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Basics of BScience Flashcards

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1
Q

5 things osteoblasts make

A 
Col 1 (collagen)
Osteocalcin
Osteonectin
Alk phos - basic environment to build bone
RANK L
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2
Q

What are some TFs that push mes stem cells to become osteoblasts

A 
CBFA / RUNX
WNT / B catenin
IHH / IGF 2
LRP 5/6 / Osterix
BMP / SMAD
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3
Q

What cells do mes stem cells becomes in 1. high strain 2. med strain 3. low strain environments

A
  1. High strain -> fibroblast
  2. Med strain + low O2 + SOX 9 -> chondroblasts
  3. Low strain + high O2 (think absolute stability + good BF) -> osteoblast
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4
Q

What are the 2 receptors on osteoblasts

A

PTH-R: binds PTH and PTHrP (tumors)

1,25 vit D - R

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5
Q

What are the 3 main products of osteoclasts?

A

MMP
Cathepsin K
TRAP

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6
Q

How do osteoclasts bind to bone?

A

alpha V beta 3 on blasts bind Vitronectin on bone

RGD sequence

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7
Q

What do osteoblasts make to DOWNREG osteoclasts?

A

OPG = decoy for RANK L receptor

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8
Q

What inflammatory markers activate osteoclasts?

A 
IL 1
IL 6
TNF alpha
PG E2
Vit D and PTH via blasts
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9
Q

What 5 factors inhibit osteoclasts?

A 
Calcitonin 
TGF beta (opposite of activating alpha)
IL 10
OPG xs RANK L from blasts
Estrogen " "
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10
Q

What molecule do osteocytes make -> what does this do?

A

Sclerostin (SOST gene)
via DKK 1 pathway
Xs WNT / B catenin TF - fewer mes stem cells become osteoblasts = decreased bone mass

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11
Q

Name 2 diseases that have sclerostin deficiency

A
  1. Sclerosteosis
  2. Van Buchem disease
    Sclerostin def
    More WNT/B cat -> more blasts = increased bone mass
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12
Q

What is cleidocranial dysplasia?

A

AD
Mutated CBFA / RUNX TF - less mes stem cell to osteoblasts
Problem with intramem oss
Missing clavicles (hyper mobile shoulders) + teeth
STRANGER THINGS
Op: inter-troch osteotomy for coxa vara (neck shaft angle <100 deg)

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13
Q

What is intra-membranous ossification?

A

Bone healing w/o cartilage model

Mes stem cells -> osteoblasts -> organic matrix deposition

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14
Q

What is the pathophys and presentation of osteopetrosis

A

CLAST malfunction - can’t acidify Howship lacuna (broken carbonic anhydrase) - can’t resorb bone
Very dense bone but fragile w/o medullary canal
- Frx
- Skull - CN palsy
- Decreased vascularity = higher risk osteomyelitis
- Coxa vara
XR: bone-in-bone w/o med canal, erlenmeyer flask prox hum/distal femur, rugger jersey spine
Trt varies by inheritance pattern
- AD = Albers Schonger ds

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15
Q

How do tumors cause osteolysis? What do labs show? Trt?

A 
Make 
1. RANK-L -> direct activate clasts
2. PTHrP -> blasts activate clasts
Net: hyperCa of malig
Trt: bisphos
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16
Q

Labs for Pagets

A

High urine N & C telopeptides
High ALP
NORMAL Ca

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17
Q

Pathophys Pagets

A 
"Focally increased remodeling of bone"
More clast activity 
Spontaneous >> AD
3 phases that may co-exist:
1. Lytic 
2. Mixed
3. Sclerotic - blast predom
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18
Q

Presentation Pagets

A 
Often asx
Bone pain
Fractures 
Intense pain + swelling - worry about Paget sarcoma
Cardiac - high output cardiac failure 
XR: bone bowing, cotton wool skull
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19
Q

Comp Pagets

A 
2ary sarcoma (osteosarc)
VERY poor prognosis - chemo, wide res
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20
Q

Trt Pagets

A

Bisphos - ONLY if sx
2nd line - calcitonin
CI = teriparatide (recombinant PTH), increases risk 2ary sarcoma
Bone bowing refractory to bracing - osteotomy and plate

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21
Q

What is the most common comp of TKA vs THA in Paget’s patients?

A

TKA: Malalignment
THA: Hemorrhage

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22
Q

What is the pathophys and presentation of osteopetrosis

A

CLAST malfunction - can’t acidify Howship lacuna (broken carbonic anhydrase) - can’t resorb bone
Very dense bone but fragile w/o medullary canal
- Frx
- Skull - CN palsy
- Decreased vascularity = higher risk osteomyelitis
- Coxa vara
XR: bone-in-bone w/o med canal, erlenmeyer flask prox hum/distal femur, rugger jersey spine
Trt varies by inheritance pattern
- AD = Albers Schonger ds

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23
Q

How do tumors cause osteolysis? What do labs show? Trt?

A 
Make 
1. RANK-L -> direct activate clasts
2. PTHrP -> blasts activate clasts
Net: hyperCa of malig
Trt: bisphos
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24
Q

Labs for Pagets

A

High urine N & C telopeptides
High ALP
NORMAL Ca

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25
Pathophys Pagets
``` "Focally increased remodeling of bone" More clast activity Spontaneous >> AD 3 phases that may co-exist: 1. Lytic 2. Mixed 3. Sclerotic - blast predom ```
26
What cell do chondrocytes come from? What 2 molecules do chondrocytes make?
From chondroblasts Collagen + PG = cartilage Collagen = tensile strength, increases via cross linking PG = hydrophilic, keratin + chondrotin sulfate bound to a protein core on a HA backbone, compressive strength
27
Is collagen make intra or extra cellular
Make intra cell | Assembled extra-cell - makes sense BIG molecule
28
Trt Pagets
Bisphos - ONLY if sx 2nd line - calcitonin CI = teriparatide (recombinant PTH), increases risk 2ary sarcoma Bone bowing refractory to bracing - osteotomy and plate
29
What is the most common comp of TKA vs THA in Paget's patients?
TKA: Malalignment THA: Hemorrhage
30
What are the 2 types of bisphos?
N containing - X clast GTPase | Non-N: toxic ATP analog -> clast apoptosis
31
Mechanism of denosumab
mAB OPG analog | Xs RANK L - can't bind receptor on clasts - less clast activation
32
What disease would result from loss of OPG?
OPG blocks RANK L from binding and activating clasts No OPG = more clasts OSTEOPOROSIS
33
What are 3 cartilage promoting growth factors (mnemonic TIP)
TGF beta IGF 1 PDGF
34
What cell do chondrocytes come from? What 2 molecules do chondrocytes make?
From chondroblasts Make collagen + PG = cartilage
35
Is collagen make intra or extra cellular
Make intra cell | Assembled extra-cell - makes sense BIG molecule
36
Type 1 collagen makes up what + disease
BONES, lig, tendon | Osteogenesis imperfecta
37
Type 2 collagen makes up what + disease
Articular cartilage, nucleus pulposus | SED congenita
38
Type 3 collagen makes up what + disease
Tendon + lig initial healing | Dupuytrens
39
Type 5 collagen makes up what + disease
Stabilizes col 1 | Ehlers Danlos
40
Type 9 collagen makes up what + disease
Stabilizes col 2 | Multiple epiphyseal dysplasia
41
Type 10 collagen makes up what + disease
Initial fracture healing | Schmid chondrodysplasia
42
Type 11 collagen makes up what + disease
Collagen glue | Stickler syndrome
43
What are 2 key molecules in synovial fluid?
Lubricin | HA - shock absorbers
44
Describe type 1 vs 2 muscle fibers
T1: slow, oxidative = slow twitch = aerobic, endurance Smaller, less force, slower but fatigue resistant RECRUITED FIRST T2 = fast twitch = anaerobic (ATP-CP), speed 2a: fast ox-glyc 2b: fast glycolytic More forceful muscle contraction, more fatigue-able
45
Describe collagen changes (up or down) w/ OA: 1. H2O 2. PG 3. Collagen quantity 4. Collagen cross linking 5. Elastic modulus
OA: "wet + soft" 1. More water 2-5. Less PG, collagen amt and cross linking, elastic modulus
46
Describe collagen changes w/ aging: 1. H2O 2. PG 3. Collagen quantity 4. Collagen cross linking 5. Elastic modulus
Aging: "dry + stiff" 1. Less water 2. Less PG 3. No change in coll quantity*** 4. More coll cross linking (stiffer) => 5. Higher modulus
47
What chemokines are pro-OA?
IL 1/6 & TNF alpha [pro-clast] Turn on 1. Collagenase/MMPs - decrease collagen 2. Stromelysin - degrade PG
48
What are the tissues/molecules in ligaments?
Col 1 (70%) - col 3 for early healing PG H2O Elastin
49
How do ligaments heal - what changes to the fibers?
Increase # fibers | But lower x linking, diameter, and mass
50
What are the 3 types of collagen in tendons?
Col 1 (95%) > col 3 > col 5
51
When in the healing phase are tendons the weakest?
Inflam phase: days 7-10
52
What type of collagen increases in early OA
10
53
What are the 2 molecules in a sarcomere?
Thick = myosin | Thin - actin
54
What do satellite cells do in muscle?
Repair muscle w/ fibrosis - reduces strength
55
Mechanism of lidocaine
x Na+ channels - can't initiate nerve AP via Na/K channels
56
Mechanism of botox
Xs ACh release from nerve endings -> can't bind to muscle on post-synapse
57
What is the Ab in myasthenia gravis?
Ab vs ACh-R
58
What type of exercise is best for building muscle?
Eccentric (lengthening) + isokinetic (constant speed)
59
What type of collagen increases in early OA
10
60
What are the 5 regions of the growth plate
``` Reserve zone Proliferative zone 3 parts hypertrophic zone: 1. Zone of maturation 2. Zone of degeneration 3. Zone of provisional calcification ```
61
What happens in the reserve zone? Diseases? (PKGD)
``` Matrix production PKGD (packaged) P = pseudoachondroplasia (COMP gene) K= Kniest syndrome (col defect) G = Gaucher (beta glucocerebrosidase) D = diastrophic dysplasia (AS, sulfate transport gene) ```
62
What happens in the proliferative zone? Diseases? (MEGA)
``` Cellular division See columnar organization MEGA: ME = MHE (AD, EXT gene) G = gigantism A = achondroplasia (AD, FGFR3 mutation) ```
63
How does 2ary bone healing occur? What type of collagen is involved?
``` Enchondral ossification Blasts lay cartilage frame Remodeled through Howship lacunae 2-10% strain -> callus Type X = early frx healing ```
64
What is the mechanism that lead poisoning affects bones?
Lead xs PTHrP PTHrP stops physeal maturation @ hypertrophic zone x PTHrP -> physis matures -> decreased peak bone mineral density
65
What is the difference between 1ary and 2ary spongiosa of the metaphysis?
``` 1ary = WOVEN bone 2ary = LAMELLAR bone ```
66
What does AER pattern
Prox-distal Apex = most proximal aspect Go distal down the ridge
67
What does ZPA pattern
Radial-ulnar | Radial and ulnar are polar opposites
68
What does WNT pattern
Dorsal-ventral | WANT front and back!
69
How does 1ary bone healing occur?
Intra-mem oss Cutting cone/Haversian remodeling 1ary bone healing = NO strain = absolute stability (compression plating) No callus
70
How does 2ary bone healing occur? What type of collagen is involved?
``` Enchondral ossification Blasts lay cartilage frame Remodeled through Howship lacunae 2-10% strain -> callus Type X = early frx healing ```
71
Mechanism that PTH works
LESS PO4 resorption @kidney Increase 1,25 vit D prod at kidney Increase blast -> blast activation -> increase Ca + PO4 in blood Increase Ca from kidney and gut, PO4 gut resorption
72
Name the disease: high Ca, PTH, alk phos / low PO4
Hyper PTH binds blasts -> high alk phos makes sense Sx: stones, groans, mona, psychiatric overtones
73
What bone changes do you see with hyper PTH
Brown tumors = focal demineralization
74
Name the disease: low Ca and PTH, high PO4
Hypo PTH
75
Name the disease: low Ca and PO4, high PTH and alk phos
Nutritional rickets = vit D def | PTH high b/c trying to compensate -> binds blasts -> high alk phos
76
Which zone of the growth plate does rickets affect
ZPC/hypertrophic
77
Name the disease: normal Ca and PTH, high alk phos, low PTH
``` X linked hypo PO4 rickets XL dom PHEX gene Can't resorb PO4 @ kidney Wide prox tibial physis -> bowing Trt: PO4 &&&& vit D ```
78
Name the disease: low Ca / high PO4, PTH, alk phos
Renal osteodystrophy Kidney retaining PO4 Can't make vit D High PTH to compensate -> high alk phos
79
What leg deformity is seen with renaL osteodystrophy
Genu vaLgum
80
What T score is osteoporosis vs osteopenia
< -2.5 = porosis | -1 - -2.5 = penia
81
What is the highest risk factor for osteoporosis fracture
Prior fragility frx | Vert > hip > wrist
82
What is osteomalacia? Labs?
Decreased mineralization -> bone QUALITY problem | Low vit D
83
What bone supplements should you give pts over >50yo
Ca 1K - 1500 mg/d Vit D 1K IU/d Reduces frx risk
84
Which disease as MARGINAL syndesmophytes
Ank spond
85
Which disease has non-marginal flowing wax syndesmophytes
DISH
86
What C spine condition should you check for w/ DISH
Hyper-ext inj w/o frx - CENTRAL CORD sx
87
What is creep
Constant load get increased deformation/displacement over time Ex: plastic
88
What is anisotropy
Material properties change w/ direct of load applied on bone
89
3 antibiotics that target transcription
Rifampin - DNA dep RNA pol Quinolones - DNA gyrase Metronidazole - DNA
90
Define material toughness
Amt energy a material can absorb before failure
91
Equation for bending rigidity of a solid cylinder (ex fix)
r^4
92
Mechanism of rivaroxaban and apixaban
Xa inhibitors (-xaban)
93
HST 4
T cells | Ex: METAL ALLERGY
94
Mechanism of daigatran
2a inhibition
95
What vit K def clotting factors does Lorelai miss
2, 7, 9, 10, C &S
96
HST rxn 1
IgE -> mast cell | Allergies (Asthma)
97
HST rxn 2
IgG - Complement mediated | auto Abs
98
What is a disease that changes lubricin in synovial fluid
``` CACP Camptodactyly - fixed flexion of fingers Arthropathy Coxa vara - waddle gait Pericarditis - cardiac rub ```
99
HST 4
T cells | Ex: METAL ALLERGY
100
What part of the nerve recovers first after injury
Sympathetic
101
What is the main difference between freeze dried and frozen allogran
Freeze dried less torsional and bending strength Longer shelf life - Similar compressive + tensile strength - None are osteoconductive aka don't have viable cells (vs osteoinductive)
102
What does each of these structures do: 1. Golgi organs 2. Ruffini endings 3. Pacini corpuscles 4. Free nerve endings
1. Proprioception 2. Deep pressure 3. Rapid vibration 4. Nociception, often at bone-tendon junction
103
How do psych meds affect bones
Early osteoporosis Phenytoin/others - change vit D metab Clonazepam - increase sclerostin -> decrease blasts
104
What is a disease that changes lubricin in synovial fluid
``` CACP Camptodactyly - fixed flexion of fingers Arthropathy Coxa vara - waddle gait Pericarditis - cardiac rub ```
105
What is the fxn of aggrecan in articular cartilage
Aggrecan attracts water "Exerts swelling pressure against the restraint of collagen" Provides cartilage the capability to dispense contact forces evenly to underlying bone
106
What is the role of decorin in articular cartilage
Controls collagen fibril size
107
What is the main difference between freeze dried and frozen allogran
Freeze dried less torsional and bending strength - Similar compressive + tensile strength - None are osteoconductive aka don't have viable cells (vs osteoinductive)
108
What does each of these structures do: 1. Golgi organs 2. Ruffini endings 3. Pacini corpuscles 4. Free nerve endings
1. Proprioception 2. Deep pressure 3. Rapid vibration 4. Nociception, often at bone-tendon junction
109
What nuclear TF is important for tendon and ligament formation
Scleraxis
110
What biomaterial has the highest rate of bacterial adherence
Titanium alloy > stainless steel > pure titanium

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