2015 Basic Science Flashcards
Question 9 Increased levels of peroxisome proliferator-activated receptor gamma 2 (PPARy2) result in increased 1. bone. 2. adipose. 3. cartilage. 4. muscle. 5. tendon or ligament
- adipose.
Regulates fatty acid and glucose metabolism.
PPAR-γ1 (found in nearly all tissues except muscle)
PPAR-γ2 (mostly found in adipose tissue and the intestine): Well established as a prime inducer of adipogenesis
RECOMMENDED READINGS
Lee FY, Drissi MH, Zuscik MJ, Chen D, Nizami S, Goto H. Molecular and cell biology in orthopaedics.
In: O’Keefe RJ, Jacobs JJ, Chu CR, Einhorn TA, eds. Orthopaedic Basic Science Foundations of Clinical
Practice. 4th ed. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2013:3-42.
Takada I, Suzawa M, Matsumoto K, Kato S. Suppression of PPAR transactivation switches cell fate of
bone marrow stem cells from adipocytes into osteoblasts. Ann N Y Acad Sci. 2007 Nov;1116:182-95.
Epub 2007 Jul 26. Review. PubMed PMID: 17656564.
Question 22
What is the mechanism of the anticoagulation effect of heparin?
1. Inhibition of Factor Xa
2. Activation of antithrombin (AT) III
3. Degradation of serine proteases
4. Interference with Factors Va and VIIIa
5. Blocking of vitamin K epoxide reductase (VKOR)
- Activation of antithrombin (AT) III
RECOMMENDED READINGS
Pellegrini VD. Thrombolic disease and fat embolism syndrome. In: O’Keefe RJ, Jacobs JJ, Chu CR,
Einhorn TA. eds. Orthopaedic Basic Science: Foundations of Clinical Practice. 4th ed. Rosemont, IL;
American Academy of Orthopaedic Surgeons. 2013:117-133.
Roehrig S, Straub A, Pohlmann J, Lampe T, Pernerstorfer J, Schlemmer KH, Reinemer P, Perzborn E.
Discovery of the novel antithrombotic agent 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-
1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide (BAY 59-7939): an oral, direct factor Xa inhibitor. J
Med Chem.2005 Sep 22;48(19):5900-8. PubMed PMID: 16161994
Question 24
What is the most likely cause of a pseudotumor in a well-positioned total hip arthroplasty?
1. Loosening of the cup at the bone interface
2. Fretting and corrosion reaction from the taper
3. Adhesive wear products from polyethylene
4. Backside wear of the polyethylene liner
5. Catastrophic polyethylene failure with metal-on-metal contact
- Fretting and corrosion reaction from the taper
The first article reports two cases of metal on poly THA where they suggest there was insufficient locking of the head/neck junction and so the distal part of it had micromotion, then toggling of the implants which lead to metal debris and pseudotumor…
Key here is that pseudotumor = metal on metal. Based on that the only other answer possible would be 5. Answer 5 uses the word” catastrophic” poly failure with MoM contact (I’m assuming where the poly splits and the metal head contacts the metal cup..??) but that doesn’t sound like a “well-positioned THA” at all
RECOMMENDED READINGS
Cook RB, Bolland BJ, Wharton JA, Tilley S, Latham JM, Wood RJ. Pseudotumour formation due to
tribocorrosion at the taper interface of large diameter metal on polymer modular total hip replacements.
J Arthroplasty. 2013 Sep;28(8):1430-6. doi: 10.1016/j.arth.2013.02.009. Epub 2013 Mar 23. PubMed
PMID: 23528556.
Lieberman JR ed. AAOS Comprehensive Orthopaedic Review. Rosemont, IL; American Academy of
Orthopaedic Surgeons. 2009: 21.
Question 36
Which gait pattern is most likely associated with knee osteoarthritis progression?
1. Abductor lurch
2. Ankle-flxed short stance
3. Increased adductor moment
4. Impulse loading after heel strike
5. Anterior cruciate ligament (ACL) protective gait
- Increased adductor moment
Peak knee adduction moment (KAM) and peak knee flexion moment (KFM) during early stance were found to be related to medial joint OA. KAM for femoral-sided cartilage wear, and KFM on tibial-sided wear
RECOMMENDED READINGS
Li J, Hosseini A, Gadikota HR, Li G. Kinesiology of the knee joint. In: O’Keefe RJ, Jacobs JJ, Chu CR,
Einhorn TA, eds. Orthopaedic Basic Science Foundations of Clinical Practice. 4th ed. Rosemont, IL:
American Academy of Orthopaedic Surgeons; 2013:261-278.
Chehab EF, Favre J, Erhart-Hledik JC, Andriacchi TP. Baseline knee adduction and flxion moments
during walking are both associated with 5 year cartilage changes in patients with medial knee
osteoarthritis. Osteoarthritis Cartilage. 2014 Nov;22(11):1833-9. doi: 10.1016/j.joca.2014.08.009. Epub
2014 Aug 27. PubMed PMID: 25211281; PubMed Central PMCID: PMC4369510.
Question 52 What is a major controlling molecule for tendon collagen fiber size? 1. Elastin 2. Fibrillin 3. Decorin 4. Biglycan 5. Fibronectin
PREFERRED RESPONSE: 3
RECOMMENDED READINGS
Reuther KE, Gray CF, Soslowsky LJ. Form and function of tendon and ligament. In: O’Keefe RJ, Jacobs
JJ, Chu CR, Einhorn TA. eds. Orthopaedic Basic Science: Foundations of Clinical Practice. 4th ed.
Rosemont, IL; American Academy of Orthopaedic Surgeons; 2013: 213-228.
Zhang G, Ezura Y, Chervoneva I, Robinson PS, Beason DP, Carine ET, Soslowsky LJ, Iozzo RV, Birk DE.
Decorin regulates assembly of collagen firils and acquisition of biomechanical properties during tendon
development. J Cell Biochem. 2006 Aug 15;98(6):1436-49. PubMed PMID: 16518859.
Question 61
What is the principal cause of age-related increase in articular cartilage brittleness?
1. More rapid cleavage of collagen
2. Increase in advanced glycation end products
3. Increased association of type IX collagen with type II collagen
4. Loss of matrilin 3 association with collagen fibrils
5. Type II collagen replacement with type III collagen
PREFERRED RESPONSE: 2
One of the best studied aging-related matrix protein modification in cartilage is the formation of advanced glycation end-products (AGEs). AGEs are produced from the spontaneous nonenzymatic glycation of proteins that occurs when reducing sugars such as glucose, fructose or ribose, react with lysine or arginine residues. Because the articular cartilage has a relatively low turnover rate, it is particularly susceptible to AGE formation. Type II collagen, the most abundant matrix protein in cartilage, has a half-life that has been calculated to be over 100 years (not answer 1, 3 or 5). The accumulation of AGEs in cartilage has been suggested to play a role in the development of osteoarthritis
RECOMMENDED READINGS
Chubinskaya S, Malfait A-M, Wimmer MA. Form and function of articular cartilage. In: O’Keefe RJ,
Jacobs JJ, Chu CR, Einhorn TA. eds. Orthopaedic Basic Science: Foundations of Clinical Practice. 4th ed.
Rosemont, IL: American Academy of Orthopaedic Surgeons; 2013:183-197.
Shane Anderson A, Loeser RF. Why is osteoarthritis an age-related disease? Best Pract Res Clin
Rheumatol. 2010 Feb;24(1):15-26. doi: 10.1016/j.berh.2009.08.006. Review. PubMed PMID: 20129196.
Question 67
The muscle energy source for a marathon athlete is predominantly
1. glycogen.
2. glycogen and fatty acids.
3. glycogen and lactic acids.
4. Adenosine triphosphate (ATP) and creatine phosphate.
5. ATP, creatine phosphate, and glycogen.
- glycogen and fatty acids.
You don't have enough glycogen for a marathon. Type I (oxidation) = marathon runner = slow twitch Type IIb (Creatine-P + ATP) = sprinter = fast twitch Type IIa (lactic acid) = 800m runner = fast twitch
RECOMMENDED READINGS
Wright A, Gharaibeh B, Huard J. Form and function of skeletal muscle. In: O’Keefe RJ, Jacobs JJ, Chu
CR, Einhorn TA, eds. Orthopaedic Basic Science Foundations of Clinical Practice. 4th ed. Rosemont, IL:
American Academy of Orthopaedic Surgeons; 2013:229-237.
Garrett WE Jr, Best TM. Anatomy, physiology, mechanics of skeletal muscle. In: Buckwalter JA, Einhorn
TA, Simon SR, eds. Orthopaedic Basic Science: Biology and Biomechanics of the Musculoskeletal
System. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2000:693-716.
Question 72 Which molecule is most responsible for the hydration of the intervertebral disk? 1. Decorin 2. Versican 3. Aggrecan 4. Type I collagen 5. Type II collagen
- Aggrecan
RECOMMENDED READINGS
Moss IL, An HS. Form and function of the intervertebral disk. In: O’Keefe RJ, Jacobs JJ, Chu CR,
Einhorn TA, eds. Orthopaedic Basic Science: Foundations of Clinical Practice. 4th ed. Rosemont, IL:
American Academy of Orthopaedic Surgeons; 2013:253-260.
Roughley PJ. Biology of intervertebral disc aging and degeneration: involvement of the extracellular
matrix. Spine (Phila Pa 1976). 2004 Dec 1;29(23):2691-9. Review. PubMed PMID: 15564918.
Question 84
What is the mechanism of action for denosumab in the treatment of osteoporosis?
1. Blocking the parathyroid receptor
2. Blocking the carbonic anhydrase receptor
3. Attachment to osteoprotegerin (OPG)
4. Attachment to receptor activator of nuclear factor kappa beta (RANK)
5. Inhibition of RANK ligand (RANKL)
- Inhibition of RANK ligand (RANKL)
OSTEOCLAST ACTIVATORS:
• RANKL: activates osteoclasts. (Tip: RANCLASTS) to stimulate bone resorption.
• PTH: binds to osteoblasts to stimulate production of RANKL
• IL-1: stimulates osteoclast differentiation
• Prostaglandin E2
• IL-6 and MIP-1A (myeloma)
OSTEOCLAST INHIBITORS:
• OPD (osteoprotegerin): decoy receptor used by osteoblasts that binds/sequesters RANKL (inhibits osteoclasts)
• Calcitonin: interacts with osteoclasts directly
• Estrogen: decreases RANKL
• TGF-B: increase in OPG
• IL-10: suppresses osteoclasts
RECOMMENDED READINGS
Bukata SV, Tyler WK. Metabolic bone disease. In: O’Keefe RJ, Jacobs JJ, Chu CR, Einhorn TA, eds.
Orthopaedic Basic Science: Foundations of Clinical Practice. 4th ed. Rosemont, IL: American Academy
of Orthopaedic Surgeons; 2013:353-364.
Yasuda H. RANKL, a necessary chance for clinical application to osteoporosis and cancer-related bone
diseases. World J Orthop. 2013 Oct 18;4(4):207-17. doi: 10.5312/wjo.v4.i4.207. Review. PubMed PMID:
24147256.
Capozzi A, Lello S, Pontecorvi A. The inhibition of RANK-ligand in the management of postmenopausal
osteoporosis and related fractures: the role of denosumab. Gynecol Endocrinol. 2014 Jun;30(6):403-8. doi:
10.3109/09513590.2014.892067. Epub 2014 Mar 5. PubMed PMID: 24592987.
Question 87
What is the function of sclerostin in adult bone homeostasis?
1. Decreases bone formation by inhibiting osteoblastogenesis
2. Decreases bone formation by promoting osteoclastogenesis
3. Decreases bone formation by inhibiting osteocytes
4. Increases bone formation by promoting osteoblastogenesis
5. Increases bone formation by inhibiting osteoclastogenesis
- Decreases bone formation by inhibiting osteoblastogenesis
3 x “decreases bone formation” vs. 2 “increases bone formation” = probably “decreases”
2x osteoclast, 2x osteoblast, 1x osteocytes = probably osteoclast or osteoblasts
So that leaves only options 1 and 2 as probably the right answer
Sclerostin inhibits the Wnt pathway = inhibits bone formation. Secreted by osteocytes.
RECOMMENDED READINGS
Suen PK, He YX, Chow DH, Huang L, Li C, Ke HZ, Ominsky MS, Qin L. Sclerostin monoclonal
antibody enhanced bone fracture healing in an open osteotomy model in rats. J Orthop Res. 2014
Aug;32(8):997-1005. doi: 10.1002/jor.22636. Epub 2014 Apr 30. PMID: 24782158.
Bukata SV, Tyler WK. Metabolic bone disease. In: O’Keefe RJ, Jacobs JJ, Chu CR, Einhorn TA, eds.
Orthopaedic Basic Science: Foundations of Clinical Practice. 4th ed. Rosemont, IL: American Academy
of Orthopaedic Surgeons; 2013:353-364.
Question 100 After initial arthroplasty surgery, infection that occurs within how many days is considered a surgical-site infection? 1. 30 days 2. 45 days 3. 60 days 4. 90 days 5. 365 days
- 365 days
Pure memorization for this one… No tips for you!
RECOMMENDED READINGS
Salava JK, Springer BD. Orthopaedic infections. In: Cannada LK, ed. Orthopaedic Knowledge Update 11.
Rosemont, IL: American Academy of Orthopaedic Surgeons; 2014:287-306.
Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for Prevention of Surgical Site
Infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices
Advisory Committee. Am J Infect Control. 1999 Apr;27(2):97-132; quiz 133-4; discussion 96. PubMed
PMID: 10196487.
Question 106 A 5-year-old boy has progressive muscle weakness. Examination reveals pseudohypertrophy of the calf and deltoid musculature and a positive Gower sign. How is this disorder most commonly inherited? 1. Non-Mendelian 2. Autosomal recessive 3. Autosomal dominant 4. X-linked dominant 5. X-linked recessive
- X-linked recessive
Pseudohypertrophy of proximal muscles is a combination of : proximal muscle wasting (which makes the distal muscles look hypertrophied in comparison), and infiltration of muscles with connective tissue.
Gower’s sign: kid rises by walking hands up legs to compensate for gluteus maximus and quadriceps weakness (proximal muscle weakness)
These signs are stereotypically synonymous with Duchenne’s muscular dystrophy, but can also be present in Becker’s muscular dystrophy. Either way, both are x-linked recessive (easy to remember cause it mostly affects boys).
This is probably Duchenne though since average age of diagnosis = 2 yo, Becker’s = 8 yo
RECOMMENDED READINGS
Babis GC, Sakellariou VI. Muscle disorders. In: Cannada LK, ed. Orthopaedic Knowledge Update 11.
Rosemont, IL: American Academy of Orthopaedic Surgeons; 2014:237-252.
Shieh PB. Muscular dystrophies and other genetic myopathies. Neurol Clin. 2013 Nov;31(4):1009-29. doi:
10.1016/j.ncl.2013.04.004. Review. PubMed PMID: 24176421.
Question 115 Which factor is most commonly used to stimulate cartilage regeneration in vitro? 1. Tumor necrosis factor (TNF)-alpha 2. Transforming growth factor (TGF)-beta 3. Platelet-derived growth factor (PDGF) 4. Fibroblast growth factor (FGF) 5. Insulin-like growth factor-1 (IGF-1)
- Transforming growth factor (TGF)-beta
TGF-B superfamily includes: TGF-B1, BMP-2, BMP-7, CDMP-1 and CDMP2 (cartilage-derived morphogenetic protein). Some show promising results but deleterious effects to the articular environment.
I don’t really get this question since they seem to be all (except TNF-a) used in studies to stimulate cartilage regeneration according to the article cited.
RECOMMENDED READINGS
Klatt BA, Chen A, Tuan R. Arthritis and other cartilage disorders. In: Cannada LK, ed. Orthopaedic
Knowledge Update 11. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2014:207-222.
Fortier LA, Barker JU, Strauss EJ, McCarrel TM, Cole BJ. The role of growth factors in cartilage repair.
Clin Orthop Relat Res. 2011 Oct;469(10):2706-15. doi: 10.1007/s11999-011-1857-3. Review. PubMed
PMID: 21403984; PubMed Central PMCID: PMC3171543.
Question 118 Which immune cell type is involved in metal allergy associated with orthopaedic implants? 1. Mast cells 2. Dendritic cells 3. Natural killer cells 4. B lymphocytes 5. T lymphocytes
- T lymphocytes
Better answer would be macrophages, but that’s not an option (Most delayed-type hypersensitivity participating cells are macrophages; only 5% of cells present are lymphocytes)
“The histologic and immunohistochemical appearance of the tissues is dominated by perivascular and diffuse infiltrates of T- and B-lymphocytes, including secondary lymphoid follicles that are morphologically suggestive of a hypersensitivity reaction”
T-cells are the initiators of the hypersensitivity by contact with the antigen. This recruits inflammatory cells…
RECOMMENDED READINGS
Jacobs JJ, Urban RM, Hallab NJ, Skipor AK, Fischer A, Wimmer MA. Metal-on-metal bearing surfaces. J
Am Acad Orthop Surg. 2009 Feb;17(2):69-76. PubMed PMID: 19202120.
O’Keefe RJ, Jacobs JJ, Chu CR, Einhorn TA, eds. Orthopaedic Basic Science: Foundations of Clinical
Practice. 4th ed. Rosemont, IL; American Academy of Orthopaedic Surgeons: 2013.
Question 126
Which ion and ion channel are responsible for generation of a nerve action potential?
1. Sodium ion through a voltage-gated channel
2. Sodium ion through a transmitter-gated channel
3. Potassium ion through a voltage-gated channel
4. Potassium ion through a mechanically-gated channel
5. Chloride ion through a mechanically-gated channel
- Sodium ion through a voltage-gated channel
Easy to remember.: Think of sodium + voltage because local anesthetics are sodium channel blockers and block sensory nerves, and neuropathic pain causes electric-shock-like pain (volt!).
Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in electrical membrane potential near the channel
Transmitter-gated channel open up when they attach to a ligand (Ex: acetylcholine)
Mechanically-gated channel: respond to mechanical cues (stretch or compress)
RECOMMENDED READINGS
O’Keefe RJ, Jacobs JJ, Chu CR, Einhorn TA, eds. Orthopaedic Basic Science: Foundations of Clinical
Practice. 4th ed. Rosemont, IL; American Academy of Orthopaedic Surgeons: 2013.
Lee DH, Claussen GC, Oh S. Clinical nerve conduction and needle electromyography studies. J Am Acad
Orthop Surg. 2004 Jul-Aug;12(4):276-87. Review. PubMed PMID: 15473679.
Catterall WA. Structure and function of voltage-gated sodium channels at atomic resolution. Exp Physiol.
2014 Jan;99(1):35-51. doi: 10.1113/expphysiol.2013.071969. Epub 2013 Oct 4. Review. PubMed PMID:
24097157; PubMed Central PMCID: PMC3885250