MSK-physiology Flashcards

1
Q

what do ligaments link?

A

bone to bone

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2
Q

what do tendons link?

A

bone to muscle

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3
Q

what is the type I collagen arrangement of ligaments?

A
  • non-parallel

- ‘wavy bundles’

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4
Q

what is the type I collagen arrangement of tendons?

A

-parallel bundles of collagen

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5
Q

what are the physical properties of ligaments?

A

elastic and strong

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6
Q

what are the physical properties of tendons?

A

non-elastic and tough

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7
Q

what type of cartilage present in tendons and ligaments?

A

fibrocartilage

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8
Q

what is a sprain?

A

an over-stretched or torn ligament

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9
Q

what is a strain?

A

an over-stretched or torn tendon

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10
Q

what is the composition of tendons?

A
  • fibroblasts-tenocytes
  • fibrous connective tissue
  • type I collagen
  • proteoglycans
  • elastin
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11
Q

what is the composition of ligaments?

A
  • fibroblasts-ligamentocytes
  • fibrous connective tissue
  • type I collagen
  • proteoglycans
  • elastin
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12
Q

what is the difference in composition of ligaments and tendons?

A
  • ligament less compact, more mixed cell morphology, more proteoglycan and elastin fibres
  • ligament also has more cartilaginous proteins: aggrecan and collagen type I
  • different ECM organisations
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13
Q

what does formation of tendons and ligaments in foetus is dependent on?

A

use muscle as a template/ axis

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14
Q

where are tendons and ligaments of the head formed from?

A

neural crest cells

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15
Q

where are the tendons and ligaments of axial body are formed?

A

somites

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16
Q

where are tendons and ligaments of the limbs formed?

A

limb buds/ lateral limb plate

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17
Q

what is scleraxis?

A

a marker for development of tendons and ligaments

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18
Q

what influences tendon and ligament development?

A

growth factors

  • TGFbeta
  • TGF8
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19
Q

what makes ligaments and tendons viscoelastic?

A
  • Elastic-cross links between collagen fibrils

- Viscous-ability of collagen fibrils to slide over each other

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20
Q

describe the creep effect on ligaments and tendons

A

when applying a constant load, deformation of tendon/ligament primarily occurs at the moment of loading –> deformation continues to increase with time

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21
Q

describe the stress effect on ligaments and tendons

A

once a load is applied onto a ligament/tendon, it initially relaxes rapidly –> rate of relaxation decreases with application of a constant load over time

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22
Q

what is the hysteresis effect on ligaments and tendons

A

when the rate at which tendon/ligament elongates during loading is not the same rate at which it shortens during unloading

when the rate at which it lengthens is faster than the rate that it shortens by.

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23
Q

what happens to ligaments and tendons beyond 2% stress?

A

collagen fibres in ligaments and tendons straighten out

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24
Q

what happens to ligaments and tendons beyond 4% stress?

A

collagen fibres might be experiencing small ruptures as fibres slide past one another and cross-links start to fail but will ultimately return to normal length/ structure when the load is taken off-microscopic failure

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25
Q

what happens to ligaments and tendons beyond 8% stress?

A

macroscopic failure of tendon/ ligament will occur

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26
Q

what does the toe region of the stress-strain curve represent?

A

the un-crimping of the collagen fibrils

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27
Q

what does the shear rate refer to?

A

how quickly collagen fibrils slide over when a load is applied to the tendon/ ligament

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28
Q

describe the steps in the synthesis of collagen

A

1-3 alpha-helix chains are hydroxylated and glycosylated-these are called propeptides
2-then wound together to form a triple helical structure-procollagen (Vit C is cofactor for this reaction)
3-procollagen leaves the cell, entering extra-cellular space-becomes part of ECM
4-there is cleavage of N 7 C terminal telopeptides—->makes 1 collagen fibril
5-many collagen fibrils can be cross-linked together-using pyridinium cross-links-when lots are cross-linked it forms 1 collagen fibre

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29
Q

where is collagen I located?

A

bone, tendons, ligaments, skin

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30
Q

where is collagen II located in ECM?

A

cartilage

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31
Q

where is collagen III located in the ECM?

A
  • found alongside type I collagen, in smaller amounts

- also found in higher abundance in healing ligaments and cartilage

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32
Q

where is collagen VI located?

A

muscle tissue

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33
Q

where is collagen IX located in the ECM?

A
  • found alongside type II collagen in smaller amounts

- found in higher abundance in articular cartilage

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34
Q

where is collagen X located in the ECM?

A

ossifying cartilage

-it is a marker for new bone formation in articular cartilage

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35
Q

what are the components of cartilage?

A
  • collagen (mainly type II)-gives structural strength
  • Elastin-allows flexibility
  • Proteoglycan-provides large osmotic effect
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36
Q

what cells are found in cartilage?

A

chondrocytes are embedded in ECM and it’s the matrix that provides cartilage with its unique characteristics

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37
Q

Name the 3 types of cartilage.

A
  • fibrocartilage
  • hyaline cartilage
  • elastic cartilage
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38
Q

where is fibrocartilage found?

A
  • pubic symphysis

- intervertebral disc

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39
Q

where is hyaline cartilage found?

A

most common type of cartilage-found in synovial joints

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40
Q

where is elastic cartilage found?

A
  • epiglottis
  • outer ear
  • larynx
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41
Q

which is the strongest type of cartilage and why?

A

fibrocartilage due to high amounts of collagen II

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42
Q

what does fibrocartilage lack?

A

a true perichondrium

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43
Q

what are the main components in the ECM of hyaline cartilage?

A
  • hyaluronan
  • aggrecan
  • negatively charged polysaccharide side chains-this attracts water
  • 20% ECM and chondrocytes
  • 80% cartilage
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44
Q

what is the most flexible cartilage and why?

A

elastic cartilage

-due to high amounts criss-crossed elastin

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45
Q

does elastic cartilage have a perichondrium?

A

yes

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46
Q

which types of cartilage always remain as cartilage?

A
  • fibrocartilage

- elastic cartilage

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47
Q

what is hyaline cartilage that stays as cartilage called?

A

articular cartilage

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48
Q

what is hyaline cartilage that develops into bone called?

A

epiphyseal growth plate

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49
Q

what gives hyaline cartilage its weight bearing properties?

A

its water content-attracted negatively charged proteoglycans

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50
Q

what is the structure of articular cartilage?

A
1- Tangential (superficial) zone
2-Transitional (middle) zone
3- Radial (deep) zone 
Tide mark
4-Calcified cartilage
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51
Q

describe the tangential zone of articular cartilage

A
  • fibres of type II collagen are parallel to the articular surface
  • chondrocytes are flattened
  • in contact with synovial fluid and tangential zone of articular cartilage of the bone it is articulating with
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52
Q

describe the transitional zone of articular cartilage

A
  • collagen arranged into Arcades of Benninghoff

- abundant proteoglycans

53
Q

what are the tide marks in articular cartilage?

A

the boundary between that which is and isn’t calcified

54
Q

where is the calcified cartilage in articular cartilage?

A

transition zone between articular cartilage and bone

55
Q

what is lambda ratio?

A

minimum film thickness in relation to the composite surface roughness

56
Q

what is lubricin?

A

mucinous glycoprotein, which covers articular cartilage at synovial joints

57
Q

what produces lubricin?

A

chondrocytes in superficial zone of articular cartilage

58
Q

when do you need more lubricin?

A

If the surfaces coming into contact are very rough (e.g. bone ends), then you need more lubricin
-eg in osteoarthiritis

59
Q

why do you normally not need a lot of lubricin?

A

as articular cartilage is smooth and it protect our bone ends

60
Q

what does higher lubricin mean in terms of lambda ratio?

A

higher lambda ratio

61
Q

describe the process of endochondral ossification?

A

1-mesenchyme clusters together in shape of bone
2-mesenchyme cells differentiate into chondroblasts- cartilage model is formed
3-perichondrium encapsulates the model
4-chondrocytes proliferate
5-cartilage calcifies
6-osteoprogenitor cells turn into osteocytes
7-bone is now replacing cartilage in the diaphysis
8-perichondrium is replaced by periosteum
9-there is now an artery supplying the bone
10-osteoclasts breakdown bone in centre to form cavity for marrow
11-the epiphyses of bones also calcify and are replaced by bone
12-articular cartilage will stay and protect articulating bone
13-growth plate will grow and over time develop into bone

62
Q

what cartilage type is involved in endochondral ossification?

A

hyaline

63
Q

what happens to the epiphyseal growth plate once a person has stopped growing?

A

it turns completely to bone

64
Q

what is the AER in the embryology of limb development?

A

structure that forms from ectodermal cells at distal end of each limb bud

65
Q

what is the proximal to distal elongation produced by?

A

AER

66
Q

what does the AER act as in limb development?

A

major signalling centre to ensure proper development of a limb

67
Q

what induces AER formation and what occurs after this?

A

limb buds induce AER formation

-the AER and limb mesoderm continue to communicate with each other to direct further limb development

68
Q

what is the initiation of limb development driven by?

A
  • fibroblast growth factors FGFs

- Hox and TBx genes/ T-Box transcription factors

69
Q

describe the initiation of limb development using fibroblasts

A
  1. The mesoderm releases FGF10
  2. FGF10 causes cells overlying the AER to proliferate
  3. The AER releases FGF8 in response
  4. FGF8 causes the underlying mesoderm to proliferate
    - positive feedback loop is formed-called reciprocal induction
70
Q

what happens in limb development as the mesoderm and AER both thicken?

A

limb gets longer

71
Q

what is the role of sonic hedgehog (SHH) in limb development?

A

acts in the zone of polarisation to differentiate the anterior-posterior axis-width of limb

72
Q

what secretes SHH?

A

ZPA

73
Q

describe the initiation of limb development using Hox and TBx genes

A
  1. Somites release retinoic acid and express Hox genes
  2. This causes TBx genes to express T-Box transcription factors
    (Tbx-2, Tbx-3, Tbx-4 and Tbx-5)
  3. Tbx-2 and Tb-x3 make all 4 limbs grow
  4. Tbx-4 makes lower limbs grow
  5. Tbx-5 makes upper limbs grow
74
Q

what are SOX9 and GDF5 essential for?

A

allowing chondrocytes to grow

and for cartilage to form

75
Q

what ere the 4 types of bone cells?

A
  • osetocytes
  • osteoblasts
  • osteoprogenitor
  • osteoclasts
76
Q

which bone cell is the most common and why?

A

osteocytes-they are mature bone cells so most common

77
Q

what is the role of osteocytes?

A
  • mechanoreceptors

- ->monitors loading on bone and maintains bone metabolism accordingly (by activating osteoblast and osteoclasts)

78
Q

what is the role of osteoblasts?

A
  • bone building cells

- ->synthesise and secrete ECM

79
Q

what has to happen before osteoblasts can become osteocytes?

A

become surrounded in their own ECM

80
Q

What is the role of osteoprogenitor cells?

A

-will form osteoblasts (precursors)

81
Q

why are osteoprogenitor cells the only bone cell type to undergo mitosis?

A

These are mesenchymal, unspecialised cells so can undergo mitosis

82
Q

where are osteoprogenitor cells found?

A

inner side of periosteum

83
Q

what is the role of osteoclasts?

A

-bone resorbing cells

84
Q

what are osteoclasts derived from?

A

fusion of 50 monocytes

mulitnucleated

85
Q

what type of cell are osteoclasts and how does it help with its function?

A

A polarised cell – it has a ‘ruffled border’ on one side which secretes enzymes and acid which acts on bone tissue to break it down

86
Q

what is interstitial growth?

A

growth in length involving hyaline epiphyseal cartilage

87
Q

what does the zone of resting cartilage do?

A

keeps epiphyses anchored

88
Q

what occurs in the zone of proliferation?

A

chondrocytes are making more cartilage and are arranged into columns

89
Q

what occurs in the zone of hypertrophy?

A

chondrocyte hypertrophy-chondrocytes mature and enlarge

90
Q

what occurs in the zone of calcification?

A

-ECM cartilage calcifies and then the chondrocytes are starved of nutrients–> chondrocytes die

91
Q

what does the calcified cartilage turn into and where is it in the bone?

A

ossified bone-closest to diaphysis

92
Q

what is appositional growth?

A

bone width growth

93
Q

what is appositional growth indirectly derived from?

A

hyaline cartilage

94
Q

describe the steps of appositional bone growth

A

1-A periosteal blood vessel lies in a groove in the periosteum
2-periosteum starts peaking around the vessel (periosteal ridges) –>This periosteum now termed the endosteum.
3-Periosteal ridges close around vessel, creating a (Haversian) canal with vessel inside. Osteoblasts build inwards, towards canal to form an osteon.
4-process repeats on top of the osteon that was just formed

95
Q

why does appositional growth not directly involve chondrocytes?

A

it occurs around the bone that was formed in the primary ossification centre-so requires no chondrocytes

96
Q

what are interstitial and appositional growth examples of?

A

endochondral ossification

97
Q

how is intramembranous ossification different from endochondral ossification?

A

bone develops straight from clustered mesenchyme-there is no cartilage involved

98
Q

what bones does intramembranous ossification form?

A
  • flat bones of skull and face
  • clavicles
  • mandible
99
Q

outline the steps of intramembranous ossification

A

1-ossification centre: mesenchymal cells–>osteoprogenitor–>osteocytes-secrete ECM

2-calcification-ECM hardens and calcifies

3-formation of trabeculae–>ECM forms into trabeculae
-red marrow fills space in between trabeculae–>forms spongey bone

4-development of periosteum-at the periphery, periosteum covers the bone

100
Q

is the complete process of mineralisation/ osteoid formation a quick one?

A

no it takes months

101
Q

outline the steps of osteoid formation

A

1-osteoblasts synthesis and secrete type I collagen fibrils (ECM)
2-collagen fibrils polymerise, forming collagen strands
3-osteoblasts secrete alkaline phosphatase (ALP) which cleaves pyrophosphate into phosphate which is required for mineralisation
4-calcium and phosphate precipitate crystals on collagen in vesicles-forms hydroxyapatite which forms the osteoid
5-the vesicles on top of the collagen strands rupture and the crystals grow

102
Q

describe the process of bone reabsorption

A
  1. Osteoblasts release RANK-Ligand (RANK-L) protein
  2. RANK-L binds to RANK receptors onto osteoclast precursors. The binding causes them to differentiate into mature osteoclasts
  3. The mature osteoclasts also express RANK receptors – RANK-L binds to them and activates the mature osteoclasts
  4. The mature activated osteoclast secretes enzymes and acid to reabsorb bone – eventually, they deactivate or die
103
Q

how is bone metabolism regulated?

A

by Sclerostin-a regulatory factor and is secreted by the osteocytes and inhibits the osteoblast
precursors from maturing

104
Q

how does bone building occur?

A

Osteoblasts secrete collagen fibres which are then mineralised

105
Q

what are 2 classifications of bone?

A
  • macroscopic

- microscopic

106
Q

what can macroscopic bone be split into?

A
  • spongy/ trabecular

- compact/ cortical

107
Q

what can microscopic bone be split into?

A
  • lamellar

- woven

108
Q

where is spongy bone located?

A

in the interior of a bone covered by a layer of compact bone

109
Q

how are the lamellae organised in spongey bone?

A

into irregular thin columns—>trabeculae

-organistaion is irregular but not random

110
Q

where are trabeculae formed along and why?

A

-lines of stress placed on bone -to increase its strength and weight-bearing ability

111
Q

what are the spaces in trabeculae filled with?

A
  • red bone marrow-produces blood cells

- yellow bone marrow (adipose tissue)

112
Q

which bones in adults does red bone marrow exist?

A
  • hip bones
  • ribs
  • sternum
  • spinal vertebrae
  • proximal ends of femur and humerus (bony sites of haematopoiesis in adults)
113
Q

what is compact bone organised into?

A

osteons

114
Q

what are osteons?

A

concentric lamellae around a Haversian canal (vasculature)

115
Q

what is situated between osteons?

A

interstitial lamellae

116
Q

what is situated around all osteons?

A

circumferential lamellae

117
Q

what lies within lamellae?

A

osteocytes that lie in spaces-lacunae-and canaliculi that radiate outwards

118
Q

how do Haversian and Volkmann’s canals differ?

A

Haversian canals run along the long axis of the bone, whereas Volkmann’s canals connect the Haversian canals to each other by running horizontally.

119
Q

which type of bone is mechanically weaker lamellar or woven?

A

woven

-due to haphazard organisation of collagen

120
Q

where is woven bone produced?

A

in all foetal bone

121
Q

what happens to woven bone?

A

gets replaced by lamellar bone

122
Q

when does woven bone appear in adults?

A

only after a fracture or in Paget’s disease

123
Q

how is woven bone produced?

A

when osteoblasts produce osteoid rapidly as complete mineralisation in lamellar bone takes too long

124
Q

what doe lamellar bone require for its production?

A

a relatively flat surface to lay collagen fibres down in parallel or concentric fibres-increasing their strength

125
Q

which 3 calcium-relating hormones play important roles in producing healthy bone?

A
  • sex hormones
  • parathyroid hormone
  • calcitriol
126
Q

what is the effect of low estrogen or testosterone on bones?

A

-bones weaken

127
Q

what is the effect of parathyroid hormone on bones?

A

maintains level of calcium and stimulates both resorption and formation of bone

128
Q

what is the effect of calcitriol on bones?

A

stimulates osteoclastic bone resorption by inducing RANKL and increasing the number and activity of osteoclasts