Miller's Review Basic Science Flashcards
Ortho basic science (323 cards)
1
Q
Linear force types
A
Normal = perpendicular to surface, tangential = parallel to surface, compressive = shrinks object, tensile = elongates object
2
Q
Rotational force types
A
Moment = rotational effect of force, Torque = moment perpendicular to long axis causing rotation, Bending moment = force parallel to long axis, mass moment of intertia = resistance to rotation
3
Q
Stress =
A
Force that causes a shape to change, it is a property of the object. Stress = Force/Area.
4
Q
Srain =
A
Deformation of an object due to stress. Strain = change in length/length. It has no unit measurement.
5
Q
Hooke’s law
A
Stress is directly proportional to the strain up to the yield point, where permanent deformation occurs.
6
Q
Elastic zone
A
When stress is removed, the object goes back to its same original shape and form.
7
Q
Young’s modulus of elasticity
A
Defines a materials specific stiffness. Measured by the slope of the stress/strain line. Materials with a steeper slope are more stiff and can withstand more force before permanent deformation.
8
Q
Plastic deformation
A
Material does not return to original shape and size once stress is removed because molecular bonds have been broken.
9
Q
Ultimate strength
A
Maximize stress material can tolerate before breaking…but it isn’t the breaking point. It has to go through necking (material cross sectional area reduces, overall stress reduces, but increases focally at the fracture point)
10
Q
Breaking point
A
Point where material actually fails
11
Q
Fatigue
A
Repetitive loading cycles cause material to fail below the ultimate strength
12
Q
Stiffness vs strength
A
Stiffness = resistance to change in shape, depends on elastic deformation (slope)
13
Q
Hardness vs ductility
A
Hardness = resistance to localized surface plastic deformation (scratches and dents)
14
Q
Toughness =
A
The whole area under the stress/strain curve. Ability of a material to absorb energy
15
Q
Which is stiffest? Which is strongest? Which is toughest? Which is most ductile? Which is most brittle?
A
Stiffest = A. Strongest = A. Toughest = B. Ductile = C. Brittle = A.
16
Q
Creep
A
Constant stress on a material over prolonged period of time causes the strain to slowly increase, the material plasticly deforms and can fail well below its ultimate tensile srength.
17
Q
Stress relaxation
A
Constant strain on a material (keeping it the same length) over time, decreases stress levels, puts the material in equilibrium and prevents creep
18
Q
How do material properties change when the load is applied quickly?
A
When stress is applied over a short period of time, materials are stiffer, stronger and tougher
19
Q
What is hysteresis?
A
Ability of viscoelastic material to dissipate energy between loading and unloading cycles. This happens in the vertebral disc and meniscus. Note there is no change in the curve in a purely elastic material.
20
Q
What is an isotropic material
A
Materials that behave the same regardless of the direction the force is applied (golf ball, woven bone)
21
Q
What is an anisotropic material
A
Materials that behave different depending on the direction they are loaded (cortical bone, cartilage)
22
Q
Microstructure of metal alloys
A
Metal ions in a crystalline lattice structure, solid-solution strengthening, impurity ions distort the lattice and increase resistance to movement of lattice defects
23
Q
What determines the hardness of a metal alloy?
A
Grain size, smaller grain = harder material
24
Q
Components of stainless steel
A
316L = iron, chromium, nickel (16%), molybdenum (3%) and carbon (L)
25
Components of titanium
Titanium, aluminum (6%) and vanadium (4%)
26
Components of cobalt-chrome
Cobalt, chrome, molybdenum, nickel, carbon, tungsten
27
Top 3 metallergies
Nickel > Cobalt > Chromium
28
In what order are metal materials least to most adherent to bacteria
Least = Tantalum, pure titanium, stainless steel, Titanium alloy = most adherent
29
Galvanic corrosion
Combining dissimilar metals like stainless steel with CoCr
30
Fretting corrosion
Micromotion during loading of an implant that is not loose. Ex at the head-neck junction of a hip replacement.
31
Passivation
Coating stainlees steel with chromium oxide creates barrier that prevents rust
32
What is a ceramic and how are its properties different from metal.
Metals covalently bound to non-metals (inert = alumina and zirconia, bioactive = beta-tricalcium phosphate and HA). It is brittle and stiff. It is sensitive to notches and cracks. It is insoluble and wettable (hydrophilic, achieves fluid film lubrication and low wear rate).
33
Why is zirconia preferred over alumina?
Lower hardness and it can’t be used on both sides of THA; however, it has superior wear rates when used on polyethylene.
34
What determines mechanical properties of a polymer?
Long and linear chains are stronger. Cross-linking these chains make the material stiffer, harder and stronger.
35
UHMWPE processing
Gamma irradiation to cross link chains (not in O2 to limit free radicals) -> anneal to just below melting point to decrease free radicals but not disrupt crystalline struction
36
UHMWPE minimal thickness
6mm or greater
37
How does cement work?
It is a space filler, like a grout. Strongest in compression.
38
Why don’t you want a 4mm cement mantle?
Heat generated can cause tissue necrosis
39
How does vacuum mixing help cement biomechanically?
Reduces porosity and increases strength
40
Suture anchor material to avoid
Dextro (D) lactide monomer associated with rapid degradation and potential for inflammation
41
How are biodegradable polymers metabolized?
Polymer chain breaks down, inflammatory process begins, PMNs and macrophages eat up monomers and implant becomes amorphous, lactic acid enters Krebs cycle and you breath it out as CO2 or eliminate it as water.
42
How to biocomposite anchors induce ingrowth?
They are biodegradable polymers with ceramic that releases a base that buffers acidic monomer (lactic acid)
43
Property that provides compressive strength to bone
Hydroxyapatite reinforced collaged fibers
44
Bones are weakest when loads are applied in ____?
Shear
45
Toe region
Region of stress/strain curve with nonlinear behavior due to crimped elastin fibers that straighten out as stress is applied
46
What determines the stiffness of a screw?
Core diameter
47
What determines the pullout strength of a screw
The outer diameter
48
Stiffness of a plate is proportional to the ____ power
3rd . More screws and shorter working length also increase stiffness
49
Stiffness of a nail is proportional the ___ power
4th
50
What increases the stiffness of your ex-fix the most?
1) Reduce the fracture 2) Larger pins 3) Pin spread 4) More pins 5) Rods closer to bone 6) Add more rods
51
Plane of freedom in intercarpal and intertarsal joints
Translation
52
Joint reaction force
Force within a joint responds to the forces acting on the joint
53
What is the difference between rolling and sliding?
Rolling maintains an instant center of rotation. In sliding, there is no instand center of rotation.
54
What is the difference between friction and lubrication?
Friction = resistance between two objects as they slide over one another. Lubrication is decreased resistance between the surfaces.
55
How is articular cartilage lubricated?
Elastohydrodynamic lubrication
56
Coefficient of friction in native joints vs arthroplasty?
Native = 0.002, arthroplasty = 0.1
57
How can you decrease joint reaction forces around the hip?
Increase offset (A) or decrease moment arm (B). A cane in the contralateral hand decreases joint reaction forces by 60%
58
Screw-home mechanism
Tibia externally rotates on femur going into extension
59
Which meniscus has the most excursion?
Lateral (1.1cm) > medial (0.5cm)
60
How do the transverse tarsal joints lock during toe off?
The TN and CC joint are no longer parallel, which makes them rigid
61
What is the primary structure that transmits loads from the hindfoot to the forefoot?
Plantar aponeurosis
62
What is the instant center of rotation of the ankle?
Talus
63
Biomechanical property that allows spine deformity over time
Creep
64
Biomechanical property that allows intervertebral disc energy absorption
Hysteresis
65
Part of the intervertebral disc that provides tensile strength? Compressive strength?
Tensile = annulus fibrosus. Compressive = nucleus pulposus.
66
Ratio of glenohumeral motion to scapulothoracic motion when moving the shoulder?
2:1 glenohumeral to scapulothoracic
67
Center of rotation of elbow
Center of trochlea
68
Secondary restraint to valgus stress in the elbow
Radial head. Primary is anterior bundle of MCL in 30-60 degrees elbow flexion. Posterior bundle of MCL in max elbow flexion.
69
Center of rotation of the wrist
Capitate
70
Primary wrist stabilizer after PRC
RSC ligament
71
Why is woven bone so weak?
It is oriented randomly, isotropic and pathologic, seen in infection, malignancy and stress reaction.
72
Why is lamellar bone stronger?
Organized in layers and stress oriented (Wolff’s law). Includes cortical and cancellous bone.
73
How do strain and O2 levels determine mesenchymal stem cell differentiation?
High strain -> fibroblast. Medium strain/low O2 = chondroblast. Low strain/high O2 = osteoblast.
74
Signaling pathway that promotes osteoblast development.
Osteoprogenitor cells release Wnt -> Wnt binds to active osteoblasts -> osteoblasts make and stabilize B-catenin -> production of RUNX2 increases -> RUNX2 increases Osx production -> Osx triggers terminal differentiation into osteocytes
75
Factors that promote chondrocyte development vs osteoblast development?
Sox-9 = chondrocytes. RUNX2/Osx/B-catenin = osteoblasts
76
Factor that triggers adipocyte development?
PPARy
77
How do osteoblasts make bone?
Pulsed PTH triggers type I collagen, alk phos and RANK-L production by the osteoblast.
78
Mediator for cell signaling from PTH receptor on osteoblasts?
Adenylyl cyclase
79
Two bone forming receptors on osteoblasts?
Intermittent PTH builds bone and Vitamin D.
80
Osteocyte negative feedback on osteoblast via ___?
Osteocytes secrete sclerostin via gap junctions in the bone canaliculi that antagonizes the Wnt pathway. PTH increases sclerostin release, calcitonin decreases sclerostin release.
81
Osteoclast cell lineage
Hematopoietic stem cell -> myeloid progenitor -> pre-osteocyte -> fuses with macrophage and becomes multi-nuclear osteoclast
82
How do osteoclasts resorb bone?
Binds to bone and seals ruflled border via integrin aVB3 and vibronectin (Arg-Gly-Asp RGD sequence). After sealed, tartrate resistance acid phosphatase (TRAP) is released, carbonic anhydrase lowers the pH and increases solubility of HA crystals. Organic material is removed by proteolytic enzyme cathepsin K at the ruffled border.
83
Disease with defective carbonic anhydrase
Osteopetrosis
84
Disease with defective cathepsin K
Pyknodysostosis
85
Factors that activate and inactivate osteoclasts?
Activate = RANKL. Inactivate = OPG, calcitonin.
86
Positive and negative feedback in osteoblast signalling?
B-catenin increases production of RUNX2 and OPG -> bone formation. PTH increases production of RANK-L -> bone resorption.
87
How do tumors cause bone resorption?
They stimulate osteoblasts to produce more RANK-L that activates osteoclasts and resorbs bone.
88
What provides compressive strength to bone? What provides tensile strength to bone?
Compressive = HA & proteoglycans. Tensile = type I collagen.
89
Most abundant noncollagenous matrix protein made by osteoblasts?
Osteocalcin, high in Paget’s and hyperparathyroidism
90
How does enchondral bone formation occur?
Chondrocytes in the proliferative zone express CBFA1 and RUNX2, chondrocytes become hypoertrophic. The ossification front approaches the physis and is composed of osteoclasts and osteoprogenitor cells. The osteoclasts destroy the hypertrophic chondrocytes and the surrounding cartilage matrix calcifies. The OPGs generate osteoblasts that lay down bone. The remaining chondrocytes grow away from the ossification front and the bone lengthens.
91
What is Indian hedgehog? What stimulates vascular invasion in the physis?
Protein secreted by chondrocytes in the proliferative zone that increases production of PTHrP -> PTHrP stimulates reserve zone chondrocytes to proliferate and inhibits proliferative zone chondrocytes from hypertrophy.
92
What cells secrete calcitonin?
Parafollicular (Clear cells) in the thyroid gland
93
Chondroprotective signalling pathways
PTH, PTHrP and Ihh
94
Reserve zone associated diseases
Diastrophic dwarfism (defective type II collagen synthesis), pseudoachondroplasia (defective processing and transport of proteoglycans), Kneist syndrome (defective proteoglycan processing)
95
Proliferative zone associated diseases
Gigantism (increased cell proliferation from hGh), achondroplasia (deficient cell proliferation), hypochondroplasia (less severe deficiency in cell proliferation), malnutrition, XRT, injury and excess glucocorticoids (decreased cell proiferation and matrix synthesis)
96
Hypertrophic pre-calcification zone diseases
Mucopolysaccharidosis (Morquio, Hurler = defcient lysosomal storage)
97
Zone of provisional calcification diseases
Rickets, osteomalacia (insufficient Ca for matrix calcification), Salter-Harris I fractures, little league shoulder
98
Primary spongiosum diseases
Metaphyseal chondrodysplasia (Jansen and Schmid), osteomyelitis
99
Secondary spongiosum diseases
Osteopetrosis, osteogensis imperfecta, scurvy, metaphyseal dysplasia (Pyle disease)
100
Where does appositional bone growth occur?
Groove of Ranvier, wedge shaped zone of chondral cells at the periphery
101
Dense fibrous tissue providing support to the physis
Perichondral fibrous ring of La Croix, also provides blood supply to the physis
102
Strain rate that determines primary vs secondary bone healing
<2% = primary. 2-10% = secondary
103
Phases of secondary bone healing
1) Inflammatory = osteoblasts and fibroblasts proliferate via BMP signalling, granulation tissue forms around fracture ends, this tolerates greatest strain before failure
104
How do u/s and electrical bone stimulators work?
U/s = increases callus via nano motion. Electrical bone stimulator = increases osteoblast activity by reducing O2 concentration and increasing pH
105
Fastest resorbing synthetic bone graft
Ca-sulfate
106
Synthetic bone graft with highest compressive strength
Ca-PO4
107
Ca daily requirements
1500mg/day
108
Peak bone mass age
3rd decade
109
Lab test for Vitamin D
25-Vit D
110
Vitamin D effect on gut
Increases Ca and PO4 absorption
111
Etiology of renal osteodystrophy
Impaired kidneys retain PO4 which decreases 1,25-Vit D production and bones demineralize.
112
Cause of vitamin D deficient rickets
Inadequate vitamin D = low calcium = elevated PTH/low PO4. Osteoclasts activate, Alk Phos increases and you see physeal cupping.
113
Cause of familial hypophosphatemic rickets.
X-linked PHEX gene mutation -> unable to resorb phosphate. Will have NORMAL CALCIUM
114
Cause of Type I hereditary Vitamin D dependent rickets
AR defect in 25-OH Vitamin D 1a-hydroxylase that normally activates 25-Vit D. Mutation on Chr 12q14. Labs show elevated 25-OH Vit D, low 1-25-OH Vit D.
115
Cause of type II hereditary vitamin D dependent rickets
Defect in intracellular receptor for 1,25-OH Vit D3
116
Medications that limit bone healing
NSAIDs, prednisone, PPIs, antiepileptics, SSRIs and heparin
117
Risk factors for osteoporosis
White, female, sedentary, low BMI, tobacco use, EtOH, phenytoin, history of breastfeeding, FHx of osteoporosis, premature menopause and clonazepam (increases Sclerostin)
118
Type I vs type II osteoporosis
Type I = post menopausal. Type II = senile age > 70
119
Strongest predictor of fragility fracture?
2 vertebral compression fractures. 1 VCF increases risk of hip fracture by 5x.
120
Osteoporosis histology
Decreased osteon size and enlarged marrow space
121
FRAX calculator use
If 10-year risk of hip fracture is >3% or major osteoporosis -related fracture >20%, you have osteoporosis.
122
Indications for medical therapy in osteoporosis in post-menopausal women and men > 50
Any hip or vertebral fracture
123
Types of bisphosphonates
Nitrogen containing – 1000x more potent, block farnesyl pyrophosphate synthase -> loss of GTPase formation in osteoclast ruffled border -> cell apoptosis
124
Atypical femur fractures usually occur how many years after treatment start?
4 years
125
How do teriparatide and estrogen work on bone?
Teriparatide induces osteoblast formation and new bone formation. Estrogen directly blocks osteoclast activity.
126
Contraindications to teriparatide use?
Paget’s disease and prior bone mets (risk of secondary osteosarcoma)
127
What is denosumab?
IgG2 antibody to RANK-L
128
What is romosozumab?
Sclerostin antibody to treat osteoporosis
129
Functional unit of muscle
Sarcomere. Thick filament = myosin, thin filmament = actin, A band = myosin, I band = actin. Allows fibers to slide past each other
130
Sliding filament theory
Ach released from presynaptic vesicles -> sarcolemma depolarizes and Ca is released from the sarcoplasmic reticulum -> Ca binds to troponin -> tropomysin moves to expose myosin binding sites on actin -> myosin crossbridges bind to actin and produce a power stroke -> ATP breaks actin-myosin link in preparation for next cycle
131
Isotonic
Constant muscle tension, length changes. Divides into eccentric anc concentric contraction.
132
Isometric
Constant length, tension changes
133
Isokinetic
Velocity changes, tension changes
134
Metabolism in 1st 10 seconds, first 4 mintues and 4+ minutes
0-10s = ATP and creatine phophate, 1-4 minutes = glycogen and lactic acid via glycolysis. 4+ minutes = glycogen and fatty acids
135
Cells responsible for muscle tear repair
Satellite cells
136
Types of nerve fibers
A = Fast, heavy myelin, touch. B = Medium, intermediate myelination, autonomic fibers. C = slow, unmyelinated, pain.
137
1st sensation to return after nerve injury
Sympathetic activity, then pain, then temperature, then touch, then proprioception, then motor
138
Level of nerve that needs to be intact for full recovery
Endoneurium
139
Proteoglycans in tendons
Decorin (most prominent, cross links fibrils, regulates tendon diameter and transfers load) and bglycan, rest is type I collagen (95%)
140
Fibers responsible for pain in tendonitis
Free nerve endings at the bone-tendon interface
141
Collagen type seen first in tendon healing
Type III in the proliferation phase
142
When is tendon healing the weakest
7 days
143
Difference between tendon and ligament
Less type I collagen in ligament, more proteoglycans and water in ligaments, uniform vascularity in a ligament
144
Histologically, where do ligament injuries occur?
Between the unmineralize and mineralized fibrocartilage layers
145
Types of ligament insertion into bone
Indirect = superficial fibers into periosteum and deep fibers into bone, seen more at midsubstance. Direct, both superficial and deep fibers go into bone.
146
What structure in the knee is anisotropic
Cartilage, mechanical properties vary depending on the direction it is loaded
147
Top 3 components that make up articular cartilage
74% water, 15% collagen, 10% proteoglycan. Dry weight is 60% collagen and 30% proteoglycan.
148
What is the structure of collagen made up of
Chains of hydrox-proline and hydroxy-lysine. The OH group is added via vitamin C. 3 alpha procollagen chains wind together in a triple helix. Half life ~20 years. Provides tenside strength and stiffness.
149
Where do you find type X collagen
Near calcified cartilage (landmark, hypertophic zone and fracture callus)
150
Type II genetic collagen disorder
Achondrogenesis (lethal at birth). Pondyloepiphyseal dysplasia congenita (short trunk and limbs, normal hands/feet, normal mentation), precocioius arthritis (12qw13.11=q13.2, OA before age 40, otherwise normal)
151
Proteoglycans that make up healthy cartilage
95% chondroitin SO4, keratin and hyaluronic acid
152
What is aggrecan
Long chain of negatively charge chondroitin, keratin and hyaluronic acid that is negatively charged.
153
How does the negative change of aggrecan affect cartilage properties?
The negative charges repel each other, attract negative cations and water
154
Disease when sulfate transporter does not work in cartilage?
Diastrophic dysplasia DTDST = dwarfism, hitchhikers thumb, cauliflower ears, clubfoot, scoliosis and DDH.
155
Transcription factor that leads to chondrocyte differentiation
SOX9
156
How do cartilage cells sense mechanical changes
Primary cilia
157
What is the metabolic pathway used by chondrocytes
Anaerobic metabolism
158
How does the metabolic activity of chondrocytes differ in the superficial and deep layer?
Deep = more active, makes mor proteoglycan. Superficial makes more collagen
159
Where in the chondrocyte is type II collagen made?
Synthesized in the cell, assembled outside the cell
160
How does cartilage matrix change with weight bearing
Weight bearing = H2O moves out, lubricates the joint. Non-weight bearing = H2O moves in, feeds cartilage
161
MRI sequences that can show cartilage
DGEMRIC, sodium and T1rho
162
Layers of cartilage
Superficial layer (horizontal/tangential orientation of collagen, highest collagen %, containes lubricin, highest water %, least proteoglycan synthesis)
163
Types of cells in synovial membrane
No epithelial cells or basement membrane. Type A cells (macrophage, removes debris from the joint), type B cells (fibroblast, make synovial fluid, hyaluronic acid, lubricin, RANK-L, connects to injured cartilage)
164
Main molecule responsible for synovial viscosity
Hyaluronic acid = nonsulfate mucopolysaccharide D-glucuronic acide N-acetyl-D-glucosamine
165
Synovial fluid lubricants
Lubricin = boundary lubricant. Hyaluronic acid = fluid-film lubrication
166
How does OA cartilage different from normal aging cartilage
OA has increases proteoglycans and increased water that decreases its modulus of elasticity. Aging has increased AGEs and decorin, decreased H2O that increases its modulus of elasicity.
167
How does OA activate the innate immune system?
Extracellular matrix debris (DAMPS) activate TLRs 2 and 4. This increases IL-1 levels, activates MMPs and ADAMTS proteolytic enzymes
168
Cytokine that triggers liver to release ESR and CRP
IL-6
169
TNFa blockers
Etanercept (receptor fusion protein), infliximab (chimeric IgG ab) and adalimumab (monocolonal ab)
170
IL-1 inhibitor
Anakinra (IL-1 receptor antagonist)
171
IL-6 inhibitor
Tocilizumab (humanized anti IL-6 ab)
172
B cell C20 antibody
Rituximab
173
Macrophage’s role in osteolysis
Eats poly/metal/ceramin -> releases cytokins (RANK-L, stimulates osteoblasts to release RANK-L)
174
Patient presents with this x-ray and minimal pain. What is your diagnosis?
Tabetic arthropathy from syphilis infection 20-30 years prior, this is a type of neuropathic arthropathy
175
Most common cause of upper extremity neuropathic joint
Syrinx, think spine MRI if neuropathic upper extremity joint to look for syrinx
176
Diagnosis?
Ochronosis. Autosomal recessive defect of homogentistic acid oxidase -> alkaptonuria
177
Hemochromatosis triad
Cirrhosis, DM and skin pigmentation. 50-80% get arthritis secondary to CPPD crystals and hemosiderein deposition in synovium and cartilage
178
Causes of CPPD
Hyperparathyroidism, hemochromatosis, hypothyroidism and hypomagnesemia
179
Crystals in CPPD vs gout
CPPD = box shaped blue cars, positively birefringent. Gout = needle shaped, yellow, negatively birefringent
180
Differntiating caldium hydroxyapatite shoulder arthropathy from neuropathic arthropathy in the shoulder?
Neuropathic arthropathy is painless, Ca-HA arthropathy is very painful
181
What causes tumoral calcinosis?
Elevated serum PO4 from chronic renal failure or genetic mutation (decreased FGF-23 activity)
182
Chikungunya presentation
Fever, maculopapular rash, myalgias and arthraglias acutely. Longer term may mimic seronegative RA and develop Raynaud phenomena.
183
Synovial biopsy findings in chikunguya
Macrophages with CHICV RNA and NK cells
184
What do NK cells do
Cytotoxic lymphocyte that identifies cells without an HLA MHC I identifyer. It is activated by interferon and macrophages and releases perforin which pokes holes in its target.
185
HLA-B27 disorders
AS, reactive arthritis, IBD, psoriatic arthritis and JRA
186
HLA in SLE
HLA DR3
187
HLA in RA
HLA DR4
188
Symptoms in RA
Morning stiffness >60 min, symmetric joint involvement
189
Pathophysiology of RA
Antigen triggers cell damage -> cell protein modified (citrullinated) -> dendritic cell presents to B cells -> B lymphocytes make auto-antibodies (RF, CCP) -> CD4 T lymphocytes infiltrate joints and release cytokines -> inflammatory synovial proliferation (pannus, CD4 T-lymphoctye, macrophages and fibroblasts) and destruction
190
Most sensitive lab for RA
Anti-CCP
191
What is an epitope?
Smallest part of an antigen that an antibody can recognize
192
Two types of antibodies
Opsonizing (coat antigen for macrophage target), neutralizing (activate cytotoxic lymphocyts and complement system)
193
What type of antibody is RF
IgM -> IgG
194
What type of allergy is latex?
IgE, type I hypersensitivity
195
What type of allergies are HIT and acute hemolytic transfusion reaction
Type II, IgM or IgG antibodies against PF4 and non-self RBCs, respectively.
196
Antibody testing in SLE
+ANA for screening (sensitive) -> +Anti-ds DNA and anti-Sm antibodies to confirm (specific)
197
What type of hypersensitivity is SLE?
Type III, Ag-Ab immune complex deposition
198
ANA in RA?
Most are ANA negative
199
Drug induced Lupus antibody test?
Anti-histone
200
Lymphocytes involved in Sjogren’s
CD4 T-lymphocytes target salivary and lacrimal glands. B plasma cells make IgA antibodies to SS-A(ro) and SS-B(la) ribonucleoproteins
201
Lympocytes involved in scleroderma
CD4 T-lymphocytes activate fibroblasts which increase type I collagen production leading to microvascular injury
202
Antibody testing for scleroderma
Anti-centromere if localized (CREST) and anti-DNA topoisomerase I (diffuse)
203
Antibody testing of mixed connective tissue disease
Anti-U1snRNP
204
Types of T-lymphocytes
Killer (CD8, cytotoxic, activated by antigen presenting cells, duplicate and attack with toxins and enzyme to destroy cell membrane). Helper (CD4, activat Killer cells, macrophages and direct B cell antibody production). Regulatory (suppress immune system).
205
Lymphocyte depleted in HIV
CD4+ T-cell
206
Lymphocyte involved in ALVAL
Killer T-cells
207
What type of hypersensitivity is ALVAL?
Type IV, delayed type
208
Most common initial symptom in ankylosing spondylitis
Sacroilitis
209
Most common physical exam finding in patients with psoriatic arthritis
Skin lesions and nail lesions (present in 90%)
210
Baterial causes of reactive arthritis
Intracellular bacteria: Chlamydia, Shigella, Yersinia, Salmonella
211
Cytokine implicated in septic joints
IL-1 triggers proteolytic enzymes
212
Most common location of osteomyelitis in adults
Vertebra and ribs
213
Infectious differential for chondroblastoma in kids
PEASAO: Pediatric epiphysial apophyseal subacute osteomyelitis. Typically Kingella if <5 and S. aureus if >5
214
Pathology differences in chronic vs acute osteomyelitis
There will be PMNs infiltrating trabecular bone. In acute osteomyelitis, there will be osteocytes within the trabeculae still alive. In chronic osteo, there will be no osteocytes because the bone is dead.
215
Newborn osteomyelitis bugs
GBS, S. aureus and enteric gram negative rods. Empiric tx = nafcillin + gent or nafcillin + 3rd gen cephalosporin
216
#1 cause of osteo-articular infection in kids <5 if diagnosed by PCR?
B-hemolytic gram negative coccobacillus, K. kingae
217
Antibiotic for K. kingella
PCN
218
Most common osteomyelitis in sickle cell
S. aureus, sickle cell is also associated with salmonella (gram negative motile rod)
219
Sickle cell increased risk for infection by encapsulated bacteria because?
Auto-spelenctomy from thrombi
220
Prophylactic abx for foot puncture wound through shoe?
3rd gen cephalosporin or cipro, give tetanus. Higher risk of pseudomonas infection (gram negative rod)
221
Gram negative intracellular bacteria seen in patients with late stage HIV and associated lesions
B. henselae, seen in 90% of HIV patients who own a cat. Skin lesion is bacillary angiomatosis (below) and painful long bone lytic lesions.
222
Stains for B. henselae
Warthin-Starry-stain (silver), IFA igG PCR
223
Most common location for extra-pulmonary Tb?
Spine (50%)
224
Fungal infections seen in PNW? SW? Midwest? SE?
PNW = cryptococcus, SW = coccidiomycosis, Midwest = histoplasmosis, SE = blastomycosis
225
Cause of erysipelas
Group A beta hemolytic strep pyogenes infects superficial layers of dermis and turns it bright red
226
Most common bug involved in cellulitis
Group A strep
227
Most common bug involved in NSTI
Gram + group A strep (exotoxin), polymicrobial in immunocompromised
228
NSTI bug in salt water lacerations
Gram negative vibrio vulnificus
229
NSTI bug in fresh water lacerations
Gram negative aeromonas hydrophilia
230
Late physical exam findings in NSTI
Numb and non-blancheable skin
231
Early physical exam findings in NSTI
Blisters, bullae, violet skin
232
Bug involved in gas gangrene
Gram + rod C. perfringens, seen in contaminated wounds, has potent alpha and theta toxins that breaks down cell membrane.
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Treatment of gas gangrene
Urgent open debridement (obligate anaerobe, can’t survive in presence of O2), hyperbaric O2 is actually effective for this
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PCN mechanism of action
Inhibits peptidoglycan cell wall synthesis in gram positive bacteria by binding and blocking transpeptidase
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Beta lactamase
B-lactamase breaks PCN’s B-lactam ring and are resistant to PCN, this is why 80% of S. aureus are PCN resistant
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MecA gene
Provides methicillin resistance to S. aureus via coding for a different transpeptidase that doesn’t bind to PCNs or cephalosporins
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Difference between hospital acquired and community acquired MRSA
Hospital acquired has larger cassette mecA gene that allows for greater abx resistance. Community acquired may be more susceptible to abx; however, it has the PVL cytotoxin that causes boils and hemorrhage PNA.
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Gene that increases bacterial adherence to titanium
Fnb
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Protein A mechanism of action in infection
Inactivates IgG
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Gram positive drum stick shaped rod and its exotoxin
C. tetani, tetanospasmin blocks inhibitory nerves and results in spasm/lock jaw
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Treatment of tetanus
Immunize every 5-10 years. If unsure of vaccination in contaminated wound, give Tdap vaccine and tetanus Ig
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Most common rabies bite in US
Bats
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Atypical mycobacteria that grows at colder temperatures from fresh or salt water
Mycobacterium marinum. Causes noncaseating granulomas (fish tank granulomas)
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Gram negative motile curved rod found in shellfish in warm brackish water
Vibrio, can cause NSTI
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Fish handler’s disease
Erysipelothrix rhusiopathiae, common in pigs, self limited gram + bacilli that causes pain, itching and ring-shaped hand lesions with purple border
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CREST syndrome
Anti-centromere antibodies cause calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly and telangiectasias
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Mechanism of action of fluoroquinolones
Act on DNA topoisomerase
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Mechanism of action of refampin
Binds bacteria RNA polymerase, inhibiting bacterial mRNA synthesis from DNA.
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Does an exon or intron code for proteins?
Exon, intron does not, they are regulatory proteins or junk DNA that get snipped out by snRNPs
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Antibodies agains snRNPs?
Anti-Sm (lupus) and Anti-U(1)RNP (mixed connective tissue disease)
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Diffences between human ribosome and bacterial ribosome
Human = 80S ribosome with 60S and 40S subunits. Bacterial = 70S ribosome with 50S and 30S subunits
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Antibiotics that act on bacteria 50S subunit
Clindamycin, macrolides and linezolid (also 23s RNA)
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Antibiotics that act on bacterial 30S subunit
Aminoglycosides and tetracycline
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What part of the bacteria does PCR amplify to identify bacteria?
The 16S ribosomal RNA gene
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Condition with bilateral scapular winging and progressive facial nerve paralysis? Mutation? Treatment?
DUX4 junk DNA is usually hypermethylated and silent, when undermethylated it causes progressive facial and shoulder weakness in fascioscapulohumeral muscular dystrophy. Treatment is scapulothoracic fusion.
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Neurofibromin gene activator or suppressor?
Suppressor, inhibits Ras protein. In NF1 the mutation turns it off and allows uncontrolled growth of neurofibromas.
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McCune-Albright gene activator or suppressor?
Activator, GNAS mutation upregulates cAMP and cell activity -> fibrous dysplasia, precocious puberty and café au lait spots
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Most common inheritance pattern in structural protein mutations like achondroplasia, pseudoachondroplasia, MED, SED, Kneist, Stickler, Schmid, OI, Ehler’s Danlos, Marfan’s and Jansens?
AD
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Most common inheritance pattern in enzyme mutations like diastrophic dysplasia, Hurler’s, Sanfilippo, Morquio, Gaucher’s, osteopetrosis and homocystinuria?
AR – Except for Hunter’s disease (iduronate sulfatase is XLR)
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X-linked recessive disorders
Hunter’s (iduronate sulfatase), SED tarda (TRAPPC2), Hemophilia A (factor VIII) and B (factor IX), Duchenne and Becker muscular dystrophy (Xp21 dystrophin)
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X-linked dominant disorder
Hypophosphatemic rickets (vitamin D resistant rickets, most common cause of rickets in US). Mutation is PHEX that no longer suppresses FGF23. FGF23 increases renal PO4 wasting
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Treatment for XLD hypophosphatemic rickets
PO4, calcitriol supplement and burosumab (anti-FGF23 monoclonal ab)
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Carter effect example
Sex-dependent polygenic inheritance, females need more gene expression to have clubfoot than males, so female have lower rates of clubfoot and higher rate of transmission to offspring
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Genetic basis of laxity in Down Syndrome patients
COL 6 overexpression (lives on Chr 21)
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Genetic cause of Prader-Willi syndrome
Paternal genes from Chr15(q11-13) are deletes and materal genes activated (imprinting)
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Embryonic layer that gives risk to the musculoskeletal system
Mesoderm
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BMPs are apart of what superfamily of transcription factors?
TGF-beta
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Marker of osteoblastic differentiation and new bone formation
Alkaline phosphatase
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Genetic disease with high levels of alk phos
Paget’s and rickets
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Genetic disease with low levels of alk phos
Phosphatasia. Genetic mutation of TNSALP makes alk phos non-functional. Pyrophyosphate levels rise and bone formation is inhibited, patients develop osteomalacia and rickets (only rickets with low alk phos)
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Genetic defect in stone man syndrome
Fibrodysplasia ossificans progressive is from an AD gain of function mutation in the BMP receptor ACVR1, it is always on and BMP4 is overexpressed, causing excess bone formation secondary to injury.
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Stone man syndrome treatment
Don’t resect because it stimulates more bone formation
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Disease associated with monophalangeal hallux valgus?
Fibrodysplasia ossificans progressively.
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Signaling molecules involved in limb formation
FGF (distal to proximal growth), Hedgehog (ulnar vs radial), Wnt (dorsal vs ventral then bone homeostasis)
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FGF effect on limb buds
Expressed at apical ectodermal ridge and increases the length of the limb bud
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Hypochondroplasia mutation
FGFR3, milder form of achondroplasia
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Thanatophoric dysplasia mutation
FGFR3, fatal, no proliferative zone in physis
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Tumoral-induced osteomalacia mutation
Increased expression of ectopic FGF23 -> creation of phosphaturic tumors
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Normal function of FGF23
Decreases renal reabsorption of phosphate and decreases serum phosphate levels and increases urin PO4
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Hyperphosphatemia genetic mutation
Deactivating mutation in FGF23 -> increased PO4 resorption in kidneys and tumoral calcinosis, commonly seen in renal failure
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Hedgehog signaling pathways
Sonic hedgehog: expressed at ZPA and determines radial-ulnar development. Indian hedgehog promotes osteoblast differentiation via Wnt/B catenin pathway.
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Limb deformities that occur secondary to over-expression of sonic hedgehog protein
Post-axial polydactyly and ulnar dimelia (2 pinkies, 2 ulnas)
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Limb deformities that occur secondary to under-expression of sonic hedgehog protein
Fibular hemimelia results with postaxial hypoplasia
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Anterolateral, anteromedial and posteromedial tibial bowing
AL= NF, AM= Fibular hemimelia, PM= physiologic
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Indian hedgehog pathway
Induces early bone transcription factors RUNX2 and osterix, also matures cartilage in endochondral ossification by inducing type X collagen, MMP13 and PTHrP in perichondrium, pathologic pathway in osteophyte formation, triggers Wnt/B catenin pathway
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Limb deformities that result from disruption of the Wnt pathway
Wnt is responsible for dorsal/ventral limb development. Nail-patella synrome (LMX1B in Wnt pathway)
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What is your diagnosis?
Nail patella syndrome = iliac horns, absent patella nd hypoplastic nails
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Wnt/B catenin signaling pathway
Wnt binds Fizzleds and LRP5/6, prevents B-catenin breakdown so it can travel to the nucleus and induce transcription factors RUNX2, Osx and osteocalcin to promote ossification.
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Type of bone healing seen in distraction osteogenesis
Intramembranous, no cartilage model, high expression of Wnt increases RUNX2, inhibits SOX9 and bone is formed directly from osteoblasts
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Wnt signaling in endochondral ossification
Wnt is low initially, favoring SOX9 and chondrocyte development, Wnt increases later to calcify the soft callus
291
Strain seen in endochondral ossification
2-10%
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Osteocyte function when bone is loaded vs. not loaded.
Loaded = sclerostin decreased. Unloaded = increased. Sclerostin blocks the LRP/Fz receptor in the Wnt/B-catenin pathway and reduces bone formation and stimulates osteoblast apoptosis.
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Antibody to sclerostin
Romosozumab
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Diseases with genetic defects in the SOST gene
Results in non-functiong Sclerostin and overproduction of bone with low risk of fractures in sclerosteosis and Van Buchem disease
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Dickkopf-related protein (DKK1) function
Blocks LRP 5/6 in Wnt-B catenin pathway and decreases bone mass… increased expression seen in multiple myeloma cells
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Genetic defect in juvenile Paget’s disease?
Osteoprotegrin
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Receptors found on osteoclasts
C-sf1 (binds M-CSF), RANK (binds RANK-L), calcitonin and aVB integrin (binds vitronectin on bone)
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Nitrogen containing bisphosphonate mechanism
Blocks farnesyl phyrophosphate synthase in the mevalonate pathway (Risedronate, Alendronate, Zolendronate, Pamidronate).
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Non-nitrogen containing bisphosphonates mechanism of action
Competes with osteoclast ATP and induces apoptosis (Tiludronate, Clodronate, Etidronate)
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How do osteoclasts resorb bone?
CO2 + H2O made into H2CO3 by carbonic anhydrase, then HCl- is released into Howship’s lacunae to acidfy the environment to pH of 4.5 and dissolve HA crystals. Cathespin K dissolves the collagen matrix. TRAP levels increase and can be measured in serum
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Genetic diseases of non-functioning osteoclasts
Osteopetrosis (most common Cl channelopathy or CA II deficiency = no ruffled border) and pyknodysostosis (cathepsin K deficiency). These have increased risk of fractures as opposed to sclerosteosis and Van Buchem’s that have rare fractures.
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Virchow’s triad
Hypercoaguability, stasis and endothelial damage
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Most common inherited clotting disorder
Facotor V Leiden
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TXA mechanism of action
Lysine analog that binds plasminogen and prevents fibrinolysis
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Drug that inhibits prostaglandin E2 via IL-1B
Acetaminophen
306
Drug that irreversibly binds COX in platelets
ASA
307
Drug that preferentially inhibits COX-2
Celicoxib
308
Drug that inhibits Vitamin K gamm carboxylation? Reversal?
Coumadin, reverse with Vit K or FFP
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Drug that reversibly inhibits Xa, ATIII, factors II, IX, XI and XII? Reversal?
Heparin, reverse with protamine sulfate. Acts by increasing ATIII activity.
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Drug that reversibly inhibits Xa, ATIII and factor II?
LMWH. Acts by increasing ATIII activity.
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Drug that irreversibly inhibits factor X and ATIII? Reversal?
Fondaparinux. Reverse with Andexanet.
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Drug that inhibits thrombin IIa only?
Hirudin/dabagatran. Reverse with Idracizumab.
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Effort thrombosis etiology? Treatment?
Upper extremity DVT from strenuous exercise. Axillary subclavian vein thrombosis. Treat with thrombolysis and/or 1st rib resection.
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Do you need to anticoagulated patients who had DVT after knee arthroscopy or casting?
No based on the NEJM RCT in 2017
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Fat Embolism Syndrom
Petechial rash, neurologic symptoms and pulmonary collapse (ARDS)
316
Best prophylaxis in prevention of fat emboli syndrome
Fix within 24 hours, higher risk if fixed after 48 hours
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CO and PVR in hypovolemic shock
CO decreased, PVR increased
318
Stages of hypovolemic blood loss
I) 0-15%, normal vitals 2) 15-30%, tachycardia, increased DBP 3) 30-40%, decreased SBP, oliguria, MS changes 4) >40%, narrowed pulse pressure, life threatening, no UOP
319
Best clinical and lab indicators for adequate perfusion
UOP >30cc/hr and lactate >2.5
320
PVR in septic shock
Decreased due to systemic vasodilation
321
Etiology of neurogenic shock
High cord injury -> loss of sympathetic tone and peripheral blood pooling -> hypotension and bradycardia
322
Earliest sign of malignant hyperthermia
Unexplained rise in EtCO2
323
Mutations associated with malignant hyperthermia?
Familial = RYR1 gene mutation. DMD muscular dystrophy as well.
