Basic Science 1 Flashcards
Toughness
Amt energy absorbed before failure
= area under stress/strain curve
Fatigue strength
Breaking after many load cycles
Osteopoikilosis
- What is it
- Inheritence
Bone islands, benign, often around joints
AD
No treatment needed
What is fretting corrosion
Micro motion at metal/metal interface
Think modular implants (aka not loose)
What is crevice corrosion
Pitting leading to ion release
What is glavanic corrosion
2 dissimilar metals in contact -> electrochem rxn -> ion release
What is adhesive wear
2 surface rub together and remove material from the less wear resistant surface
Mutation Marfans
Fibrillin 1 mutation - AD
Elevated TGF-beta
What do the following tests measure
- Northern blot
- Southern blot
- PCR
North: RNA
South: DNA
PCR: amplifies DNA fragments
What is the difference between the organization of woven vs lamellar bone?
Woven (frx callus, pathologic states)
- Randomly organized
- High cellularity
Lamellar (cortical, cancellous)
- Layers oriented by stress (Wolff’s law)
- Less cellular
What is the strain environment for each of the following osteoprogenitor cells?
- Fibroblast
- Chondroblast
- Osteoblast/cyte
Strain = change length/length
Fibroblast - high strain
(Why high strain fractures ie bridging a simple pattern results in a fibrous union)
Chondroblast - med strain, low O2
Osteoblast/cyte - low strain, high O2
(Why want low strain and good blood flow for frx healing)
What are 3 TF critical for osteoblast development?
Wnt signaling pathway
1. In response to mechanical stress, progenitor cells release Wnt proteins that cause production of B-Catenin
2. B-catenin -> Runx2 -> Osx
Runx2
B-catenin
Osx
What cells do the following TFs control?
1. Sox9
2. PPARgamma
Sox9 - chondrocytes
(Sox sux for making bone)
PPARgamma - adipoctyes
What 3 substances do osteoblasts produce? What 2 receptors on osteoblasts control this?
- PTH - via adenylyl cyclase, if pulsed anabolic effect on bone
- Vit
- Bind to:
BLASTS
- Make: - Type 1 collagen
- Alk phos
- RANK-L
How do osteocytes inhibit osteoblasts?
Sclerostin - inhibits bone formation via Xs osteoblasts
Want LOW levels if supplementing a patient with Vitamin D
What molecules increase vs decrease sclerostin?
PTH increases sclerostin = less bone
- PTH reduces bone if chronically high (vs pulsed is anabolic)
- High serum Ca, low PO4
Calcitonin deceases sclerostin = more bone
Where do osteoclasts come from?
How/where does resorption occur?
Hematopoietic cells aka macrophage lineage
- Don’t worry about TFs
Resorption:
- At ruffled border (capthesin K = enzyme here)
- Forms Howships lacunae
- TRAP (tartrate resistant acid phosphate) lowers pH w/ carbonic anhydrase to dissolve hydroxyapatite crystals
How do osteoclasts bind to bone?
Binds via integrins -> vibronectin
- Vibronectin: Arg - Gly - Asp (RGD) sequence
Carbonic anhydrase mutation disease
- Mechanism of disease
- Inheritance
- Clinical presentation
- XRs
- Trt
CA: osteopetrosis
- Osteoclasts can’t acidify Howship lacuna = high bone density
- Don’t see a ruffled border on the histo
AR form of the disease (vs AR proton pump dysfxn that is fatal)
Progressive blind/deaf, anemia as bone marrow gets squashed (bleeding)
XRs: rugger jersey spine (aka v dense bone), erlenmeyer flask prox hum/dist fem, coxa vara
Trt:
- Definitive: bone marrow transplant
- Plate frx (avoid IM fixation) - surg fixation has high union rates
What 2 molecules made by osteoblasts regulate osteoclasts?
OPG - inactivates RANK to inactivate clasts
- B-catenin is TF that stimulates blasts to release OPG to shut down clasts
- OPG = decoy receptor for RANK
RANKL - activates clasts
- PTH stimulates blasts to release RANK to stimulate clasts
How does calcitonin regulate bone?
From parafollicular cells thyroid
Binds to clasts to shut down
Decreases serum Ca bc keeping it in bone
Calcitonin is the opposite of PTH
- PTH increases Ca, decrease PO4
How does cancer cause lytic lesions in bone?
IL 1 and PTHrP stimulates RANK
RANK resorbs!
What 2 molecules suppress osteoblasts?
TNF
DKK1
How does cortical vs cancellous bone remodel?
Cortical: cutting cones in osteons
Cancellous: on bone surface via blast/clast cycle
What are the 3 types of bone formation?
Intramemb - no cartilage model, flat bones
- Haversian remodeling
- Primary bone healing
Enchondral - calcified cartilage (bone replaces cartilage), long bones / callus / physis
Appositional - on top of old bone, periosteal bone enlargement by width
What collagen do chondrocytes secrete in the hypertrophic zone of the growth plate?
Type X col
VEGF also here to induce vascular invasion
What part of the growth plate do salter harris fractures occur through
Zone of provisional Ca WITHIN the hypertrophic zone
What are the 3 stages of 2ary bone healing?
Inflam
- Osteo/fibroblasts
- In theory, COX2 inhibition represses runx2/osterix here, changes the differentiation pathway for blasts
Repair
- If stable environment (low strain) - get blasts
- If unstable environment (higher strain) - get chondrocytes (medium) or fibroblasts (high)
- MMPs degrade the ECM
- Enchondral oss changes soft -> hard callus : T 2/9/10 col -> T1 col
Remodel according to Wolffs law
What is the theory behind electrical bone stimulators
Increase blasts
- Decrease O2
- Increase pH
Define the following + give examples
1. Osteoconductive
2. Osteoinductive
3. Osteogenic
- Conductive = scaffold
- Cancellous allo - Inductive = GFs to stim bone
- DBM, BMP - Geneic = cellular elements to make new bone
- AUTOGRAFT
How do cancellous graft incorporate?
Creeping substitution
Vitamin D
- What is the active form
- How does it work
1,25 Vit D = active
25 vit D = lab study to det vit D def
Resorbs Ca in kidneys
What is the structure of T1 col
Triple helix
2 alpha1 chains
1 alpha 2 chain
What are the labs for renal osteodystrophy
Kidneys are impaired
- Can’t excrete PO2 -> high PO4 (uremia)
- Can’t make 1,25 vit D -> low Ca
Changes PTH
Sx are of low Ca: stones, groans, psychiatric overtones
What are the 2 forms of renal osteodystrophy?
- High PTH
- low Ca = 2ary hyper PT
- Brown tumors -> pathologic frx
Labs: low Ca, high PO4 / alk phos / PTH - Normal PTH
- No hyperPT
What is Rickets? 4 major causes/types?
Can’t mineralize bone @ ZPA (in hypertrophic zone)
In kids = Rickets = problem at cartilage matrix
In adults = osteomalacia = problem at bone matrix
- Nutritional (vit D def)
- Hereditary vit D dep
- Familial hypophos rickets
- Hypophosphatasia
Mutation + labs familial hypophos rickets
X-dom
PHEX gene
Can’t absorb PO4
**Normal serum Ca
What are the levels of T score for osteopenia vs osteoporosis?
DEXA tells you your T score
> 1 = normal
-1 to -2.5 = penia
< -2.5 = porosis
Who do you treat for osteoporosis?
T score < -2.5
If post meno women or men >50yo have:
- Hip or vertebral fracture
- Penia w/ hx frx, FRAX score for hip frx risk >3% and other osteoporotic frx risk >20%
What are the Ca and vit D doses when treating osteoporosis?
What is the goal serum vit D?
Ca: 1200-1500 mg/d
Vit D: 800-1000 IU/d
Want serum 25 vit D to be 41-250 ng/mL
Think 1000/1000/50-250
What hormones are bone metabolic vs anabolic?
Metabolic: estrogen
- Raloxifene - reduces osteoclast activity
Anabolic: PTH
- Teriparatide (CI Pagets for 2ary osteosarcoma)
Bisphos
1. General mechanism
2. Nitrogen mechanism
3. Non-nitrogen mechanism
Mechanism: taken up by clasts -> clast apoptosis
Nitrogen: 1000x more potent
- Xs farnesyl pyrophosphate synthase
- Lose GTPase formation at ruffled border
Non-nitrogen
- Breakdown into a non-useable form of ATP -> apoptosis
What is denosumab (Prolia)
IgG vs RANKL
No RANK = no clasts
What is the structure of a sarcomere?
Individual muscle unit
Thick filament = myosin (A band)
Thin filament = actin (I band)
Define the following
Isotonic
Isometric
Isokinetic
Isotonic = length changes, tension constant
Isometric = length constant, tension changes
Isokinetic = VELOCITY constant, tension changes
How does muscle change with strength conditioning
Increase fiber size
If increase fiber size -> increase cross sectional area = proportional to force
What is the order of energy substrate used in muscle
- <10s = ATP + creatine phosphate (no O2 use so no lactate)
- 1-4 min = glycogen + lactic acid
- > 4min = glycogen + fatty acid (O2 system)
What cells repair muscle injury
Satellite cells
Heal w/ dense fibrosis via TGF beta
Tears at MT jxn > mid substance
Order of nerve structure (small to large)
Axon
Myelin sheath - made by Schwann cells CNS, glial cells PNS
Endoneurium
Fascicles
Perineurium
Epineurium - cushions against external pressure
Name the nerve cell type for the following sensations:
1. Touch
2. Autonomic NS
3. Pain
- Type A - heavy myelin, fast conduction speed - TOUCH
- Type B - intermediate myelin, medium speed - ANS
- Type C - no myelin, slow conduction - pain
Order the following in the way in which they RECOVER after nerve injury (aka first to come back -> last)
Loss of function would be opposite order
Recover first: sympathetic
Pain
Temp
Touch
Proprioception
Recover last: motor - endoneurium must be intact for full recovery
Define the following
Neurapraxia
Axonotmesis
Neurotmesis
Neurapraxia - reversible nerve injury
Axonotmesis - disrupt the axon and myelin sheath but the epineurium is intact (aka very outside)
Neurotmesis - complete nerve division, worst prognosis
What is the role of decorin and aggregan in tendon?
Decorin = regulates diameter
- Transfers loads as cross links between fibers
Aggregan @ points of tendon compression
What are Sharpey’s fibers?
Mineralized fibrocartilage that binds tendon to bone
Tendon -> fibrocart -> mineralized fibrocart (Sharpey) -> bone
Timeframe for tendon repair strength
7-10d weakest
21d original strength
6mo max strength = 2/3 original strength
