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Basic Science Flashcards

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1
Q

What are canaliculi within bone?

A

System within the lacunar network used by osteocytes to communicate with each other.

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2
Q

What are Haversian canals?

A

Found in the center of an osteon in compact bone. They contain blood vessels and nerves.

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3
Q

What are Volkmann canals?

A

They run perpendicular to Haversian canals and connect them to each other.

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4
Q

Mechanism of Rituximab?

A

Monoclonal antibody to CD20 antigen (inhibits b cells) Used in Rheumatoid patients who are intolerant to methotrexate or DMARDs

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5
Q

Mechanism of Etanercept?

A

TNF alpha antagonist Tumor necrosis factor receptor immunoglobulin G fusion protein.

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6
Q

What is the mechanism of Methotrexate?

A

folic acid analogue Binds to dihydrofolate reductase and prevents synthesis of tetrahydrofolate. Usually first line treatment for Rheumatoid.

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7
Q

True or false chlorhexidine gluconate wash the night before surgery decreases surgical site infection?

A

False.

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8
Q

What bacteria is of concern with soil contamination? What abx coverage should be added?

A

Clostridia botulinum (anaerobic gram positive bacilli) High dose penicillin

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9
Q

What are the zones of the physis?

A
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10
Q

What zone of the physis do Salter-Harris fractures occur through?

A

Hypertrophic zone. Specifically the Zone of calcification within the hypertrophic zone.

Hypertrophic zone can be subdivided into zones of maturation, degeneration, and calcification.

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11
Q

Mechanism of acetominophen?

A

inhibits prostaglandin E2 production through interleukin-1 beta.

exerts its effects on the central nervous system.

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12
Q

What is the mechanism of fluoroquinolones?

A

inhibition of DNA gyrase.

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13
Q

What is released from cells within a joint that causes articular surface damage in septic arthrits?

A

proteolytic enzymes

such as matrix metalloproteinases(MMP)

Have also been implicates in rheumatoid and osteoarthritis.

Toll like receptors such as TRL-2 activate NF-kB pathway that leads to production of MMPs.

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14
Q

What is the most common cause of septic arthritis in adolescents?

A

Neisseria gonorrhoeae

Gram negative diplococci.

Patients usually have preceding migratory polyarthralgia, multiple joints involved, and small red papules.

Gram stain is negative over 50% of the time.

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15
Q

What will you see on histology from the tissue surrounding a metal on metal hip that has Delayed Type Hypersensitivity?

A

diffuse infiltrates of both T and B lymphocytes.

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16
Q

What is the function of Osteoprotegrin?

A

Limits the activity of RANKL.

This promotes osteoblast activity and increases bone formation.

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17
Q

What is Osteonectin?

A

Secreted by platelets and osteoblasts and functions to regulate calcium and organzing mineral in the bone matrix.

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18
Q

What affect do Bone morphogenic proteins have on inervertebral disk cells and matrix synthesis?

A

Increase chondrogenic phenotype expression

Increase matrix syntheis.

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19
Q

What causes tumoral calcinosis?

What is the main laboratory abnormaility?

What gentic abnormality is most common?

A

pathologic deposition of calcium adjacent to joints and occurs in the presence of phosphate dysregulation.

Hyperphosphatemia

FGF-23

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20
Q

Defect in isocitrate dehydrogenase 1 can cause what syndrome?

A

Maffucci’s syndrome

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21
Q

Deficiency in alpha-1 hydroxylase can lead to?

A

Hypovitaminosis D.

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22
Q

Genetic defect in Activin A receptor type 1 has been linked to?

A

Fibrodysplasia ossificans progressiva.

Abnormal ossification of connective tissue at a young age.

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23
Q

What is the function of Linezolid?

A

prevents the formation of the initiation complex between the 30S and 50S subunits of the ribosome.

Unique in that it disrupts protein synthesis at its origin.

Binds to the 50s subunit of the bacterial ribosome preventing the formation of the initiation complex.

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24
Q

Describe the mechanism of action of the following antibiotics?

Lenezolid

Aminoglycosides

Macrolides

Tetracycline

Chloramphenicol

A
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25
What is the inheritance pattern of neurofibromatosis? What embryonic structure is it a disorder of? What is the mutation of?
autosomal dominant. neural crest. Mutated neurofibromin(NF1) gene on chromosome 17q21.
26
What is the most common genetic disorder caused by a new mutation of a single gene?
Neurofibromatosis type I
27
On a histology slide how do you differentiate acute vs chronic osteomyelitis?
Acute has live osteocytes(have nuclei) and neutrophils. Chronic has no nuclei in the osteocytes and lymphocytes. Also has fibrosis of marrow.
28
What gene mutation is associated with congenital vertical talus?
HOXD10 gene mutation | (transcription factor)
29
What should be on your differential for congenital vertical talus? How can you tell the difference between the two?
Oblique talus the talonavicular subluxation reduces with forced plantarflexion of the foot. Treatment is observation and shoe inserts. Only some will require pinning.
30
What two characteristic physical exam findings are found in congenital vertical talus?
rigid rockerbottom deformity prominent talar head.
31
What is a normal talocalcaneal angle?
20-40 degrees \> 40 is associated iwth congenital vertical talus. Olbique talus will reduces with forced dorsiflexion.
32
Do you need an MRI for congenital vertical talus?
Yes! Not for the foot but neuraxial imaging should be perfomred to rule out neurologic disorders.
33
Treatment for a congenital vertical talus? When?
Serial manipulation can be performed but this is just pre-operative. Still require surgery. Done to stretch dorsolateral soft tissue stuctures. Foot placed in inversion and plantarflexion. Treatment should be performed as early as possible(6-12 months). Surgical release, reduction, and pinning: Plantar release, lengthening of peroneals, achilles, and toe extensors. Tib ant transfer to talar neck.
34
What do you do for a 12 year old with a missed vertical talus?
triple arthrodesis
35
What do you after excision of an accessory navicular with the tenond that is relfected?
Do not advance the posterior tibial tendon. Increases downtime and morbidity.
36
What is a calcaneovalgus foot?
benign soft tissue contracture deformity characterized by hindfoot eversion and dorsiflexion. Not a congential deformity or dislocation. Passiviely correctable. One way you differentiate it from vertical talus. typically resolves spontaneously by 3-6 months. Can do passive stretching exercises.
37
What is the most common associated condition with calcaneovlagus foot? What is the most common surgery needed?
Posteromedial tibial bowing. Most have a LLD. Some will need a surgery to address the LLD.
38
What transcription factor has been associated with clubfoot?
PITX1 Critical for limb development.
39
What is the mechanism of botulinum toxin A?
Competitive inhibitor of presynaptic cholinergic receptors. Finite lifetime, usually does not last longer than 2-3 months. Helpful in dynamic contractures, little benefit in static contractures.
40
What is the mechanism of Baclofen?
Not clearly understood. Thought to act as a GABA agonist. Intra-thecal administration is preferred to avoid the cognitive impairment of oral administration. Usually only used for wheelchair bound children with CP.
41
When are contracture releases or tendon transfers most commonly performed in children with CP?
3-5 years. Have spasticity but also voluntary muscle control.
42
What disease occurs from a repeat mutation that leads to lack of the frataxin gene? How is it inherited?
Friedreich's Ataxia Autosomal recessive Frataxin is a mitochondrial protein involved in iron metabolism and oxidative stress. Usually wheelchair bound by age 30. Die by age 50 from cardiopmyopathy.
43
What is the mutation that leads to Marfan Syndrome? How is it inherited?
Fibrillin-1 (FBN1) gene Autosomal dominant Sporadic mutation can occur in up to 30%
44
What mutations are linked to Larsen's Syndrome?
Filamin B for autosomal dominant Carbohydrate sulfotransferase 3 deficiency for autosomal recessive.
45
What gene mutation leads to spinal muscular atrophy?
survival motor neuron gene (SMN) Lack SMN-1 protein with severity of disease based on number of functional copies of SMN-II SMN critical to RNA metabolism and is a mediator of apoptosis. A telomeric gene deletion.
46
What does mutation in the androgen receptor gene on chromosome X lead to?
Spinobulbar muscular atrophy. Trinucleotide CAG expansion.
47
What is the inheritance pattern of Duchenne Muscular Dystrophy?
X-linked recessive.
48
What are the orthopaedic manifestations of DMD?
Calf pseudohypertrophy Scoliosis Equinovarus foot deformity Joint contractures.
49
What are the non-orthopaedic manifestations of DMD?
Cardiomyopathy Static encephalopathy
50
How is Becker's Muscular Dystrophy Similar to Duchenne's? How does it differ?
Sex-linked, calf pseudohypertrophy, and CPK is elevated. Dystrophin protein is decreased instead of absent, Later onset with slower progression. More prone to cadiomyopathy. Average ate at diagnosis of BMD is 8 years Average age at diagnosis with DMD is 2 years.
51
What is the prognosis of Duchenne's?
Most unable to ambulate independently by age 10 Most are wheelchair bound by age 15 Most die of cardiorespiratory problems by age 20
52
What is a gower's sign?
In DMD a child rises by walking hands up legs to compensate for gluteus maximus and quadriceps weakness.
53
What Lab is markedly elevated in DMD? How much?
CPK 10-200x normal
54
What will a muscle biopsy show in DMD?
connective tissue infiltration and foci of necrosis. Absent dystrophin with staining.
55
What is the most common skeletal dysplasia?
Achondroplasia
56
What mutation leads to Achondroplasia? What is the inheritance pattern?
G380 mutation of **FGFR3** (fibroblast growth factor receptor 3, on chromosome 4P) **80% is a sporadic mutation then autosomal dominant.** Gain of function mutation that increases inhibition of chondrocyte proliferation in the proliferative zone of the physis Results in defect in endochondral bone formation. It is a quantitative cartilage defect.
57
What zone of the physis is involved in Achondroplasia?
Proliferative zone.
58
What mutation is associated with multiple epiphyseal dysplasia? What is the inheritance?
Most common and most severe is COMP gene. Can also have COL9A1, COL9A2, COL9A3, Matrillin 3, and SLC26A2 (diastrophic dysplasia sulfate transporter gene. Halp of patients with clinical diagnosis of MED do not have the typical genetic mutations. Autosomal dominant most common. The SLC26A2 mutation is autosomal recessive. Will present with at least one of the following: Clubfoot, cleft palate, clinodactyly(abnormal curvature of the small finger).
59
What is the mutation and inheritance of diastrophic dysplasia?
DTDST gene (SLC26A2) on Chromosome 5 **Encodes for a sulfate transporter protein.** Leads to undersulfation of cartilage proteoglycan.
60
What is the mutation that leads to cleidocranial dysplasia? What is the inheritance pattern?
RUNX2/CBFA1 mutation-transcription factor which regulates osteoblastic differentiation Autosomal dominant
61
What is the most common lysosomal enzyme malfunction syndrome?
Morquio syndrome
62
What is the pathophysiology of lysosomal storage disorders?
Incomplete gylcosaminoglycan breakdown products (mucopolysaccharides accumulating and causing dysfunction in various organs.
63
What are the CRTAP and LEPRE1 genes associated with?
Severe, lethal forms of OI not associated with primary structural defect of type I collagen.
64
What is the difference between the AD and AR forms of Osteogenesis Imperfecta?
AD forms (Types I and IV) are milder. AR forms (Types II and III) are more severe
65
What is the result of COL 1A1 and COL 1A2 gene mutations?
Osteogenisis Imperfecta Causes abnormal collagen corss-linking via a glycine substitution in the procollage molecule.
66
What is different about Type V, VI, and VII Osteogenesis Imperfecta?
They have abnormal bone on microscopy and similar phenotype but **no Type I collage mutation.**
67
What is the structure of Type I collagen?
Triple Helix structure- possible because of glycine at every 3rd amino acid residue. Two alpha-1 chains coded by genes COL1A1 One alpha-2 chain coded by gene COL1A2
68
What will you see on histology slides for Osteogenesis Imperfecta?
Increased diameter of haversion canals and osteocyte lacunae replicated cement lines Increased number of osteoblasts and osteoclasts decreased number of trabeculae decreased cortical thickness.
69
What is the most common pattern of inheritance for osteopetrosis?
benign autosomal dominant. Also malignant autosomal recessive and intermediate autosomal recessive forms. May skip generations. 75% gene penetrance.
70
What is Albers-Schonderg disease?
autosomal dominant osteopetrosis Type II. Anemia, pathologic fractures, and premature osteoarthritis.
71
What is a risk factor for having a child with down syndrome?
Advanced maternal age. 1 in 250 in mother \> 35 years.
72
What genetic mutation is associated with Trisomy 21?
COL6A1 and COL6A2 which code for Type VI Collagen. Component of skeletal muscle extracellular matrix Contributes to generalized joint laxity.
73
What HLA markers are associated with JIA?
DR4 with polyarticular DR8, DR5, and DR2. Associated with pauciarticular
74
What percent of JIA patients are RF seropositive?
\<15%
75
What is the classical form of Ehler's Danlos syndrome? What mutation? What inheritance pattern?
Type 1 and Type II Hyperextensible skin, widened atrophic scars, and joint hypermobility. COL5A1 or COL5A2 mutation. Type V collage Autosomal dominant.
76
What factor is decreased or absent in Hemophilia A?
Factor VIII
77
What factor is decreased or absent in Hemophilia B?
Factor IX. Less common for.
78
How is Hemophilia inherited?
X-linked recessive. Typically affects males only. Ther is a rare form with a autoimmune etiology with no genetic inheritence.
79
What is a Bethesda Assay used for?
Measures the amount of factor VIII or IX antibody in the blood \<5 BU = low levels \> 5 BU = high levels
80
What labs findings are seen in a patient with hemophilia?
PTT prolonged with PT normal LFTs normal
81
What is the signifigance of IgG antibodies to clotting factor proteins being present in a patient with Hemophilia?
Inhibits the response of therapeutic factor replacement. Present in 4-20% of patients Relative contraindication fur surgery.
82
What factor levels would you watn in a hemophiliac patient with the following issues: Acute hematomas? Aute hemarthrosis and soft tissue surgery? Skeletal surgery?
Increase levels to 30% Increase levels to 40-50% Increae levels to 100% for the first week following surgery and then maintian \> 50% for the second week.
83
What is responsbile for the major source of nutrition to the physis?
Perichondrial artery.
84
Mutations in DMPK and CNBP gene are responsible for what disease process?
Myotonic dystrophy
85
A mutation of what gene leads to absence of the dystrophin protein? What disease process does this lead to?
Xp21 Gene Duchenne's Muscular dystrophy
86
What is the percent chance of septic arthritis based on 0,1,2,3, or all 4 of Kocher's Criteria?
.2% 3% 40% 93. 1% 99. 6% Criteria are ability to bear weight, fever \>101.3 or 38.5, WBC \>12, and ESR \>40
87
In what patients are capnocytophaga canimorsus infections seen?
Dog bites Rare, but potentially fatal in splenectomy patients Mortality rate of 30-60% in immunocompromised Causes cellulitis, sepsis, endocarditis, meningitis, DIC, ARDS, and death.
88
What is the first line antibiotic for Pasteurella multocida?
Amoxicillin/clavulanic acid Commercial name is Augmentin
89
What condition is associated with HLA-B8
DISH
90
What percent nerve elongation will diminish a nerve's microcirculation? What percent will disrupt axons?
8% 15%
91
What 25-hydroxy vitamin D level is considered to be deficient?
\<20ng/ml
92
What secretes Stromelysin and plasmin?
Both are metalloproteinases that are secredted by chondrocytes and have degradative action against cartilage.
93
What role does sclerostin play in bone metabolism?
Inhibits the WNT pathway and leads to decreased bone mass.
94
What is the function of Peroxisome proliferator-activated receptor gamma (PPARG)
Regulator of mesenchymal progenitor cells that induces adipocyte formation.
95
Osteoarthritis and formation of osteophytes is thought to be mediated by the differentiation of quiescent chondrocytes through what signaling pathway?
Indian hedgehog (Ihh)
96
What medication works by binding to and enhancing the ability of antithrombin III?
Unfractionated heparin works by promoting the ability of antithrombin III to inhibit factors IIa, III, and Xa. Risks are bleeding and heparing induced thrombocytopenia (HIT). The reversal agent is protamine sulfate.
97
What does the picture demonstrate?
The D-test. This should be performed when erythromycin-resistant MRSA is identified as a pathogen and clindamycin is being considered as the antibiotic to be used. Inducible clindamycin resistance can occur. It theh pathogen is an inducible strain a zone of inhibition in the shape of the letter D will occur. This is considered a positive test.
98
What is a CAMP test?
Used to identify group B Beta-hemolytic streptococci
99
What is an Etest?
used to determine the MIC(minimum inhibitory concentration and whether or not a specific strain of bacteriurm is susceptible to the action of a specific antibiotic.
100
what disease is associated with a mutation in the GNAS gene?
Fibrous dysplasia
101
What is Metabolic Syndrome?
Collectio of medical comorbidities that are known to be risk fractors for developing cardiovascular disease. Increased risk of knee pain and OA with these patients. **Includes:** Central obesity, dyslipidemia, HTN, and elevated fasting glucose levels.
102
What are the differences between Aging and Osteoarthritis in articular cartilage for categories listed in the image?
103
What does an increased adductor moment during gait lead to progression of what disease process within the limb?
Increased adductor moment during gait is associated with progression of knee osteoarthritis Increased medial compartment pressures.
104
What are the four types of Gell-Coombs Reactions?
Type I- Allergic (Anaphylaxis) Type II- Cytotoxic, antibody dependent. Ex Grave's Disease or hemolytic anemia Type III- Immune complex diseases such as serums ickness or SLE Type IV- delayed type
105
What does Sclerostin do?
Direct antagonist of the WntB-catenin pathway and thus a key regulator of the formation of mineralized bone matrix and bone mass. Anti sclerostin antiboides result in inactivation of sclerostin, therby promoting the anabolic Wnt/B-catenin pathway and resulting in increased bone density.
106
What factor stimulates differentiation and proliferation of myofibroblasts?
TGF-beta- leads to production of scar tissue. Muscle regeneration occurs 7-10 days after injury. **Facilitated by IGF-1, FGF, and NGF.**
107
What is the function of tobramycin
It is an aminoglycoside. Disrupts protein synthesis through irreversibly binding to 30S ribosomal subunit. Leads to altered cell membrane permeability, disruption of the cell envelope, and eventual cell death.
108
What is the inheritance of amniotic band syndrome?
Sporadic
109
What is Anakinra used for? What is its mechanism?
Disease-modifying antirheumatic drug. Interleukin IL-1 receptor antagonist that blocks the binding of IL-1 to its cell membrane Prevents this pro-inflammatory cascade.
110
What is the mechanism of tranexamic acid?
Antifibrinolytic that prevents the activation of plasmin from the inactive zymogen plasminogen. Plasmin breaks down fibrin which is factor Ia.
111
Common X-Linked disorders include?
Hemophilia A Duchenne muscular dystrophy Becker's muscular dystrophy Hunter's sundrome Spondyloepiphyseal dysplasia (SED) tarda
112
What cellular structures are increased in bone cells relative to other cells?
Endoplasmic reticulum, Golgi apparatus, and mitochondira. Allows for synthesis and secretion of bone matrix.
113
What is the most specific marker for osteoblasts?
Osteoclacin
114
What is Cbfa1(core binding factor alpha-1)/Runx2?
key transcription factor associated with osteoblast differentiation
115
What factors are involved in osteoblastic differentiation?
BMP- stimulates mesenchymal cells to become osteoprogenitor cells. cbf alpha 1: RUNX2 Stable beta-catenin PDGF IDGF
116
What effect does estrogen have on bone production?
inhibits bone resorption and stimulates bone production by inhibiting adenyly cyclase.
117
What effect to glucocorticoids have on osteoblas bone production?
inhibit collage and bone matrix production.
118
What role does 1,25 dihydroxyvitamin D have in bone production.
Involved in osteoblast bone production. Stimulates matrix and alkaline phosphatase synthesis Production of bone specific proteins (Osteocalcin)
119
What do osteoblasts secrete than inhibits osteoclasts?
Osteoprotegrin (OPG) OPG binds to RANKL on osteoblasts, preventing RANK activation
120
What activates the Jagged1-Notch pathway on osteoblasts? What does this pathway regulate?
Parathyroid hormone Hematopoietic stem cells
121
What is the origin of osteoclasts?
originate from myeloid hematopoietic cells from monocyte/macrophage cell lineage. monocyte progenitors fuse together to form mature multinuclear cells. -\> multinucleated giant cells
122
What is tartrate resistant acid phosphate?
Secreted by osteoclasts to lower the Ph (utilizing carbonic anhydrase) and increases the solubility of hydroxyapatite crystals
123
What role does Cathepsin K play in bone regulation?
major proteolytic enxyme that digests organic matrix at ruffled border.
124
In simple terms what is the mechanism of bisphosphonates?
Prevents osteoclasts from formin ruffled border and producing acid hydrolases
125
At what zone does the osteoclast attach to the bone matrix?
Sealing zone Attach via integrins (avB3, a2B1, avB1) they are receptros for **vitronectin** that is found on the bone surface. Arg-Gly-Asp (RGD) sequence allows extracellular bone proteins to bind directly to integrins.
126
What signaling factors activate osteoclasts? Inhibit?
RANKL and IL-1 Calcitonin and IL-10
127
Is there a difference between mineralized bone matrix degradation and organic bone matrix degradation by osteoclasts?
Yes Hydroxyapatite crystals dissolved by HCL secreted through ruffled border into resorption lacuna for Mineralized matrix. Lysosomal cysteine proteinases, MMPs, and Cathepsin K for organic bone matrix degradation
128
What determines the function of osteoprogenitor cells?
Environment: Low strain and high oxygen tension = osteoblasts Intermediate strain and low oxygen tension = cartilage High strain = fibrous tissue
129
What is responsible for tensile strength in bone?
Collagen 40% of bone is organic and 90% of that is Type I collage triple helix composed of one alpha-2 and two alpha-1 chains.
130
What is responsible for the compressive strength of bone.
Proteoglycans (organic) Composes of glycosaminoglycan-protein complexes. Calcium hydroxyapatite (inorganic)
131
What is the inorganic component in bone?
Calcium hydroxyapatite (Ca10(PO4)6(OH)2- provides compressive strength Osteocalcium phosphate brushite
132
What are the three main types of proteins involved in bone matrix?
**Osteoclacin**: Most abundant non-collagenous protein (10-20% of total). Produced by mature osteoblasts. Promotes mineralization and formation of bone. Marker of bone turnover. Can be measured in serum or urine. **Osteonectin:** secreted by platelets and osteoblasts. Believed to have a role in regulating calcium or oganizing mineral in matrix. **Osteopontin:** Cell binding protein
133
What is the blood supply to long bones?
Nutrient artery system Metaphyseal-epiphyseal system Periosteal system Bone receives 5-10% of cardiac output
134
What system supplies the major blood supply to a long bone? What about when it is immature?
Nutrient artery system. Supplies the inner 2/3 of mature bone via the haversion system. Immature bone recieves the majority from the periosteal system. Flow is centripetal (outside to inside)
135
How does direction of predominate blood flow differ within a bone for the following: Arterial Venous Mature Immature Fracture
centrifugal (inside to outside) Centripetal (outside to inside) Centrifugal Centripetal Centripetal. Nutrient artery system is disrupted and periosteal system predominates.
136
What predominately stimulates osteoclast in a normal process? Pathologic process?
RANKL PTH (such as metastatic disease)
137
What is osteoprotegrin?
decoy receptor produced by osteoblasts and stromal cells that binds to and sequesters RANKL.
138
What molecules inhibit Osteoclasts?
Osteoprotegerin Calcitonin Estrogen- decrease in RANKL TGF-beta IL-10
139
What molecules stimulate bone resportion?
RANKL PTH IL-1- stimulates osteoclast differentiation 1,25 dihydroxy vitamin D Prostaglandin E2- activates adenylyl cyclase and stimulates resorption IL-6 (myeloma) MIP-1A (myeloma)
140
When does peak mone mass occur? What population has greater bone mass?
For the hip between ages 16 and 25. Greater in men and African Americans.
141
What is the rate of bone loss after skeletal maturity in adults? Women after menopause?
.3-.5% per year 2-3% per year for untreated woemn during the 6th-10th years after menopause
142
What are the dietary requirements for calcium: Lactating women. Pregnant women, postmenopausal women, and patients with a healing bone fracture. Adolescents and young adults Adults Children
2000 mg/day 1500 mg/day 1300 mg/day 750 mg/day 600 mg/day
143
What is the mechanism of PTH in: Bone? Kidney? Intestine?
**Bone-** Stimulates osteoblasts to secrete IL-6, IL-1, and other cytokines to activate osteoclasts and increase resorption of bone. Increases osteblast production of M-CSF and RANKL which increases number of osteoclasts. Osteoclasts do no express receptor for PTH. **Kidney-** Stimulates enzymatic conversion of 25-OH-vitamin D3 to 1,25-(OH)2-vitamin D3 (active hormone form) which: increases resoprtion of Ca++ in kidney (increasing serum Ca++). Increases excretion of PO4- from kidney (decreasing serum phosphate) **Intestine-** No direct action. Indirectly increase Ca++ absorption by activating 1,25-(OH)2-vitamin D3
144
What can recombinant calcitonin be used to treat?
Paget disease Osteoporosis Hypercalcemia
145
What kind of tumors secret calcitonin?
medullary thyroid tumors and multiple endocrine neoplasia type II tumors.
146
What is the origin and function of calcitonin?
Produced by clear cells in the parafollicles of the thyroid gland (C cells) inhibit the number and activity of osteoclasts. Osteoclasts have a receptor for calcitonin.
147
What has to happen before the ingested form of vitamin D is the active metabolite?
two hydroxylations in the liver and the kidney needed to form 1,25-(OH)2-vitamin D3
148
What is the function of Vitamin D in: Liver Kidney Bone
**Liver-** activated vitamin D3 converted to 25-(OH)-vitamin D3 **Kidney-** 1,25-(OH)2-vitamin D3 (active hormone form) can be inactivated to 24,25-(OH)2-vitamin D3. This inactivity occurs with decreased levels of PTH or increased levels of serum Ca++,P. Vitamin D parallels that of PTH by increasing reabsorption of Ca in the kidneys. **Bone-** 1,25-(OH)2-vitamin D3 stimulates terminal differentiation of osteoclasts. Once they are mature osteoclasts vitamin D3 does not have an effect and they respond to cytokines released by osteoblasts. 1,25-(OH)2-vitamin D3 promotes the mineralization of osteoid matrix produced by osteoblasts
149
Peak bone mass attainement in both men and women is most dependent on what sex-steroid?
Estrogen
150
Therapeutic estrogen for women: increases risk of? decreases risk of?
Increases risk of heart disease and breast cancer Decreases the risk of hip fracture and endometrial cancer(if combined with cyclic progestin)
151
Someone on therapeutic estrogen will have changes in what lab values?
Decrease in urinary pyridoline Decrease in serum alkaline phosphatase
152
What function does thyroid hormone have bone formation?
Regulartes skeletal growth at the physis by stimulating: Chondrocyte growth type X collagen synthesis Alkaline phosphatase activity **Thyroid hormoes such as therapeutinc thyroxine increase bone resorption and can lead to osteoporosis.**
153
What effect does growth hormone have on the physis?
Effects the proliferative zone of the physis and in cases of oversecretion or increased response can lead to Gigantism.
154
What effect does growth hormone have on serium calcium?
Increased absorption in the intestine Decreases urinary excretion Function is interdependent with insulin, somatomedins, and growth factors (TGF-B, PDGF, mono/lyphokines)
155
What is the function of anabolic steroids on bone mass?
Increases bone loss by: Decreasing Ca++ absorption in intestine through a decrease in binding proteins Decreasing bone formation (cancellous more so than cortical bone) by decreasing collage synthesis and inhibiting osteoblast activity.
156
Limb bud development is under control of?
Fibroblast growth factor. Enlargement of the limb bud is due to interaction between the apical ectodermal ridge and the mesodermal cells in the progress zone. First identifiable by transvaginal ultrasound at 8 weeks.
157
What proteins are involved in chondrogenesis at sites of future joints during embryonic development?
WNT4 WNT14 growth and differentiation factor 5 (also known as cartilage-derived morphogenetic protein 1)
158
What is the difference in gain of funcion in FGFR2c affinity for FGF2 and Loss of function in FGFR2c specificity for FGF2?
Gain of function in FGFR2c affinity for FGF2 -\>patients with severe craniofaacial features and mild hand syndactyly. Loss of function in FGFR2c specificity for FGF2 leads to it being able to bind FGF10 which is expressed more in hands -\>mild craniofacial featurs and severe hand syndactyly.
159
What signaling center and growth factor are involved in Proximodistal limb development?
Signaling center = Apical ectodermal ridge Most important growth factor is FGF8 Issues in these areas will lead to proximal limb truncation such as radial absence or dysplasia. Can also lead to central deficiency such as a cleft hand.
160
What signaling center is needed for anteroposterior (radioulnar) limb growth?
Zone of polarizing activity- along posterior (ulnar) part of limb bud. Signaling molecule Shh is critical. Normal is high concentration on posterio (ulnar side) and low concentration on anterior (radial) side. Abnormal upregulation of Shh in the ZPA can lead to polydactly Downregulation leads to loss of ulnar digits. Upregulation in the anterior side can lead to loss of thumb.
161
What role does HOX genes have in limb development?
Anterior-posterior (radioulnar) patterning together with Shh Regulate somatization of the axial skeleton, essentially patterning digit formation.
162
What is the third signaling center invovled in limb development? What does it control?
non-AER limb ectoderm/ Wnt signalling center (progress zone, PZ) Dorsoventral axis. Dorsal limb expresses WNT7a to regulate dorsal patterning. Responsible for dorsal features such as nails. Ventral ectoderm expresses en-1 (engrailed-1 protein, antagonistic to WNT7a) allows ventral limb development.
163
What happens if there is a duplication of the zone of polarizing activity?
Mirror-image duplication of the limb.
164
The spinal column originates from what embryonic sturctures during development?
Paris of mesodermal sturctures known as somites Develop in a cranial to caudal direction on either sife of the notochord and neural tube. **Process is dependent on the presence of the paraxis gene** Somite layers: SCLEROTOME- layer will become the vertebral bodies and annulus fibrosus MYOTOME- will lead to myoblasts DERMATOME- becomes skin
165
For spine and spinal cord development what eventually develops from the following sturctures: Neural crest? Neural tube? Notochord?
Neural crest- forms PNS, pia mater, spinal ganglia, and sympathetic trunk. Neural tube- forms spinal cord Notochord- forms nucleus pulposus and anterior vertebral body Sclerotome fors the remainder of the vertebral bodies and the annulus fibrosus.
166
What are the three ossification centers of the vertebrae?
**Centrum**- anterior vertebral body. **Neural arch**- posterior elements, pedicles, small portion of anterior vertebra. **Costal element**- (anterior part of lateral mass, transverse process, or rib.
167
Where does endochondral bone formation occur?
Embryonic long bone formation longitudinal physeal growth non-rigid fracture healing (secondary healing)
168
What type of collagen is associated with endochondral ossification?
Type X collagen
169
What is the Hueter-Volkmann Law?
Compression across the growth plate slows longitudinal growth. Tension accelerates longitudinal growth.
170
What transcription factors are involved in the regulation of chondrocytes?
**Sox-9:** Considered a major regulator of chondrogenesis, regulates several cartilage-specific genes during endochondral ossification, including collagen types II, IV, and XI and aggrecan. **PTHrP:** Delays differentiation of chondrocytes in the zone of hypertrophy.
171
What is the Groove on Ranvier? What pathologic process is invovled with this area?
Zone of the physis periphery During the first year of life, the zone spreads over the adjacent metaphysis to form a fibrous circumferential ring bridging from the epiphysis to the diaphysis. The ring increase the mechanical strength of the physis and is responsible for appositional (width) bone growths. Supplies chondrocytes to periphery. **Osteochondroma**
172
What are the steps of formation for embryonic long bone formation?
**Vascularization**- vascular buds invade the mesenchymal model **Primary ossification centers form at 8 weeks.** **Cartilage model forms-** grows through appositional (width) and interstitial (length) growth. **Marrow forms** **Secondary ossification centers form**
173
What is Wolff's Law?
Bone remodels in response to mechanical stress.
174
How are Piezoelectric charges involved in bone remodeling?
Bone remodels in response to electric charges. Compression side is elctronegative and stimulates osteoblast formation. Tension side is electropositive and stimulates oteoclasts.
175
What is the mechanism by which cortical bone remodels?
Osteoclastic resorption \> layering of osteoblasts \> layering of lamellae \> cment line laid down Osteoclast make up head of cutting cone, followed by capillaries and then osteoblasts which lay down the osteoid to fill the cutting cone. Sclerostin inhibits osteoblastogenesis to decrease bone formation.
176
How does cancellous bone remodel?
Osteoclastic resorption Osteoblastic deposition of layers of lamellae
177
What % strain corresponds to following kinds of healing: Primary bone healing? Secondary bone healing? Fibrous non-union?
\<2% 2-10% \>10%
178
What are the stages of secondary bone healing?
Inflammation Repair Remodeling
179
What effect does NSAIDs have on bone healing?
COX-2 causes repression of runx-2/osterix, which are critical for differentiation of osteolastic cells. Controversial on how clinically significant this effect is on bone healing.
180
Does Low intensity pulsed ultrasound decrease time to union? Decrease non-union? What is the benefticial ultrasound signal?
Yes Yes Healing rates for delayes unions/nonunions has been reported to be close to 80% 30 mW/cm2 pulsed wave.
181
What are the four main delivery modes for bone stimulators?
All are modes of electrical stimulation Direct current- decreas osteoclast activity and increase osteoblast activity by reducing oxygen concentration and increasing local tissue pH. Capcitively coupled electrical fields (alternating current, AC) Pulsed electromagnetic fields Combined magnetic fields
182
What percent of patients with nonunion were found to have matabolic issues? vitamin D debiciencies?
84% 66% protein malnourishment decreases fracture callus strength.
183
What effect does gastric bypass have on bone healing?
Duodenal bypass leads to decreased clacium absorption. Decreased Ca/Vit D levels, secondary hyperparathyroidism, and increased Ca resorption from bone. Need to treat with Ca/Vit D supplementation. Gastric banding does not lead to these abnormalitites because the duodenum is not bypassed.
184
What effect does diabetes mellitus have on bone healing?
Decreased cellularity and strength of the fracture callus. Delayed endochondral ossification. Fracture healing takes 1.6 times longer in diabetic patients versus non-diabetic patients.
185
True or fale patients with HIV have higher prevalence of fragility fractures and associated delayed healing?
True Contributing factors: anti-retroviral medication poor intraosseous circulation TNF-Alpha deficiency Poor nutritional intact
186
How much is pseudoarthrosis in spine fusion increases by smoking?
500% Smokers cna also take 70% longer to heal open tibial shaft fractures versus non-smokers.
187
What are contraindications to bone stimulators?
synovial pseudoarthroses nonunions that move greater than 1 cm between fracture ends
188
What are the direct effects of bone stimulators which stimulate bone growth?
Increasing expression of BMP7 Increasing expression of BMP2 Increasing expression of TGF-beta1 Increasing osteoblast proliferation
189
What is the source, receptor class, and function for the following growth factors?
190
What is the signalling pathway and cellular targets of BMP?
Targets undifferentiated perivascular mesenchymal cells. Activates a transmembrane serine/threonine kinase receptor that leads to the activation of intracellular signalling molecules called SMADs SMADS lead to different cellular responses
191
What are the contraindications to use of BMP?
Pregnancy Allergy to bovine type I collagen or recombinant human rhBMP-2 Infection Tumor Skeletal immaturity
192
FDA approved use for BMP-2 and BMP-2
**BMP-2:** single level ALIF from L2-S1 levels in degenerative disc disease together with the lumbar tapered fusion device (LT Cage; Medtronic) **BMP-7:** Long bone non-unions where autograft can't be used. Alternative to autograft in patients (with osteoporosis, smoking, or diabetes) requiring revision posterolateral/intertransverse lumbar fusion for whom autologous bone and bone marrow harvest are not feasible or are not expected to promote fusion.
193
What is the most abundant growth factor in bone?
IGF-1 Products of the GH-IGF-1 system induce proliferation without maturation of the growth plate and thus induce linear skeletal growth. May have a role in enhancing bone formation in defects that heal via intramembranous ossification.
194
True or false IGF-2 is more potent that IGF-1
True Stimulates type I collagen production, cartilage matrix synthesis, cellular proliferation, and bone formation.
195
What effect does peroxisome proliferator-activated receptor gamma (PPAR-gamma) have?
adipogenic differentiation of mesechymal precursor cells in vitro.
196
Organize from fastest to slowest rates of resorption of the following materials: Hydroxyapatite Tricalcium phosphate Calcium Sulfate
Fastest to slowest Calcium sulfate \> tricalcium phosphate \> hydroxyapatite
197
Define osteoconductive?
Material acts as a structural framework for bone gowth.
198
Define Osteoinductive?
Material contains factors that stimulate bone growth and induction of stem cells down a bone forming lineage. BMP is an example.
199
Define Osteogenic?
Material directly provides cells that will produce bone including primitive mesenchymal stem cells, osteoblasts, and osteocytes.
200
What synthetic graft material is associated with increased serous wound drainage?
Calcium sulfate.
201
What disease has the highest risk of transmission with use of fresh frozen allograft?
Hep B 1 in 63,000 Hep C 1 in 100,000 HIV 1 in 1,000,000 Allografts are tested for HIV, HBV, HCV, HTLV-1, and syphilis.
202
Describe The Vitamin D Pathway
7-Dehydrocholesterol is stored in the skin where UV exposure converts it to previtamin D3 25-hydroxyvitamin D3: When calcium is low, PTH levles become elevated which activates 1-alpha-hydroxylase in the kidney. This converts 25-hydroxyvitamin D to the active Vitamin D (calcitriol) Laboratory level study of choice to determine Vitamin D deficiency.
203
Describe the PTH Pathway.
Function of PTH Increase serum Ca++ and decrease serum phosphate in response to hypocalcemia/hypomagnesemia via: Increased bone resorption of calcium and phosphate (bone is destroyed) PTH receptor is on the osteoblasts which secretes IL-1 to activate osteoclasts Increase kidney resorption of calcium in distal convoluted tubule Decrease kidney resorption of phosphate Increase 1,25-(OH)2 vitamin D production
204
Myasthenia gravis patients have a shortage of what?
Ach receptors.
205
What happens when acetylcholine bind to its receptor?
depolarization of the sarcoplasmic reticulum and release of calcium into muscles cytoplasm. Calcium binds to troponin leading to a configuartion change of tropomyosin. Exposing myosin-binding sites on actin filament Actin forms cross-bridges to myosin, and the ATP breakdown, the two fibers contract past one another.
206
Describe the composition of the sarcomere?
FILAMENTS: Thick myosin filaments and thin actin filaments. BANDS: H band is myosin only I band is actin olnly Z line flanks each sarcomere and acts as site of attachment for actin filament DURING MUSCLE CONTRACTION: A ban stays the same length. I band reduces in length. H zone reduces in length.
207
What type of muscle contraction is a plyometric?
Rapid lengthening followed by contraction of muscle groups (e.g. jumping up and down on boxes)
208
Describe the difference between Type I and Type II muscle fibers
209
What are the three energy systems?
**ATP-CP anaerobic system**- ATP, less than 20 seconds, no lactic acid, does not use oxygen **Lactic anaerobic system** (lactic acid metabolism)- 20 to 120 seconds. hydrolysis of one glucose molecule. **Aerobic system-** used in longer duration and lower intensity exercises. Krebs cycle generates ATP from glucose and fatty acids through oxidative phophorylation.
210
What are the most abundant cells early on after acute injury?
Neutrophils Generates free radicals that possibly increase muscle damage.
211
True or false wheelchair propulsion requires 9% more energy than ambulation in normal subjects?
True
212
Which amputation in a patients is the best candidate for a myoelectric prostheses?
Midlength transradial amputation.
213
What is the most common through knee or above knee prosthesis for children?
Constant friction (single axis) knee. Patients can walk on uneven terrain. Not recommended for older or weaker patients. Only allows a single speed of walking
214
With regard to prosthetic complications what is choke syndrome?
Obstructed venous outflow due to a socked that is too snug. Acute phase- red, indurated skin with orange-peel appearance. Chronic phase- hemosiderin deposits and venous stasis ulcers.
215
For the various foot alignment abnormalities describe the effect? Inset foot Outset foot Anterior foot placement Posterior foot placement Dorsiflexed foot Plantar-flexed foot
**Inset foot-** varus strain, circumduction and pain **Outset foot-** valgus strain, borad-based gait and pain **Anterior foot plaement-** stable increased knee extension with patellar pain **Posterior foot placement-** unstable increased knee flexion **Dorsiflexed foot-** Increased patellar pressure **Plantar-flexed foot-** Drop-off and increased patellar pressure
216
For transtibial prostheses what is the cause of the following: Swing-phase pistoning? Stance-phase pistoning?
**Swing phase pistoning-** ineffective suspension system **Stance phase pistoning-** poor socket fit Stump volume changes -\> stump sock may need to be changed.
217
What is the main cell type in both tendons and ligaments?
Fibroblasts. Both tendons and liaments show low vascularity and cellularity.
218
What are the extracellular components of ligaments and tendons? What is the number one component by dry weight?
Water, Type I collagen, elastin, lipids, proteoglycans and epiligament coats (present in some ligaments not all is analogous to epitenon. Type 1 collage is 70% by dry weight.
219
How does ligament and tendon composition differ?
Ligaments have lower percentage of collagen than tendons. Ligaments have a higher percentage of proteoglycans and water. Ligaments have less organized collagen fibers. Ligaments have rounder fibroblasts.
220
What is Hysteresis?
Energy dissipation. When tissue is loaded and unloaded, the unloading curve will not follow the loading cruve. The difference between the two curves is the energy that is dissipated.
221
What is the difference on a stress strain curve between tendons and ligaments?
Tendons carry higher loads and recruit fibers quickly -\> Smaller toe region. Ligaments recruit fibers gradually -\> elongated toe region. **Toe region-** significant deformation for given load. In this region the crimped and relaxed fibers of the ligament straightened to take load.
222
What is the difference between where ligaments fail in adults vs children?
Usually midsubstance in adults Usually at bony insertion in children Ligament avulsion occurs at juntion of mineralized and unmineralized fibrocartilage layers.
223
What are the two types of ligament bone insertion?
Indirect (fibrous insertion) Direct (fibrocartilaginous insertion)
224
What are the phases of ligament healing?
225
Factors that impair ligament helaing?
Intra-articular Increasing age Immobilization NSAIDs Diabetes Alcohol intake Decreased growth factors and expression of genes
226
Factors that improve ligament healing?
Many of these are experimental. Extra-articular Compromised immune response. CD$4 knockout mice have faster patellar tendon healing. Depletion of macrophages (source of TGF-B1 that stimulates fibrosis) Mesenchymal stem cells Growth factors such as PDGF-BB, GCSF, and BMP-2 and 12.
227
What are the two main proteoglycans found in tendons? What are their roles?
228
After tendon surgical repair when are tendon reparis weakest? When is maximum strength?
7-10 days 6 months. Final strength only reaches 2/3 of normal eve years after repair.
229
What are the five forms of cartilage?
Hyaline or articular cartilage Fibroelastic cartialge (meniscus) Fibrocartilage (at tendon and ligament insertion into bone) Elastic cartilage (trachea) Physeal cartilage (growth plate)
230
What makes up the extracellular matrix of hyaline cartilage?
**Water** 65-80% of mass of cartilage. Water content decreases with normal aging and increases with osteoarthritis. **Collagen-** 1-20% of total mass. Type II collagen accounts for 90-95% of the total collage content **Proteoglycans-** Make up 10-15% of cartilage. Function to provide compressive strength and attract water.
231
What are the layers of articular cartilage?
232
For the following factors how does age change them and how does osteoarthritis change them?
233
How does healing differ between a superficial cartilage laceration and a deep laceration that extends through the tidemark?
Superficial leads to chondrocyte proliferation but no healing because the cartilage is avascular. DEEP leads to fibrocartilage healing. Because subchondral bone is penetrated there is stem cell migration and vascular ingrowth.
234
What transcription factor is critical for mesenchymal stem cell differentiation towards the cartilage lineage?
SOX-9
235
True or false a disruption in pH can lead to an abnormal cartilage structure?
True pH of cartilage is 7.4
236
What besides articular cartilage is composed of hyaline cartilage?
Ribs and nasal septum.
237
What structures are composed of fibrocartilage?
Pubic symphysis, tendon/ligament junction with bone, annulus fibrosis of the intervertebral disc, and menisci. Predominantly Type I collagen.
238
What is the composition of collagen?
Composed of a triple helix: Two alpha 1 chains One alpha 2 chain. Several common amino acid sequences are found in collagen including: Glycine-X-hydroxyproline Glycine-Proline-X
239
Descire the formation of collagen fibers?
240
Type III collagen is predominantly found in? What are some related clinical conditions?
skin and blood vessels Ehler-Danlos syndrome Dupuytren's contracture
241
Where is Type IV collagen found? Related clinical conditions?
Basement membrane Renal diseases like Goodpasture's and Alport syndromes type VII and VIII are also found in epithelial basement membranes.
242
What types of collagen occur in small amounts in articular cartilage?
Type V, VI, IX
243
Where is type X collagen found?
Found in the deep calcified layer of cartilage Produced only by hypertrophic chondrocytes during endochondral ossification (growth plate, fracture callus, heterotopic ossification). Increased in early arthrits Related condition is Schmid metaphyseal chondrodysplasia
244
What is the function of Type XI collagen?
An adhesive with the function of holding the collagen lattice together in cartilage.
245
What is the difference between and exon and intron?
Both are parts of genes exon- coding information intron- does not code for mRNA
246
What is a codon?
sequence of three nucleotides (thymine, adenine, guanine, and cytosine) Each codon correlates to one of the 20 amino acids.
247
What do the following identify? Southern blot Northern blot Western blot
DNA sequence RNA sequence Protein
248
Briefly describe the cell cycle?
249
What are the two antigen presenting cells (APC) involved in the acquired immune response?
B cells and dendritic cells The APC cells above break down the protein antigen and presents the key peptide sequences via the major histocompatibility complex receptors. Once presented on the surface of the APC, the T-cell receptor recognizes the MHC/antigen complex prior to the T-cell activation. **CD8 T lymphocytes, T helper cells, delta gamma T cells, B cells, and Plasma cells are involved in acquired immune response.**
250
What is benign ethnic neutropenia?
Most common neutropenia in the world Approximatel 25-50% of people of African descent and some sub-groups in the Middle East found to have low ANC without increased infection risk. ANC \<1.5 x 10(9) cells/L More common in males, athletes, and children under the age of 5.
251
Match the following immunoglobulins IgG, IgM, IgA, and IgE with the facts below: Important in conferring protection against parasites and allergic reactions. The major class of antibody in external secretions. The first class of antibody to appear in our serum after exposure to an antigen. The most abundant immunoglobulin.
**IgE-**Important in conferring protection against parasites and allergic reactions. **IgA-**The major class of antibody in external secretions. **IgM-**The first class of antibody to appear in our serum after exposure to an antigen. **IgG-**The most abundant immunoglobulin.
252
Describe Types I, II, III, and IV immuological reactions.
253
In general how are defective structural proteins and defective enzymes inherited?
Defective structural proteins = autosomal dominant. Defective enzymes = autosomal recessive.
254
Name as many examples as you can of orthopaedic conditions that are inherited through an autosomal dominant pattern?
Syndactyly, Polydactyly Marfan's Syndrome, Cleidocranial dysostosis, Hereditary Multiple Exostosis Achondroplasia, MED, Metaphyseal Chondrodysplasia (Schmid and Jansen types) Kniest dysplasia, Malignant hyperthermia, Ehlers-Danlos syndrome Osteogensis Imperfecta Type I and IV Osteochondromatosis/Multiple Hereditary Exostosis and Osteopetrosis (tarda, mild form)
255
Orthopaedic disroders that are inherited through a autosomal recessive pattern?
Diastrophic dysplasia Friedreich's Ataxia Gaucher disease Spinal muscular atrophy Sickle cell anemia Osteogenesis Imperfecta Type II and III Hypophosphatasia Osteopetrosis (infantile and malignant form)
256
What are examples of sex-linked recessive orthopaedic conditions?
Duchenne muscular dystrophy Becker's muscular dystrophy Hunter's syndrome Hemophilia SED tarda **Usually occur in males only.**
257
What are examples of Sex-Linked dominant orthopaedic conditions?
Hypophosphatemic rickets Leri-Weill dyschondrosteosis (bilateral Madelung's deformity
258
What are some examples of diseases that demonstrate imprinting?
Angelman Syndrome Prader-Willi syndrome A genetic phenomenon by which certain genes ae expressed in a parent-of-origin-specific manner
259
What orthopaedic conditions demonstrate multiple inheritance patterns?
Charcot-Marie-Tooth (AD, AR, Xlink) Osteopetrosis (AD, AR) Osteogenesis Imperfecta (AR, AD) Neurofibromatosis (AD, AR) SED (AD, Xlink)
260
What happens to the retinoblastoma protein (pRB-1) in patients with retinoblastoma?
It becomes phosphorylated and is unable to bind to DNA to regulate. Recessive suppressor Both alleles must be mutated to have uncontrolled growth
261
What gene mutation is found in 50% of all tumors, osteosarcoma 20-65% of the time, and in chondrosarcoma?
p53
262
What is a tumor antigen? What disease is associated with the following tumor antigens? CEA CA-19-9 CA-125 CA-15-3 AFP
Expressed by tumor cells. Used in the diagnosis, monitoring of treatment response, and are being researched for treatment options as anti-cancer vaccines. CEA: colorectal carcinoma CA-19-9: pancreatic cancer CA-125: ovarian cancer CA-15-3: Breast cancer AFP: hepatocellular carcinomas
263
What is a siRNA used for?
It is a small interfering RNA Blocks translation of mRNA Useful for loss-of-function experiment designs
264
For the following diseases what are the translocations and diseases involved?
265
For the following skeletal dysplasia what is the mutation?
266
What is cytogenetic analysis used for?
Allows for the detection of gene translocations by evaluating the size and number of chromosomes isolated from the cell nucleus. Present in up to 95% of sarcomas
267
How do you calculate stress?
Force/Area
268
What is the definition of strain? How do you calculate strain?
relative measure of the deformation of an object Change in length/original length
269
How do you calculate toughness?
area under the stress/strain curve Joules per meter cubed is the units. J/m3
270
What is Hooke's Law?
When a material is loaded in the elastic zone, the sress is proportional to the strain.
271
Describe Youngs modulus of elasticity.
Measure of the stiffness (ability to resist deformation) of a material in the elastic zone. Calculated by measuring the stress/strain curve in the elastic zone. A higher modulus of elasticity indicates a stiffer material. Relative values of Young's modulus of elasticity: 1. Ceramic (Al2O3) 2. Alloy (Co-Cr-Mo) 3. Stainless steel 4. Titanium 5. Cortical bone 6. Matrix polymers 7. PMMA 8. Polyethylene 9. Cancelous bone 10. Tendon/ligament 11. Cartilage
272
What is an isotropic material? What is an anisotropic material?
A material that possess the same mecahnical properties in all directions. A materail that possess different mechanical properties depending on the direction of the applied load. Ex-ligaments and bones.
273
What is a viscoelastic material?
A material that exhibits a stress-strain relationship that is dependent on duration of applied load and the rate by which the load is applied (strain rate) Examples are ligaments and bone
274
What is fatigue failure and endurance limit as it applies to metals?
**Fatigue failure**- Failure at a point below the ultimate tensile strength secondary to repetitive loading. Depends on magnitude of sress and number of cycles. **Endurance limit-** defined as the maximal stess under which an object is immune to fatigue failure regardless of the number of cycles.
275
What are the different types of corrosion involved in orthopaedic metals?
**Galvanic corrosion-** dissimilar metals leads to electrochemical destruction. Mixing metals 316L Stainless steel and cobalt chromium (Co-Cr) has the highest risk of galvanic corrosion. **Crevice corrosion-** occurs in fatigue cracks due to differences in oxygen tension. 316L stainless most prone. **Fretting corrosion-** A mode of destruction at the contact site from the relative micromotionof two materials or two components. Common at head neck junction in hip arthroplasty. Modular components are at increased risk.
276
What are the two components of PMMA?
POWDER: Polymer, benzoyl peroxide (**initiator**), barium sulfate (radio-opacifier), coloring agent (green chlorophyll or blue cobalt). LIQUID: monomer, DMPT (N,N-Dimethyl para-toluidine, **accelerator**), hydroquinone (**stabilizer**) Reaches ultimate strength at 24 hrs. Modulus between cortical and cancelous bone. Strong in compression, poor tensile and shear strength.
277
How do you calculate the bending rigidity of the following structures? Solid Cylinder Hollow Cylinder Rectangular Object
Solid Cylinder- proportional to the radius to 4th power for a solid cylinder. Hollow Cylinder- proportional to the radius to the 3rd power. **This is sited in orthopaedic literature but not at all true.** Rectangular object- proportional to the (base x height) to the 3rd power.
278
Pullout strength of a screw is maximized by?
Large outer to inner diameter difference. Fine Pitch Most of all by quality of bone. Pullout strength is proprotionate to outer(major) diameter to the 2nd power.
279
What will increase locking plate construct stability?
bicortical locking screws. Increased number of screws Screw divergence from screw hole \< 5 degrees Longer plate
280
torsional rigidity of an intramedullary nail is proportional to what?
Radius to the 4th power.
281
What factors increase stability of conventional external fixators in order of effectiveness?
Contact of ends of fracture Larger diamter pins Additional pins Decreased bone to rod distance Pins in different planes Increasing size or stacking rods Rods in different planes Increased spacing between pins.
282
Factors that increase stability of circular (Ilizarov) external fixators?
Larger diameter wires Decreasing ring diamter Olive wires Extra wires Wires cross perpendicular to each other Increased wire tension Placement of two central rings close to fracture Increased number of rings.
283
What is secondary osteoporosis? What population is it more common in male or female?
Osteoporosis caused by things like hypogonadism, glucocorticoid excess, and alcoholism. Can begin at any age.
284
What osteoporotic fracture are most common overall and for the following age ranges? 50-60 years 60-70 years 70-80 years
Vertebral body \> hip \> wrist fractures wrist vertebral hip
285
What are the four categories of osteporosis risk factors?
Lifestyle Medications Genetic polymorphisms Diseases
286
Do men or women have a higher risk of mortality after hip fractures?
Men
287
Is there an increased risk of a second hip fracture in a patient who experiences a hip fracture?
Yes 10-fold increase.
288
What is the main difference between post-menopausal and senile osteopororsis?
Senile affects both cortical and trabecular bone (still affects trabecular more) while post-menopausal is almost exclusively trabecular.
289
On histology what leads to increased osteoclast ruffled border? What leads to a flattened ruffled border?
PTH. 1,25 dihydroxy Vit D3. Prostaglandin E Bisphosphonates and Calcitonin
290
What is tetracycline labeling used for in relation to bone biopsy testing?
Helpful in determining if bone condition is osteoporosis or osteomalacia? Osteoporosis = Normal tetracycline labeling Osteomalacia = Abnormal tetracycline labeling.
291
What are the side effects of Teriparatide? When is it contraindicated?
Teriparatide (Forteo) Transient hypercalcemia, dizziness, nausea, and headache. Contraindicated in Paget's disease due to potential osteosarcoma risk.
292
What is the mechanism of Forteo? How is it given?
Forteo or teriparatide is 1-34 amino terminal residues of parathyroid hormone (1-84) Activates receptors on osteoblasts and renal tubule cells. Is actually anabolic. Stimulates intestinal absorption Ca and PO4.
293
What is the mechanism of Prolia(Denosumab)? What effect does it have on reduction of fragility fractures? What are the side effects and contraindications?
Monoclonal Ig2 against RANKL (inhibits binding of RANKL to RANK, like osteoprotegerin) Reduced vertebral fractures by 68%, hip fractures by 40%, nonvertebral fractures by 20% Side effects: arhtralgia, nasopharyngitis, back pain. Contrainidcated in severe hypoclacemia.
294
What is the mechanism of Romosozumab (Evenity) What effect does it have on reduction of fragility fractures? What are the side effects and contraindications?
Humanized monoclonal Ig2 that activates Wnt pathway by binding sclerostin (sclerostin normally inhibits Wnt pathway). Promotes bone formation and inhibits resorption. Reduced new vertebral fracture by 73% through month 12 and by 75% through month 24. Given Sub-c injection monthly. Side effects: Hyperostosis, cardiovascular events, osteoarthritis, and cancer. Watch out for osteonecrosis of the jaw, atypical femoral fractures. Reserved for post-menopausal women with history of osteoporotic fracture, multiple risk factors who have failed other therapies.
295
What are the non-nitrogen containing bisphosphonates? What are their mechanism? Side effects:
Etidronate, clodronate, tiludronate Produce toxic ATP analog Esophagitis, dysphagia, gastric ulcers, osteonecrosis of the jaw, and atypical subtroch fractures.
296
What are the nitrogen containing bisphosphonates? What are their mechanism? Side effects?
Pamidronate. Alendronate (Fosamax). Risedronate (Actonel). Zolendronate (Reclast). Ibandronate (Boniva) Inhibits farnesyl pyrophosphate synthase (mevalonate pathway) Esophagitis, dysphagia, gastric ulcers, ONJ, atypical subtroch fractures
297
What are the associated orthopaedic manifestations of renal osteodystrophy?
Osteomalacia (adults) and growth retardation (children) AVN tendinitis and tendon rupture Carpal tunnel syndrome- deposition of amyloid (B2 microglobulin) Pathologic fracture- from brown tumors (hyperparathyroidism) or amyloid depotis Osteomyelitis and septic arthritis.
298
What is the pathophysiology of the following in renal osteodystrophy? hypocalcemia? Hyperparathyroidism and secondary hyperphosphatemia? Uremia related phosphate retention?
**Hypocalcemia-** due to the inability of the damaged kidney to convert vitamin D3 to calcitrol (the active form). Because of phosphate retention (hyperphosphatemia) **Hyperparathyroidsim and secondary hyperphosphatemia-** cause by hypocalcemia and lack of phosphate excretion by damaged kidney. **Uremia related phosphate retention-** The damged kidneys are not able to adquately secret phosphorus. THis causes insoluble calcium phosphate to form in the body which removes calcium from circulation. This leads to the hypocalcemia and secondary hyperparathyroidism and hyperparathyrodism. **This it key pahtophysiological step responsible for osteomalacia.**
299
What are the two broad classifications of renal osteodystrophy?
300
What are symptoms of hypocalcemia?
Abdominal pain Muscle cramps Dyspnea Convulsions/seizures Mental status changes
301
What are provocative tests for tetany found in some patiens with renal osteodystrophy?
**Trousseau's Sign-** Carpalpedal spasm (painful cramps of the muscles in hands and feet) after blood pressue readings **Chvostek's Sign-** Facial muscle contractions after tapping on the facial nerve.
302
What is the treatment for renal osteodystrophy
Treat underlying renal condition and or relieve urologic obstruction.
303
What conditios does the radiographic findings suggest? What are other radiographic findings?
Image is of a brown tumor that is found in patients with renal osteodystrophy. Image below is of a looser's zone Will also see osteosclerosis from mineralization of osteomalacia bone. Rugger jersey spine Soft tissue calcifications In children will see varus deformity of the femurs. Widened growth plate and zone of provisional calcification.
304
What will histology of renal osteodystrophy show?
Thinned trabeculae. See below. Amyloid stains pink on Congo red stain.
305
Describe the different osteodystrophy conditions based on labs and their genetic inheritance?
306
What are the orthopaedic manifestations of Rickets?
Brittle bones with physeal cupping/widening Bowing of long bones Ligamentous laxity Flattening of skull Enlargement of costal cartilage (rachitic rosary) Kyphosis (cat back)
307
What do you see on histology of a patient with Rickets?
Disordered and elongated zone of proliferation Poorly defined zone of provisional calcification Widened osteoid seams Swiss cheese trabeculae Abnormally arranged collagen fibers- run perpendicular to haversian canals.
308
What will you find on physical exam of a patient with Rickets?
Tibial bowing Rachitic rosary Bowing of knees Retarded bone growth Muscle hypotonia Waddling gait Dental abnormalities- Dleayed dentla eruption and defective enamel Pathologic fractures
309
Who is at risk for nutritional Rickets?
Rare now that Vitamin D is added to milk Presents ar 6 months - 3 years of age RISK FACTORS: premature infants Black children \> 6 months who are still breastfed Patients with malabsorption syndromes (celiac sprue) or chronic parenteral nutrition Asian immigrants Patients with unusual dietary choices (vegetarian diet)
310
Describe Vitamin D-resistant (familial hypophosphatemic) Rickets. What are the three genetic forms.
311
What is Vitamin D-dependent Rickets?
312
What is the treatment for Rickets?
**Nutritional Rickets-** Vitamin D 5000 IV/day for 6-10 weeks **Famililia hypophosphatemic Rickets-** Calcitriol. 20-30 mg/kg/day split into 203 doses in children. .5-.75 ug/day split into 2 doses in adults. Phosphate replacement 20-40 mg/kg/day split into 3-5 doses in children. 750-1000 mg/day split into 3-4 doses in adults. **Recent research calls into question the addition of phophate.** **Type I Vitamin D dependent Rickets-** Calcitriol **Type II Vitamin D dependent Rickets-** Vitamin D
313
What is the role of rheumatoid factor in rheumatoid arthritis?
It ias an IgM antiboday that targets native IgG antibodies. Immune complexes then get deposited in end tissues liek the kidney as part of the pathophysiology.
314
What is the role of mononuclear cells in RA?
They are the primary cellular mediator of tissue destruction.
315
What factors are part of the cascade that leads to joint damage in RA?
IL-1, TNF-alpha CASCADE OF EVENTS INCLUDE: antigen-antibody and antibody-antibody reactions microvascular proliferation and obstruction Synovial pannus formation (histology shows prominent intimal hyperplasia) Joint subluxation, chodnrocyte death/joint destruction, and deformity Tendon tenosysnovitis and rupture.
316
What are associated medical conditions & comorbidities with RA?
Rehumatoid vasculitis Pericarditis Pulmondary disease Felty's syndrome (RA wiht splenomegaly and leukopenia) Still's disease (acute onset of FA with fever, rash, and splenomegaly) Sjogren's syndrome (autoimmune condition affecting exocrine glands) Decreased secretions from salivary and tear duct glands. Lymphoid tissue proliferation
317
What lat test is most sensitive and specific for RA?
Anit-CCP Postive RF titer is elevated in 75-80% of patients with RA
318
What my you find on physical exam of a patient with RA?
subcutaneous nodules in 20% (strong association with positive serum RF). Ulnar deviation with metacarpophalangeal subluxation and swan neck deformity Hallux valgus, claw toes, and MTP subluxation Joints become affected at later stage in disease process.
319
For the following drugs specify when to stop and when to restart with regards to surgical procedures?
320
What is the diagnostic criteria for Rheumatoid arthritis.
321
What is the mechanism of leflunomide and what is it used for?
inhibitor of pyrimidine synthesis DMARD used in treatment of RA
322
What are the biologic, TNF anatagonist DMARDs?
323
What is the mechanism and use of ANakinra (Kineret)?
Recombinant IL1 receptor antagonist DMARD used in the treatment of RA.
324
What is the mechanism of Rituximab (Rituxan)
Monoclonal antibody to CD20 antigen (inhibits B cells) Biologic agent used in treatment of RA
325
What is the mechanism of Abatacept (Orencia)?
Selective costimulation modulator that binds to CD80 and CD86 (inhibits T cells) Has been used in the treatment of RA
326
What is the mechanism of Tocilizumab (Actemra)?
IL6 receptor inhibitor (2nd line treatment for poor response to TNF-antagoinst therapy. HAs been used in treatment of RA
327
What is the most common extra-articular manifestions of RA?
Rheumatoid nodules. Seen in up to 25% of patients with RA Associated with aggressive disease. Found over IP joints, olecranon, and ulnar border of the forearm. Can eroid through skin. Can be treated with steroid injections or surgical excision.
328
What is arthritis mutilans?
digits develop gross instability with bone loss (pencil in cup deformity or wind chime fingers). Seen in patients with RA or psoriatic arthritis. Treated with interposition bone grafting and fusion.
329
What is the operative treatment for early ulnar drift in a patient with RA?
Synovectomy, extensor tendon centralization, and intrinsic release.
330
When do you perform a MCP arthroplasty vs a MCP fusion for patients with Rheumatoid diseases and severe symptoms?
MCP arthroplasty when there is thumb MCP involvement + thumb IP involvment MCP fusion when there is only thumb MCP involvement.
331
What is the pathoanatomy of a Boutonniere deformity?
Synovitis of PIP leads to central slip and dorsal capsule attenuation Increasing PIP flexion Lateral bands subluxate volar to axis of rotation of PIP Oblique retinacular ligament contracture causes extension contracture of DIP.
332
What is the pathoantomy of a Swan neck deformity in RA?
Terminal tendon rupture from DIP synovitis leads to DIP flexion/PIP hyperextension FDS, volar plate, and collateral ligament attenuation from synovitis leads to decreased volar support of PIP, and hyperextension deformity. Lateral band subluxate dorsal to pIP axis of rotation Contracture of triangular ligament, attenuation of transverse retinacular ligament.
333
Briefly descirbe Flexor tendon conditions in RA?
334
Describe Extensor Tendon Conditions in RA?
335
Name as many of the primary hypercoagulopathies that are inhertied as you can?
MTHFR/C677T/TT gene mutation carries highest risk Factor V Leiden mutation Antithrombin III deficiencey Protein C deficiency Protein S deficiency Activated protein C resistance Elevated factor VIII Hyperhomocyteinemia Prothrombin II G20210A
336
What are secondary or acquired factors that increase risk of thromboembolism?
**Malignancy**- recently been associated with up to 20% of all new diagnosed VTE **Elevated hormone conditions**- recombinant erythropoeitin, hormone replacement, oral contraceptive therapy, and late pregnancy **Elevated antiphospholipid antibody conditions-** Lupus anticoagulant and anticardiolipin antibody History of thromboembolism, obesity, agiing, CHF, varicose veins, smoking, general anesthetics, immobilization, increased blood viscosity, rapid increase in INR following unopposed intiitation of warfarin therapy in arthroplasty patients.
337
Describe the Extrinsic and Intrinsic coagulation cascades?
338
What factor is released as a direct result of surgical dissection that leads to clot formation?
Thromboplastin.
339
For standard patients what is recommended for anticoagulation by the AAOS for: Upper extremity procedures Arthroscopy Isolated fractures at knee and below
No clear evidence for any of these to receive chemoprophylaxis
340
True or False the AAOS and the American College of Chest Physicians support ASA as a monotherapy in Hip and Knee arthroplasty?
True
341
For the anticoagulants listed below describe their mechanism?
342
For the following medications list where in the coagulation cascade they exert their effect: Unfractionated heparin Lovenox Warfarin Fondaparinaux (Arixtra) Rivaroxaban (Xarelto) and Apixiban (Eliquis). Same class less common Edoxaban (Savaysa or Lixiana) Dabigatran (Pradaxa)
343
What is thei difference in the mechanism of aspirin and NSAIDs?
Aspirin is a irreversible inhibitor of cyclooxygenase enzyme NSAIDs are reversible inhibitors of cyclooxygenase enzyme
344
What is the specific mechanism of aspirin?
Acts as an acetylating agent where an acetyl group is covalently and irreversibly attached to a serine resiude in the active site of the cyclooxygenase enzyme. Inhibits the production of prostaglandins and thromboxanes through irreversible inactivation of the cyclooxygenase enzyme within platelets.
345
What is the function of thromboxane?
Under normal conditions thromboxane is responsible for the aggregation of platelets that form blood clots.
346
What is the function of prostaglandins?
Are involved in The transmission of pain information to the brain Modulation of the hypothalamic thermostat Inflammation
347
Is there a difference in the metabolism of Unfractionated heparin and Low Molecular weight Heparin?
Yes Unfractionated heparin is metabolized in the liver. Low molecular weight heparin is metabolized in the kidney.
348
What is the specific mechanism of warfarin?
**Inhibits vitamin K 2,3-epoxide reductase**- prevents reduction of vitamin K epoxide back to active vitamin K **Vitamin K is needed for gamma-carboxylation of glutamic aacid for factors-** II (prothrombin), VII (first affected), IX, X Protein C and Protein S
349
Warfarin can have adverse reactions with what other drugs?
rifampin phenobarbital diuretics cholestyramine
350
What is the antidote for Dabigatran (Pradaxa)?
Idarucizumab
351
What dietary supplements have been found to increase the rate of bleeding by haveing an effect on platelets?
Gingko, ginseng, and garlic
352
What products can increase the effect of Warfarin? What products can reduce the effect of warfarin?
Omega-3 Fish Oil Reduced warfarin effect from Coenzyme Q10, Green tea, and St. John's wort.
353
What other ways does hypocalcemia present besides neruomuscular irritability?
Cataracts Fungal infections of the nail Hair loss Skin changes- vitiligo and blotchiness of skin
354
What is the most common cause of hypoparathyroidsim? What does it result in?
iatrogenic- thyroidectomy most common cause Decreased production of PTH by chief cells results in: Decreased plasma calcium levels Increased plasma posphate levels Decreased 1,25 (OH)2 Vitamin D levels **No current hormone replacement therapy available. Treatment is aimed at supplementing Vit D and calcium.**
355
For the following disorders describe the changes in Serum Ca, Serum Phos, PTH, and the most common cause: Hyperparathyroidism Hypoparathyroidism Ectopic PTH Vit D Malabsorption Hypo vit D with no phosphate excretion frim the kidney
356
What are the three symptoms of hyperparathyroidsim?
**Stones**- kidney stones **Bones**- Bone pain **Groans**- constipations
357
What are the complications of hyperparathyroidism?
**Peptic ulcer disease-** Increased gastrin production stimulated by increased ca++ **Acute pancreatitis-** Increased lipase activty stimulate by increased ca++ **CNS dysfunction-** anxiety, confusion, coma, result of metastatic calcification of the brain **Osteoporosis-** Bone loss occurs as result of bone resorption due to excess PTH. Orthopaedic surgeons should recognize lab abnormalities as patients may present with fragility fractures.
358
Treatment for Hyperparathyroidism?
ACUTE HYPERCALCEMIA- IV fluids and loop diuretics SYMPTOMATIC HYPERCALCEMIA- Treated surgically with parathyroidectomy. Complication is post-op hypocalcemia that should be treated with IV calcium gluconate.
359
What are the three classes of hyperparathyroidism? What serum lab values are to be expected?
PRIMARY: hypersecretion of PTH by a parathyroid adenoma(90%)/hyperplasia(10%) SECONDARY: Secondary parathyroid hyperplasia as compensation from hypocalcemia or hyperphosphatemia. Decreaed gut Ca++ absorption with increased phosphorus. Associated conditions are chronic renal disease and renal osteodystrophy TERTIARY: parathyroid gland becomes dysregulated after secondary hyperparathyroidism and secrete PTH regardless of Ca++ levels.
360
What mutation causes hypophosphatasia? What is the pathophysiology of the disorder?
mutation in the tissue-nonspecific isoenzyme of alkaline phophatase (TNSALP). Low levels of alkaline phosphate result in decreased synthesis of inorganic phosphate necessary for bone matrix formation. Osteoid that forms in the hypertrophic zone of the growth plate fails to mineralize The zone of provisional calcification never forms and growth is inhibited. Autosomal recessive
361
This image is consistent with what disease process?
hypophosphatasia Image shows deossification of bone adjacent to growth plate. Presentation is similar to Rickets. Genu varum and short stature. Will also see abnormal dentition **No approved therapies or treatments.**
362
What is Von willebrand's disease?
Genetic bleeding disorder caused by missing or defective von Willebrand Factor (VWF) a clotting protein.
363
In what cases should prophylactic antibiotics exceed 24 hours.
In clean and clean contaminated procedures where the incision is closed prophylactic abx should never exceed 24 hours. Even in the presence of a drain.
364
What patients should have prophylactic abx prior to dental procedures?
All patients for the first two years after TJA. Immunocompromised patients Drug induced innumon suppression Radiation induced immunosuppression Inflammatory arthropathies including SLE and RA COMORBIDITES INCLUDING: previous joint infection, Type I diabetes, malnourishment, hemophilia. HIV, and malignancy. According to AAOS and ADA there is limited eveidence to support this so need to use clinical judgment.
365
How and what abx should be administered prior to dental procedures?
Amoxicillin or cephalexin 2 grams orally 1 hour prior to procedure If allergic to penicillin then 600mg orally.
366
What immunizations should be given to a splenectomized patient?
Pneumococcal Haemophilus influenze type B Meningococcal Group C Influenza Lifelong prophylactic antibiotics (oral phenoxymethylpenicillin or erythromycin.
367
What enzymes are targeted by NSAIDs? What do these enzymes do?
COX-1 and COX-2 There are some COX-2 spefic inhibitors. Celebrex and Vioxx (rofecoxib). Maintains the beneficial effects of COX-1 (maintaining gastric mucosa, regulating renal blood flow, and influencing platelet aggregation). **Also can be used in the perioperative period because they do not affect platelet function.** COX enzymes catalyze the formation of prostaglandins and thromboxane from arachidonic acid.
368
What is the biggest reason concurrent NSAID and anticoagulant use is discouraged.
Greatly increases risk of gastrointetsintal side effects. Peptic ulcer perforation, bleeding, or obstruction. NSAIDs also have some cardiac toxicity.
369
True or false bisphosphonate use following lumbar fusion leads to decreased fusion mass, but no chane in the actual fusion rate?
False Leads to increased fusion mass but decreased actual fusion rate.
370
What medication can be given to patients with osteogenesis imperfecta that reduces bone pain and fracture incidence? Also increases level of ambulation and bone density.
Cyclical IV pamidronate Nitrogen containing bisphosphonate- inhibits farnesyl pyrophosphate synthase enzyme, required in mevalonate (cholesterol pathway). Inhibits GTPase formation.
371
What is substance P?
A sensory neurotransmitter that plays an important role in pain. Depletion of substance P increases the threshold to painful stimuli Capsaicin is thought to function by decreasing substance P
372
What is the most accurate method to control pain and avoid respiratory depression in the morbidly obese patient?
PCA which is based on the patients ideal weight.
373
True or false: Red haired patients often require more anesthesia to maintain MAC levels and higher opioid dosages postoperatively compared to other hair types.
True
374
What is the mechanism of methadone? What is its metabolism?
Synthetic diphenylheptaine-derivative opioid receptor agonist High bioavailability (three times as much as morphine), effective, and inexpensive. Metabolism: Cytochrome P450 CAUTION: can accumulate to high levels with repeated dosing. Rates of elimination very considerably. Risk of respiratory depression and cardiac toxicity (**torsades de pointes**)
375
What is the mechanism and use of cyclobenzaprine?
Mechansim not fully understood but it is centrally acting and potentiates norepinephrine and binds serotonin receptros. Useful in decreasing pain during first two weeks after an injury. No proven benefit after first two weeks. May interact with MAOIs and alcohol.
376
Describe the mechanism of the various classes of antibiotics?
377
What are non-orthopaedic effects of anabolic steroids in a patient that should be considered prior to surgery?
Increase of procoagulant factors VII and IX and thromboxane, which leads to hypercoagulability. Liver function is upregulated as the steroids induce hepatic enzymes and patients are therefore less sensitive to anesthetic agents. Have a mineralcorticoid effect on the kidnes leading to edema and hypertension. Often have fluid and electrolyte imbalances because of this. Higher oxygen consumption and CO2 production.
378
What is associated with a MECP2 mutation?
Rett syndrome? Inherited in an x-linked dominant fashion. Will have a C-shaped curve.
379
What diseases are associated with the following mutations? GNAS1 CLCN7 TGF-BR2 PHEX COLIA1
**GNAS1**- fibrous dysplasia **CLCN7 and TC1RG1**- Osteopetrosis **TGF-BR2 and FBN1**- Marfan syndrome **PHEX**- x-linked hypophophatemic rickets **COLIA1 and COLIA2**- Osteogenesis imperfecta
380
Name 5 TNF-a inhibitor medications?
Etanercept Infliximab Adalimumab Golimumab Certolizumab pegol
381
What kind of medication is Imatinib?
Tyrosine-kinase inhibitor Used to treat Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML)
382
What is the mechanism of Denosumab? What are the two commerical forms of Denosumab? What are they used to treat?
RANKL inhibitor **Prolia-** used to treat osteoporosis **Xgeva-** Used for prevention of skeleton-related events in patients with bone metastases, giant cell tumors, multiple myeloma with bone mets, and hypercalcemia of malignancy.
383
what disease process is most likely depicted by the radiograph below?
This is a "White line of Frankl" Seen in scurvy. also will see bluish-purple hue of the gums with areas of hemorrhages. Affects the spongiosa layer of the physis most.
384
What cell produces synovial fluid?
fibroblast-like type B synovial cell. Type A synovial cells are important phagocytic cells.
385
The addition of what antibiotic with mexotrexate has been shown to be more effective in the treatment of rheumatoid arthritis?
Doxycycline Tetracyclines have biologic effects on the inflammatory and immunologic cascade inhibiting collagenase activity. Collagenase is an enzyme invovled in breaking down macromolecules in the connective tissue, contributing to the pathologic changes of RA.
386
What disease process is associated with altered BMP-4 signal transduction?
Fibrodysplasia ossificans progressiva Also known as "stone man disease" Massive spontaneous heterotopic bone so much that their bodies literally ossify.
387
What is osteopoikilosis?
Spotted bone disease Caused by defective LEMD3 gene
388
What type of collagen production is found during the inflammatory phase of tendon and ligament healing.
Type III However tendons and ligaments are still predominantly composed of Type I collagen.
389
What is released by the osteoclasts to resorb bone?
Cathepsin K, Matrix metalloproteinase, and carbonic anhydrase (CA II)
390
airbags have been found to not have any significant effect on decreasing what kind of injuries?
Pelvic ring injuries. Decrease closed head injuries, facial fractures, shock, thoracoabdominal injuries, and need for extraction.
391
What is the mechanism of Linezolid?
Unique inhibition of the bacterial ribosome. Binds to the site on the 23S ribosomal RNA of the 50S subunit, preventing formation of the 70S initiation complex and interrupting the translational process.
392
What is the mechanism of action of Rifampin?
Inhibition of DNA-dependent RNA polymerase
393
That is the mechanism of action of Daptomycin?
Bacterial cell membrane depolarization interrupting DNA, RNA, and protein synthesis.
394
What products can be given to Jehovah witnesses? What things are a gray area and dependent upon individaul choice? What is not accepted?
Crystalloid, starch products such as Hetastarch and Hespan. Colloids are generally accepted. Cell saver and hemoglobin based oxygen carries are generally accpeted but should check with the individual patient. Whole blood, PRBC, platelets, white cells, or plasma. Autologous transfusion whether from the patient or donor directed is forbidden.
395
What is hypophosphatasia?
autosomal recessive disorder caused by an inborn error in the production of alkaline phosphatase (tissue-nonspecific isoenzyme of alkaline phophatase: TNSALP), leading to **low alkaline phophatase levels.** Increased urinary phosphoethanolamine is also diagnostic.
396
What is the cause of myasthenia gravis?
autoimmune antibodies at the NM junction leading to loss of acetylcholine receptors. Progressive weakness. Rest periods may allow early strength but easy fatigability. Acetyl cholinesterase inhibitors along with thymectomy can help control symptoms.
397
What is a high Alveolar-arterial gradient? What may it incidcate?
\> 20mm Hg or 2.7 kPa on aterial blood gas May indicate pulmonary embolism.
398
What is Ogilvie Syndrome?
Acute colonic pseudo-obstruction ASsociated with advanced age, male gender, narcotic pain medications, and patients who have undergone hip arthroplasty. Diagnosis made with abdominal radiograph that demonstrates dilation of the large intestine.
399
What is added to whole blood as an anticoagulant during the process of preparation of the PRP before centrifugation? What is used to initiate platelet activation?
Citrate Dextrose Calcium chloride and thrombin are added to initiate platelet activation.
400
Besides Type I collagen what is found in tendons?
Types III, V, VI, and proteogylcans. (5%) Decorin is the most common proteoglycan in tendons.
401
What role does quorum sensing play in the development of a bacterial biofilm?
After several bacteria have attached quorum sensing (cell-to-cell communication) allows maturation of the biofilm and **expression of genes that activate virulence factors**.
402
What enzyme is blocked by Warfarin?
vitamin K 2, 3-epoxide reductase, the enzyme needed for the reduction of vitamin K epoxide back to its active form. Active vitamin K is required for the postribosomal synthesis of acitve coagulation factors II, VII, IX, and X, as well as protein S and C.
403
What disorder is caused by a glycine substitution in the procollagen molecule?
Osteogenesis imperfecta
404
What are the differences between VDDR type 1 and VDDR type 2? VDDR (vitamin D-Dependent Rickets.
Type 1 is a deficiency of 1a-hydroxylase Type 2 is caused by an inactivating mutation of the receptor for 1,25 (OH)2 vitamin D3.
405
What diseases are involved with the following genes? ASPL ATF1 EWS PAX3 USPR
ASPL- alveolar soft part sarcoma (tX;17) ATF1- Clear cell chondrosarcoma EWS- Ewing's sarcoma (EWS-FLI1) (t11;22) but also
406
Where are the following mechanoreceptors located in a tendon and what is their function?
Golgi organs- steady state information when underoging large stimulation for prolonged periods Pacini corpuscles- sensitive, fast adapting mechanoreceptors Ruffini endings- very sensitive, acan also be long acting All of the above are in the myotendinous junction. Free nerve endings are in the enthesis and are responsible for nociception
407
What disease processes are the following associated with? **USP6-** ubiquitin-specific protease 6 **CSF-1** colony-stimulating factor 1 **MDM2-** mouse double minute-2 homolog **PDGFB-** platelet-derived growth factor beta
**USP6**- aneurysmal bone cysts and nodular fasciitis **CSF-1** diffuse pigmented villonodular synovitis **MDM2**- low-grade and parosteal osteosarcoma and atypical lipomatous tumors **PDGFB**- Dermatofibrosarcoma protuberans
408
What is the shelf life of freeze dried bone?
The shelf life is limited only by the duration of its sterility as dtermined by the packaging. usually 5 or more years.
409
What is the mechanism of abatacept?
Selective costimulation molecule that binds to CD80 and CD86 cells. Inhibits T cells Also has been described as a major histocompatibility complet (MHC) receptor antagonist Commercial name **Orencia**
410
Name some of the non-rhizomelic dwarfisms?
Diastrophic dysplasia Multiple epiphyseal dysplasia Metaphyseal chondrodysplasia Spondyloepiphyseal dysplasia Kniest Dysplasia Chondroectodermal dysplasia/ Ellis-van Creveld syndrome

ABOS1 (13 decks)

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