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MSK 1 Flashcards

1
Q

at what week of development do the limb buds form

A

4th week of development

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2
Q

describe the formation of the limb buds

A
  1. begins with activation of mesenchymal cells in the LATERAL MESODERM
  2. begins as a mass of mesenchyme covered by ectoderm–> look like small elevations of ventrolateral body wall
  3. development of upper limbs occurs slightly before lower limbs
  4. mesenchyme is derived from SOMATIC layer of the lateral mesoderm
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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:

  1. dermatome–> dermis of skin
  2. myotome–> skeletal muscle
  3. sclerotome–> bone
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4
Q

at what week do the limb bones begin to form

A

week 5

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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

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6
Q

at what point in development is the entire skeleton cartilaginous

A

by the 6th week

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7
Q

what happens to the shape of the limb bud in the 6th week

A

becomes paddle shaped

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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

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9
Q

by what week have the mesenchymal cells in the hand plates condensed to form finger buds

A

end of the 6th

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10
Q

by what week have the mesenchymal cells in the foot plates condensed to form toe buds

A

end of the 7th

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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

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12
Q

when is the most vulnerable time for limb development

A

24-36 days post fertilization (5-7 weeks gestation)

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13
Q

what results due to loss or damage of the AER?

A
  1. amelia–> complete failure of limb development

2. micromelia–> partial limb development

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14
Q

what abnormality leads to polydactyly or syndactyly (fused digits)?

A

improper gradient of the ZPA and Shh

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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

  1. ventromedial
  2. dorsolateral
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16
Q

into what two parts does each somite differentiate into

A
  1. ventromedial–> SCLEROTOME (forms vertebrae and ribs)

2. dorsolateral–> DERMOMYOTOME (cells from myotome form myoblasts and dermatome forms dermis)

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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

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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

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19
Q

what is Shh responsible for

A

controls patterning of the limb along the anteroposterior axis

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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

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21
Q

what cells give rise to the bones, ligaments and blood vessels

A

the mesenchyme of the limb buds

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22
Q

what is the function of the chondrification centers

A

result in the entire limb skeleton being cartilaginous

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23
Q

where does osteogenesis begin in the 7th week

A

from primary ossification centers in the diaphysis of long bones

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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

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25
Q

when do the limb buds rotate

A

by the 7th week

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26
Q

in what direction do the upper limbs rotate

A

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

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27
Q

in what direction do the lower limbs rotate

A

rotate medially through 90 degrees

extensor muscle lie on anterior aspect of the limb and knee points ventrally

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28
Q

what gene controls the anterior/posterior axis of the limb

A

Shh gene

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29
Q

what gene controls the dorso/ventral axis of the limb

A

determined later and controlled by Wnt7 and engrailed

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30
Q

what gene controls the proximal/distal axis of the limb

A

(outgrowth)

maintained by Wnt7 and Shh

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31
Q

what early cell type gives rise to the three basic groups of ectoderm, mesoderm, and endoderm

A

epiblast cells

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32
Q

what cell types are derived from ectoderm

A
  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
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33
Q

into what separate cell groups/structures does the mesoderm first differentiate into?

A
  1. notochord
  2. somites
  3. intermediate mesoderm
  4. lateral plate mesoderm (somatic versus splanchnic mesoderm subdivisions)
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34
Q

what structures are derived from the following mesodermal structure:

notochord

A

nucleus pulposus of the intervertebral discs

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35
Q

what structures are derived from the following mesodermal structure:

somites

A
  1. sclerotome–> vertebrae and ribs
  2. dermatome–> dermis of dorsal body region
  3. myotome–> trunk and limb musculature
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36
Q

what structures are derived from the following mesodermal structure:

intermediate medoserm

A

kidneys and gonads

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37
Q

what structures are derived from the following mesodermal structure:

somatic mesoderm (from lateral plate mesoderm )

A
  1. parietal serosa
  2. dermis of ventral region of body
  3. connective tissues of limbs (bones, joints and ligaments)
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38
Q

what structures are derived from the following mesodermal structure:

splanchnic mesoderm (from lateral plate mesoderm)

A
  1. wall of digestive and respiratory tracts (except epithelial lining)
  2. visceral serosa
  3. heart
  4. blood vessels
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39
Q

what structures are derived from entoderm

A

epithelial lining and glands of digestive and respiratory tracts

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40
Q

when and from what cell group does cartilage develop

A

develops from mesenchyme during 5th week

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41
Q

list the 3 types of cartilage

A
  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)
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42
Q

how does cartilage form in development

A

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

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43
Q

what is the location of the primary center of ossification

A

the diaphysis

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44
Q

when do the joint begin to develop?

A

6th week

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45
Q

what does BMP stand for?

A

bone morphogenic protein

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46
Q

what other process is happening when the joints begin to develop?

A

joints begin to develop with the appearance of condensed mesenchyme in the 6th week

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47
Q

what does mesenchyme secrete as it condenses?

A

BMP

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48
Q

why is BMP important?

A

it is necessary for mesenchyme to develop into cartilage and bone

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49
Q

what is secreted by regions that will form synovial joints?

A

a protein called Noggin that antagonizes BMP

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50
Q

what is the consequence of the secretions of BMP-antagonist protein Noggin by areas that will become synovial joints?

A

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

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51
Q

what are the 4 stages of joint formation

A
  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
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52
Q

do joints develop from the mesenchyme?

A

no they develop from the blastema

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53
Q

what is the blastema

A

mass of cells capable of regeneration

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54
Q

what are the 3 types of joints based on structure

A
  1. fibrous
  2. cartilaginous
  3. synovial
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55
Q

what characterizes a fibrous joint

A

the interzonal mesenchyme between the developing bones differentiates into dense fibrous tissue (i.e the sutures of the cranium)

no space between bones

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56
Q

what characterizes a cartilaginous joint

A

interzonal mesenchyme between the developing bones differentiates into hyaline (i.e the costochondral joints) or fibrocartilage (the public symphysis)

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57
Q

what characterizes a synovial joint and how does this develop?

A

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
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58
Q

what is osteogenesis

A

the formation of bone

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59
Q

what are the two patterns of osteogenesis

A
  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

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60
Q

what is the human skeleton made up of before week 8 of development in utero

A

made up of hyaline cartilage and fibrous membranes–> these are the precursors to bone

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61
Q

what is the precursor for endochondral osteogenesis

A

hyaline cartilage

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62
Q

what is the precursor for intramembranous osteogenesis

A

fibrous connective tissue membranes

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63
Q

which bones form through endochondral osteogenesis?

which form through intramembranous?

A
  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
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64
Q

what are mesenchymal stem cells?

A

precursors to osteoblasts and chondrocyte progenitor cells

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65
Q

what are chondrocyte progenitor cells

A

eventually become chondrocytes (cartilage)

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66
Q

what are osteoblasts

A

responsible for bone formation–> secrete osteoid (unmineralized bone matrix) around themselves

get stuck in the bone matrix and become osteocytes

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67
Q

what are osetoclasts

A

responsible for bone resorption (both in remodeling and repair)–> made from fusion of monocytes–> are like “bone macrophages”

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68
Q

what are osteocytes

A

responsible for bone maintenance

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69
Q

describe the process of intramembranous bone formation

A
  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
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70
Q

what is osteoid?

what are its two components?

A

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
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71
Q

what is the periosteum and what is it formed from

A

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
Q

what are the 10 steps of endochondral osteogenesis

A
  1. develop a hyaline cartilage model
  2. develop a bony collar
    3, 4. death of central chondrocytes and invasion of blood vessels
  3. formation of primary ossification center
  4. growth on endochondral bone
    7, 8. secondary ossification center
    9,10. skeletal maturity
73
Q

what happens in step 1. of endochondral bone formation: development of a hyaline cartilage? (how does this happen)

A
  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
Q

what is interstitial bone growth

A

growth in length

due to division of chondrocytes

75
Q

what is appositional bone growth

A

growth in width

due to deposition of cartilage from new chondrocytes that differentiate from the perichondrium

76
Q

what happens in step 2. of endochondral bone formation: develop a bony collar (how does this happen)

A
  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
Q

what happens in step 3 and 4 of endochondral bone formation: death of central chondrocytes and invasion of blood vessels (how does this happen)

A
  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
Q

what happens in step 5. of endochondral bone formation: formation of primary ossification center (how does this happen)

A
  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
Q

what happens in step 6 of endochondral bone formation: growth on endochondral bone?(how does this happen)

A
  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
Q

what happens in steps 7 and 8 of endochondral bone formation: secondary ossification center? (how does this happen)

A
  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
Q

what happens in steps 9 and 10 of endochondral bone formation: skeletal maturity? (how does this happen)

A

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
Q

what is the epiphyseal growth plate?

A

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
Q

what is the function of the growth plate?

A

allows for lengthening of bone during development

84
Q

what are the 5 zones that make up the growth plate structure?

A
  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
Q

what happens at the zone of reserve cartilage in the growth plate?

A

contains normal, resting hyaline cartilage cells–> cells exhibit no proliferation or active matrix production

86
Q

what happens at the zone of proliferation in the growth plate?

A

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
Q

what happens at the zone of hypertrophy in the growth plate?

A

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
Q

what happens at the zone of calcified cartilage in the growth plate?

A

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
Q

what happens at the zone of resorption/ossification in the growth plate?

A

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
Q

what are the 3 types of bone

A
  1. women bone
  2. mature compact bone (cortical bone)
  3. mature spongy bone (trabecular bone)
91
Q

what is s synonym for cortical bone

A

mature compact bone

92
Q

what is a synonym for mature spongy bone

A

trabecular bone

93
Q

what is unique about woven bone

A

it is primary bone

94
Q

when is woven bone formed

A

formed in time of NO STRESS

95
Q

describe the structure of woven bone

A

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
Q

what is the structural unit of cortical/compact bone?

A

the osteon

97
Q

describe the structure of the osteon

A
  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
Q

in the growth plate, what type of bone replaces resorbed cartilage in zone 5?

A

spongy bone (trabecular)

99
Q

what are Volkmann canals

A

found in compact/cortical bone

bring blood vessels/nerves from outside to inside (not surrounded by concentric lamellae)

100
Q

what are interstitial lamellae

A

found in cortical bone

are remnants of previous concentric lamellae

101
Q

where is compact/cortical bone found?

A

compact bone is limited to the outer shell (or cortex) of bone while spongy bone is found in the internal areas of bone

102
Q

describe the structure and process of formation of cortical bone

A
  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
Q

what lines each haversian canal?

A

osteoblasts

104
Q

where is spongy bone found

A

internal part of bone and at the metaphysis

105
Q

describe the structure of spongy bone

A

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
Q

how can spongy bone be formed

A

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
Q

what part of the bone is the diaphysis

A

the shaft

it is dense cortical bone with a thick cortex to provide strength (structure is osteons with a haversian system)

108
Q

what part of the bone is the metaphysis

A

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
Q

what is the periosteum

A

outer surface of bone except parts covered by articular cartilage

vessels enetrate this layer to run in the volkmann canals

110
Q

describe the structure of the periosteum

A

tough, fibrous, specialized connective tissue

outer layer–> fibroblasts, type I collagen, nerves, blood vessels

inner layer–> blood vessels, osteoprogenitor cells, osteoblasts

111
Q

describe what is found in the outer layer of the periosteum

A

fibroblasts, type I collagen, nerves, blood vessels

112
Q

describe what is found in the inner layer of the periosteum

A

blood vessels, osetoprogenitor cells, osteoblasts

113
Q

what anchors the periosteum to the bone?

A

anchored by collagen fibers known as Sharpey fibers

114
Q

why is the periosteum important

A

important for appositional growth and fracture repair

115
Q

what important cells are found in the inner cambium of the periosteum

A

quiescent stem cells which differentiate to osteoblasts during periods of bone growth and during fracture healing

116
Q

what is the endosteum

A

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
Q

what type of cells make up the endosteum

A

osteoprogenitor cells

bone matrix secreting cells

bone lining cells

osteogenic potential

118
Q

what are endosteal cells?

A

osteoprogenitor cells + bone lining cells

119
Q

what are osteoblasts

A

the bone-forming cells responsible for synthesis of bone matrix

120
Q

what are the secretory functions of osteoblasts

A
  1. Type I collagen
  2. Bone matrix protein
  3. proteoglycans
  4. calcification of bone matrix
121
Q

what two substances are used as clinical markers of osteoblast activity

A

circulating levels of ALP and osetocalcin

122
Q

what are the two components of bone matrix protein (secreted by osteoblasts)

A
  1. calcium binding proteins (osteocalcin)

2. multiadhesive glycoproteins (osteopontin)

123
Q

describe how osteoblasts cause the calcification of bone matrix

A

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
Q

what are osteocytes

A

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
Q

how do osteocytes communicate with osteoblasts

A

via fillipodial processes in the cannaliculi

126
Q

what are osteoclasts

A

large, multinucleated cells

derived from monocyte precursors involved in the resporption of bone

active secretory cell

127
Q

what is the cavity called the osteoclasts occupy as they resorb bone

A

the Howship Lacuna

128
Q

how many nuclei do osteoclasts have

A

can have upwards of 50 nuclei

129
Q

list the 4 specialized regions of osteoclasts

A
  1. basal zone
  2. ruffled border
  3. clear zone
  4. basolateral region
130
Q

what is found in the basal zone of osteoclasts

A

houses nuclei and organelles and tend to congregate away from site of resorption

131
Q

what is found in the ruffled border zone of osteoclasts

A

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
Q

what % of bone is inorganic components

A

65%

133
Q

what % of bone is organic components

A

35%

134
Q

list the inorganic components of bone

A
  1. hydroxyapatite
  2. calcium
  3. phosphorus
  4. magnesium
  5. citrate
  6. potassium
  7. sodium
135
Q

what is osteoid

A

organic

unmineralized portion of the bone that forms prior to maturation of bone tissue

136
Q

list the organic components of bone

A
  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
Q

how is collagen formed inside the cell

A
  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
Q

why is vitamin c important for collagen formation

A

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
Q

how is collagen formed outside the cell (after procollagen is released from the golgi)?

A
  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
Q

how many type of collagen are there?

A

28 have been identified, but there are 5 most common types that we care about

141
Q

what type of structures are associated with the following types of collagen:

type I collagen

A

skin

tendon

vascular ligature

fibrocartilage

organs

bone (main component of bone)

142
Q

what type of structures are associated with the following types of collagen:

type II collagen

A

cartilage (main component of hyaline cartilage)

143
Q

what type of structures are associated with the following types of collagen:

type III collagen

A

reticular (main component of reticular fibres)

commonly found alongside type I

144
Q

what type of structures are associated with the following types of collagen:

type IV collagen

A

forms bases of cell basement membrane

145
Q

what type of structures are associated with the following types of collagen:

type V collagen

A

cell surfaces

hair

placenta

146
Q

what determines the shape of bone

A

in part it is the forces acting on it that determine its shape

147
Q

like 4 reasons for bone remodeling

A
  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
Q

what are the 4 phases of bone remodeling and what happens in each phase

A
  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
Q

what is Wolff’s law

A

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
Q

how is bone remodelling regulated systemically (positive and negative)

A

positive: growth hormone, thyroid hormone, parathyroid hormone, vitamin D
negatively: calcitonin, cortisone, calcium

151
Q

how is bone remodelling regulated locally

A
  1. local factors (IGF, EGF, interleukins)
  2. mechanical stressors (fractures, defects, implants)
  3. inflammatory processes
  4. blood supply
152
Q

in what type of bone would you find osteons

A

only found in cortical (compact) bone

153
Q

how are osteons formed

A

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
Q

what is unique about the formation of osteons in woven bone versus cortical bone

A

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
Q

what are the 5 general stages of fracture healing

A

hematoma–> resorption–> soft callus–> hard callus–> remodelling

156
Q

what are the phases associated with secondary bone healing

A
  1. inflammation
  2. repair
  3. remodelling
157
Q

in secondary bone healing, what happens in the inflammation phase

A

bleeding, hematoma formation–> this is the source of progenitor cells

granulation tissue forms

initial stability from tissue turgidity (relative)

bone ends are resorbed

158
Q

in secondary bone healing, what happens in the repair phase

A

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
Q

in secondary bone healing, what happens in the remodelling phase

A

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
Q

how does secondary healing differ in metaphyseal bone versus diaphyseal bone

A

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
Q

when does primary healing occur?

A

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
Q

how does primary healing differ from secondary bone healing

A

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
Q

how many classifications for fractures are there under the Salter-Harris scheme?

what does the SH scheme describe?

A

I, II, III, IV, V

a way to classify fractures in children when the growth plate is still open

164
Q

what does Salter-Harris I describe?

A

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
Q

what does Salter-Harris II describe?

A

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
Q

what does Salter-Harris III describe?

A

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
Q

what does Salter-Harris IV describe?

A

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
Q

what does Salter-Harris V describe?

A

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
Q

how long does a fracture in a metaphyseal bone in an adult take to heal

A

6-8 weeks

170
Q

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
A
  1. double
  2. double
  3. double
  4. double
  5. double or quadruple
  6. halved
171
Q

what is the importance of the formation of the fracture hematoma to the inflammatory phase of secondary healing?

A

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
Q

what % of the osetoid is type I collagen

A

about 90%

173
Q

what is the other 10% of osteoid that is not type I collagen

A

ground substance

ground substance is mostly made up of chondroitin sulfate and osteocalcin

174
Q

what is a compound fracture and why do they heal slower

A

compound fractures mean that the skin is disrupted and therefore the fracture hematoma is contaminated and partially lost thru the skin

175
Q

what is the result of too much motion during fracture healing

A

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
Q

what is the blood supply for the femoral head

A

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

MSK (5 decks)

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