Basic Science Flashcards
(76 cards)
1
Q
- Compressive strength of bone =
- Tensile strength of bone =
A
- Proteoglycans & Calcium Hydroxyapatite
- Type I collagen
2
Q
Articular/Hyaline Cartilage:
- Isotropic or anisotropic
- Mostly what type of collagen?
- What are the 4 zones? And what is the orientation and appearance of collagen and chondrocytes in each layer?
- what % is water?
- what gives ability to attract water?
- what is responsible for boundary lubrication?
A
- Anisotropic
- Type II
- Superficial zone -
- contains articular cartilage progenitor cells
- highest collagen content
- lowest Proteoglycan content
- High water concentration (*remember superficial is slippery! And deep layer is the inverse)
- Transitional zone
- Deep zone
- round cartilage cells aligned perpendicular to joint surface
- large diameter collagen fibrils
- highest concentration of Proteoglycans
- low water concentration
- Superficial zone -
- /TIDEMARK/ (only if injury passes through this layer there is healing potential)
- Zone of calcified cartilage
- small volume of cells with low metabolic activity
- Zone of calcified cartilage
- 60-85%
- Aggrecan
- HA and Lubricin
3
Q
- Ligament attachment to bone: direct vs indirect
A
- Direct: ligament-fibrocartilage-mineralized fibrocartilage-bone
- Indirect (more common): ligament-mineralized fibrocartilage-periosteum-bone
- MCL attaches indirectly to bone via Sharpey’s fibers (made of Type I collagen)
- Indirect (more common): ligament-mineralized fibrocartilage-periosteum-bone
4
Q
- Muscle motor unit recruitment order during muscle contraction:
A
- Slow-twitch fatigue resistant units (Type I)
- Fast-twitch fatigue resistant units (Type IIa)
- Fast-twitch easily fatigable units (Type IIb)
5
Q
TENDONS
- Tendons detect loading by
- Tendon repair is weakest during the ??? PERIOD, which occurs ??? days following repair.
- Increased training will cause a net increase in Type ?? collagen fibers within tendons
- Decorin regulates the
- Tendons are composed mainly of Collagen Type
- Aggrecan is found in areas of tendon compression and contributes to the
A
- Tendons detect loading by deflection of cell-cilia
- Tendon repair is weakest during the INFLAMMATORY PERIOD, which occurs 5-21 days following repair. During this period neutrophils and macrophages migrate into injury site and release chemotactic factors that recruit fibroblasts
- Increased training will cause a net increase in Type I collagen fibers within tendons
- Decorin regulates the assembly/organization of collagen fibrils and collagen fiber size.
- Tendons are composed mainly of Collagen Type I (95%), and < 5% Type III, V, VI
- Aggrecan is found in areas of tendon compression and contributes to the binding of collagen fibers to specific locations
6
Q
Groove of Ranvier:
A
wedge-shaped zone of cells contiguous with the epiphysis at the periphery that supplies chondrocytes to periphery and is responsible for APPOSITIONAL (width) GROWTH OF PHYSIS.
7
Q
Perichondrial Ring (of La Croix):
A
dense fibrous ring that is a component of physis periphery and critical to stability.
8
Q
enchondral ossification - describe
What type of collagen a/w it?
A
osteoblasts lay down bone on cartilage framework (bone replaces cartilage, cartilage is not converted to bone!)
- * TYPE X COLLAGEN a/w enchondral ossification
9
Q
Main Blood supply to growth plate
A
PERICHONDRIAL artery
10
Q
Heuter-Volkmann Law
A
- COMPRESSION SLOWS longitudinal growth
- TENSION accelerates longitudinal growth
11
Q
Describe the basic science of physeal growth arrest
A
- Physeal growth arrest after physeal injury occurs due to -> vascular invasion across the physis which brings in osteoblasts -> which form a bony bar
12
Q
Name different zones of the growth plate and key facts about each including what disease result for each (see pic in notes)
A
- Epiphysis
- Resting/Reserve Zone: supplies developing cartilage cells
- Proliferative Zone: responsible for LONGITUDINAL GROWTH
- Hypertrophic Zone: contains zone of provisional calcification, zone of maturation, zone of degeneration; and get calcification of matrix (PTHrP and IHh work here)
- Hypertrophic zone is biomechanically the WEAKEST zone of the physics
- **Zone of provisional calcification is location of Salter-Harris fractures (physeal fx) occur through, which is within the hypertrophic zone
- PTHrP delays differentiation of chondrocytes in zone of hypertrophy (w/ loss/mutation of this protein get accelerated maturation in zone of hypertrophy)
- Collagen X plays and important role in this zone for bone mineralization
- Primary Spongiosa: vascular invasion, mineralizes to form woven bone
- Secondary Spongiosa: internal remodeling (replacement of woven bone w/ lamellar bone), external remodeling
- Metaphysis
13
Q
Parathyroid Hormone-related Peptide Stuff:
A
- Ollier’s Syndrome - multiple enchondromas, likely due to mutations of PTH-related protein and Indian Hedgehog (IHh) protein
- Lead toxicity affects growth by inhibiting PTHrP
- PTHrP plays important role in regulation of cell proliferation at the physis and a MAJOR role in maintaining articular cartilage from fetal development to adult life. Physeal chondrocytes regulate PTHrP production via IHh.
14
Q
- Osteoblasts originate from ??? cells
- Osteoclasts originate from ??? cells
A
- Osteoblasts originate from mesenchymal cells
- Osteoclasts originate from myeloid cells
15
Q
Name the 3 things that Osteoblasts secrete and what each do
A
- RANKL: ACTIVATES OSTEOCLASTS, on surface of osteoblast and binds RANK receptor on osteoclast precursors to activate differentiation of mature osteoclast to resorb bone
- OPG: INHIBITS OSTEOCLASTS, binds to RANKL to prevent binding to RANK receptor
- Osteocalcin is only expressed on mature osteoblasts and is the most specific marker of mature osteoblasts, most abundant non-collagenous protein in bone, involved in Ca-homeostasis, during osteoporosis tx serum levels correlate w/ increases in bone mineral density.
16
Q
Besides osteoclasts, what else do Osteoblasts regulate?
A
Osteoblasts regulate hematopoietic stem cells via Jagged/Notch pathway, which is activated by PTH
17
Q
How do osteoclasts bind to bone?
A
- Vitronectin and Fibronectin have the Arg-Gly-Asp sequence on their surface which allow Integrins on the surface of osteoclasts to bind to bone
18
Q
How do osteoclasts resorb bone?
A
- Bone is resorbed by proteolytic digestion by lysosomal enzyme cathepsin K
19
Q
How does Calcitonin work on osteoclasts?
A
- Calcitonin works on osteoclasts by binding them and decreasing osteoclast number and activity and decreases serum Ca.
20
Q
- Wnt pathway stimulates production of bone via:
A
- Wnt binds LRP5/6 (lipoprotein receptor-related protein) -> intracellular cascade that leads to translocation of beta-catenin into the nucleus to activate transcription of genes that control osteoblast differentiation
21
Q
Explain role of Sclerostin and Dickkopf.
How is Sclerostin effected by Vit D?
A
- SCLEROSTIN (SOST in above pic)& Dickkopf (Dkk-1): is osteocyte derived and inhibits Wnt pathway by preventing binding of Wnt to LRP5/6-> leads to INHIBITION OF BONE FORMATION. Part of normal feedback mechanism -> when bone is not loaded (ie go to outer space or during stress shielding), SOST is responsible for the lack of bone formation - it is the chemical link to Wolff’s law!
- With Vit D supplementation 1,25-Vit D and 25-Vit D levels will go up; Sclerostin levels will go down b/c osteocytes have receptors for 1,25-Vit D and those will downregulate sclerostin which will lead to osteoblasts being more active and increased bone formation
22
Q
Indian Hedgehog (Ihh)
A
- Indian Hedgehog (Ihh) - is critically important in osteoblast and chondrocyte differentiation bot prenatally and postnatally.
- In OA osteophytes are formed due to activation of endochondral ossification via Ihh mediation.
23
Q
What are transcription factors? Which ones are * Related to tendons -> * Related to bone -> * Related to cartilage -> * Related to fibroblast -> * Related to T cell and osteoclastogenesis ->
A
- proteins that bind to DNA to activate gene transcription
- Related to tendons -> Scleraxis
- Related to bone -> RUNX2, Osterix
- Related to cartilage -> SOX9
- Related to fibroblast -> Twist1
- Related to T cell and osteoclastogenesis -<> NFATc1 (Nuclear factor of activated T cell, cytoplasmic 1)
24
Q
Describe how bone remodeling works
A
- Bone remodeling of trabecular bone occurs via formation of Howships lacunae (a pit) by osteoclasts - osteoblasts then follow behind and make new bone.
25
* Osteoporosis: diagnosed by ???
| Defined by???
* Osteoporosis: diagnosed by T-score < -2.5. Defined by decreased bone quantity with normal bone quality
26
Osteopenia
* Osteopenia ( = decreased bone mineral density w/o fx risk) : T-score -1 - -2.5
27
T score vs Z score
* **BOTH Osteoporosis and Osteopenia are DEFINED BY T SCORE
* Normal bone: T-score > -1
* T-score = comparison to young normals
* Z-score = comparison to age-matched normals (Z same age!)
28
When should you perform bone density screening?
* Bone density screening should begin at 65 yo in those with low risk. Others should start earlier (low body wt, chronic steroid use, malabsorption disorders, hx of low impact fx)
29
* Peak bone mass attainment for both men and women is driven by ?
Timing of peak bone mass
* Peak bone mass attainment for both men and women is driven by Estrogen
* Timing of peak bone mass varies based on anatomic site - in general 3rd decade of life is the peak
30
What percentage of bone density loss needs to happen before can notice this on XR?
bone mineral density loss on XRs can’t be really identified until there has been a 40% loss! - so don’t get fooled by just thinking XRs look okay bc they do for a while despite significant loss!
31
What are typical locations of fragility fractures?
| When you see them what test should to person get in the near future?
Metaphyseal bone * With aging there is loss of BOTH cortical and cancellous bone - however CANCELLOUS BONE IS LOST MORE QUICKLY (corresponds with clinical finding of most age-related fx occurring in cancellous bone)
dist rad fx, femoral neck fx, vertebral compression fx -> if have these from low energy mechanism, get DEXA!
32
What is the greatest prognostic indicator for future fragility fx?
Specifically which location has the strongest predictor?
* Greatest prognostic indicator for future fragility fx is a previous one
* Specifically, a previous vertebral fragility fx is the STRONGEST predictor of future fragility fx
33
What medicines increase risk of osteoporosis?
* Phenytoin, phenobarbital, carbamazepine, valproate (anticonvulsant Meds): increases risk of osteoporosis and therefore increases risk of fx!
* SSRI
* Glucocorticoids:
* Promotes osteoblast apoptosis
* Decreases differentiation of monocytes into osteoclasts and increases osteoclast apoptosis - though short term can lead to an increase in osteoclast survival
* Reduced vascularization
* NSAIDS DO NOT increase risk of osteoporosis
34
Recommended daily intake of Vit D and Ca for adults > 50
* Recommended daily intake for adults over the age of 50 yrs for osteoporosis prevention is:
- Calcium: 1,200-1,500 mg
- Vit D: 800-1,000 IU
35
What patients qualify for treatment with osteoporosis medication?
How should progress of treatment be followed?
* Advocated for patients who are post menopause or men > 50 who:
* Have prior hip or vertebral fx OR
* T score -2.5 or less at femoral neck or vertebrae OR
* Osteopenia (T-score between -1 and -2.5) AND
* FRAX score suggestive of 10 yr risk of hip fx is 3% or more OR
* major osteoporosis fx risk 20% or more
* Treatment should be followed with DEXA scans every 1-2 yrs
36
Teriparatide (aka Forteo)
* - PARATHYROID HORMONE ANALOG (1st 34 AA's of the hormone) - activates adenyl cyclase. CONTINUOUS INFUSION results in persistent elevation of PTH - leads to NET BONE RESORPTION due to stimulation of osteoclasts. However DAILY INJECTIONS causes only TRANSIENT increases and results in NET ANABOLIC EFFECT on bone. (This is bc PTH works via osteoblasts which then activate osteoclasts).Has been a/w causing OSTEOSARCOMA in animal models (not in humans).
* PTH is typically produced by the parathyroid gland by the CHIEF cells (note the parafollicular cells of the thyroid gland produce calcitonin - don’t get these mixed up! Remember - P/C combo in both cases!)
* ***Current rec's: DO NOT USE IN PTs AT INCREASED RISK FOR OSTEOSARCOMA - i.e. Paget's Dz, high Alk Phos w/ unknown cause, hypercalcemic dz, metastatic bone lesions, osteosarcoma, open epiphysis, or for people getting/will get radiation.
* NOTE: The ONLY available medicine for osteoporosis that has anabolic activity and works on osteoblasts is PTH (Teraperatide = Forteo)! ALL OF THE BELOW GENEARLLY DECREASE EFFECTIVENESS OF OSTEOCLASTS
* A/w increased spinal fusion rates - esp in postmenopausal women w/ osteoporosis
37
* Bisphosphonates
* Class of drugs that prevent bone mass loss by inhibiting osteoclasts.
* Used in: Osteoporosis, Paget's Dz, Metastatic bone dz, Osteogenesis Imperfecta
* Decrease risk of vertebral compression fx and non-vertebral fx by 40% after 3 years of treatment.
* Note: IV bisphosphonates (Zolendronate and Ibandronate) are recommended by AAOS guidelines for treatment of pain after osteoporotic spinal compression fx.
* Accumulate in high concentrations in bone by binding to calcium on bone and then get ingested by osteoclasts and cause apoptosis via 2 different mechanisms: 2 Types
1. NON-nitrogen containing: only "ChET III" - Clodronate, Etidronate, Tiludronate; MoA:target ATP to form toxic analog
2. Nitrogen-containing (MC = Alendronate = Fosamax); MOA: inhibiting osteoclast farnesyl pyrophosphate synthase enzyme which inhibits protein prenylation and GTPase formation needed in cholesterol pathway.
- SIDE EFFECTS: jaw osteonecrosis, atypical subtroch fx (transverse, no comminution, medial beaking) and femoral stress fx (c/o lateral thigh pain -> XR show lateral cortical thickening in subtroch region = impending fx)
* *Note: if pt gets subtroch fx -> STOP Bisphosphonate, consult endocrinologist, routine contralateral femur surveillance for fx - if see signs...prophylactic IMN! Also Teriparatide can be used to promote healing of atypical subtroch fx’s b/c these are a/w delayed healing.
- Can cause osteopetrosis in children.
- CONTRAINDICATIONS: renal dz, s/p lumbar fusion (b/c a/w DECREASED FUSION RATES!)
- EXCRETION: Renal
38
* Denosumab
* Inhibits osteoclast activity via binding RANK-L which prevents it from stimulating RANK
* Used in osteoporosis, bone mets, MM, GCT
* Also a/w jaw osteonecrosis
39
Warfarin(Coumadin)
- inhibits Vit K dependent enzyme (Vit K epoxide reductase) that performs CARBOXYLATION needed for factors II, VII, IX, X, Protein C & S. Reverse w/ Vitamin K &/or FFP
- Half-life -> 36 to 42 hrs, metabolized and excreted via the liver
- Takes 72-96 hrs
- Stop 3-5 days prior to elective surgery
40
Heparin
enhances antithrombin III to inhibit factors II, III, X (HIT = Abs form that activate platelets, get clots, and use up platelets = thrombocytopenia). Reverse w/ Protamine Sulfate
41
LMWH
Lovenox or Dalteparin: inhibit Xa (more rare but can cause HIT). Reverse w/ Protamine Sulfate
Has been a/w increased rate of postop hematoma and wound complications when compared to ASA and clopidogrel
42
Rivaroxaban
- Xarelto) & Apixaban (Eliquis): DIRECT inhibitor of factor Xa
- Taken orally, max effect achieved in 2-4 hrs
- Mostly excreted by liver (but also kidneys and intestines)
43
Fondaparinux
INDIRECT inhibitor of factor Xa
44
Celecoxib
selective COX-2 inhibitor: prevents pathway of arachadonic acid ->prostaglandin...thromboxane A2 which stimulates platelet aggregation
(doesn't affect COX-1 so gastric mucosa is maintained, renal blood flow not affected)
45
NSAIDS
reversibly inhibit COX enzymes (arachadonic acid ->prostaglandin...thromboxane A2 which stimulates platelet aggregation). ***remember long-term use is BAD ON KIDNEYS!!!
46
Aspirin
IRREVERSIBLY binds COX (other NSAIDS bind reversibly) so can't form thromboxane A2 - which stimulates platelet aggregation
47
Clopidogrel (Plavix)
inhibits ADP receptor on platelets and blocks glycoproteins IIb/IIIa pathway
48
Hirudin
natural anticoagulant from the salivary glands of leeches
49
Tranexamic acid
- competitive inhibition of plasminogen activation (reversibly blocks Lysine bindings sites), which prevents the breakdown of Fibrin clots (aka Factor Ia). Promotes and stabilizes clot formation.
- DOES NOT INCREASE RISK OF PE!
- Reduces need for blood transfusions
50
Factor V Leiden Thrombophilia
* Typically factor V serves as a cofactor to factor Xa and together they drive Prothrombin II to activate to Thrombin IIa. Protein C regulates the process by binding Factor V and inhibiting it to prevent hypercoagulability.
* However, in this disease the altered Factor V cannot be inhibited by Protein C -> so they get hypercoaguable.
* This is due to amino acid substitution of Glutamine for Arginine in the Protein C binding region of Factor V
51
* Protein S Deficiency
* Protein S is a cofactor of Protein C; and without S, C cannot be activated -> without C, Factor V cannot be inhibited -> Factor V continues to combine as cofactor to Factor Xa which drives Prothrombin to be activated to Thrombin (which ultimately activates Fibrinogen -> Fibrin that makes clot!)
52
* Antiphospholipid syndrome
* Autoimmune dz w/ antibodies against proteins that bind phospholipids -> get antibodies to Protein C and possibly Protein S
53
* Glanzmann thrombasthenia
* Rare, genetic platelet disorder in which platelets have qualitative or quantitative deficiencies causing increased bleeding
54
* Von Willebrands dz
* Genetic bleeding disorder caused by missing or defective VWF (a clotting protein)
55
Pulmonary Embolism:
* EKG Findings:
* Lab findings:
* Dx:
Pulmonary Embolism:
* EKG Findings: S1Q3T3, tachy, R axis deviation, RBBB
* Lab findings: hypoxia (PaO2 < 80) hypocapnea (PaCO2 < 35), high A-a gradient (> 20 mmHg). Note: Pulse Ox NOT reliable bc patient can hyperventilate to keep up!
* Dx: CTA!
56
COX ENZYMES:
| Which Meds target COX?
* Converts Arachadonic acid -> prostaglandins
* COX-1: constitutive; stomach, kidneys!
* COX-2: inducible; inflammatory sites
- COX plays role in enchondral ossification- only been shown in mouse models. Therefore, NSAIDS NOT RECOMMENDED FOR PAIN CONTROL AFTER FX!!!
- COX2 knockout mice have been shown to heal fractures more slowly
Celecoxib, NSAIDS, Aspirin
57
Define Stress and Strain
- Stress = intensity of internal force; = force/area
- Strain = relative measure of deformation of an object; = change in length/original length = magnitude of displacement b/t fragments during loading/total resting distance between fragments after stabilization
- Strain can be compressive or tensile
58
Talk about strain as it relates to the fracture site
**Fx strain = interfrag mvmt/size of fx gap
- Locking plates allow for a stiffer construct and thus reduce interfragmentary strain.
**Note: comminuted fractures have force dissipated over multiple fx lines and
interfragmentary strain is thus less compared to non-comminuted fx
- A low strain at fracture site and high stiffness of treatment construct is an interfragmentary lag screw (no motion b/t fragments is low strain and allow for primary/no callus fracture healing) with a neutralization plate (stiff construct). However, if the fracture is not reduced and you lag it and there is a gap -> this creates a higher strain environment and you will not get primary bone healing bc the cutting cones cannot jump the gap -> so will get a nonunion or will get secondary fx healing and a callus once the screws loosen or break
59
Yield Strength
maximal stress a material can take before permanent deformation
60
Elastic region
goes until yield strength (material returns to its original form once strain removed)
61
Plastic region
after yield strength (material does not return to its original form once strain removed)
62
Hooke's law
when material loaded in elastic zone, stress is proportional to strain
63
Ultimate (tensile) strength
load to failure = highest point on curve and is max stress a material can absorb before "necking"
64
Necking
when cross-sectional area of material begins to contract
65
Toughness
amount of energy material can absorb before failure = area under curve
66
Creep
deformation with time under constant load
67
Young's Modulus
- Young's Modulus = Stiffness = ability of object to resist deformation = slope of stress/strain curve
68
Fatigue strength
Endurance limit = amount of cyclic stress that can be applied before failure
69
Viscoelasticity
change in stress-strain relationship dependent on rate of loading
70
* Bending Rigidity:
- Solid cylindrical pin:
- Hollow IMN:
- Fx plate:
* Bending Rigidity:
- Solid cylindrical pin: R to the 4th power
- Hollow IMN: R to the 3rd power
- Fx plate: plate thickness to 3rd power
71
* Ultimate tensile strength order:
* Young's Modulus order
Which is the least tough?
* Ultimate tensile strength order: Cobalt Chrome > Titanium > Stainless Steel > Cortical Bone
* Young's Modulus = Stiffness: Ceramic > Co-Cr > Stainless steel > Titanium > Cortical bone > PMMA > Cancellous bone > Tendon/ligament > Cartilage
* “Sir Kobe Steals Tricks” nemonic to remember
* Ceramic is also the least tough
72
- What natural supplements have inhibitory effect on platelets?
- Ginkgo, garlic and Ginseng
73
The major factors for thromboembolic dz include...
The major factors include previous VTE, obesity, type of surgery (such as total joint arthroplasty), hypercoagulable states, myocardial infarction, congestive heart failure, family history of VTE, and hormonal replacement therapy.
74
How is the Extrinsic Pathway of the coagulation cascade activated?
- Tissue Factor aka Thromboplastin is released due to injury to endothelial walls of blood vessels during surgical dissection and activates the external pathway of the coagulation cascade.
75
What is a synonym for elastic modulus?
Stiffness
76
What is the MoA of Acetaminophen?
Inhibits prostaglandin E2 via IL-1Beta
