Basic Science Flashcards
1
Q
Articular cartilage consists mainly of what?
A
-ECM, w/ only a small percentage of chondrocytes, which are responsible for synthesis, maintenance, and homeostasis of cartilage
2
Q
what are the major components of ECM in articular cartilage?
A
-Water, proteoglycans, and collagen
3
Q
What are the four layers of articular cartilage?
A
- superficial, middle, deep, and calcified
- classified according to collagen orientation, chondrocyte organization, and proteoglycan distribution
4
Q
Cartilage is an avascular structure in the adult; this has implications for repair and healing
A
.
5
Q
The breakdown of the cartilage matrix in normal turnover and in degeneration appears to be the action of what?
A
-Proteinases (their overactivity is implicated in OA)
6
Q
how does water content of cartilage change w/ aging and OA?
A
-decreases w/ aging and INCREASES w/ OA
7
Q
how does proteoglycan content and keratan sulfate concentration change w/ OA?
A
- they decrease w/ OA
- proteoglycan degradation and chondroitin-4-sulfate concentration INCREASE
8
Q
what is the principal mode of lubrication of articular cartilage?
A
-Elastohydrodynamic lubrication
9
Q
superficial lacerations to cartilage rarely heal; deeper lacerations may heal w/ fibrocartilage
A
.
10
Q
what are responsible for the macroscopic and histologic changes seen in OA?
A
-Inflammatory cytokines and metalloproteinases
11
Q
tendons and ligaments are materials w/ highly ordered hierarchical structure
A
.
12
Q
the composition of tendons and ligaments is primarily what type of collagen?
A
type 1 collagen (aligned in the direction of loading, anisotropic)
13
Q
structural vs material properties?
A
structural: describe the capacity of the tissue to bear load
material: describe the quality of the tissue
14
Q
tendons and ligaments are viscoelastic
A
-their properties are time dependent
15
Q
several biologic (eg age) and environmental (eg temperature) factors influence the mechanical properties of tendons and ligaments
A
.
16
Q
tendon/ligament healing phases?
A
hemostasis/inflammation–> matrix and cell proliferation–> remodeling/maturation
17
Q
sheathed vs nonsheathed and extra-articular vs intra-articular tendons and ligaments, how does this affect healing?
A
-nonsheathed tendons and extra-articular ligaments have a GREATER capacity to heal than do sheathed tendons and intra-articular ligaments
18
Q
how does loading effect tendon and ligament healing?
A
-for tendon and ligament healing, increased loading can be either beneficial or detrimental, depending on the anatomic location and type of injury
19
Q
the physical environment influences tissue maintenance: immobilization is detrimental and exercise is beneficial to the biomechanical properties of tendon and ligament
A
.
20
Q
what is the tendon/ligament enthesis?
A
-specialized tissue that is necessary to minimize stress concentrations at the interface between two very different materials (tendon/ligament and bone).
21
Q
Schwann cell myelination
A
-speeds transmission of action potentials by SALTATORY conduction at nodes of Ranvier
22
Q
Most motor and sensory nerves are myelinated, except for which ones?
A
autonomic and slow pain fibers
23
Q
Nerve organization
A
-nerve fibers (axons) are surrounded by ENDONEURIUM, collections of nerve fibers (fascicles) by PERINEURIUM, and collections of fascicles by EPINEURIUM
24
Q
Nerve injury causes loss of distal function in what sequence?
A
- motor–> proprioception–> touch–> temperature–> pain–> sympathetics
- nerves recover in the inverse order
25
Neurapraxia
-a reversible conduction block (traction or compression)
26
axonotmesis
-involves axon disruption w/ preserved neural connective tissue (stretch or crush)
27
neurotmesis
-complete disruption of a nerve (open crush or laceration)
28
tissue pressures up to what mmHg can cause paresthesias and increased nerve conduction latencies?
30mmHg
29
what decreases rate of transmission of nerve signals?
-temperature, age, demyelination, and loss of axons
30
Fibrillations
-an EMG finding of abnormal spontaneous activity that occur in muscle fibers 2 to 3 weeks after denervation (transient or complete)
31
nerve repair (neurorrhaphy)
- involves reapproximation of the nerve ends w/ fascicles appropriately oriented under minimal tension using a fine monofilament epineural suture
- group fascicular repair increases scarring at the repair site
32
nerve grafts
- may be cabled to increase diameter
| - they should also be reversed to minimize early arborization of regenerating nerve fibers
33
muscle fiber
-collection of myofibrils
34
fascicles (muscle)
-collections of muscle fibers (which are collections of myofibrils)
35
actin's binding sites for myosin are blocked by what?
tropomyosin
36
You must know all bands and lines of sarcomere organization! (A, I, H, M, and Z)
A band: composed of both actin and myosin
M line: central set of interconnecting filaments for myosin
H band: contains only myosin
I band: composed of actin filaments only, which are joined together at the interconnecting Z-line
37
Site of action of both depolarizing and non-depolarizing drugs?
NMJ
38
maximal force production is proportional to what?
-muscle physiologic cross-sectional area (PCSA)
39
phosphagen energy system
-has enough ATP for approximately 20 seconds of activity
40
Delayed onset muscle soreness (DOMS)
- peaks at 24 to 72 hrs post-exercise
- most common in type IIB fibers
- associated primarily w/ ECCENTRIC exercise
41
Eccentric contraction
-generates the highest tension and greatest risk for musculotendinous injury
42
muscle strain
-most likely in muscles that cross two joints
43
The intervertebral disk
-allows motion and provides mechanical stability of the functional spinal unit
44
intervertebral disk nutrition
-mostly avascular and depends on diffusion through pores in the end plate to provide nutrition to the disk cells
45
Nucleus pulposus cells
-more synthetically active in a hypoxic environment
46
nucleus pulposus
- normally rich in aggregating proteoglycans (aggrecan and versican), which attract water and help maintain disk height
- nucleus pulposus has a higher concentration of type II collagen than the anulus fibrosus
47
anulus fibrosus
-well organized laminated fibrous tissue composed primarily of type I collagen
48
what happens to intervertebral disk as it ages?
- with increasing age, the disk cells produce less aggrecan and type II collagen, leading to decreases in proteoglycan and water content
- as the nucleus pulposus dessicates, disk height is lost and the anulus fibrosus develops fissures
49
what percentage of asymptomatic individuals older than 60 yrs have MRI evidence of disk degeneration?
-90%
50
Genetics plays a strong role in disk degeneration, but this seems to involve a multifactorial process that does not fit a Mendelian pattern.
.
51
Disk degeneration is NOT necessarily a painful condition
.
52
Diskography
-has a high false positive rate in pts w/ abnormal psychometric testing results
53
what is the most common general infectious symptom?
PAIN localized to the site of infection
| -it is rare for pts to not report pain as a presenting symptom of infection
54
Septic arthritis in adults (most common organisms)
- most commonly associated w/ N. gonorrhea in otherwise healthy pts
- S. aureus is the second most common pathogen causing adult septic arthritis
55
triad of symptoms strongly suggesting Clostridial myonecrosis
1. progressively severe pain out of proportion to obvious injury
2. tachycardia not explained by fever
3. crepitus
56
how much bone loss is required before the classic signs of osteomyelitis (bone resorption, destruction, periosteal elevation) can be seen on radiographs?
bone loss of 30-40%
57
The most sensitive imaging tool for diagnosing osteomyelitis?
MRI
58
what are the classic findings on MRI of osteomyelitis?
- signal change that is due to the increased edema and water content in bone, which is manifested as a reduction in T1 and an increase in T2 marrow signal
- the increased signal intensity on T2 images results because the fatty marrow has been replaced by inflammation
59
Synovial fluid WBC count strongly indicative of infection in a TKA?
-WBC count > 2,500/mm3 or w/ > 90% PMNs
60
S. aureus is protected from host immune defenses by what 3 mechanisms?
- excretion of protein A, which inactivates IgG
- production of a capsular polysaccharide, which reduces opsonization and phagocytosis of the organism
- formation of a biofilm (a "slime" containing an aggregation of microbial colonies embedded within a glycocalyx matrix that most commonly develops on THA/TKA implants or a devitalized bone surface), which also secludes the organism from host defense mechanisms
61
modes of action of penicillin and cephalosporins?
-inhibition of cell wall synthesis
62
modes of action of clindamycin
-binds 50s ribosomal subunit
63
tuberculosis treatment
-extended triple drug therapy of isoniazid, rifampin, and pyrazinamide for 6 to 12 months has shown to be effective w/ osseous extra-pulmonary involvement
64
treatment of choice for MRSA?
vancomycin
65
3 types of bone grafts
-osteogenic, osteoinductive, osteoconductive
66
bone healing stages
early (inflammation)--> middle (reparative)--> late (remodeling)
67
bone healing may be affected by host and local factors
.
68
what is the gold standard bone graft material?
autograft
69
reported rate of potential HIV transmission from allografts?
1 per million
70
Demineralized bone matrix (DBM)
- have been shown to have significant interproduct and interlot variability
- predominantly osteoCONDUCTIVE
71
bone marrow aspirates
-provide potential access to osteoGENIC mesenchymal precursor cells
72
Ceramics
-inorganic compounds consisting of metallic and nonmetallic elements held together by ionic or covalent bonds
73
BMPs
-potent osteoINDUCTIVE factors of the TGF-b superfamily
74
T of F: several forms of electromagnetic stimulation may facilitate bone healing?
True
75
Clonazepam effect on bone mineral density?
Clonazepam increases sclerostin levels, and long-term use can result in osteoporosis.
76
the best test for vitamin D levels in the absence of renal disease?
25 hydroxycholecalciferol
77
Following peripheral nerve injury, distal recovery typically occurs first in...?
Sympathetic activity
-Nerve injury causes loss of distal function in this sequence: motor, proprioception, touch, temperature, pain, and sympathetic activity. Nerve function recovery occurs in the reverse order.
78
sequestrum vs involucrum
- sequestrum is infected, dead bone in setting of chronic osteomyelitis
- involucrum is new bone laid down around the infection
79
vancomycin use in cement
Vancomycin is a common antibiotic used in cement delivery. Its mechanism of action disrupts cell-wall synthesis. It also kills bacteria in a time-dependent manner, not in a concentration-dependent way like tobramycin and other aminoglycosides. This means that, for the drug to be effective, the concentration must be above the minimal inhibitory concentration between doses, illustrating why following a vancomycin trough is important. Drugs that kill in a concentration-dependent way still have effect, even after a limited exposure; this fact explains why the dosing for gentamycin is recommended once per day for open fractures.
80
compartment syndrome pathophysiology
The progression of compartment syndrome results from a compromise of venous outflow relative to arterial inflow. As this imbalance increases, venous congestion further raises already elevated compartment pressures and, if the imbalance is untreated, eventually results in arterial collapse.
81
The amount of strain required to transition from elastic to plastic deformation?
Yield point
82
basic biomechanics definitions
Materials exhibit a different stress-strain curve during loading based on their inherent properties. As a load is applied, the curve can be linear (brittle material), can undergo plastic deformation (ductile material), or can vary based on the rate of the load applied (viscoelastic material). As the material relaxes, it may or may not return to its original shape. Hysteresis describes a material whose relaxation curve does not match the loading curve. A material that is able to return to its original shape is said to have elastic deformation, whereas plastic deformation is permanent. The transition from elastic to plastic deformation is the yield point at which the material will no longer return to its original shape.
83
The maximal tension generated by a given skeletal muscle is most closely predicted by?
physiologic cross-sectional area
84
screw stress in bridge plate vs compression plating
- The screws nearest the fracture absorb the highest stress in bridge plating, unlike the application of rigid fixation with direct compression of the bone ends, in which the stress is maximal at the screws farthest from the fracture.
- The rigidity of a construct can be manipulated by changing the working length of the plate. Creating a longer working length by leaving the screw holes closer to the fracture site empty reduces the rigidity of the construct. In the second item, two screws close to the fracture and then one screw far away on either side creates the most rigid construct, much like an external fixator. Remembering that strain is (change in length)/length, the surgeon could reduce the strain seen in the implant by increasing the working length of the plate or by placing screws farther away from the fracture.
85
what determines torsional stability in plate and screw fixation?
Torsional stability is different from bending or axial compression stability. Torsional stability depends more on the number of screws on either side of the fracture than on the location of the screws. Biomechanical studies have shown that adding more than four screws will not improve torsional stability statistically, provided good purchase is achieved within the bone.
86
working length of the plate in bridge plate vs compression plate
bridge plate: the distance between the innermost screws spanning the fracture site.
compression plate: the distance between the screws farthest from the fracture site
87
calcitriol (1/25-dihydroxycholecalciferol)
Calcitriol is the active metabolite of vitamin D that is formed by 1 alpha-hydroxylase from calcidiol (25-hydroxyvitamin D). Secondary hyperparathyroidism is a condition commonly seen in patients with chronic kidney disease characterized by hyerphosphatemia, hypocalcemia, high parathyroid hormone levels, and a reduced amount of calcitriol from damage to the kidney.
88
The anulus fibrosus of the intervertebral disk develops directly from which embryonic structure?
Sclerotomal cells
-Following resegmentation of the sclerotomes, cells from the sclerotomes themselves are differentiated into anulus fibrosus components.
89
type 2 errors
Type 2 error occurs when a clinical trial is underpowered to detect the treatment outcome differences between two groups. Type 1 error occurs when a false positive effect is detected. Selection bias refers to failure to properly randomize to achieve a representative sampling of the population. Intent to treat is a method of analysis based on initial allocation.
90
Mortality rates among trauma pts can decrease w/ use of which hemostatic agent?
-Tranexamic Acid (TXA)
The Military Application of Tranexamic Acid in Trauma Emergency Resuscitation study retrospectively evaluated the use of TXA in 896 casualties of combat who needed blood transfusions and were admitted to a medical facility at Camp Bastion, Afghanistan, over a 2-year period. Despite severe trauma, mortality in the TXA group was significantly lower than patients in the non-TXA group (17.4% vs 23.9% [P = .03]). TXA use was independently associated with lower mortality in the subset of patients necessitating massive transfusions. A randomized controlled trial initially showed decreased transfusion requirements in patients with blunt (nonpenetrating) trauma; however, recombinant factor VIIa offered no mortality benefit.
91
Which feature of noncollagenous bone extracellular proteins allows interaction with integrins on bone cells?
Arg-Gly-Asp (RGD) sequence
92
what is the primary function of the Pacinian corpuscle?
Pacinian corpuscles convey deep pressure and vibration sensation. Golgi organs relay muscle length and tension proprioception. Ruffini endings convey sustained pressure sensation, whereas Merkel cells convey sustained touch and pressure sensation. Free nerve endings and nociceptors convey pain sensation.
93
Lesch-Nyhan syndrome
rare X-linked recessive disorder found almost exclusively in males. It is characterized most notably by self-mutilation and aggressive behavior. Additionally, patients typically have severe mental retardation and may exhibit choreoathetosis. The underlying etiology is an absence of HPRT. This enzyme is involved in purine metabolism, and affected individuals have considerably elevated uric acid. Self-mutilation frequently involves biting of the lips and fingers; dental extractions frequently are needed. Hip dysplasia, including subluxation and dislocation, is very common in patients with Lesch-Nyhan syndrome, occurring in 66% of individuals in one study. Clinical manifestations of gout also are seen frequently. Scoliosis and other spinal problems as well as infections related to self-mutilation also may be seen.
94
deficiency of N-acetylgalactosamine-6-sulfate sulfatase
Morquio syndrome
95
deficiency of alpha-L-iduronidase
Hurler syndrome
96
deficiency of beta-glucocerebrosidase
Gaucher disease
97
Congenital pseudarthrosis of the tibia (CPT) frequently is associated with neurofibromatosis (NF) type 1, and approximately 50% of those with CPT have NF.
.
98
Congenital radial head dislocation may present in isolation or may be seen with Nail-patella syndrome or Cornelia de Lange syndrome.
.
99
Equinovarus foot deformity can be observed in multiple neuromuscular syndromes, including cerebral palsy and myelomeningocele,
.
100
what is the effect of the mutation in factor V Leiden?
Prevents inhibition by activated protein C
101
What is the most appropriate definition of an eccentric contraction
The muscle fibers lengthen as the muscle contracts
102
Hemophilia A inheritance pattern
Hemophilia (types A or B) is a hereditary disorder that has an X-linked recessive inheritance pattern.
103
The elution of antibiotics from a cement spacer is increased by...?
INCREASED CEMENT POROSITY
-increased surface porosity results in increased surface area, which allows for greater elution of antibiotic into the environment
104
What is the most appropriate definition of epigenetics?
Genetic alterations that do NOT involve DNA mutation
105
genetic linkage
tendency of certain alleles to be inherited together
106
production of amino acid chains from nucleotide sequences
translation
107
Renal osteodystrophy is initiated in part by which mechanism?
Phosphate retention
108
CD8+ T-lymphocytes
mediators of chronic inflammation and are detrimental to fracture healing
109
Intrasynovial tendons are those enclosed within a synovial sheath. Intrinsic repair mechanisms describe the healing processes that rely on the proliferation and migration of cells within the injured tendon itself to help bridge the injury. In extrinsic healing mechanisms, cells from the surrounding tissue outside the tendon invade the damaged area. Extrinsic healing can represent a substantial part of the overall healing response and is faster than intrinsic healing for intrasynovial flexor tendons. Extrinsic healing results in adhesion formation between the tendon and the surrounding tissue, however.
.
110
Rheumatoid factor as clinically measured detects antibodies to which antigen?
IgG
111
failure modes in common soft-tissue fixation methods
The surgical fixation of soft tissue to bone is a common orthopaedic procedure. Numerous factors influence the strength of the soft–tissue-to-bone fixation construct, including tissue quality, implant strength, contact area, tensioning, and the biology of the location. Each fixation technique differs with respect to stability and failure mechanism. Interference screws can achieve excellent fixation but have the potential for graft pullout or laceration. Staples have less stiffness than interference screws and can irritate the overlying tissues. Transfixion pins fail secondary to pin breakage or partial tearing of the graft. Primary failure of cortical buttons includes pulling through cortical bone or migration.
112
solates of MRSA that are resistant to erythromycin have been shown to become resistant to clindamycin, a process called inducible resistance, which is conferred by a plasmid that alters the 50S ribosome binding site for both clindamycin and erythromycin.
Because of inducible resistance, a D-Zone test should be requested before ordering CLINDAMYCIN!
113
Common histologic stains
The hematoxylin and eosin stain is used very broadly in standard histology, such as to evaluate for the presence of polymorphonuclear cells in infection or osteomyelitis. Hematoxylin makes nuclei blue and therefore easier to identify. Cartilage and proteoglycan are evaluated well with safranin-O and alcian blue histology stains. The differentiation of osteoclasts, as when attempting to evaluate how briskly remodeling of bone is occurring, could employ tartrate-resistant acidic phosphatase histology staining or cathepsin-K immunostaining. Cell signaling, between parathyroid–hormone-related protein (PTHrP) and indian hedgehog protein in the growth plate has been evaluated by Immunostain for PTHrP.
114
Most common cause of sudden cardiac death
The most common cause of sudden cardiac death independent of the underlying structural or electrical cardiac disorder is abrupt ventricular tachyarrhythmia. The most important factor in defining the probable underlying cardiac condition is the athlete's age. Among athletes 35 years of age and older, coronary artery disease accounts for the vast majority of fatalities. HCM, the most common cause of sudden cardiac death in younger athletes, accounts for 36% of cases, followed by congenital coronary artery anomalies (17%), arrhythmia syndromes (7%), and myocarditis (6%). HCM is an autosomal-dominant condition and can be identified with genetic testing in 60% of patients with a positive family history.
115
what is the most common symptom associated w/ pulmonary embolism?
Dyspnea (shortness of breath)
116
Which nuclear transcription factor is important in tendon and ligament formation?
Scleraxis
| -Scleraxis is a transcription factor for chondrogenesis and a marker for tendon and ligament progenitors.
117
Sclerostin
secreted by osteocytes, inhibits osteoblast function, and increases osteoclastogenesis.
118
osterix
secreted by osteoblasts and is required for the differentiation of preosteoblasts to osteoblasts. It plays a role in cell patterning during limb morphogenesis.
119
CCAAT/enhancer-binding protein (C/EBP)
regulates the differentiation of mesenchymal progenitor cells into adipocytes.
120
which disorder is associated with a loss-of-function mutation in the carbonic anhydrase II gene?
Osteopetrosis
121
What is the dominant contributing factor in intervertebral disk degeneration?
Genetics
-Genetics is increasingly recognized for its predominant role in development of disk disease. Genetics also may play a future role in nonsurgical intervention.
122
innate and adaptive immunity cells
The immune system is divided into innate and adaptive immunity. The innate system consists of epithelial barriers that prevent microbial invasion, nonspecific phagocytes, NK cells, and the complement system. Adaptive immunity occurs in a more delayed fashion after the offending antigens have been processed by the antigen-presenting cells and stimulated T cell and B cell antigen-specific responses. Plasma cells are involved in the adaptive immune response because they represent fully differentiated B cells.
123
In the synthesis of type II collagen, a coenzyme critical to the hydroxylation of lysine and proline is?
- Vitamin C (ascorbic acid)
- Ascorbic acid (vitamin C) plays a role in the hydroxylation of both proline and lysine after these amino acids have been incorporated into the alpha collagen chain. A deficiency in vitamin C can lead to scurvy because of abnormal collagen cross linking.
124
Necrotizing fasciitis that occurs following varicella infection in children most often is caused by what bacteria?
- Group A steptococcus
- Varicella zoster virus infection leads to one of two clinically distinct forms of disease: varicella (chickenpox) and herpes zoster (shingles). Before a vaccine was introduced in 1995, an estimated four million cases occurred per year in the United States, along with nearly 11,000 hospital admissions and 100 deaths annually. In children, chickenpox is generally a mild disease and presents with fever, malaise, pharyngitis, and loss of appetite, followed by the development of a pruritic vesicular rash. Complications, including invasive skin and soft-tissue infections, pneumonia, and encephalitis, occur in around 2% of patients, with skin and soft-tissue infections being most common. Necrotizing fasciitis is an uncommon but devastating complication and is associated with a high mortality rate. Early identification, followed by aggressive surgical debridement and appropriate antibiotic selection is critical. Group A β-hemolytic Streptococcus, most commonly Streptococcus pyogenes, is the most common causative organism, occurring in up to 80% of patients in some series. In fact, between 15% and 30% of invasive group A streptococcal infections are associated with varicella.
125
RANKL
protein that is released by osteoblasts, which bind to RANK on osteoclasts, leading to activation of the osteoclasts.
126
Which protein overexpression resulting from a translocation in a subpopulation of cells within the synovium is associated with pigmented villonodular synovitis (PVNS) or giant cell tumor of the tendon sheath (GCTTS)?
Colony stimulating factor 1 (CSF 1)
127
An activating mutation in the parathyroid hormone (PTH)/PTH related protein receptor would be expected to have what effect on the physis?
Delayed maturation in the zone of hypertrophy
128
ex-fix principles
The application of external fixation always involves a risk-benefit evaluation that includes the key considerations of stability, soft-tissue protection, and the potential forfuture surgery. An external fixation device may be constructed in many ways, but certain principles are to be considered. The ideal construct for stability generally consists of one pin as close to the fracture site as possible and another pin as far away as possible in the same bone. Stability can be enhanced by increasing the pin diameter, the number of pins used, the pin spread, the number of planes of fixation, the diameter of the rods, and the number of rods and by decreasing thebone-to-rod distance. A fixation pin’s weakest point is the thread-shank junction. Burying the shank into the proximal cortex can double the pin’s stiffness. Hydroxyapatite-coated pins have been shown to improve the pin-bone interface and require greater extraction torque. It is thought that excessive motion of muscle and skin around the pin results in local inflammation, leading to pin tract infections. This riskcan be reduced by using a gentle compressive dressing around the pin that serves as a bolster between the skin and the clamp.
129
Multiple hereditary exostoses (MHE)
The average age at diagnosis is 3 years old, and 94% of patients have exostoses about the knee. Other common sites include the proximal humerus, scapula, wrist, and proximal femur. The vast majority of patients display an autosomal dominant inheritance pattern, although spontaneous mutations have been described.
In most patients, the underlying genetic abnormality involves the EXT1 or EXT2 gene, located on chromosomes 8 and 11, respectively. These genes encode glycosyltransferases involved in the synthesis of heparan sulfate. Heparan sulfate plays an important role in physeal signaling (Hurts when Pete Ran because of the exostoses around his knees), and chondrocyte disorganization leads to exostosis development. Chondroitin sulfate, dermatan sulfate, and keratan sulfate are other proteoglycans, but they are not involved in the pathogenesis of HME.
The lifetime risk of malignant transformation to chondrosarcoma in patients with HME has been reported to range between 1% and 25%; however, more recent studies have placed the risk between between 3% and 7%. The most recent study demonstrated a 3% risk of malignant transformation at an average age of 29 years. Malignant transformation can occur in an exostosis in any location; however, pelvic exostoses have been shown to have a higher rate of malignant transformation.
The risk of malignant transformation has been noted to be higher in disorders involving multiple enchondromas, including Mafucci syndrome and Ollier disease. Some studies have demonstrated a nearly 100% risk of malignant transformation in Mafucci syndrome.
130
Achondroplasia is caused by a mutation in the gene encoding for fibroblast growth factor receptor 3 (FGFR3). This genetic mutation leads to
GAIN OF FUNCTION of FGFR3 (turned on)
131
The most widely accepted scoring system used to evaluate generalized joint hypermobility is the Beighton-Horan scale. Under this scoring system, 5 criteria are evaluated for a total maximum score of
9
132
Which portion of the cortical bone of a long bone is vascularized by nutrient arteries?
60%
133
Calcitonin's mechanism of action is?
inhibition of sclerostin formation and inhibition of osteoclast apoptosis
-Parathyroid hormone acts on osteoblasts and osteocytes, inducing sclerostin secretion and RANKL by osteocytes and stimulating RANKL secretion by osteoblasts. Intermittent parathyroid hormone prolongs osteoblast survival and causes a decrease in serum sclerostin. Calcitonin inhibits sclerostin formation and inhibits osteoclast apoptosis.
134
Intramedullary nailing of a 12-year-old boy's midshaft femur fracture, with a starting point in the piriformis fossa, is associated with disruption of which structure?
-deep branch of the medial femoral circumflex artery
135
How does the proteoglycan content of the nucleus pulposus intervertebral disk change from the newborn period into adolescence?
- chondroitin sulfate DECREASES and keratan sulfate INCREASES with age
- The intervertebral disk is made up of a nucleus pulposus and an anulus fibrosus. The dry weight of the nucleus pulposus of the intervertebral disk consists mostly of collagen and proteoglycans. After birth, the side chains of the aggrecans are made mostly of chondroitin sulfate, which gradually is replaced by keratan sulfate with age.
136
Pacinian corpuscles
convey deep pressure and vibration sensation
137
Golgi organs
relay muscle length and tension proprioception
138
Ruffini endings
convey sustained pressure sensation
139
Merkel cells
convey sustained touch and pressure sensation
140
Free nerve endings and nociceptors
convey pain sensation
141
Intranasal medication indicated for woman with osteoporosis who have failed other treatments
Calcitonin (Miacalcin)
-Calcitonin is a naturally occurring hormone that is produced by the thyroid. It inhibits osteoclastic activity. When used a medication, it is administered as an intranasal spray. It is generally not used as primary therapy, but is indicated when other options have failed.
142
Teriparatide (Forteo)
Teriparatide is a recombinant form of parathyroid hormone. It is the only anabolic osteoporosis treatment, meaning that it stimulates osteoblasts to form new bone rather than prevent osteoclastic resorption. It is administered as a daily injection for 2 years. It should be avoided in patients with cancer risk, especially osteosarcoma, or in patients with Paget disease.
143
Oncogenic osteomalacia
Laboratory data show hypophosphatemia and low 1,25 hydroxy vitamin D levels. Oncogenic osteomalacia is seen in association with mesenchymal tumors, especially osteoblastoma, fibrous dysplasia, and fibromas. Osteomalacia is caused by the overactivity of FGF23, which decreases phosphate reabsorption in the kidneys, causing hypophosphatemia. It also inhibits the activity of 1 alpha hydroxylase (responsible for converting 25 hydroxy vitamin D to 1,25 hydroxy vitamin D), causing decreased levels of 1,25 hydroxy vitamin D.
144
FGFR 3 activating mutation
causes achondroplasia
145
TGF-b excess
seen in Marfan syndrome
146
FGF23 excess
seen in oncogenic osteomalacia
147
t test (independent or paired)
compares the means of a variable from two groups
148
paired t test
compares the means of the same group at two different times
149
ANOVA
compares the means of 3 or more groups
150
chi-square test
compares nominal or categorical data (eg # of correct responses, # of infections, fusion or nonfusion, etc.)
151
Pearson correlation
should be used only when there is a linear relationship between variables. It can be a positive or negative relationship, as long as it is significant. Correlation is used for testing in Within Groups studies.
- correlation is a technique for investigating the relationship between two quantitative, continuous variables, for example, age and blood pressure.
- Pearson's correlation coefficient is a measure of the strength of the association between the two variables
152
What is the predominant function of aggrecan in articular cartilage?
- exerts swelling pressure against the restraint of collagen
- Aggrecan has an avidity to water of up to 50 times its weight, which keeps the scaffold of collagen and other matrix molecules inflated. This provides the cartilage with the capability to dispense contact forces evenly to the underlying bone. The control of collagen fiber orientation relies on matrix homeostasis and mechanical forces. Decorin is a major controller of collagen fibril size. Osmotic effect is influenced by ion concentration relative to water and aggrecan. Type VI collagen plays a major role in mechanical signaling to chondrocytes.
153
Fischer exact test
-compares categorical data (fusion or nonfusion, etc) in smaller distinct numbers
154
T tests
-compare continuous data, unpaired for different individuals and paired for matched samples
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chi-square test
compares categorical data in larger formats (as compared to Fischer exact test which compares categorical data in smaller distinct numbers)
156
During the course of intervertebral disk degeneration and enzymatic degradation, the molecular release that plays a predominant role in disk degeneration is
Fibronectin fragmentation
-Fibronectin, along with decorin and biglycan, are glycoproteins associated with matrix assembly and regulation of collagen fibril size. During early disk degeneration, fibronectin is cleaved and fragments are known to be associated with progression of disk degeneration.
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when do peak concentrations of BMP-2 and VEGF occur and then return to baseline when using the induced-membrane technique of Masquelet?
Peak concentration at 4 wks and returns to baseline by 6 months
158
Postnatal skeletal linear growth occurs most rapidly during
First year of life
159
Which percentage of boys sustain a fracture before age 16?
40 to 60%
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Scleraxis
transcription factor for chondrogenesis and a marker for tendon and ligament progenitors
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Sclerostin
secreted by osteocytes, inhibits OSTEOBLAST function and increases osteoclastogenesis
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Osterix
secreted by osteoblasts and is required for differentiation of preosteoblasts to osteoblasts. Plays a role in cell patterning during limb morphogenesis
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C/EBP
regulates the differentiation of mesenchymal progenitor cells into adipocytes
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Twist 1
cell differentiation factor of early morphogenesis
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A very important secondary function of osteoblasts is the direct regulation of hematopoietic cells and the immune response. This interaction occurs through
- the Jagged1-Notch pathway
- Osteoblasts directly regulate the hematopoietic stem cell population. This interaction occurs in part with PTH. PTH induces a membrane-bound protein Jagged 1 on osteoblasts. Jagged 1 then stimulates Notch receptors on the membrane of hematopoietic stem cells, which results in cell proliferation. In this manner, osteoblasts influence the development of immune cells.
- Think of osteoblasts creating the "jagged ones" that kill everything in their path
166
The tissue enveloping a tendon that transmits neurovascular elements along the tendon is the
- Endotenon
- The paratenon is the most superficial layer of connective tissue enveloping a tendon. The epitenon is a single-cell synovial layer that is continuous with the paratenon superficially, and the endotenon deep. The endotenon is the closest layer to the tendon, carrying the neurovascular elements along the tendon. Vinculae are found along the flexor tendons as discrete structures, and carry nutrient vessels.
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chromosomal translocation associated w/ synovial sarcoma?
t(X;18)
- SYT-SSX1,2, or 4 fusion protein
- stains positive for VIMENTIN, EPITHELIAL MEMBRANE ANTIGEN, S-100, and KERATIN
168
Commonly used to produce orthopaedic implants, 316L stainless steel is an alloy of what elements?
Iron, carbon, chromium, nickel, molybdenum, manganese
-Iron makes up the bulk of stainless steel, and carbon is limited to less than 0.03% to limit intragranular corrosion. Chromium increases hardness and corrosion resistance. Likewise, nickel and molybdenum help prevent corrosion
169
what is cobalt chrome alloy composed of ?
commonly used in spinal implants, is composed of cobalt, chromium, and molybdenum.
170
what is Titanium alloy (Ti6Al4V) composed of ?
titanium, aluminum, vanadium, iron, oxygen
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Scoliosis is a three-dimensional deformity of the spine that is multifactorial in etiology. Halting progression by achieving fusion is the primary aim of surgical intervention, but safe correction with instrumentation maneuvers aims to improve each of the planes of deformity. Rod rotation at the apex assists in coronal translation. Distraction and compression affect both the coronal and sagittal planes. Direct vertebral rotation maneuvers address vertebral rotation.
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Which immune cell type is involved in metal allergy associated with orthopaedic implants?
T lymphocytes
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In what zone of the articular cartilage are the chondrocytes arranged in columns and the collagen fibers oriented vertical to the articular surface?
Deep zone
-Four zones are identified in the articular cartilage. In the superficial zone, the chondrocytes are elongated, and the collagen fibers are oriented parallel to the articular surface. In the middle zone or transitional zone, chondrocytes and collagen fibers are oriented randomly. In the deep aone, the chondrocytes are arranged in columns, and the collagen fibers are oriented vertical to the articular cartilage. The calcified zone is the transitional zone between the cartilage and the subchondral bone.
174
What is a major difference between thrombogenesis following orthopaedic surgery and the same issue after chest or abdominal surgery?
Decrease in antithrombin III (the target of unfractionated heparin)
175
What is the most likely cause of a pseudotumor in a well-positioned total hip arthroplasty?
Fretting and corrosion reaction from the taper
176
What is the main function of lubricin in synovial joints?
Reduces the coefficient of friction in the joint
- Lubricin reduces the friction between the surfaces in the joint, leading to decreased shear forces going through the hyaline cartilage. It is a glycoprotein that is produced by the chondrocytes in the superficial zone and is not a primary component of the extracellular matrix. A lack of lubricin has been associated with syndromes causing arthritic changes at an early age.
- Lubricin lubricates!
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What is the principal cause of age-related increase in articular cartilage brittleness?
Increase in advanced glycation end products
-There is a gradual passive covalent bonding of sugars to collagen over time. This process results in advanced glycation end products and is responsible for the yellowish appearance of cartilage in older people.
178
What is a major controlling molecule for tendon collagen fiber size?
Decorin
-Decorin is influential in collagen fiber size for tendon formation and repair after injury. Elastin is associated with tendon crimp. Fibrillin is associated with elastin deposition. Fibronectin has roles in cell adhesion, growth, cell migration, and development. Biglycan is important in initial tendon development, but not fibrillar control.
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The reporting of domestic violence injuries by treating physicians remains a controversial topic. In the setting of possible spousal abuse, the medical staff is not legally required to report abuse in most states (this is not the case in scenarios involving possible child abuse, however). Legal immunity that is granted to a reporting agent in the case of suspected child abuse is not provided in cases of suspected spousal abuse. The physician should encourage self-protection and may introduce a social worker if the patientis interested in this course of action. If the patient is not willing to pursue the matter, there is little the physician can do to intervene on his or her behalf.
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180
What is a primary manifestation of cerebral palsy?
Abnormal muscle tone
181
Compared with intrinsic tendon repair mechanisms for intrasubstance intrasynovial flexion tendon tears, extrinsic tendon repair mechanisms have what effects on the speed of healing and adhesion formation?
Faster healing and increased adhesion formation
-Intrasynovial tendons are those enclosed within a synovial sheath. Intrinsic repair mechanisms describe the healing processes that rely on the proliferation and migration of cells within the injured tendon itself to help bridge the injury. In extrinsic healing mechanisms, cells from the surrounding tissue outside the tendon invade the damaged area. Extrinsic healing can represent a substantial part of the overall healing response and is faster than intrinsic healing for intrasynovial flexor tendons. Extrinsic healing results in adhesion formation between the tendon and the surrounding tissue, however.
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Sheathed tendons receive their blood supply from
Vincula
-Remember that unsheathed tendons are paratenon-covered and examples of sheathed tendons are the flexor tendons in the hand, which are supplied by vincula
183
elution characteristics of antibiotic cement
The elution characteristics often vary by cement type, but generally, peak concentrations are reached in 24 hours, and the concentrations can remain bactericidal for 4 months.
184
Which assay is commonly used to identify a genetic mutation at the DNA level?
Standard PCR
-Standard PCR is used to detect specific genes or genetic mutations at the DNA level by targeting a particular DNA sequence. RT-PCR and northern blot are used to detect specific gene expression at the RNA level. Western blot is used to determine protein expression levels after translation from RNA.
185
What is the dominant contributing factor in intervertebral disk degeneration?
Genetics
186
What is the inheritance pattern of Duchenne muscular dystrophy?
X-linked RECESSIVE
