MSK 1 Flashcards
(176 cards)
1
Q
at what week of development do the limb buds form
A
4th week of development
2
Q
describe the formation of the limb buds
A
- begins with activation of mesenchymal cells in the LATERAL MESODERM
- begins as a mass of mesenchyme covered by ectoderm–> look like small elevations of ventrolateral body wall
- development of upper limbs occurs slightly before lower limbs
- mesenchyme is derived from SOMATIC layer of the lateral mesoderm
3
Q
what is somitogenesis
A
committed mesoderm cells form somites in a cranial to caudal direction
the vertebral column (axial) and the limbs (appendicular) are derived from somites and portions of the lateral plates
3 parts:
- dermatome–> dermis of skin
- myotome–> skeletal muscle
- sclerotome–> bone
4
Q
at what week do the limb bones begin to form
A
week 5
5
Q
describe the formation of the limb bones
A
as the limb bud elongates during the 5th week, mesenchymal models of the bone are formed by cellular aggregations
the limb bones form as condensations of mesenchyme surrounded by ectoderm derived epithelium
mesenchyma cells also give rise to chondrocytes
CHONDRIFICATION CENTRES appear late in the 5th week
epithelium at the tip of the bud is thickened–> apical ectodermal ridge (AER)
AER interacts with mesenchyme of limb by causing it to keep growing
mesenchyme growth slows as it gets further from the AER and begins differentiating into cartilage and muscle
6
Q
at what point in development is the entire skeleton cartilaginous
A
by the 6th week
7
Q
what happens to the shape of the limb bud in the 6th week
A
becomes paddle shaped
8
Q
at what week does the osteogenesis of long bones begin?
at what point is osteogenesis present in all long bones?
A
starts in the 7th week
present in all by the 12th week
9
Q
by what week have the mesenchymal cells in the hand plates condensed to form finger buds
A
end of the 6th
10
Q
by what week have the mesenchymal cells in the foot plates condensed to form toe buds
A
end of the 7th
11
Q
what cellular processes are happening in the 6th and 7th weeks that allow for the differentiation of the hands and feet
A
RETINOIC ACID acts on the region of the ZONE OF PROLIFERATION causing the induced sonic hedgehog (Shh) and bone morphogenic proteins determine the pattern of programmed cell death and limb development
12
Q
when is the most vulnerable time for limb development
A
24-36 days post fertilization (5-7 weeks gestation)
13
Q
what results due to loss or damage of the AER?
A
- amelia–> complete failure of limb development
2. micromelia–> partial limb development
14
Q
what abnormality leads to polydactyly or syndactyly (fused digits)?
A
improper gradient of the ZPA and Shh
15
Q
describe the foundation and formation of somites
A
intraembryonic mesoderm lateral to the notochord and neural tube thickens to form two columns of PARAXIAL mesoderm
toward the end of the 3rd week, the paraxial mesoderm becomes segmented into blocks (somites)
each somite differentiates into two parts
- ventromedial
- dorsolateral
16
Q
into what two parts does each somite differentiate into
A
- ventromedial–> SCLEROTOME (forms vertebrae and ribs)
2. dorsolateral–> DERMOMYOTOME (cells from myotome form myoblasts and dermatome forms dermis)
17
Q
what is the AER
A
apical ectodermal ridge
thickening of the ectoderm at the apex of the limb bud
it is a specialized layer of cells which interacts with mesenchyme of limb bud promoting outgrowth of the bud (BMP is essential)–> causes the release of fibroblast growth factors (FGFs) which stimulate the ZONE OF POLARIZING ACTIVITY
18
Q
what is the zone of polarizing activity
A
stimulated by BMPs and FGFs around the AER during limb bud development
it is an aggregation of mesenchymal cells at the posterior margin of the limb bud
once activated by FGF, this area expressive SONIC HEDGEHOG (Shh) which controls patterning of limd along the anteroposterior axis
19
Q
what is Shh responsible for
A
controls patterning of the limb along the anteroposterior axis
20
Q
describe the formation of the hands and fingers
A
hand plates–> digital rays–> AER induces formation of bones (phalanges)
the areas in between the fingers undergo apoptosis due to antagonism between retinoic acid and TGF-beta
21
Q
what cells give rise to the bones, ligaments and blood vessels
A
the mesenchyme of the limb buds
22
Q
what is the function of the chondrification centers
A
result in the entire limb skeleton being cartilaginous
23
Q
where does osteogenesis begin in the 7th week
A
from primary ossification centers in the diaphysis of long bones
24
Q
from where do myoblasts form and then what do they do
A
from the dermomyotome regions of somites–> myogenic precursor cells migrate to the limb bud to form myoblasts
myoblasts aggregate and form muscle mass in each limb bud
muscle mass separates into dorsal (extensors) and ventral (flexor) components
25
when do the limb buds rotate
by the 7th week
26
in what direction do the upper limbs rotate
laterally through 90 degrees on their longitudinal axis
extensor muscle lie on the lateral and posterior aspect of the limb and the elbow points dorsally
27
in what direction do the lower limbs rotate
rotate medially through 90 degrees
extensor muscle lie on anterior aspect of the limb and knee points ventrally
28
what gene controls the anterior/posterior axis of the limb
Shh gene
29
what gene controls the dorso/ventral axis of the limb
determined later and controlled by Wnt7 and engrailed
30
what gene controls the proximal/distal axis of the limb
(outgrowth)
maintained by Wnt7 and Shh
31
what early cell type gives rise to the three basic groups of ectoderm, mesoderm, and endoderm
epiblast cells
32
what cell types are derived from ectoderm
1. epidermis, hair, nails, glands of skin
2. brain and spinal cord
3. neural crest--> sensory nerve cells and some nervous structures; pigment cells; portions of skeleton; blood vessels in head and neck
33
into what separate cell groups/structures does the mesoderm first differentiate into?
1. notochord
2. somites
3. intermediate mesoderm
4. lateral plate mesoderm (somatic versus splanchnic mesoderm subdivisions)
34
what structures are derived from the following mesodermal structure:
notochord
nucleus pulposus of the intervertebral discs
35
what structures are derived from the following mesodermal structure:
somites
1. sclerotome--> vertebrae and ribs
2. dermatome--> dermis of dorsal body region
3. myotome--> trunk and limb musculature
36
what structures are derived from the following mesodermal structure:
intermediate medoserm
kidneys and gonads
37
what structures are derived from the following mesodermal structure:
somatic mesoderm (from lateral plate mesoderm )
1. parietal serosa
2. dermis of ventral region of body
3. connective tissues of limbs (bones, joints and ligaments)
38
what structures are derived from the following mesodermal structure:
splanchnic mesoderm (from lateral plate mesoderm)
1. wall of digestive and respiratory tracts (except epithelial lining)
2. visceral serosa
3. heart
4. blood vessels
39
what structures are derived from entoderm
epithelial lining and glands of digestive and respiratory tracts
40
when and from what cell group does cartilage develop
develops from mesenchyme during 5th week
41
list the 3 types of cartilage
1. hyaline (most widely distributed i.e in synovial joints)
2. fibrocartilage (i.e intervertebral discs)
3. elastic (i.e in auricles of external ears)
42
how does cartilage form in development
mesenchyme condenses to form chondrification centers
these centers differentiate into chondroblasts which secrete collagenous fibrils and ECM
in the 4th phase, chondrocytes stop dividing and become hypertrophic
large chondrocytes alter their matrix and add collagen X and more fibronectin
this enables it to become mineralized by calcium carbonate
collagenous and/or elastic fibers are deposited int he intracellular substance or matrix
diaphysis is the location of the primary center of ossification and forms the shaft of the bone
43
what is the location of the primary center of ossification
the diaphysis
44
when do the joint begin to develop?
6th week
45
what does BMP stand for?
bone morphogenic protein
46
what other process is happening when the joints begin to develop?
joints begin to develop with the appearance of condensed mesenchyme in the 6th week
47
what does mesenchyme secrete as it condenses?
BMP
48
why is BMP important?
it is necessary for mesenchyme to develop into cartilage and bone
49
what is secreted by regions that will form synovial joints?
a protein called Noggin that antagonizes BMP
50
what is the consequence of the secretions of BMP-antagonist protein Noggin by areas that will become synovial joints?
condensation of the mesenchyme in these regions results in apoptosis and the formation of fluid filled spaces between the cartilaginous rods
articular cartilage forms on ends of these rods
51
what are the 4 stages of joint formation
1. homogenous interzone (regions that is morphological precursoe of the eventual joint)
2. 3 layer interzone
3. early liquefaction of middle layer
4. full separation and joint cavitation
52
do joints develop from the mesenchyme?
no they develop from the blastema
53
what is the blastema
mass of cells capable of regeneration
54
what are the 3 types of joints based on structure
1. fibrous
2. cartilaginous
3. synovial
55
what characterizes a fibrous joint
the interzonal mesenchyme between the developing bones differentiates into dense fibrous tissue (i.e the sutures of the cranium)
no space between bones
56
what characterizes a cartilaginous joint
interzonal mesenchyme between the developing bones differentiates into hyaline (i.e the costochondral joints) or fibrocartilage (the public symphysis)
57
what characterizes a synovial joint and how does this develop?
interzonal mesenchyme between bones differentiates into:
1. peripherally--> interzonal mesenchyme forms the joint capsular ligament and other ligaments
2. centrally--> mesenchyme disappears and space becomes the joint cavity or synovial cavity
3. where the mesenchyme lines the joint capsule and articular surfaces it forms the synovial membrane which secretes the synovial fluid
4. mesenchyme interzone develops before the development of the synovial membrane
58
what is osteogenesis
the formation of bone
59
what are the two patterns of osteogenesis
1. intramembranous
2. endochondral
*both of these processes lead to the formation of immature woven bone, which is eventually remodeled into either compact or spongy bone
60
what is the human skeleton made up of before week 8 of development in utero
made up of hyaline cartilage and fibrous membranes--> these are the precursors to bone
61
what is the precursor for endochondral osteogenesis
hyaline cartilage
62
what is the precursor for intramembranous osteogenesis
fibrous connective tissue membranes
63
which bones form through endochondral osteogenesis?
which form through intramembranous?
1. endochondral--> bones of extremities and parts of axial skeleton that bear weight (i.e vertebrae); mostly long bones
2. intramembranous--> flat bones of the skull and face, mandible, clavicle
64
what are mesenchymal stem cells?
precursors to osteoblasts and chondrocyte progenitor cells
65
what are chondrocyte progenitor cells
eventually become chondrocytes (cartilage)
66
what are osteoblasts
responsible for bone formation--> secrete osteoid (unmineralized bone matrix) around themselves
get stuck in the bone matrix and become osteocytes
67
what are osetoclasts
responsible for bone resorption (both in remodeling and repair)--> made from fusion of monocytes--> are like "bone macrophages"
68
what are osteocytes
responsible for bone maintenance
69
describe the process of intramembranous bone formation
1. develops directly from the mesenchyme--> there is no cartilage model precursor!!!
2. forms within membranes from clustering of mesenchymal cells
3. mesenchymal cells migrate and aggregate
4. cells differentiate into osteoprogenitor cells and osteoblasts--> ossification center appears in the fibrous connective tissue
5. osteoblasts begin to secrete osteoid and become trapped in matrix
6. newly formed matrix begins to calcify and form spicules (calcification due to alkaline phosphatase in osteoid)
7. mesenchyme cells on surface of the trabeculae (plates of bone) condense to form periosteum
8. osteoblasts continue to produce bony matrix--> 3D lattice of spongy bone is formed (known as appositional growth...woven bone forms first)
9. in the intervening spaces, vascular tissue containing primary bone marrow forms--> note that osteoid is laid down in between blood vessels leading to a random arrangment of trabeculae known as woven bone which will eventually be remodelled into lamellae and form spongy or compact bone
10. osteoclasts migrate in and begin bone remodeling
11. formation of woven bone collar by the trabeculae just deep to the periosteum thickening--> later replaced by mature lamellar bone
12. trabeculae on the inside of the woven bone and periosteum persist forming spongy bone--> its vascular tissue becomes red marrow
70
what is osteoid?
what are its two components?
unmineralized bone matrix secreted by osteoblasts
two components:
1. organic matrix--> proteoglycans and type 1 collagen
2. alkaline phosphatase which induces mineralization via precipitation of calcium and phosphate salts, causing the matrix to harden
71
what is the periosteum and what is it formed from
periosteum is dense connective tissue on the surface of trabeculae that forms a site of attachment for muscles, ligaments and tendons
it is formed from mesenchyme calls that condense on the surface of the trabeculae
72
what are the 10 steps of endochondral osteogenesis
1. develop a hyaline cartilage model
2. develop a bony collar
3, 4. death of central chondrocytes and invasion of blood vessels
5. formation of primary ossification center
6. growth on endochondral bone
7, 8. secondary ossification center
9,10. skeletal maturity
73
what happens in step 1. of endochondral bone formation: development of a hyaline cartilage? (how does this happen)
1. aggregation of mesenchymal cells
2. cells differentiate into chondrocytes
3. produce cartilage matrix
4. model grows by interstitial and appositional growth--> the cartilage model is like a mini version of the bone but made of cartilage
this model is used as scaffolding for the laying down of bone matrix and is broken down as ossification proceeds
74
what is interstitial bone growth
growth in length
due to division of chondrocytes
75
what is appositional bone growth
growth in width
due to deposition of cartilage from new chondrocytes that differentiate from the perichondrium
76
what happens in step 2. of endochondral bone formation: develop a bony collar (how does this happen)
1. cells in the perichondrial region no longer produce chondrocytes and instead produce osteoblasts
2. perichondrial region now becomes a periosteum with an identifiable osteogenic layer
3. layer of bone is formed around the cartilage model and this is called the bony collar (in diaphysis of long bones)--> formed through intramembranous ossification
*the bony collar eventually becomes compact bone
77
what happens in step 3 and 4 of endochondral bone formation: death of central chondrocytes and invasion of blood vessels (how does this happen)
1. bony collar cuts off blood supply to chondrocytes within the mid-region and they become hypertrophic--> matrix is resorbed leaving irregular plates of cartilage; hypertrophic cells secrete alkaline phosphatase and the surrounding matrix becomes calcified
2. death of chondrocytes results in matrix breakdown producing a large cavity
3. blood vessels grow through the thin bone collar
78
what happens in step 5. of endochondral bone formation: formation of primary ossification center (how does this happen)
1. periostel mesenchyme cells periosteum migrate along the blood vessels and differentiate into osteoprogenitor cells in the narrow cavity
2. osteoprogenitor cells come into contact with calcified cartilage plates--> differentiate into osteoblasts and lay down osteoid on cartilage spicules (this is endochondral ossification)
3. first site where bone begins to form is known as the primary ossification center
4. bone and cartilage together form mixed spicules
79
what happens in step 6 of endochondral bone formation: growth on endochondral bone?(how does this happen)
1. as the diaphyseal marrow cavity enlarges, there forms a distinct zone of cartilage at bone ends--> this is epiphyseal cartilage
2. the growth plate is the replacement of avascular cartilage with vascularized bone--> division between the diaphyseal cavity and the cartilage--> the growth plate is responsible for growth in length of long bones and continues until skeletal maturity
80
what happens in steps 7 and 8 of endochondral bone formation: secondary ossification center? (how does this happen)
1. as bone is laid down on calcified spicules, cartilage is resorbed leaving primary spongy bone
2. shortly after birth, a secondary ossification center develops at the PROXIMAL epiphysis
3. replacement of cartilage with the primary spongy bone is the same as the process in diaphysis
4. a 2nd secondary ossification center develops at the distal end of the bone
81
what happens in steps 9 and 10 of endochondral bone formation: skeletal maturity? (how does this happen)
when an individual reaches maximal growth, proliferation of cartilage within the epiphyseal plate ceases
1. deposition of new bone continues until no more cartilage
2. epiphyseal and marrow cavities become confluent
3. elimination of epiphyseal plate occurs--> epiphyseal closure
4. only remaining cartilage is at the articular surfaces!!
82
what is the epiphyseal growth plate?
the division between the diaphyseal cavity and the cartilage and is the site of replacement of avascular cartilage with vascularized bone --> this is responsible for the growth in bone length and continues until skeletal maturity
83
what is the function of the growth plate?
allows for lengthening of bone during development
84
what are the 5 zones that make up the growth plate structure?
1. zone of reserve cartilage (reserve zone)
2. zone of proliferation
3. zone of hypertrophy
4. zone of calcified cartilage/matrix
5. zone of resorption/ossification (this is also called the metaphysis or the transitional zone)
85
what happens at the zone of reserve cartilage in the growth plate?
contains normal, resting hyaline cartilage cells--> cells exhibit no proliferation or active matrix production
86
what happens at the zone of proliferation in the growth plate?
contains actively dividing cartilage cells that are larger than those in the reserve zone and organized into distinct columns
actively producing collagen and cartilage matrix proteins
gives rise to the cartilage on which bone is later laid down--> responsible for the actual lengthening of bone during growth
87
what happens at the zone of hypertrophy in the growth plate?
cells in this zone are greatly enlarged (hypertrophic) cartilage cells
the cytoplasm of these cells is clear because of the glycoprotein that accumulate
metabolically active cells continue to secrete type I collagen and increasing levels of type X collagen
chondrocytes synthesize alkaline phosphatase which induces calcification of the cartilage matrix
88
what happens at the zone of calcified cartilage in the growth plate?
hypertrophied chondrocytes begin to degenerate and the cartilage matrix becomes calcified
the calcified cartilage matrix then serves as a scaffold for deposition of new bone
89
what happens at the zone of resorption/ossification in the growth plate?
this is the zone nearest the diaphysis
the calcified cartilage is in direct contact with the marrow cavity
small blood vessels invade the space previously occupied by dying chondrocytes and the source of the osteoprogenitor cells and differentiate into bone-producing cells
cartilage is being resorbed and replaced by bone--> histologically, mixed spicules are visible
90
what are the 3 types of bone
1. women bone
2. mature compact bone (cortical bone)
3. mature spongy bone (trabecular bone)
91
what is s synonym for cortical bone
mature compact bone
92
what is a synonym for mature spongy bone
trabecular bone
93
what is unique about woven bone
it is primary bone
94
when is woven bone formed
formed in time of NO STRESS
95
describe the structure of woven bone
no organized lamellae
formed in time of no stress--> without any directional characteristics
contains more cells per unity area, and cells are randomly arranged
matrix has more ground substance
less mineralization
numerous osteophytes, high density, rapidly forming
formed predominantly in EMBRYOS, during physiological growth, fracture repair or pathological bone tumors
96
what is the structural unit of cortical/compact bone?
the osteon
97
describe the structure of the osteon
1. central canal/Haversian canal--> contains vascular and nerve supply for the osteon
2. concentric lamellae
3. osteocytes in the lacunae-> typically arranged in a radial pattern (concentric lamellae)
4. cannaliculi--> send stress signals, exchange cellular waste for nutrient and oxygen
98
in the growth plate, what type of bone replaces resorbed cartilage in zone 5?
spongy bone (trabecular)
99
what are Volkmann canals
found in compact/cortical bone
bring blood vessels/nerves from outside to inside (not surrounded by concentric lamellae)
100
what are interstitial lamellae
found in cortical bone
are remnants of previous concentric lamellae
101
where is compact/cortical bone found?
compact bone is limited to the outer shell (or cortex) of bone while spongy bone is found in the internal areas of bone
102
describe the structure and process of formation of cortical bone
1. covered on exterior surface by periosteum, and internal surface by endosteum --> the endosteum is less well defined but it has osteogenic potential during periods of bone growth and development and during fracture healing
2. forms initially at the primary center of ossification by intramembranous ossification (bony collar)--> later when the cortex thickens, it does so by appositional growth beneath the periosteum and beneath the endosteum (fills the space between lamellae)
3. also forms as primary osteons around longitudinal blood vessels during bone development
103
what lines each haversian canal?
osteoblasts
104
where is spongy bone found
internal part of bone and at the metaphysis
105
describe the structure of spongy bone
similar to mature compact/cortical bone except the tissue is arranged as trabeculae or spicules with bone marrow and sinuses in intervening spaces
matrix of spongy bone is lamellated with lamellae arranged in PARALLEL (versus concentric in compact)
each trabeculae that forms on these layers of cartilage is lined with osteoblasts
osteoblasts become osteocytes when trapped and can communicate with each other through cannaliculi (fine bone tunnels containing cellular processes)
106
how can spongy bone be formed
by endochondral ossifications on "scaffolds" from pre-existing calcified cartilage spicules
can also be formed during intramembranous ossification, where bone scaffold forms de novo in fibrous tissue
107
what part of the bone is the diaphysis
the shaft
it is dense cortical bone with a thick cortex to provide strength (structure is osteons with a haversian system)
108
what part of the bone is the metaphysis
in adults, it is the entire head of the bone (once the growth plate closes, you no longer distinguish between the meta and epiphysis)
in children, it is the space between the epiphysis and diaphysis (i.e where cartilage turns to bone)
trabecular (spongy/cancellous) bone--> transmits force from the joint surface to the bone
is lamellar bone but does not contain osteons
cortex is thin
trabeculae surrounded by marrow
109
what is the periosteum
outer surface of bone except parts covered by articular cartilage
vessels enetrate this layer to run in the volkmann canals
110
describe the structure of the periosteum
tough, fibrous, specialized connective tissue
outer layer--> fibroblasts, type I collagen, nerves, blood vessels
inner layer--> blood vessels, osteoprogenitor cells, osteoblasts
111
describe what is found in the outer layer of the periosteum
fibroblasts, type I collagen, nerves, blood vessels
112
describe what is found in the inner layer of the periosteum
blood vessels, osetoprogenitor cells, osteoblasts
113
what anchors the periosteum to the bone?
anchored by collagen fibers known as Sharpey fibers
114
why is the periosteum important
important for appositional growth and fracture repair
115
what important cells are found in the inner cambium of the periosteum
quiescent stem cells which differentiate to osteoblasts during periods of bone growth and during fracture healing
116
what is the endosteum
the membranous inner surface of compact bone and spongy bone
it is in contact with the bone marrow space
often one cell layer thick
117
what type of cells make up the endosteum
osteoprogenitor cells
bone matrix secreting cells
bone lining cells
*osteogenic potential*
118
what are endosteal cells?
osteoprogenitor cells + bone lining cells
119
what are osteoblasts
the bone-forming cells responsible for synthesis of bone matrix
120
what are the secretory functions of osteoblasts
1. Type I collagen
2. Bone matrix protein
3. proteoglycans
4. calcification of bone matrix
121
what two substances are used as clinical markers of osteoblast activity
circulating levels of ALP and osetocalcin
122
what are the two components of bone matrix protein (secreted by osteoblasts)
1. calcium binding proteins (osteocalcin)
| 2. multiadhesive glycoproteins (osteopontin)
123
describe how osteoblasts cause the calcification of bone matrix
initiated when local concentration of Ca2+ and PO4 ions in the matrix exceed a threshhold
calcium will induce osteoblasts to secrete matrix vesicles rich in ALP and pyrophosphatase (cleaves PO4)
the accumulation of calcium and cleavage of PO4 results in the crystallization of hydroxyapatite
124
what are osteocytes
osteoblasts that have ceased producing osteoid and have become completely embedded in the bone matrix
are mature bone cells enclosed within a boney matrix
secrete matrix proteins
sit in the lacuna
linked thru gap junctions
transduce STRESS SIGNALS--> bending or stretching
125
how do osteocytes communicate with osteoblasts
via fillipodial processes in the cannaliculi
126
what are osteoclasts
large, multinucleated cells
derived from monocyte precursors involved in the resporption of bone
active secretory cell
127
what is the cavity called the osteoclasts occupy as they resorb bone
the Howship Lacuna
128
how many nuclei do osteoclasts have
can have upwards of 50 nuclei
129
list the 4 specialized regions of osteoclasts
1. basal zone
2. ruffled border
3. clear zone
4. basolateral region
130
what is found in the basal zone of osteoclasts
houses nuclei and organelles and tend to congregate away from site of resorption
131
what is found in the ruffled border zone of osteoclasts
part of the cell that is in direct contact with the bone
projections increase surface area for the release of hydrolytic enzymes, secretion of protons and endocytosis of degraded products
132
what % of bone is inorganic components
65%
133
what % of bone is organic components
35%
134
list the inorganic components of bone
1. hydroxyapatite
2. calcium
3. phosphorus
4. magnesium
5. citrate
6. potassium
7. sodium
135
what is osteoid
organic
unmineralized portion of the bone that forms prior to maturation of bone tissue
136
list the organic components of bone
1. major structural components (type I collagen)
2. proteoglycans
3. multi-adhesive glycoproteins (osteopontin, osteonecin)
4. bone-specific vitamin K dependent proteins (osteocalci)
5. growth factors/cytokines (BMP)
137
how is collagen formed inside the cell
1. two types of peptide chains are formed during translation--> alpha 1 and alpha 2
2. polypeptide chains are released into the lumen of the RER
3. signal peptides are cleaved inside the RER and become pro-alpha chains
4. hydroxylation of lysine and proline amino acids occurs inside the lumen--> this step is dependent of VITAMIN C as a cofactor!!!
5. glycosylation of specific hydroxylysine residues occurs
6. triple helical structure is formed inside the endoplasmic reticulum from each two alpha-1 and alpha-2 chains
7. pro-collagen is shipped to the golgi and it is exocytosed
138
why is vitamin c important for collagen formation
because one of the steps, the hydroxylation of lysine and proline amino acids that occurs inside the lumen of the RER is dependent on vitamin C as a cofactor
139
how is collagen formed outside the cell (after procollagen is released from the golgi)?
1. procollagen peptidase cleaves procollagen into tropocollagen units
2. multiple tropocollagen molecules form collagen fibrils via covalent cross-linking (an aldol reaction) which links hyxrodylysine and lysine residues
3. collagen may be attached to cell membranes via several types of proteins--> fibronectin and integrin
140
how many type of collagen are there?
28 have been identified, but there are 5 most common types that we care about
141
what type of structures are associated with the following types of collagen:
type I collagen
skin
tendon
vascular ligature
fibrocartilage
organs
bone (**main component of bone**)
142
what type of structures are associated with the following types of collagen:
type II collagen
cartilage (main component of hyaline cartilage)
143
what type of structures are associated with the following types of collagen:
type III collagen
reticular (main component of reticular fibres)
commonly found alongside type I
144
what type of structures are associated with the following types of collagen:
type IV collagen
forms bases of cell basement membrane
145
what type of structures are associated with the following types of collagen:
type V collagen
cell surfaces
hair
placenta
146
what determines the shape of bone
in part it is the forces acting on it that determine its shape
147
like 4 reasons for bone remodeling
1. tissue renewal--> process occurs throughout life
2. changes in requirements--> change in physical activity
3. injury/micro injury repair--> micro fracture, stress fracture, clinical/gross fracture
4. change in anatomy--> fracture maturation, malunion, post surgical realignment
148
what are the 4 phases of bone remodeling and what happens in each phase
1. activation--> steps needed to recruit osteoclasts (3-7 days)
2. resorption--> osteoclasts tunnel out a resorptive space (2-4 weeks)
3. reversal--> interval of time between end of resorption and beginning of osteoblastic bone formation
4. formation--> osteoblasts lay down matrix, mineralization occurs (4-6 months)
149
what is Wolff's law
bone will ADAPT to the loads it is placed under
if loading on a particular bone increases, the bone will become stronger to resist loading
if loading on a bone decreases, bone will adapt and become weaker
150
how is bone remodelling regulated systemically (positive and negative)
positive: growth hormone, thyroid hormone, parathyroid hormone, vitamin D
negatively: calcitonin, cortisone, calcium
151
how is bone remodelling regulated locally
1. local factors (IGF, EGF, interleukins)
2. mechanical stressors (fractures, defects, implants)
3. inflammatory processes
4. blood supply
152
in what type of bone would you find osteons
only found in cortical (compact) bone
153
how are osteons formed
formed when capillaries invade cortical bone (or immature woven bone that will become cortical bone)
secondary osteons are preceeded by osteoclasts called a "cutting cone"
new concentric lamellae are laid down by osteoblasts (from outside to inside)
osteoblasts become trapped in the usual way to form osteocytes
successive concentric lamellae are laid down until only the Haversian Canal containing the capillary and lined by osteoblasts remains
**the further down the cutting cone you go, the more layers of concentric lamellae are seen--> proximal end has less lamellae**
154
what is unique about the formation of osteons in woven bone versus cortical bone
if this process is taking place in immature woven bone, the osteon that is formed is referred to as a primary osteon
if its taking place in mature cortical bone, the osteon is called a secondary osteon
155
what are the 5 general stages of fracture healing
hematoma--> resorption--> soft callus--> hard callus--> remodelling
156
what are the phases associated with secondary bone healing
1. inflammation
2. repair
3. remodelling
157
in secondary bone healing, what happens in the inflammation phase
bleeding, hematoma formation--> this is the source of progenitor cells
granulation tissue forms
initial stability from tissue turgidity (relative)
bone ends are resorbed
158
in secondary bone healing, what happens in the repair phase
begins within 2 weeks and continues for weeks to months
bridging (soft) callus--> non ossified fibrous and cartilaginous tissue
soft callus is replaced by hard (ossified) callus--> replaces soft callus via a process of endochondral ossification into woven bone
amount of callus is proportional to the amount of motion at the fracture
159
in secondary bone healing, what happens in the remodelling phase
process that begins during the repair phase
involves the conversion of woven bone into lamellar bone
continues long after the fracture is clinically healed (i.e years)
woven bone replaced by laminar cortical bone through haversian remodelling
allows bone to assume more normal shape
based on the stress experienced by the bone according to wolffs law
160
how does secondary healing differ in metaphyseal bone versus diaphyseal bone
it is trabecular bone so the callus normally forms WITHIN the bone although it may be external depending on location
since the cortex is thin, there is usually minimal external callus when the fracture heals (large callus would interfere with the joint)
instead, a large internal callus forms due to copious trabecular bone at the metaphysis
fracture line appears sclerotic and filled in rather than showing a large external callus on radiograph
(diaphyseal bone shows large external callus)
161
when does primary healing occur?
occurs when there is no motion at the fracture site and when the fracture gap is less than 1 mm (i.e stress fractures)
also occurs in surgery when reduction is achieved and plates/screws are used to hold the fracture in place
162
how does primary healing differ from secondary bone healing
no fracture callus formation--> bone heals directly
gaps are filled in with woven bone
cutting cones then cross the fracture site causing new osteons to bridge the fracture and thus direct remodelling
163
how many classifications for fractures are there under the Salter-Harris scheme?
what does the SH scheme describe?
I, II, III, IV, V
a way to classify fractures in children when the growth plate is still open
164
what does Salter-Harris I describe?
5-7% of fractures are SH I
"slipped"
type I fractures go through the growth plate only --> if they are not displaced, they can be hard to see on radiographs (sometimes diagnosis made on clinical tenderness only)
not involving mature bone
good prognosis
165
what does Salter-Harris II describe?
75% of fractures--> most common
"above"
fracture plane passes across most of growth plate and up through the metaphysis (type II fracture start through the growth plate and then exit through the metaphysis)
good prognosis
166
what does Salter-Harris III describe?
7-10% of fractures
"below"
type III fractures go through the epiphysis and then exit along the growth plate-->
poorer prognosis--> joint surface is involved
167
what does Salter-Harris IV describe?
10%
intra-articular
"through transverse"
fractures go through the epiphysis and then cross the growth plate and exit through the metaphysis
poorer prognosis--> joint surface is involved plus the petaphyseal bone can heal to epiphyseal bone and cause a GROWTH ARREST
168
what does Salter-Harris V describe?
less than 1%
"ruined"
crushing type injury to the growth plate
does not displace growth plate but damages it by compression
worst prognosis --> GROWTH ARREST is very likely
169
how long does a fracture in a metaphyseal bone in an adult take to heal
6-8 weeks
170
how long does it take for a metaphyseal bone to heal, comparatively, in the following populations/structures:
1. elderly
2. cortical bone
3. open fracture (soft tissue injury)
4. smoker
5. noncompliant patient
6. children
1. double
2. double
3. double
4. double
5. double or quadruple
6. halved
171
what is the importance of the formation of the fracture hematoma to the inflammatory phase of secondary healing?
the fracture hematoma causes platelets to degranulate and initiates the clotting cascade
dying cells in damaged tissue and in the necrotic bone ends also release inflammatory mediators that recruit PMNs and macrophages (granulation tissue formation)
172
what % of the osetoid is type I collagen
about 90%
173
what is the other 10% of osteoid that is not type I collagen
ground substance
ground substance is mostly made up of chondroitin sulfate and osteocalcin
174
what is a compound fracture and why do they heal slower
compound fractures mean that the skin is disrupted and therefore the fracture hematoma is contaminated and partially lost thru the skin
175
what is the result of too much motion during fracture healing
SOME motion helps because instigates fracture formation
too much motion can result in cartilage formation instead of bone formation and thus a pseudoarthritis (false joint) develops
176
what is the blood supply for the femoral head
acetabular branch of the obturator artery, via ligamentum teres femoris that passes in the acetabular notch
media circumflex artery branch of the profunda femoris artery
