General Orthopaedics Flashcards
Most likely metal to experience crevice corrosion?
316L Stainless steel
Metal with highest risk of galvanic corrosion?
316L stainless steel and Co:Cr alloy
How to reduce metal corrosion?
Use similar metals and plates
Passivation (coat metal)
Titanium alloy undergoes self-passivation
Types of corrosion
1) Galvanic
2) Crevice
3) Pitting
4) Stress
5) Fretting
Labs to get with thumb hypoplasia?
CBC (Fanconi anemia)
Chromosomal challenge test
What is Parona’s space?
Potential space of communication between small finger and thumb - lies between fascia of PQ and FDP conjoined tendon sheaths.
Types of Nerve injury?
Neuropraxia (Sunderland 1st) - focal demyelination (no fibrillation on EMG)
Anonotmesis (Sunderland 2nd degree) - conduction block and Wallerian degeneration. Endoneurium intact.
Neurotmesis - disruption of endoneurium.
Latency and velocities seen in CTS?
Distal sensory latency > 3.2ms Motor latency > 4.3ms Velocity < 52m/sec Motor action potential decreases Sensory nerve action potential decreases
How to differentiate TAR from radial clubhand?
TAR (AR) - thrombocytopenia and absent radius - typically has thumb present.
Medial talar dome vs. lateral talar dome OCD lesions
Medial talar dome - more common, posterior, larger/deeper, no trauma.
Lateral talar dome - trauma, superficial, central or anterior, lower healing rates, more symptomatic.
Pathophysiology of dupuytrens disease
Myofibroblast is dominant cell type - actin along long axis and extracellular fibronectin
Type III collagen predominates
What is not invloved in Dypuytren’s disease?
Cleland’s ligament and transverse ligament
Dexa Scan Measurements?
BMD: absolute scores from Lumbar spine and hip
T-Score: BMD relative to young women (30 yo)
Z-Score: BMD relative to similar aged patients
Osteopenia: L2-L4 density 1 - 2.5 SD below T-score
Osteoporosis: L2-4 density > 2.5 SD below T-score
Biologics to to be used on osteoporosis?
Raloxifene - SERM (dont use if hx DVT)
Teriparatide (Forteo) - 1-34 amino terminal residues of parathyroid hormone, activates osteoblasts. Osteosarcoma risk in Pagets disease.
Denosumab (Prolia) - Ig2 against RANKL, don’t use longer than 2 years. Continuous infusion causes resorption.
Mnemonic for bisphosphonates?
PRAZI-N and TEC-No
Pamidronate, Risedronate, Alendronate, Zolendronate, Ibanddronate - Nitrogen containing (inhibit farnesyl pyrophosphate synthase which is a mavelonate pathway to ultimately inhibit small GTPases)
Tiludronate, Etidronate, Clodronate - Non-nitrogen containing (Toxic ATP analog)
Vitamin D and Calcium dosing recommendations?
1200-1500mg Calcium and 400-800 IU Vit D
Pharmacologic agents in osteoporosis?
Calcium/Vitamin D Bisphosphonates (PRAZI-N and TEC-No) HRT Estrogen Replacement Calcitonin - reduce bone pain in osteoporotic fractures, binds to osteoclasts to inhibit Raloxifene (Evista) - SREM Teriparatide (Forteo) - 1-34 amino terminal of PTH Denosumab (Prolia) - anti RANK-L
Types of Bone mineralization disorders
1) Vitamin D Resistant Rickets (Hypophosphatemic) - XLD
2) Vitamin D Deficiency Rickets (Nutritional)
3) Type I Vitamin D Dependent - AR
4) Type II Vitamin D Dependent - AR
5) Hypophosphatasia - AR
6) Renal Osteodystrophy High Turnover - Renal Dx
7) Renal Osteodystrophy Low Turnover - Renal Dx
8) Hyperparathyroidism - 90% adenoma
Pathophysiology of Renal Osteodystrophy?
Low Ca, high phos, refractory high PTH, high alk Phos
Hypocalcemia - inability of kidney to convert vit D3 (25-OH Vit D3) to calcitriol by 1alpha-hydroxylase due to hyperphosphatemia. Results in insoluble CaPO4 to form and remove from circulation.
Hyperparathyroidism and Secondary Hyperphosphatemia - caused by hypocalcemia and lack of phosphate excretion.
Uremia related phosphate retention.
Complications - genu Valgum and B/L SCFE (Secondary spongiosa of metaphysis).
Labs in metabolic bone disease?
Calcium Phosphorus Alk Phos PTH Vitamin D - 25(OH) Vitamin D 1,25(OH) Vitamin D
Metabolic bone diseases with Elevated calcium?
Hypophosphatasia
Hyperparathyroidism
All others are low or low normal (Nutritional Rickets)
Metabolic Bone diseases with elevated phosphate?
Hypophosphatasia
Renal Osteodystrophy
Metabolic Bone diseases with decreased alkaline phosphatase?
Hypophosphatasia
All others elevated
Metabolic Bone diseases with elevated PTH?
All with the exception of low turnover renal osteodystrophy Vit D resistant rickets Type II Vit D dependent Hypophosphatasia
Type 1 vs Type 2 Vitamin D dependent metabolic bone disease?
Type I has decreased 1,25(OH) Vit D - missing enzyme in proximal tubule of kidney (1-alpha-hydroxylase)
Type II has INCREASED 1,25(OH) Vit D - missing receptor for 1,25(OH) Vit D
High turn over renal bone disease vs. Low turnover renal bone disease
High turnover bone disease - secondary hyper PTH - Hyperphosphatemia lowers serum Ca, stimulates PTH results in bone resorption
Low turnover bone disease - No secondary hyper PTH
- Normal PTH levels - you get aluminum deposition into bone mineralization that impairs osteoblast proliferation and PTH release from PTH gland
Regulators of Ca and Phosphate metabolism
PTH - Chief cells of parathyroid glands
1,25(OH) Vitamin D - proximal tubule of kidney
Calcitonin - parafollicular cells of thyroid gland
Actions of parathyroid Hormone?
Decreased Ca levels cause release
Increased Ca and 1,25(OH) Vit D inhibit release
Results in increased Ca level and decreased Phosphate (phosphate thrashing hormone).
Kidney: Stimulates 1-alpha-hydroxylase to make active vitamin D, increase resorption of Ca, urinary excretion of Phosphorus
Bone: Direct cAMP mediated osteoclastic resorption of bone
Intestine: No direct effect, increased active Vitamin D results in increased absorption of Ca and P
Actions of 1,25(OH) Vitamin D
Stimulates intestinal resorption of Ca and P
Stimulates Osteoclastic resorption of bone
Results in increased Ca and P levels
Action of calcitonin?
From parafollicular cells of thyroid
Stimulated by elevated Ca levels
Inhibits osteoclastic resorption of bone (direct)
Results in decreased Ca levels
What is rickets?
Defect in mineralization of osteoid matrix due to inadequate calcium and phosphate
Prior to physeal closure called Rickets
After physeal closure called osteomalacia
Most common form of rickets?
Familial Hypophosphatemic Rickets (Vitamin D resistant Rickets)
- X Linked Dominant - PHEX gene
- inability of tubules to resorb phosphate, results in high phosphate in urine
- Low Phosphate and elevated alk phos. Normal PTH, Ca, Vitamin D.
- Triad of hypophosphatemia, short, lower limb deformities.
What zone of physis is widened in Rickets?
Hypertrophic zone
Nutritional vs. hypophosphatemic rickets?
Nutritional - low vitamin D levels is primary problem so there are low-norm Ca levels, low phos, high alk phos, and increased PTH levels - Tx vitamin D
Hypophosphatemic - XLD (PHEX gene) - low phosphate resorption and near normal Ca levels results in normal PTH levels, Tx with VitD and Phos
Mechanism of Factor V Leiden thrombophilia?
Altered Factor V cannot be inhibited by protein C. Thus Factor V (co-factor for Factor Xa) binds to Factor Xa to produce high amounts of thrombin and drive clotting.
Hypercoagulable disorders?
MTHFR/C677 gene (highest risk) factor V Leiden Antithrombin III deficiency Protein C deficiency Protein S deficiency Activated protein C resistance
(M,3,5,C,S)
Brief overview of clotting cascade
Intrinsic Pathway - XII, XI, IX Extrinsic pathway (endothelial damage) VII activated by TF (thromboplastin)
Factor X to Xa activates Factor II (prothrombin) to Factor IIa (thrombin) which activates factor I (Fibrinogen) to Factor Ia (fibrin)
Mechanism of Heparin?
Binds and activates antithrombin III to inhibit factors IIa, IIIm and Xa.
Subcutaneous version is unfractionated heparin.
What is fractionated heparin and mechanism of action?
Also known as low molecular weight heparin - enoxaparin (Lovenox) or Dalteparin
Several sites but main is inhibits Factor Xa.
Direct factor Xa inhibitors?
Rivaroxaban (Xarelto)
Apixaban (Eliquis)
Edoxaban (Savaysa)
Metabolized in Liver
Indirect Xa inhibitors?
Fondaparinux (Arixtra)
Coumadin mechanism?
Affects extrinsic clotting pathway and Vitamin K dependent factors (II, VII, IX, X)
Inhibits vitamin K 2,3 epoxide reductase
Direct thrombin inhibitor?
Thrombin = Factor IIa
Dabigatran (Pradaxa) - Metabolized in kidney
Argatroban
Mechanism of TXA?
Antifibrinolytic that promotes and stabilizes clot formation
Competitively inhibits activation of plasminogen and binds lysine binding site. Plasmin breaks down fibrin.
Antiplatelet agents?
Aspirin (acetylsalicylic acid) - inhibits prostaglandins and thromboxanes (causes platelet aggregation).
Clopidogrel (Plavix) - binds ADP receptor on platelet to activate GPIIb/IIIa complex.
Mechanism of penicillins?
Bactericidal - blocks cross linking via competitive inhibition of the transpeptidase enzyme
Carbapenems
Imipenem
Meropenem
Doripenem
Ertapenem
Broadest activity - no MRSA or mycoplasma
Abx that bind 30S ribosomal subunit?
Aminoglycosides - Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin
Tetracyclines - Tetracycline, Doxycycline, Minocycline
Aminoglycosides and mechanism of action?
Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin
Bactericidal - irreversible binding to 30S
Aerobic gram-negatives, enterobacter, pseudomonas
Tetracyclines and mechanism of action?
Tetracycline
Doxycycline
Minocycline
Bacterostatic - blocks tRNA
Abx that bind 50S subunit?
Macrolides (erythromycin, azithromycin, clarithromycin)
Chloramphenicol
Lincosamides (Clindamycin) - inbibits peptidyl transferase by interfering with amino acyl-tRNA complex
Linezolid
Streptogramins
Abx that interfere with DNA synthesis?
Fluoroquinolones - Ciprofloxacin, Norfloxacin, Levofloxacin
Metronidazole
Floroquinilones and mechanism of action?
Ciprofloxacin, Norfloxacin, Levofloxacin
4th generation: moxifloxacin, gemifloxacin
Inhibit DNA gyrase
Achilles tendon rupture, impaired fracture healing
Mechanism of rifampin?
Inhibits RNA transcription by inhibiting RNA polymerase (DNA dependent RNA polymerase)
Definition of sensitivity?
Probability that test results will be positive in patients with the disease
Detects disease! True positive.
A/(A+C)
Remember: set up 4x4 table with Test on left and Disease on top. A (upper left), B (upper right), C (lower left), D lower right.
Definition of specificity
Probability that test results will be negative in patients without the disease.
Detects Health!! True Negative.
D/(D+B)
Remember: set up 4x4 table with Test on left and Disease on top. A (upper left), B (upper right), C (lower left), D lower right.
Definition of positive predictive value?
Probability a patient with positive test will have the disease.
A/(A+B)
Remember: set up 4x4 table with Test on left and Disease on top. A (upper left), B (upper right), C (lower left), D lower right.
Definition of negative predictive value?
Probability a patient with a negative test will not have the disease.
D/(D+C)
Remember: set up 4x4 table with Test on left and Disease on top. A (upper left), B (upper right), C (lower left), D lower right.
Likelihood ratio?
Likelihood a given test result will be expected in a patient with the target disorder
Positive likelihood (Chances of a disease is changed by a positive rest) = Sensitivity /(1-Specificity)
Negative likelihood = (1-Sensitivity)/Specificity`
Relative Risk Definition.
Risk of developing disease for people with known exposure compared to risk of developing disease without exposure
= Incidence of exposure/incidence of no exposure.
- This is basically incidence (incidence in exposed/risk in unexposed). And a prospective cohort study design is the only type to calculate incidence.
Odds ratio definition?
Represents the odds that an outcome will occur given a particular exposure, compared to the odds that the outcome will occur without the exposure
= (axd)/bxc)
Where are odds ratios calculated from?
From case control studies (retrospective)
From logistic regression models
Odds ratios approximate RR when outcome is rare (<10%)
Number needed to treat definition?
Number of patients needed to treat to get favorable outcome.
NNT = 1/ARR
Type 1 vs Type 2 error
Type I Error: Reject null hypothesis even though true, alpha error set to 0.05
Type II Error: Accept null hypothesis even though false (Beta usually 0.2) Power = 1-Beta
What is a bonferroni correction?
Post-Hoc correction made to P values when several dependent or independent statistical tests are being performed simultaneously on a single data set.
Parametric data vs. non-parametric data?
Parametric: normally distributed
Non-parametric: Not normally distributed
Continuous data tests?
Parametric
- Two Groups (Paired) - Dependent (paired) t-test
- Two Groups (Unpaired) - Independent t-test
- Three or more - ANOVA
Non-parametric
- Two Groups (Paired) - Wilcoxon Rank-Sum Test
- Two Groups (Unpaired) - Mann-Whitney U Test
- Three or more - Kruskal-Wallis Test
Categorical Data Tests?
Parametric/Nonparametric
- Two or more variables: Chi Square
- Two or more variables (Small sample size): Fisher’s exact test
What is a funnel plot used for?
Scatter plot of the intervention to detect bias in meta-analysis
Design of the ROC curve?
X-axis: False positive rate (1-specificity)
Y-axis: True positive rate (sensitivity)
Area under the curve - used to compare different tests, higher c-statistics mean better test.
Levels of Evidence?
Level 1: RCT, Meta-analysis
Level 2: Bad RCT (F/u <80%), Prospective cohort study, meta-analysis of level II
Level 3: Retrospective cohort study, case-control study, meta-analysis of level III
Level 4: Case series
Level 5: Case report, opinion, observation
What is a prospective cohort study?
Groups separated non-randomly into treatment groups and followed/compared. Exposure occurs after initiation of study.
Analysis reported as relative-risk
Level II evidence
What is a case control study?
Groups are separated by presence or absence of disease and examined for the prior exposure of interest.
Analysis reported as odds-ratio
Level III
Most common clinical study type in orthopaedics?
Level 4 (retrospective case series)
Hereditary neuropathies?
Friedreich Ataxia - AR disorder, cardiomyopathy and cavus foot, scoliosis
Charcot Marie Tooth - AD, myelin degeneration (PMP22 on Chr 17), Pes cavus from Tib ant and P brevis.
Anterior horn cell disorders
Spinal Muscular Atrophy (SMA) - AR with SMN gene lack of SMN-1 protein
Type 1 (Acute Werdnig Hoffman) - <6mo, no DTR, tongue fasciculations
Type II (Chronic WH) - 6-24 months may live to 40s
Type III (Kugelberg Welander) - 2-10 years, walk as children
Treat hip subluxation non-op
Causes of limb length discrepancies?
Congenital - PFFD, fibular deficiency, hemihypertrophy, DDH
Paralytic - CP, Polio
Infection, tumors, trauma
Angle in infantile blount disease?
Drennan metaphyseal-diaphyseal angle > 16 deg
Treatment of infantile blount disease?
If <3 years and stage I or II brace
Stage II and III proximal osteotomy
Higher stage need something crazy
Types of tibial bowing?
Posteromedial - probably mild, calcaneovalgus foot, will develop LLD (3-4cm)
Anteromedial - fibular hemimelia, equinovarus foot, assoc with coxa vara and PFFD, tarsal coalition and ball and socket ankle joint
Anterolateral - congenital pseudoarthrosis, NF, brace to prevent fx
Gene associated with clubfoot mutation?
PITX1 mutation
Deformity associated with club foot?
Cavus (tight intrinsics, FHL, FDL)
Adductus of forefoot (tight tibialis posterior)
Varus (tight tendoachilles, tibialis posterior, tibialis anterior)
Equinus (tight tendoachilles)
Most common types of tarsal coalitions?
Calcaneonavicular
Talocalcaneal
AIS MRI Indications?
Left thoracic curves Pain Apical Kyphosis Rapid curve progression Neurologic signs (abdominal reflexes) Congenital anomalies
Factors affecting AIS progression?
Skeletal maturity - Risser sign, hand digit physes
Peak growth velocity - Prior to menarche, occurs prior to Risser 1, tri-radiate cartilage
Curve magnitude > 20 deg
Curve Type Thoracic>Lumbar and Double>Single
Scoliosis progression after maturity?
Thoracic > 50
Lumbar >30
1-2 deg per year
Treatment of AIS?
<25 deg and immature - observe
< 40 and mature - observe
25-40 deg and immature - brace
>50 - surgery
Measurement in early onset scoliosis?
RVAD - rib vertebral angle difference (Mheta)
> 20 has high risk for progression
RVAD = Concave - Convex
Congenital scoliosis with worst prognosis?
Unilateral bar with contralateral hemivertebrae
Measurement in congenital coxa vara?
Hilgenreiner-Physeal line - should be < 25 degrees
Classification for Legg-Calve-Perthes Disease?
Lateral pillar classification - only at the end of fragmentation phase.
A = none
B = <50% loss of height
B/C border - lateral pillar narrowed with height 50%
C = >50% loss of height
Prognosis in Legg-Calve-Perthes Disease
Worse if 6 and older and if total head involvement
Good outcome is good ROM and spherical head
Differentiation between multiple epiphyseal dysplasia and Spondyloepiphyseal dysplasia?
MED - autosomal dominant, COMP gene mutation, spine is normal, disproportionate dwarfism
SED - AD, Mutation on chromosome 12 (COL2A1), proportionate, spine involvement
Features and genetics of Diastrophic dysplasia?
Genetics - DTD gene (Chr 5), sulfate transporter protein results in undersulfation of proteoglycans, autosomal recessive
Features - short, cauliflower ears, hitch hikers thumb, fused PIPJs, severe club feet, kyphosis and scoliosis
Cervical kyphosis severe, quadriplegia a risk, urgent management required
Composition of bone?
40% Organic - Collagen (resistes tensile forces), proteoglycan (resists compressive forces), matrix protein
60% Non-organic - Hydroxyapatite (resists compression)
Composition of hydroxyapatite?
Ca10(PO4)6(OH)2
Resists compression!
Defect in Osteopetrosis?
Osteoclast malfunction - Carbonic anhydrase defect, OPG over expression, get decreased remodeling
Ruger jersey spine and erlenmyer femur
Pynknodysostosis
Cathepsin K deficiency
Casuses acro-osteolysis of terminal phalanges
Sclerosteosis
Sclerostin deficiency
Increased WNT/B-catenin and increased osteoblast activity.
Function of sclerostin and dickkoph-1 (Dkk-1)
Direct inhibitors of Wnt/B-catenin pathway (activates osteoblasts)
Chondroblast promoting conditions and growth factors?
hMSC in medium strain and low O2 conditions and in presence of SOX-9
Growth Factors (TIP) - TGF-B, IGF-1, PDGF
Function of chondrocytes?
Produce cartilage (collagen and PG)
From chondroblasts in the superficial/tangential layer
What gives cartilage compressive strength?
Composition of proteoglycan aggregate?
Proteoglycans (hydrophilic)
Keratin sulfate and chondroitin sulfate bind to protein core and chains are linked together on a hyaluronic acid backbone
Cartilage changes in osteoarthritis?
H2O increases while collagen and quantity decrease
Decreased x-linking and lower modulus
Chondrocyte number unchanged
Increased IL1, IL6, and TNFa. Collagenase/MMPs degrade collagen and stromelysin degrades PG
Cartilage changes in aging?
Old and stiff…
H2O decreases, collagen quantity unchanged
Stiffer collagen (increased x-linking and diameter)
Proteoglycan: increased keratin sulfate and decreased chondroitin sulfate.
Decreased chondrocytes
Intervertebral disc composition?
85% water, PG, collagen 1 and II
Nucleus pulposus
- high PG, low Col
- Type II collagen
- Compressive strength
Annulus Fibrosis
- Low PG and high Collagen
- Type I collagen
- Tensile strength
Changes seen in an aging disc?
Decreased H2O and decreased PG
Protein specific to ligaments?
Elastin
Also has type I collagen
What type of collagen dominates in ligament healing?
Type III Collagen
Changes in a healed ligament?
Increased number of fibers but lower x-linking, diameter, and mass
Protein that regulates tendon diameter?
Decorin
When are tendon repairs weakest?
During inflammatory phase (7-10 days)
In early OA what collagen type increases?
Type X
Diseases in reserve zone?
PKGD - matrix production
Pseudoachondroplasia (COMP gene) Kneist syndrome (Col 2A1 gene) Gaugher Disease (B-glucocerebrosidase) Diastrophic dysplasia (AR, DTDST sulfate transport gene)
Diseases in the proliferative zone?
Cellular division
MEGA
MHE (AD, EXT 1, 2, 3)
Gigantism
Achondroplasia (AD, FGFR3)
Diseases in the Hypertrophic Zone?
Cellular hypertrophy - longitudinal growth
3 Ss
SCFE
SH Fx
Schmid
Nutritional rickets (ZPC)
Zone of provisional calcification involves Col X and is the last to calcify
Pathology of lead poisoning?
PTHrP regulates (inhibits) physeal maturation in the hypertrophic zone
Lead inhibits PTHrP and leads to accelerated maturation of bone at an earlier age (decreased peak BMD)
Diseases in the metaphysis of the growth plate?
Primary Spongiosa - woven bone - Corner Fx
Secondary spongiosa - lamellar bone - Endocrine SCFE and Renal osteodystrophy
Appositional growth of the growth plate?
Zone of Ranvier - fibrous ring from epiphysis to the diaphysis
Perichondral ring of Lacroix - contributes to physeal strength
Limb Embryology - Growth patterns
AER - proximal to distal (interdigital apoptosis) - FGF growth factor
ZPA - radial to ulnar - Shh gene
WNT - dorsal to ventral - Wnt (Wings on your dorsal surface)
Renal osteodystrophy knee deformity?
Genu valgum
Most common disorder of bone mineralization, genetics, mechanism, labs, treatment?
X-linked hypophosphatemic rickets (Vitamin D dependent), XLD - PHEX gene
Inability to resorb phosphate in the kidney
Low phos - everything else normal (Normal Ca, PTH, and Vitamin D)
Treat with phosphate and vitamin D
Hypercoaguable states?
M, 3, 5, C, S MTHFR Gene AT3 Deficiency Factor V Leiden Protein C and S deficiency
Osteoblasts derived from?
Mesenchymal stem cells
Transcription factors directing cells down osteoblast lineage?
RUNX2
Function of osteoblasts?
Form Bone
Regulate osteoclast activity
What causes a cell in the Osteoblast lineage to become an osteoblast?
Low strain, high O2 environment
BMP/SMAD (Ser-Thr) Core binding factor a1 (Cbfa1)/RUNX-2 WNT/B-catenin PDGF IHH/IGF-2
Osteoblasts produce what?
Alkaline phosphatase Osteocalcin Type I collagen Bone sialoprotein RANKL Osteoprotegrin (binds RANK to decrease activity)
Osteoblast activity is stimulated by what?
Intermittent PTH
Functions of Wnt proteins?
Promote osteoblast survival and proliferation
What can sequester Wnts?
Sclerostin (Scl) and dickkoph related protein 1 (dkk1)
Osteocytes are from what?
Former osteoblasts that are now enclosed in bone.