Basic Science Flashcards
1
Q
A southern blot detects….
A
DNA.
2
Q
A western blot detects…
A
protein.
3
Q
A northern blot detects…
A
RNA.
4
Q
siRNA blocks…
A
mRNA translation.
5
Q
RT-PCR converts…
A
RNA to DNA.
6
Q
Diseases that show anticipation (more severe form of disease at earlier age)
A
Huntington, myotonic dystrophy, Friedreich ataxia
7
Q
Imprinting
A
gene expression (phenotype) occurs from one allele only
8
Q
Examples of imprinting
A
Prader-Willi (paternal inheritance)
Angelman (maternal inheritance)
9
Q
Epigenetics
A
inheritance by modifying gene expression rather than altering the genetic code
10
Q
Examples of epigenetics
A
DNA methylation, histone acetylation/deacetylation
11
Q
Rheumatoid pathway
A
T cells produce RANKL causing bone erosion
12
Q
Cancer cells produce…
A
RANKL which leads to osteoclastogenesis which is responsible for lytic lesions.
13
Q
What is responsible for osteolysis around ortho implants?
A
RANK/RANKL
14
Q
What molecule is responsible for osteoclast differentiation from monocyte/macrophage lineage?
A
RANKL
15
Q
Sclerostin blocks…
A
the Wnt/BMP pathway which inhibits osteoblastogenesis leading to decreased bone formation.
16
Q
Gene expression for adipose lineage
A
PPARy2
17
Q
Gene expression for cartilage lineage
A
SOX9
18
Q
Gene expression for osteoblast lineage
A
Cbfa1/Runx2
19
Q
What factor stimulates cartilage regeneration in vitro?
A
TFG-beta
20
Q
What factor stimulates tendon and ligament formation?
A
scleraxis
21
Q
What factor causes osteolysis around implants?
A
IL-6
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
23
Q
Active form of vitamin D
A
1,25-dihydroxyvitaim D3
24
Q
Lab test for vitamin D deficiency is…
A
25-hydroxyvitamin D3.
25
Vitamin D increases serum...
calcium and phosphate while PTH (from chief cells of parathyroid glands) increases calcium and decreases phosphate.
26
Limb buds are first seen at...
8 weeks of gestation
27
what gene regulates limb bud formation/development?
sonic hedge-hog
28
the zone of polarizing activity controls...
AP axis (radioulnar axis, or thumb to SF, great toe to small toe)
29
The apical ectodermal ridge controls...
longitudinal limb growth.
30
Wnt controls...
dorsoventral axis development.
31
Wolff law
bone remodels in response to mechanical stress applied to it
32
Intramembranous bone formation
the no cartilage model
flat bones, physeal growth, primary bone healing (haversian remodeling), with absolute stability
33
Primary bone healing involves...
cutting cones, osteoclasts and osteoblasts remodeling lamellar bone
34
Cleidocrainal dysplasia is caused by...
Cbfa1/Runx2 mutation leading to dysfunction of intramembranous ossification.
35
Endochondral bone formation
cartilage model
long bones, 2ndary bone healing with relative stability. Callus formation
36
What initiates the SMAD signaling pathway?
BMP binds to serine/threonine kinase receptor
37
BMPs induce...
host progenitor cell migration and differentiation at fracture sites (inflammatory stage of fx healing).
38
BMP2 is FDA approved for...
acute open tibia fractures after IMN and ALIF.
39
BMP2 is the best alternative to...
iliac crest autograft.
40
BMP2 is involved in...
chondrogenic differentiation from mesenchymal cells.
41
BMPs 5, 6, and 7 are involved in...
osteoinduction and osteogenesis.
42
BMP7 is FDA approved for...
long bone nonunion and posterolateral lumbar fusion.
43
Which BMP has no osteoinductive potential?
BMP3
44
What factor is important in the apoptosis of interdigital web spaces during development?
BMP
45
Osteoclasts are derived from...
monocyte/macrophage lineage.
46
When PTH binds to a PTH receptor on an osteoblast, then...
the osteoblast secretes RANKL which leads to RANKL binding RANK on an osteoclast leading to bone resorption.
47
What secretes osteoprotegerin?
osteoblasts
48
OPG binds...
RANKL which inhibits osteoclast activity.
49
Bone resorption at Howship's lacunae
ruffled border of osteoclast attaches to the bone surface --> integrin on osteoclast binds to vibronectin on bone surface
50
Vibronectin contains...
Arg-Gly-Asp (RGD) sequence, which is an integrin recognition sequence.
51
Carbonic anhydrase acts to...
lower pH of Howship's lacunae and cathepsin K breaks down organic bone matrix.
52
Bone gets its compressive strength from...
proteoglycans and calcium hydroxyapatite.
53
Bone gets its tensile strength from...
type I collagen.
54
What supplies the outer 1/3 of the diaphysis blood supply?
periosteal arterioles
55
What blood sources supplies the inner 2/3 of bone (60% of cortical bone of a long bone)?
nutrient artery
56
What supplies the growth plate?
Perichondral artery
57
Cancellous chips properties
osteoconductive
58
DBM properties
osteoconductive and osteoinductive
59
MOA of bone stimulator
electrical stimulation --> upregulation of TGF-beta and BMPs
60
What is the relevance of the proliferative zone?
Chrondrocyte proliferation
**Achondroplasia is affected by this zone.
61
The hypertrophic zone is made up of...
zones of maturation, degeneration, and provisional calcification.
62
What is the importance of the zone of provisional calcification?
chondrocyte death, matrix calcification (type X collagen is important)
63
Which growth plate zone is affected in SCFE and salter harris fractures?
hypertrophic zone
64
What growth plate zone is affected in rickets?
zone of provisional calcification
65
What zone of the growth plate is affected in scurvy?
primary spongiosa (metaphysis)
66
The groove of ranvier is important for....
appositional growth of the long bone.
67
Collagen restrains the swelling pressure of...
aggrecan in articular cartilage.
68
Which structures are predominantly type I collagen?
- bone
- tendon
- ligament
- meniscus
- fibrocartilage
- annulus fibrosis
69
What structures are predominantly type II collagen?
- articular cartilage
| - nucleus pulposus
70
The superficial zone of articular cartilage has...
high collagen and low proteoglycan. The chondrocytes are flat and collagen fibers oriented parallel to the joint surface.
71
What zone of cartilage are the chondrocyte progenitor cells located in?
superficial zone
72
In the deep zone of articular cartilage, the chondrocytes are...
round. Collagen fibers are oriented perpendicular to the joint surface. This layer has highest proteoglycan content.
73
The tidemark separates...
articular cartilage form subchondral bone.
74
Articular cartilage only heals if...
injury crosses the tidemark into the subchondral bone.
75
With advanced age, articular cartilage becomes...
more brittle bc of increase in glycation end products.
76
in the spine, aging leads to conversion of...
disc to fibrocartilage and an increase keratin sulfate to chondroitin sulfate ratio.
77
PTHrP is important in the maintenance of...
articular cartilage phenotype during growth and development.
78
What type of cells produce synovial fluid?
type B
79
Prolonged non-weight bearing results in..
cartilage thinning
80
The annulus fibrosus is derived from...
mesoderm (sclerotomal cells).
81
The nucleus pulposus is derived from...
the notochord.
82
The nucleus pulposus has the highest...
proteoglycan content (low collagen to proteoglycan ratio)
83
With aging, size and cellualrity of the nucleus pulposus...
decreases. So does aggrecan.
84
Disc degeneration is associated with...
increased fibronectin fragmentation and proteoglycan fragmentation.
85
Greatest risk factor for degeneration of the disc is...
genetics.
86
Disc degeneration is associated with...
increase in collagen I and decrease in collagen II.
87
Type I muscle fibers
slow twitch
red
low activation threshold and therefore are recruited first
aerobic/oxidative
88
Type II muscle fibers
fast twitch
white
anaerobic/glycolytic
89
aerobic activity lasting < 10 seconds utilizes...
ATP and creatine phosphate for energy
90
Aerobic activity lasting longer than 4 minutes gets muscle energy from...
glycogen an dfatty acids.
91
Portions of the sarcomere
A band: myosin filament
I band: actin only
H zone: myosin only
92
Force is proportional to...
cross sectional area of muscle.
93
Working out increases...
muscle mass via muscle fiber hypertrophy (not in children tho).
94
Decorin is...
a proteoglycan that controls tendon collagen fiber size.
95
A sheathed tendon receives nutrients via...
diffusion from synovial sheath.
96
Tendon repair is weakest at...
7-10 days post op and strongest at 6 months post op.
97
Intrinsic tendon repair is...
slower healing but decreased adhesion formation (compared to extrinsic).
98
Indirect ligament insertion
ligament attaches to periosteum via sharpey's fibers
99
Direct ligament insertion
(4 transition zones)
ligament --> fibrocartilage --> mineralized fibrocartilage --> bone
100
Neurapraxia
myelin is disrupted, reversible prognosis
101
Axonotmesis
myelin and axon disrupted, reversible prognosis, wallerian degeneration present
102
Neurotmesis
myelin, axon and endoneurium disrupted, wallerian degeneration present and irreversible prognosis
103
What nerve has the best potential for recovery after graft repair?
radial nerve
104
Treatment of nerve injury
-collagen conduit if defect <2.5 cm; autologous nerve graft if defect is > 2.5 cm
105
Hierarchical structure of peripheral nerve (inside out)
axon --> myelin --> enodneurium --> fascicles --> perineum --> epineurium
106
MOA of heparin/lovenox
ATIII activation
107
Reverse heparin with...
protamine.
108
Warfarin MOA
blocks vitamin K epoxide reductase --> inhibits factors 2, 7, 9 and 10
109
Reverse warfarin with...
vitamin K.
110
MOA of Fondaparinux
indirect Xa inhibitor
111
MOA of aspirin
inhibits thromboxane A2 (irreversible)
112
MOA of rivaroxaban/apixaban
direct Xa inhibitor
113
MOA of dabigatran, argatroban, ---rudin
direct thrombin (IIa) inhibitor
114
TXA acts by...
inhibiting plasminogen.
115
Hypercoagulability (thombophilia) diseases
Factor V Leiden: increased thrombin activation
| Protein C or S deficiency
116
Surgery causes release of...
thromboplastin (tissue factor), thought to be responsible for higher DVT post-op.
117
Most common presenting symptom of PE
dyspnea
118
Genetics of hemophilia a (factor VIII deficiency) and hemophila B (factor IX deficiency)
X-linked recessive
119
Antibiotics that inhibit cell wall synthesis
- penicillin
- cephalosporins
- vanc
- bacitracin
120
Vancomycin acts by...
inhibiting crosslinking of peptidoglycans.
121
MRSA has a gene...
mecA that encodes penicillin binding protein which is responsible for bacterial resistance to penicillin.
122
Abx that inhibit 30S
aminogylcosides (gent, tobra) and tetracyclines (doxy)
123
abx that inhibit 50S
clinda, macrolides (erythromycin), linezolid
124
abx that inhibit DnA synthesis
- fluoroquinolones (cipro)
| - metronidazole
125
MOA of rifampin
inhibits RNA synthesis
126
MOA of TMP-SMX
inhibits folate syntehsis
127
MOA of bupivicaine, lidocaine
inhibit Na channel
128
MOA of gapapentin
binds presynaptic Ca channel and inhibits release of NTs
129
MOA of tylenol
inhibits PGE2 production through IL-1beta
130
Incidence
total new cases over a specific time period
131
Sensitivity =
true positive/(true positive + false negative)
132
Best screening test has...
high sensitivity
133
Specificity
true negative/(true negative + false positive)
134
False positive rate
false positive/all patients without disease
135
False negative frate
false negatives/all patients with disease
136
PPV
true positives/(true positives + falses positives)
137
NPV
true negative/(true negative + false negative)
138
Number needed to treat
1/ARR
139
Type I (alpha) error
reject the null hypothesis although it is true
140
Type II (beta) error
accept null hypothesis although it is false
141
A power analysis minimizes the...
type II error.
142
Power =
1-beta
143
chi-square test is used for...
2 categorical variables.
144
Student's t-test is used for....
2 continuous variables (comparing means)
145
ANOVA is used for...
3 or more continuous variables
146
Funnel plot is used to...
detect bias in a meta-analysis study.
147
ROC curve determines...
accuracy of a test. The larger the area under the ROC curve, the more reliable the test is.
148
Kaplan Meier curve
survival probability (y axis) vs years (x axis)
149
Level I study
Well designed RCT
150
Level II study
Poorly designed RCT, prospective cohort
151
Level III study
retrospective cohort, case control
152
Level IV study
case series
153
Level V study
case report, expert opinion
154
The level of evidence of a systematic review depends on...
the quality of studies used in the meta-analysis.
155
Stress
force (or load)/area
156
Strain
change in length/original length
157
Elastic deformation
* reversible
| - toe region: straigtening of elastin fibers
158
The slope of the stress strain curve in the elastic zone is...
Young's modulus of elasticity (stiffness)
159
Least to most stiff (lowest to highest modulus):
cartilage --> cancellous bone --> polyethylene --> PMMA --> cortical bone --> titanium --> ceramic
160
Yield point is when...
elastic deformation becomes plastic (irreversible).
161
Yield strength
the amount of stress to reach the yield point
162
Ultimate tensile strength
maximum stress before breaking
163
Fatigue failure
material fails below ultimate tensile strength due to repetitive loading
164
Toughness
total energy per volume a material can absorb before fracturing
165
The area under the stress strain curve is...
toughness.
166
A brittle material has low...
toughness vs a ductile material which has high toughness.
167
Viscoelasticity
time-dependent stress-strain relationship
168
Anisotropic material
mechanical properties depend on direction of applied force
169
Creep
progressive deformation with a constant force applied over a period of time
170
Load relaxation
over time, less stress is required to achieve the same amount of elongation
171
Compared to a unicortical screw, a bicortical screw has...
better torsional strength.
172
PMMA is...
a liquid monomer (monomethacrylate) which contains an activator (N, N-Dimethyl-p-toluidine) added to polymer powder which contains initiator (benzoyl peroxide) --> polymerization
173
Galvanic corrosion
electrochemical gradient between 2 dissimilar metals
174
crevice (pitting) corrosion
formation of pits (fatigue cracks) 2/2 oxygen tension
175
Fretting corrosion
micromotion at the junction of modular stems
176
peak bone mass is achieved during...
the 3rd decade of life
177
what is the most important hormone for peak bone mass?
estrogen
178
WHO criteria of osteoporosis
T score below -2.5
| osteopenia is T score -1 to -2.5
179
FRAX calculates...
the 10 year risk for hip fracture
180
PTH is an...
anabolic agent.
181
Anti-resorptive agents
- bisphosphonates
- denosumab
- estrogen
- calcitonin
- selective estrogen receptor modulators
182
MOA of non-nitrogen containing bisphosphonates
compete with ATP --> apoptosis of osteoclasts
183
MOA of nitrogen containing bisphosphonates
inhibit farnesyl pyrophosphate synthase in HMG-CoA reductase pathway
184
Bisphosphonates are contraindicated in...
patients with severe CKD because it is renally cleared.
185
Side effects of bisphosphonates
jaw osteonecrosis
subtroch fractures
esophagitis
**consider invasive dental work prior to initiating
186
Teriparitide (Forteo)
1st 34 amino acids of PTH
intermittent: bone formation
continuous: bone resorption
187
Teriparitide acts to...
increase spinal fusion and fracture union rates.
188
Calcitonin MOA
inhibits sclerostin formation and inhibits osteoclast apoptosis
189
Denosumab
monoclonal antibody that inhibits RANKL
190
Rickets characteristics
- genu varum
- physeal widening
- metaphyseal cupping
- rachitic rosary
191
Nutritional Rickets
Vitamin D deficiency
| Osteomalacia in adults
192
Oncogenic osteomalacia is...
tumor-induced increase FGF23 activity.
193
Vitamin D dependent Rickets
Type I: mutation in renal 25-(OH) vitamin D-1alpha hydroxylase
Type II: mutation in receptor for 1,25(OH) vit D3
194
Vitamin D resistant rickets
aka X-linked hypophosphatemic rickets
XLD mutation in phosphate regulating endopeptidase leads to impaired phosphate resorption by the kidneys
195
Scurvy is...
vitamin C deficiency --> impaired collagen synthesis (hydroxylation)
196
What part of bone does scurvy affect
primary spongiosa of the metaphysis
197
Paget's disease is...
a dysfunction of osteoclasts that leads to increased bone resorption, focally increasing skeletal remodeling. Will see coarse trabeculae and cortical thickening.
198
Paget's is associated with a mutation in the...
sequestosome gene.
199
What should be administered to Paget's patients undergoing joint replacement?
Pamidronate to minimize EBL.
200
What is the most common Paget's sarcoma?
osteosarcoma
201
In paget's there is high bone turnover leading to...
elevated urinary hydroxyproline, N- and C- telopeptide
202
If paget's is symptomatic, treat with...
bisphosphonates.
203
Can you use teriparatide in pagets?
no - increased risk of 2ndary osteosarcoma
204
Renal osteodystrophy leads to...
vitamin D deficiency ---> hypocalcemia.
205
In renal osteodystrophy, there is poor secretion of...
phosphate leading to hyperphosphatemia.
**Low calcium and high phosphate --> 2ndary hyperparathyroidism.
206
Primary hyperparathyroidism leads to....
high calcium and low phosphate.
| ex parathyroid adenoma
207
Gout crystals are...
needle-shaped, negatively birefringent.
208
Tx for acute gout flare
indomethacin or colchicine
209
Gout ppx
colchicine
210
Pseudogout crystals
rhomboid shaped and positively birefringent
211
Bacteria form a biofilm made of...
extracellular polymeric substrances (exopolysaccharide) such as glycocalyx (esp. S epi).
212
What phase of growth are bacteria in a biofilm in?
no growth (sessile)
**resistant to abx
213
Sequestrum
devitalized, necrotic bone
214
Involcrum
new bone formation around sequestrum
215
Panton-Valentine leucociden (PVL)
cytotoxin that causes injury to endothelium and therefore increases risk of DVT and septic emboli in MRSA
216
Marjolin's ulcer
malignant transformation of chronic draining sinus or wound bed
(usually squamous cell carcinoma)
217
Most common bacteria in ALL patients septic arthritis
staph aureus
218
Newborn patient with septic arthritsi
Group B strep (S agalactiae)
219
Neisseria gonorrhea
gram negative diplococci
220
Kocher Criteria
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
Transient synovitis
recent URI
no fevers/chills/malaise
normal WBC/ESR/CRP
Treat with NSAIDs/observation
222
In a septic hip, what destroys articular cartilage?
MMPs
223
Metaphyseal osteomyelitis can directly spread to cause septic arthirtis in...
hip, shoulder, ankle, and elbow joints but NOT knee.
(Metaphysis of the knee is extra-articular).
224
What is a major risk factor for necrotizing fasciitis?
DM
225
What bacteria usually grows in necrotizing fasciitis?
Usually polymicrobial!!!
Group A beta-hemolytic strep
