Week 1 Flashcards
1
Q
What are the bio functions of the skeleton
A
provides framework
uses joints - motion
provides muscle leverage
protects organs
2
Q
what are examples of non-mineralized CT
A
notochord and cartilage
3
Q
what are examples of mineralized CT
A
calcified cartilage and bone
4
Q
what is the notochord in vertebrate adults
A
nucelus pulpose in each intervertebral disc
5
Q
what is cartilage
A
non-mineralized (lacks hydroxyapatite)
flexible - stronger under compression
easily injured & difficult to repair
growth tissue in fetus
6
Q
what is cartilage composed of
A
gel matrix
collagen or elastic fibers
chondrocytes
7
Q
what is calcified cartilage
A
mineralized (hydroxyapatite)
unorganized microstructure
stronger than cartilage
transitional tissue (EO)
calcification can be pathogenic
8
Q
bone is a composite tissue made of____ and ___ components
A
organic components (osteoids - type I collagen and cells)
inorganic components (hydroxyapatite and water)
9
Q
what is bone capable of
A
growth - only at surface
and remodeled throughout life
10
Q
what are the physiological functions of bone
A
mineral reservoir
calcium homeostasis
source of blood cells
energy storage/source
11
Q
what are the endocrine functions of bone
A
osteocalcin hormone
- insulin regulation
- brain development & function
- testosterone formation & release
12
Q
what are the classifications of bone
A
long, short, flat, irregular
13
Q
where do osteocytes live
A
in lacunae
between lamella surrounding haversian canals
connected to adjacent osteocytes by canaliculi
14
Q
what are osteons
A
made of haversian canals surrounding lamella
contains vessels and nerves
15
Q
what percent do bones get of total cardiac output
A
5-10%
16
Q
where does endochondral bone grow from
A
cartilage precursor
17
Q
where does endochondral bone form in
A
mesenchyme
18
Q
where does ossification begin
A
in utero
- first in diaphysis
- then in epiphyses
19
Q
what are the two ways bone is added to shaft
A
- replacement of cartilage
- conversion of perichondrium to periosteum
20
Q
all EO-dervived bones have periosteal bone that forms concomitantly via
A
intramembranous ossification
21
Q
how does membrane bone grow
A
no cartilage precursor
intramembranous ossification
grow outward
22
Q
what is a sesamoid bone
A
bones that form within tendons
prevent muscle from deforming
improve muscle leverage
23
Q
how is the skeleton held together
A
ligaments
joint capsules
menisci
bursae
24
Q
what do synovial joints include
A
synovial fluid
synovial membrane
fibrous outer layer
capsular ligaments
25
what is menisci
cartilage spaces or pads
26
what is bursae
protective cushions
have synovial membrane and synovial fluid
27
what are the three types of joints
synovial
fibrous
cartilaginous
28
what is the most mobile joint
synovial joint
29
what are the different shapes of synovial joints
flat (plane)
barrel-shaped (hinge)
pivot
ball-and-socket
30
what are the types of motions that can occur at synovial joints
flexion
extension
pronation
supination
abduction
adduction
overextension
circumduction
31
which joint allows limited motion
fibrous joints
32
what are the three types of fibrous joints
sutures
syndesmoses
gomphosis
33
what is the least mobile joint
cartilaginous joints
34
what is synchondrosis
connected by cartilage
35
what is symphysis
multiple tissues together (sandwich)
bone-cartilage-CT-cartilage-bone
36
what is connective tissue
complex of cells and extracellular matrix that provides supporting and connecting framework for all other tissues of the body
37
what are the components of ECM
fibers and ground substance
38
what are the types of fibers
collagenous or fibrillar
reticular (non-fibril-forming collagens)
elastic (elasin)
39
what is in ground substance
glycosaminoglycans (GAGs)/Proteoglycans (PGs)
&
Structural glycoproteins
40
how is CT types and subtypes defined
according to amount, type, and proportions of ECM components
41
what are the properties of an individual collagen molecule
- type II collagen
- trimeric
- rigid, rope-like
- (+) charged (basic aa's)
42
what are the properties of collagen fibril
- composed of individual, quarter-staggered collagen molecules
- eosinophilic
43
what are in GAG molecules
-chondroitin sulfate
- keratin sulfate (contains sulfate groups); highly (-) charge
44
what are the effects of ground substance being (-) charged
- spread out
- hydrophilic
- basophilic
- metachromatic
45
what makes up ground substance
- hyaluronic acid (GAG)
- link protein
- core protein
- PG molecule
- GAG molecule
46
what is type II collagen
- trimeric molecule
- laterally aggregates into fibrils
- fibrils criss-cross randomly
- slightly basic, eosinophilic
- slight positive charge
- provides rigid structural support
47
what is PG/GAG aggregates
- hyaluronic acid backbone
- mainly chondroitin/keratan sulfate side chains (highly neg charge)
- hydrophilic
- basophilic, metachromatic stain
48
what is in hyaline cartilage
- capillary
- perichondrium
- chondroblast
- chondrocyte
- collagen (type II) fibril
- ground substance (sulfated proteoglycans)
49
is hyaline cartilage vascular or avascular
avascular
50
explain hydrated sponge concept in hyaline cartilage
can withstand compressive forces due to stabilizing collagen matrix, and ability of PG aggregates to bind or release water and allow matric to compress/expand
51
explain the molecular sieve concept
nutrient and gas exchange occurs via ECM and perichondrial blood vessels; ECM selectively sequesters various molecules/ factors
52
what is the formation of cartilage process called
chondrogenesis
53
what is the start of chondrogenesis
mesenchymal condensation
54
what is the second step in chondrogenesis
chondroblasts form
- divide and secrete ECM
- distance between neighboring cells increases
55
what is the third step of chondrogenesis
chondrocyte form
- cells surround entirely by ECM
56
what is the last step of chondrogenesis
isogenic groups
- as cells divide, daughter cells remain in close proximity, forming chondrocyte clusters
57
what is the matrix called that immediately surrounds chondrocytes
territorial matrix
58
what is the matrix called that is further away from chondrocytes
interterritorial matrix
59
what are the two mechanisms that cartilage grows by
apositional and interstitial
60
what is apositional cartilage growth mechanism
differentiation of chondroprogenitors and chondroblasts on the inner surface of the perichondrium into chondrocytes
61
what is interstitial cartilage growth mechanism
involves division of pre-existing chondrocytes within a cartilage matrix, giving rise to isogenous groups
62
what are the three cartilage types
- hyaline cartilage
- elastic cartilage
- fibrocartilage
63
what is the function and location of hyaline cartilage
function: structural support, rapid growth, ability to withstand compression, temporary skeleton during embryogenesis
location: fetal skeleton, respiratory passages, cushioning of joints
64
what is the function and location of elastic cartilage
function: flexible support, ability to withstand deformation
location: external ear, auditory tubes, epiglottis, larynx cartilages
65
what is the function and structure of fibrocartilage
function: attachment to bone, provides restricted (type I and II) mobility under great mechanical stress
location: annulus fibrosus of intervertebral discs, pubic symphysis, bone-ligament junctions
66
where is fibrocartilage always found
in association with dense connective tissue
67
why does hyaline cartilage serve as a temporary skeleton during embyogenesis
- ECM composition
- enables hyaline cartilage to be firm and compressible
- provide protection and structural support
- grow increase rapidly by interstitial and apositional growth
68
how is this skeletal "blue-print" gradually replaced by trabecular bone and marrow
Endochondral ossification
69
why is endochondral ossification called the substitution process
ossification means formation of bone, endochondral means without cartilage
process is formation of bone within a cartilage blueprint within cartilage model
70
how are most skeletal elements neck down and a few skull bones formed in vertebrates
by EO
71
what is the EO outcome
gives rise to future skeletal elements that are going to have a bone marrow cavity where hematopoiesis takes place
72
describe the steps of EO in this picture
1. skeleton initially comprised of hyaline cartilage that grows via intersitial and appositional growth
2. at genetically predetermined stage, periosteal bony collage forms within perichondroum (via IO)
3. as collar minerallizes, perichondrium becomes periostrum and compact bone is laid down on outer surface of shaft
73
describe steps of EO in this picture
1. as periosteal bony collar extends to epiphysis, chondrocytes stack and then enlarge to ~10 fold in size (hypertrophy), hypertrophic cartilage beings to calcify
2. presence of periosteal bony collar and calcified cartilage matrix inhibits oxygen and nutrient diffusion
74
describe EO in this picture
1. diaphysis is penetrated by periosteal bud made up of blood vessels, mesenchymal cells, and chondro/osteoclasts - establishes the primary ossification center
2. chondro/osteoclasts secrete enzymes that degrade hypertrophic cartilage, while mesenchymal cells differentiate into cells of primitve bone marrow and into osteoblasts
75
describe EO in this picture
1. vascular invasion and gradual degradation of hypertrophic cartilage results in establishment of a marrow cavity and deposition of ostepblasts along hypertrophic cartilage remnants
2. formation of secondary ossification center at the epiphyses defines 5 distinct growth plate cartilage zones
76
what are the 5 growth plate zone
1. resting zone
2. zone of proliferation
3. zone of hypertrophy
4. zone of degradation
5. zone of ossification
77
describe EO in this picture
transition from hypertrophic cartilage to bone and marrow continues within growth plate and responsible for longitudinal growth
78
describe EO in this picture
1. growth plate closure results in termination of longitudinal growth
2. in adults the only cartilage (hyaline) that remains is the articular cartilage at the outer ends of (epiphyses) of bone
3. carilage lacks perichondrium
79
what is the clinical significance of cartilage lacking perichondrium
reduced ability to repair itself
osteoarthritis
80
what is the purpose of articular cartilage
- low friction gliding surface
- transmits weight bearing forces to underlying bone
- withstand high cyclic loads
81
what are the two ways articular cartilage can be damaged
- abnormal loading (physical): cyclic trauma & direct
- biochemical damage: inflammation
82
what is an example of a predisposition to cartilage injury
canine hip dysplasia
| some animals more predisposed
83
what is canine hip dysplasia
- improper alignment of the femoral head within the acetabulum
- 3 mutations in glycoproteins, PG, fibrillar structure
- abnormal mechanical stress
- articular cartilage damage
84
injury starts a cascade of inflammation and increase in ____
catabolism/degradation
85
what are chondrocytes activated by
| imbalance due to injury
stress
86
what do chondrocytes act as
| imbalance due to injury
their own inflammatory mediators
87
what gets released when imbalance is caused due to injury
cytokines
88
catabolic enzymes are released by ____
chondrocytes
89
what do catabolic enzymes cause
* collagen breakdown
* proteoglycan breakdown
90
what do catabolic enzymes result in
degradation of ECM
91
what two processes happen in tissue repair
* replacement of damaged cells and matrix
* regeneration
92
what are the general phases of tissue healing
1. inflammation
2. repair
3. remodeling
93
what is inflammation
| tissue healing
* vascular response
* cellular infiltration
* scaffold for repair
* 3-5 days
94
what is repair
| tissue healing
* cellular infiltration - fibroblasts
* local cellular repsonse
* 3 days - 2 weeks
95
what is remodeling
| tissue healing
* removal of inferior tissue, replacement
* 2 weeks - 1 year
96
why is cartilage being avascular a problem in response to injury
* different inflammatory phase
* no scaffold
* no cellular infiltration
* limited repair
97
why is fibrocartilage a problem in cartilage response to injury
* GAG concentration decreased
* Type 1 collegen put in
* biomechanically inferior - reduced funtion
98
what is intrinsic cartilage repair
* no vascular ingrowth
* relies on local chondrocytes
* sub-par
99
what is matrix flow
* forms lips of cartilage from perimeter that migrates towards center of defect
* surface chondrocytes are more fibroblast like
* fibroblast > hyaline cartilage
* heal small defects
100
what is extrinsic cartilage repair
* vascular ingrowth from surrounding tissue (bone)
* mesenchymal elements from subchondral bone
* helps form new CT
101
what are the two major limitations of cartilage
1. avascular
2. inferior repair tissue
102
osteoprogenitors
"stem cells" for bone
spindle shaped
found near bone surfaces in periosteum and endosteum
103
bone lining cells
flattened
line bone surfaces
quiescent osteoblasts
104
osteoblasts
"bone forming"
proliferative
cuboidal
appear as sheets on bone surface
deposit osteoid (unmineralized bone ECM)
105
osteocyte
"mature" bone cells
non-proliferative
encased in mineral
extensive filopodia for monitoring Ca levels and communicating with osteoblasts and osteoclasts
106
osteoclasts
"breakdown" or resorb bone
large
multinucleate
found on bone surface
not mesenchymal cells
107
inorganic phase of bone is ___
mineral (hydroxyapatite) - 75%
108
organic phase of bone is
type 1 collagen
small PG and glycoproteins - 25%
109
in bone, initial mineral deposition occurs where
in hole zones of type 1 collagen molecules in a collagen fiber from 1/4 staggered arrangement
110
do collagen fibers mineralize
no - this is why bones are able to bend
111
osteogenesis
formation of bone; proceeds through EO and IO
112
endochondral ossification
- involves a hyaline cartilage model, which serves as a blueprint for the future skeleton and marrow
- cartilage undergoes hypertrophy and is replaced by trabecular (spongy) bone, and bone marrow
113
intramembranous ossification
- involves a direct differentiation of mesenchymal/osteoprogenitor cells to osteoblasts, which secrete bone matrix
- bone forms through appositional growth
- end result: compact bone (membranous) without a marrow cavity
114
what is primary bone
- first bone that is laid down, regardless of whether it is formed by EO or IO - temporary immature skeleton
- not well organized
- greater cell-to-matrix ratio
115
primary bone is replaced by mature ______ through ____ and _____
secondary bone, modeling, remodeling
116
what is another term for secondary bone
lamellar bone
117
lamellar bone is organized in functional units called ___
osteons
118
what do osteons consist of
- central Haversian canal w/ blood vessels and nerves
- concentric lamellae of bone matrix
- inhabiting cells
119
what is bone remodeling
- balance between osteoclasts degrading bone and osteoblasts depositing bone
- OCLs create resorption pits
- blood vessels invate pits and import osteoprogenitors that differentiate into osteoblasts
- OBs align along exposed bone surface and secrete osteoid in lamellae around haversian canals
120
what stage is bone in during skeletogenesis
modeling
- bone change width and shape
- primary to secondary
121
what stage is bone in during adult-homeostasis
remodeling
- bone adapt to mechanical pressure
- Ca storage and release
122
what stage is bone in during pathology
remodeling
- fracture repair
- Ca imbalance
- OB/OCL dysfunction
123
what is woven bone
immature bone/temporary
- highly cellular
- random matrix organization
- rapid formation
- poorly mineralized
- weak
124
what is lamellar bone
mature bone
- low cellularity
- organized
- slow formation
- strong
- well mineralized
125
what is the difference between structure of lamellar and woven bone
rate of formation (time)
126
where are sites of new "repair" bone formation
- periosteum
- endosteum
127
traumatic fracture
normal bone broken by excessive force
128
pathologic fracture
abnormal (diseased) bone broken by minimal trauma or during normal weight bearing forces
129
avulsion
fractures that occur at site of ligament/tendon insertion
130
articular
worse prognosis because of incongruent joint surface - secondary DJD
131
what is direct (primary) healing
- contact healing (surgical fixation)
- gap healing (<1mm)
- required rigid fracture stabilization
132
what is indirect (secondary) healing
- biomechanical environment dictates which type takes place
- rigid, stable fixation vs limited intervention
133
what are the stages of indirect bone healing
- inflammation
- repair (soft callus and bony callus)
- remodel
134
what will low O2 tension result in
hyaline cartilage formation which eventually turns into EO and radiopaque
135
what are the 3 complications of fracture healing
- excessive motion (fibrous non-union)
- inadequate blood supply
- infection = osteomyelitis
136
necrotic (dead) bone is called
sequestrum
137
the embryo develops in 3 germ layers ___
ectoderm, mesoderm, endoderm
138
the ectoderm is responsible for forming the ___
nervous system and skin
139
the mesoderm is responsible for forming the ____
musculoskeletal system and circulatory system
140
the ectoderm is responsible for the ___
GI tract and other organs
141
the ectoderm creates the ___ and ___ via ____
neural tube; neural crest cells; neurulation
142
the mesoderm is divided into___
paraxial, intermediate, and lateral plate mesoderm
143
somites form as sections of ___
paraxial mesoderm
144
lateral plate mesoderm has two players called?
splanchnic and somatic
145
the sternum is formed from
somatic player of lateral plate mesoderm
146
what are somitocoels
"holes" form in the center of somites
147
the somitocoel expants to cut somite into dorsal and ventral parts called
dermatomyotome and sclerotome
148
the dermomyotome divides again into
dermatome, myotome, syndetome
149
dermatome
makes skin
150
myotome
makes muscle
151
syndetome
makes tendon
152
the sclerotome doesn't divide and makes ___
bone via EO around neural tube and notochord
153
vertebrae and ribs are created from
sclerotome
154
there is a ___ and ___ portion of sclerotomes
rostral; caudal
155
what is resegmentation
when the caudal portion of somite is fused with the rostral portion - allows intervertebral space for spinal nerves
156
the sclerotome makes structures including:
- vertebral arches w/ spinous process
- vertebral body
- transverse process
- intervertebral discs
157
what happens after resegmentation
each myotome becomes associated with 2 adjacent vertebrae and crosses the intervertebral space
158
what is the intervertebral space
- where the spinal nerve passes through and can innervate the muscles created by that myotome and provides sensory innervation to the skin
- can trace sensory nerve fibers to spine
159
what is the dorsolateral part of the myotome and what does it create
epimere; epaxial muscles (deep back muscles)
160
what is the ventralmedial part of the myotome and what does it create
hypomere; hypaxial muscles (trunk/limb muscles)
161
what are HOX genes
responsible for establishing patterning of vertebrae and limbs
162
what are some consequences of homeotic mutations of HOX genes
- flawed differentiation
- polydactyly
- syndactyly
163
what are fibroblast growth factors (fgf) and what can result from mutations
cell signaling proteins; abnormal growth plate function (dwarfism)
164
what can mutations in fibroblast growth factor receptors (fgfr) result in
- FGFR3 = achondroplasia
- FGFR1/2 = premature cranial synostosis
165
what are TBX genes
determine which limbs are upper and lower (TBX 4 & 5)
166
what does FGF10 lead to
continued growth of limb buds
167
limb buds first grow from ___ and then from ___
ectoderm; somatic lateral of lateral plate mesoderm
168
what is the thickened area on the tip of a limb bud called and what is it stimulated by and what does it secrete
apical ectodermal ridge (AER); FGF10; FGF4/8
169
what is the part of the lateral plate mesoderm that is closest to the AER called
progress/proliferating zone (PZ)
170
what is bone differentiation
- as limb bud grows, growth factors are not as saturated in lateral plate mesoderm that is furthest away from AER
- differentiate into cartilage then into bone (EO)
- creates stylopod, zeuopod, and autopod
171
some tissue at AER starts to undergo apoptosis because...
- high levels of bone morphogenic protein (BMP) and retinoic acid
- forms fingers
- AER still proliferates to make digits
172
AER dies off so they stop ___
proliferating and start differentiating into phalanges
173
how do you get differentiation of the autopod
- on dorsal portion of autopod there is zone of polarizing activity (ZPA)
- drives directional development of autopod by releasing molecules that create a gradient (Sonic Hedgehog protein)
174
how are limb muscles developed
- myotome migration into ventral and dorsal condensation (portions)
- syndetome migrates to make tendons
- dermatome migrates to make skin
175
what does ventral condensation create
**forelimb**
- flexor
- pronator
**hindlimb**
- extensor
- adductor
- digital extensor
176
what does dorsal condensation create
**forelimb**
- extensor
- supinator
**hindlimb**
- flexor
- abductor
- digital flexor
177
what are the somites toward the cranial end of the neural tube called
occipital somites
178
neural crest cells and occipital somites create ___ around ______ with the brain
neurocranium; rostral end of neural tube
179
what are the two types of bone in the skull
endochondral and membrane bone
180
what does endochondral bone make up
- chondrocranium
- splanchnocranium
181
what does membrane bone make up
dermatocranium
182
how is membrane bone made
intramembranous ossification
182
how is membrane bone made
intramembranous ossification
183
what is chondro(osteo)dysplasia
- congenital with defects present at birth
--> cartilage/bone formation impacted (ex: chondrodsyplastic dwarfism vs OI)
--> remodeling impacted (ex: OCL defect)
- clinical manifestations can be immediate or delayed
184
what are the causes of congenital skeletal abnormalities
- genetic (HOX gene)
- in utero exposures (toxin/nutritional)
185
what is generalized chondrodysplasia
congenital defects involving the cartilage template and generalized defect in EO
186
what are the origins of chondrodysplasias
- defect in cartilage template required for EO (spontaneous or heritable mutations)
- defects can be generalized or regional
187
what does heritable mutations in chondrodysplasias cause
disproportionate (chondrodysplastic) dwarfism
- early DJD from malformations in shape of epiphysis = joint instability and incongruence
188
what is K9 chondrodysplasia
- chondrodysplastic
- CFA18-FGF4
- disproportionate dwarfism
(shortened limbs/breed standard)
189
what is K9 Chondrodystrophy
- chondrodystrophic
-CFA12-FGF4
- shortened limbs
-IVDD - IVD herniation - Neurologic signs
190
what is bovine chondrodysplasia (Bulldog Calf syndrome)
- shorted malformed limbs
- skull malformations
191
what are generalized osteodysplasia
- cartilage ok
- bone not ok
- generalized deformities, monostotic or polyostotic malformations
192
what is osteogenesis imperfecta
- affects puppies, calves, lambs, humans
- osteopenic disease (decreased bone density and increased bone fragility)
- mutation in Type 1 collagen synthesis
193
what is focal chondrodysplasias
- developmental defects in EO at focal, repeatable sites
- osteochondrosis (OC) and osteochondritis dissecans (OCD)
194
what is OC and OCD
- heterogeneous lesions in growth cartilage (epiphyseal)
- dogs, horses, pigs, cattle, poultry
- focal defect (delay or failure) of EO
- bilaterally symmetrical (50%)
- secondary osteoarthritis common
195
what are the causes of OC/OCD
damage to vasculature in growth cartilage
196
Equine OC is:
vascular necrosis - focal retained necrotic cartilage core - cartilage folds - subchondral bone trauma
