulfate ratio.

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77
Q

PTHrP is important in the maintenance of…

A

articular cartilage phenotype during growth and development.

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78
Q

What type of cells produce synovial fluid?

A

type B

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79
Q

Prolonged non-weight bearing results in..

A

cartilage thinning

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80
Q

The annulus fibrosus is derived from…

A

mesoderm (sclerotomal cells).

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81
Q

The nucleus pulposus is derived from…

A

the notochord.

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82
Q

The nucleus pulposus has the highest…

A

proteoglycan content (low collagen to proteoglycan ratio)

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83
Q

With aging, size and cellualrity of the nucleus pulposus…

A

decreases. So does aggrecan.

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84
Q

Disc degeneration is associated with…

A

increased fibronectin fragmentation and proteoglycan fragmentation.

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85
Q

Greatest risk factor for degeneration of the disc is…

A

genetics.

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86
Q

Disc degeneration is associated with…

A

increase in collagen I and decrease in collagen II.

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87
Q

Type I muscle fibers

A

slow twitch
red
low activation threshold and therefore are recruited first
aerobic/oxidative

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88
Q

Type II muscle fibers

A

fast twitch
white
anaerobic/glycolytic

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89
Q

aerobic activity lasting < 10 seconds utilizes…

A

ATP and creatine phosphate for energy

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90
Q

Aerobic activity lasting longer than 4 minutes gets muscle energy from…

A

glycogen an dfatty acids.

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91
Q

Portions of the sarcomere

A

A band: myosin filament
I band: actin only
H zone: myosin only

92
Q

Force is proportional to…

A

cross sectional area of muscle.

93
Q

Working out increases…

A

muscle mass via muscle fiber hypertrophy (not in children tho).

94
Q

Decorin is…

A

a proteoglycan that controls tendon collagen fiber size.

95
Q

A sheathed tendon receives nutrients via…

A

diffusion from synovial sheath.

96
Q

Tendon repair is weakest at…

A

7-10 days post op and strongest at 6 months post op.

97
Q

Intrinsic tendon repair is…

A

slower healing but decreased adhesion formation (compared to extrinsic).

98
Q

Indirect ligament insertion

A

ligament attaches to periosteum via sharpey’s fibers

99
Q

Direct ligament insertion

A

(4 transition zones)

ligament –> fibrocartilage –> mineralized fibrocartilage –> bone

100
Q

Neurapraxia

A

myelin is disrupted, reversible prognosis

101
Q

Axonotmesis

A

myelin and axon disrupted, reversible prognosis, wallerian degeneration present

102
Q

Neurotmesis

A

myelin, axon and endoneurium disrupted, wallerian degeneration present and irreversible prognosis

103
Q

What nerve has the best potential for recovery after graft repair?

A

radial nerve

104
Q

Treatment of nerve injury

A

-collagen conduit if defect <2.5 cm; autologous nerve graft if defect is > 2.5 cm

105
Q

Hierarchical structure of peripheral nerve (inside out)

A

axon –> myelin –> enodneurium –> fascicles –> perineum –> epineurium

106
Q

MOA of heparin/lovenox

A

ATIII activation

107
Q

Reverse heparin with…

A

protamine.

108
Q

Warfarin MOA

A

blocks vitamin K epoxide reductase –> inhibits factors 2, 7, 9 and 10

109
Q

Reverse warfarin with…

A

vitamin K.

110
Q

MOA of Fondaparinux

A

indirect Xa inhibitor

111
Q

MOA of aspirin

A

inhibits thromboxane A2 (irreversible)

112
Q

MOA of rivaroxaban/apixaban

A

direct Xa inhibitor

113
Q

MOA of dabigatran, argatroban, —rudin

A

direct thrombin (IIa) inhibitor

114
Q

TXA acts by…

A

inhibiting plasminogen.

115
Q

Hypercoagulability (thombophilia) diseases

A

Factor V Leiden: increased thrombin activation

Protein C or S deficiency

116
Q

Surgery causes release of…

A

thromboplastin (tissue factor), thought to be responsible for higher DVT post-op.

117
Q

Most common presenting symptom of PE

A

dyspnea

118
Q

Genetics of hemophilia a (factor VIII deficiency) and hemophila B (factor IX deficiency)

A

X-linked recessive

119
Q

Antibiotics that inhibit cell wall synthesis

A
  • penicillin
  • cephalosporins
  • vanc
  • bacitracin
120
Q

Vancomycin acts by…

A

inhibiting crosslinking of peptidoglycans.

121
Q

MRSA has a gene…

A

mecA that encodes penicillin binding protein which is responsible for bacterial resistance to penicillin.

122
Q

Abx that inhibit 30S

A

aminogylcosides (gent, tobra) and tetracyclines (doxy)

123
Q

abx that inhibit 50S

A

clinda, macrolides (erythromycin), linezolid

124
Q

abx that inhibit DnA synthesis

A
  • fluoroquinolones (cipro)

- metronidazole

125
Q

MOA of rifampin

A

inhibits RNA synthesis

126
Q

MOA of TMP-SMX

A

inhibits folate syntehsis

127
Q

MOA of bupivicaine, lidocaine

A

inhibit Na channel

128
Q

MOA of gapapentin

A

binds presynaptic Ca channel and inhibits release of NTs

129
Q

MOA of tylenol

A

inhibits PGE2 production through IL-1beta

130
Q

Incidence

A

total new cases over a specific time period

131
Q

Sensitivity =

A

true positive/(true positive + false negative)

132
Q

Best screening test has…

A

high sensitivity

133
Q

Specificity

A

true negative/(true negative + false positive)

134
Q

False positive rate

A

false positive/all patients without disease

135
Q

False negative frate

A

false negatives/all patients with disease

136
Q

PPV

A

true positives/(true positives + falses positives)

137
Q

NPV

A

true negative/(true negative + false negative)

138
Q

Number needed to treat

A

1/ARR

139
Q

Type I (alpha) error

A

reject the null hypothesis although it is true

140
Q

Type II (beta) error

A

accept null hypothesis although it is false

141
Q

A power analysis minimizes the…

A

type II error.

142
Q

Power =

A

1-beta

143
Q

chi-square test is used for…

A

2 categorical variables.

144
Q

Student’s t-test is used for….

A

2 continuous variables (comparing means)

145
Q

ANOVA is used for…

A

3 or more continuous variables

146
Q

Funnel plot is used to…

A

detect bias in a meta-analysis study.

147
Q

ROC curve determines…

A

accuracy of a test. The larger the area under the ROC curve, the more reliable the test is.

148
Q

Kaplan Meier curve

A

survival probability (y axis) vs years (x axis)

149
Q

Level I study

A

Well designed RCT

150
Q

Level II study

A

Poorly designed RCT, prospective cohort

151
Q

Level III study

A

retrospective cohort, case control

152
Q

Level IV study

A

case series

153
Q

Level V study

A

case report, expert opinion

154
Q

The level of evidence of a systematic review depends on…

A

the quality of studies used in the meta-analysis.

155
Q

Stress

A

force (or load)/area

156
Q

Strain

A

change in length/original length

157
Q

Elastic deformation

A
  • reversible

- toe region: straigtening of elastin fibers

158
Q

The slope of the stress strain curve in the elastic zone is…

A

Young’s modulus of elasticity (stiffness)

159
Q

Least to most stiff (lowest to highest modulus):

A

cartilage –> cancellous bone –> polyethylene –> PMMA –> cortical bone –> titanium –> ceramic

160
Q

Yield point is when…

A

elastic deformation becomes plastic (irreversible).

161
Q

Yield strength

A

the amount of stress to reach the yield point

162
Q

Ultimate tensile strength

A

maximum stress before breaking

163
Q

Fatigue failure

A

material fails below ultimate tensile strength due to repetitive loading

164
Q

Toughness

A

total energy per volume a material can absorb before fracturing

165
Q

The area under the stress strain curve is…

A

toughness.

166
Q

A brittle material has low…

A

toughness vs a ductile material which has high toughness.

167
Q

Viscoelasticity

A

time-dependent stress-strain relationship

168
Q

Anisotropic material

A

mechanical properties depend on direction of applied force

169
Q

Creep

A

progressive deformation with a constant force applied over a period of time

170
Q

Load relaxation

A

over time, less stress is required to achieve the same amount of elongation

171
Q

Compared to a unicortical screw, a bicortical screw has…

A

better torsional strength.

172
Q

PMMA is…

A

a liquid monomer (monomethacrylate) which contains an activator (N, N-Dimethyl-p-toluidine) added to polymer powder which contains initiator (benzoyl peroxide) –> polymerization

173
Q

Galvanic corrosion

A

electrochemical gradient between 2 dissimilar metals

174
Q

crevice (pitting) corrosion

A

formation of pits (fatigue cracks) 2/2 oxygen tension

175
Q

Fretting corrosion

A

micromotion at the junction of modular stems

176
Q

peak bone mass is achieved during…

A

the 3rd decade of life

177
Q

what is the most important hormone for peak bone mass?

A

estrogen

178
Q

WHO criteria of osteoporosis

A

T score below -2.5

osteopenia is T score -1 to -2.5

179
Q

FRAX calculates…

A

the 10 year risk for hip fracture

180
Q

PTH is an…

A

anabolic agent.

181
Q

Anti-resorptive agents

A
  • bisphosphonates
  • denosumab
  • estrogen
  • calcitonin
  • selective estrogen receptor modulators
182
Q

MOA of non-nitrogen containing bisphosphonates

A

compete with ATP –> apoptosis of osteoclasts

183
Q

MOA of nitrogen containing bisphosphonates

A

inhibit farnesyl pyrophosphate synthase in HMG-CoA reductase pathway

184
Q

Bisphosphonates are contraindicated in…

A

patients with severe CKD because it is renally cleared.

185
Q

Side effects of bisphosphonates

A

jaw osteonecrosis
subtroch fractures
esophagitis

**consider invasive dental work prior to initiating

186
Q

Teriparitide (Forteo)

A

1st 34 amino acids of PTH

intermittent: bone formation
continuous: bone resorption

187
Q

Teriparitide acts to…

A

increase spinal fusion and fracture union rates.

188
Q

Calcitonin MOA

A

inhibits sclerostin formation and inhibits osteoclast apoptosis

189
Q

Denosumab

A

monoclonal antibody that inhibits RANKL

190
Q

Rickets characteristics

A
  • genu varum
  • physeal widening
  • metaphyseal cupping
  • rachitic rosary
191
Q

Nutritional Rickets

A

Vitamin D deficiency

Osteomalacia in adults

192
Q

Oncogenic osteomalacia is…

A

tumor-induced increase FGF23 activity.

193
Q

Vitamin D dependent Rickets

A

Type I: mutation in renal 25-(OH) vitamin D-1alpha hydroxylase

Type II: mutation in receptor for 1,25(OH) vit D3

194
Q

Vitamin D resistant rickets

A

aka X-linked hypophosphatemic rickets

XLD mutation in phosphate regulating endopeptidase leads to impaired phosphate resorption by the kidneys

195
Q

Scurvy is…

A

vitamin C deficiency –> impaired collagen synthesis (hydroxylation)

196
Q

What part of bone does scurvy affect

A

primary spongiosa of the metaphysis

197
Q

Paget’s disease is…

A

a dysfunction of osteoclasts that leads to increased bone resorption, focally increasing skeletal remodeling. Will see coarse trabeculae and cortical thickening.

198
Q

Paget’s is associated with a mutation in the…

A

sequestosome gene.

199
Q

What should be administered to Paget’s patients undergoing joint replacement?

A

Pamidronate to minimize EBL.

200
Q

What is the most common Paget’s sarcoma?

A

osteosarcoma

201
Q

In paget’s there is high bone turnover leading to…

A

elevated urinary hydroxyproline, N- and C- telopeptide

202
Q

If paget’s is symptomatic, treat with…

A

bisphosphonates.

203
Q

Can you use teriparatide in pagets?

A

no - increased risk of 2ndary osteosarcoma

204
Q

Renal osteodystrophy leads to…

A

vitamin D deficiency —> hypocalcemia.

205
Q

In renal osteodystrophy, there is poor secretion of…

A

phosphate leading to hyperphosphatemia.

**Low calcium and high phosphate –> 2ndary hyperparathyroidism.

206
Q

Primary hyperparathyroidism leads to….

A

high calcium and low phosphate.

ex parathyroid adenoma

207
Q

Gout crystals are…

A

needle-shaped, negatively birefringent.

208
Q

Tx for acute gout flare

A

indomethacin or colchicine

209
Q

Gout ppx

A

colchicine

210
Q

Pseudogout crystals

A

rhomboid shaped and positively birefringent

211
Q

Bacteria form a biofilm made of…

A

extracellular polymeric substrances (exopolysaccharide) such as glycocalyx (esp. S epi).

212
Q

What phase of growth are bacteria in a biofilm in?

A

no growth (sessile)

**resistant to abx

213
Q

Sequestrum

A

devitalized, necrotic bone

214
Q

Involcrum

A

new bone formation around sequestrum

215
Q

Panton-Valentine leucociden (PVL)

A

cytotoxin that causes injury to endothelium and therefore increases risk of DVT and septic emboli in MRSA

216
Q

Marjolin’s ulcer

A

malignant transformation of chronic draining sinus or wound bed

(usually squamous cell carcinoma)

217
Q

Most common bacteria in ALL patients septic arthritis

A

staph aureus

218
Q

Newborn patient with septic arthritsi

A

Group B strep (S agalactiae)

219
Q

Neisseria gonorrhea

A

gram negative diplococci

220
Q

Kocher Criteria

A

1 - WB status
2 - T 38.5/101.3
3 - ESR > 40
4 - WBC > 12,000

3/4 - 93.1%
4/4 - 99.6%

221
Q

Transient synovitis

A

recent URI
no fevers/chills/malaise
normal WBC/ESR/CRP

Treat with NSAIDs/observation

222
Q

In a septic hip, what destroys articular cartilage?

A

MMPs

223
Q

Metaphyseal osteomyelitis can directly spread to cause septic arthirtis in…

A

hip, shoulder, ankle, and elbow joints but NOT knee.

(Metaphysis of the knee is extra-articular).

224
Q

What is a major risk factor for necrotizing fasciitis?

A

DM

225
Q

What bacteria usually grows in necrotizing fasciitis?

A

Usually polymicrobial!!!

Group A beta-hemolytic strep