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Block 4 > Bone and Muscle Physiology > Flashcards

Bone and Muscle Physiology Flashcards

1
Q

What 2 things is connective tissues made from?

A

Cells

Extracellular matrix

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2
Q

What 2 things is extracellular matrix formed of?

Give properties of each

A

Fibrous proteins

  • collagen
  • elastin

Ground substances

  • transparent
  • colourless
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3
Q

What 3 things is ground substance formed from?

Give properties of each

A

Proteoglycans

  • repeated disaccharides (GAG) around a protein core
  • GAG attracts water

Glycoproteins
-allow cells to adhere to the ECM

Water
-attracted by GAG

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4
Q

What provides the rigidity of bones?

A

Mineralised extracellular matrix (hydroxyapatite)

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5
Q

What provides the resilience of bones?

A

Type 1 collagen fibres

part of the fibrous proteins component of ECM, other component is ground substance remember

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6
Q

What is the condition caused by too little bone called?

A

Osteoporosis

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7
Q

What is the condition caused by too much bone called?

A

Osteopetrosis

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8
Q

What is osteoporosis?

A

A complex skeletal disease characterised by low bone density and micro-archeitectural defects in bone tissue, resulting in increased bone fragility and susceptibility to fracture.

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9
Q

Name 5 wider implications of osteoporosis

A

Future #

Pain

QOL

Long term admission

Mortality

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10
Q

Describe the general pathophysiology of osteoporosis

A

Menopause decreases oestrogen levels

Aging decreases replication of osteoprogenitor cells - fewer osteoblasts being made

Aging decreases activity of remaining osteoblasts - less new bone being made

Increases expression of RANKL and RANK on osteoclasts - favours bone re absorption

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11
Q

What scan is used to assess bone mineral density?

A

DEXA scan

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12
Q

What would a normal T score on a DEXA scan be?

A

T score _> 1

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13
Q

What would an osteopenia T score on a DEXA scan be?

A

T score less than -1 but above 2.5

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14
Q

What would a osteoporosis T score on a DEXA scan be?

A

T score <2.5

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15
Q

What is first line management according to NICE in osteoporosis?

A

Bisphosphonates

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16
Q

Name the 2 bisphosphonates on the drugs list

A

Alendronic acid (alendronate)

Resedronate

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17
Q

What is the MOA for bisphosphonates?

A

Bisphosphonates attach to hydroxyapatite binding sites on bony surfaces, especially surfaces undergoing active resorption.

When osteoclasts begin to reabsorb bone that is impregnated with bisphosphonate, the bisphosphonate released during reabsorption impairs the ability of the osteoclasts to form the ruffled border, to adhere to the bony surface, and to produce the protons necessary for continued bone resorption

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18
Q

How does alendronic acid have to be taken?

A

First thing in the morning, half an hour before food, glass of water, sit upright for half an hour

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19
Q

What are the side effects of bisphosphonates?

A

Asymptomatic hypocalcaemia

GI disturbances

Oesophageal reactions (sit upright)

Osteonecrosis of the jaw (larger doses)

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20
Q

What class of drugs is given is bisphosphantes are not tolerated?

Name the drug

A

Selective estrogen receptor modulators

Raloxifene

Does not stimulate breast or uterine tissue, less at risk of CA.

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21
Q

What SC injection can be given to treat osteoporosis?

A

Parathyroid hormone

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22
Q

What is denosumab’s mechanism of action?

How is it given?

A

It is a monoclonal antibody

Acts in a similar way to OPG

Mops up excess RANKL, reduced activation of osteoclasts

Inhibits osteoclast formation, function, survival.

SC injection once every 6 months

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23
Q

Rickets and osteomalacia are characterised by…..

What is the most common cause?

A

inadequate mineralisation of bone

Vitamin D deficiency

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24
Q

Describe Rickets

A

Defective bone mineralisation at the growth plate only affecting children

Widening of the growth plate

Vitamin D deficiency - chondrocytes fail to apoptose after hypertrophy - growth plate remains soft.

Growth retardation

Bony deformities

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25
Q

Describe osteomalacia

A

Defective osteoid mineralisation affecting adults and children

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26
Q

What is a lytic lesion?

A

Parts of the bone that have been destroyed, usually due to secondary malignancies/metastasis e.g. breast and lung CA

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27
Q

What is a schlerotic lesion?

A

Thickening/hardening of the bone. Stimulation of bone production so the bone is denser

Usually secondary to prostate CA.

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28
Q

Describe Paget’s disease of the bone

A

Increased bone turnover

Increase in osteoclast activity, which increases osteoblast activity. Increased amount of woven bone being laid down.

Can have focal or multifocal sites.

Results in overgrowth, bowing, pain, fractures and deformity

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29
Q

What investigations would you do to diagnose Paget’s disease of the bone?

A

Bloods - Ca, PTH (normal), ALK P (high)

X rays

Radionuclide bone scans

Bone biopsy if malignancy is suspected

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30
Q

How do we treat Paget’s disease of the bone?

A

Walking aids

Analgaesia

Supplements

Bisphosphonates

Surgery

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31
Q

What is osteogenesis Imperfecta?

A

A group of hereditary disorders characterised by defective production of type 1 collagen.

Type 1 - more prone to #, but unlikely to have deformities from them

Type 2 - brittle bone disease. Bones can break during labour, can have respiratory compromise, likely to die in the first few years.

32
Q

Which part of the connective tissue determines the tissue’s physical properties?

A

Extracellular matrix

33
Q

Name 2 important fibres that can be present in the extracellular matrix

A

Collagen

Elastin

34
Q

Where is collagen found?

A

Type 1 - bone, tendons, ligaments

Type 2 - hyaline cartilage

Type 3 - structural framework of spleen, liver, smooth muscle

Good at resisting tensile forces

35
Q

Name some properties of elastin

A

Major component of elastic fibres

Enables stretch and recoil of tissues

Usually mixed with collagen to prevent overstretch

Found in walls of large arteries, lungs, skin

36
Q

Name 3 characteristics of cartilage

A

Strong, flexible, semi-rigid

Can withstand compression forces (shock absorber)

Smooth surface enables friction-free movement

37
Q

Name 3 functions of cartilage

A

Forms articulating surface of bones

Growth and development bones (endochondral ossification)

Supporting framework of some organs e.g. walls of airways

38
Q

Name some specialist features of cartilage extracellular matrix

A

Contains aggrecan - this is a proteoglycan that contains glycosaminoglycans, which are hydrophillic and therefore attract a lot of water to the cartilage

Collagen fibres

Elastin fibres

39
Q

Name the proteoglycan found in the ECM of cartilage

A

Aggrecan

A proteoglycan that contains glycosaminoglycans which attract water

40
Q

What is the layer surrounding cartilage called?

What is special about this outer layer compared to the rest of the cartilage?

A

Perichondrium

  • outer fibrous layer
  • inner cellular layer

The perichondrium contains blood vessels: the rest of the cartilage is avascular

41
Q

Why does cartilage take a long time to heal?

A

Because it is avascular

Cartilage cells get their nutrients by diffusion from the perichondrium

42
Q

What do cartilage cells derive from?

A

Mesenchymal stem cells

43
Q

Outline the formation of a chondrocyte (cartilage cell)

A

Mesenchymal stem cells differentiate into chondroblasts (cartilage building cells)

Chondroblasts are found in the inner cellular layer of the perichondrium

Chondroblasts secrete extracellular matrix and get trapped inside lacuna (spaces)

Chondroblasts then mature into chondrocytes

44
Q

Name the 2 types of growth cartilage can undergo

A

Appositional

Interstitial

45
Q

Describe the process of appositional growth of cartilage

A

Surface layers of matrix added by chondroblasts in perichondrium

46
Q

Describe the process of interstitial growth of cartilage

A

Chondrocytes grow and divide and lay down new matrix.

As more matrix is being made, the chondrocytes get pushed away from each other.

Multiple chondrocytes can end up occupying one lacuna and the lacuna will get further away from each other

Happens in childhood and adolescence

47
Q

Why does cartilage repair badly in adults?

A

Because most interstitial growth happens in childhood and adolescence

May be some regeneration of damaged cartilage from chondrogeneic cells in the perichondrium

But if the damage is large or the cartilage has been removed from the perichondrium, the defect will be replaced with dense connective tissue

48
Q

Name the 3 types of cartilage

A

Hyaline

Fibrocartilage

Elastic

49
Q

What is the most common and weakest type of cartilage?

A

Hyaline cartilage

50
Q

Briefly describe hyaline cartilage

A

Contains short and dispersed type II collagen fibres and large amounts of proteoglycans

Has a perichondrium layer (except at articular surfaces)

51
Q

Name 3 places where hyaline cartilage is found

A

Articular surfaces of joints

Costal cartilages

Epiphyseal growth plates

52
Q

What is the strongest form of cartilage?

A

Fibrocartilage

53
Q

Briefly describe fibrocartilage

A

Contains thick parallel bundles of type I collagen alternating with hyaline cartilage matrix

No perichondrium

Found in places that need to resist significant forces

  • insertion points of ligaments/tendons
  • IV discs
  • pubic symphisis
54
Q

Briefly describe elastic cartilage

A

Strong, flexible, resilient

Structures that require deformation but can regain original shape

Contains elastic fibres and type II collagen fibres

Has a perichondrium

55
Q

What is a joint?

A

Where 2 or more bones articulate

56
Q

Name the 3 types of joints, according to movement, and their characteristics

A

Synarthrodial joint - fixed no movement

Amphiarthrodial joint - slightly movable

Diarthrodial joint - freely movable

57
Q

Name the 3 types of joints

A

Fibrous

Cartilaginous

Synovial

58
Q

Name the 2 types of fibrous joints

Briefly outline their structure

A

Sutures

Syndesmoses

Fibrous joints are bones connected by dense connective tissue, containing mainly collagen but no cartilage

59
Q

Give an example of a suture fibrous joint

What type of movement does this joint undergo?

A

Flat bones of the skull

Synarthrodial joint - no movement

60
Q

Give an example of a syndesmoses fibrous joint

What type of movement does this joint undergo?

A

Interosseous connective tissue membrane connecting long bones

Amphiarthrodial joint - slightly moveable

61
Q

Briefly describe cartilaginous joints

A

Bones connected entirely by cartilage

Can be immovable or slightly movable

Primary and secondary cartilaginous joints

62
Q

Describe a primary cartilaginous joint

A

Hyaline cartilage only

Found at epiphyseal growth plates and costal cartilages

63
Q

Describe a secondary cartilaginous joint

A

Hyaline cartilage lines the bones with fibrocartilage in between

IV discs, pubic symphysis, manubriosternal joint

64
Q

Describe 3 characteristics of a synovial joint

A

Prescence of a joint cavity between the bones, which contains synovial fluid

Hyaline cartilage

Joint enclosed by a joint capsule with outer fibrous membrane and inner synovial membrane

65
Q

Which layer of the joint capsule secretes synovial fluid?

A

Inner synovial membrane

66
Q

Describe a bursa

A

A sac made of synovial membrane containing synovial fluid that reduce friction of one structure moving over another

67
Q

How are synovial joints reinforced?

Give an example

A

Fibroelastic ligaments crossing the joint prevent excessive movements

Lateral meniscus of the knee

68
Q

Name the 6 types of synovial joints

A

Hinge

Ball and socket

Plane

Saddle

Pivot

Condyloid

69
Q

Briefly outline osteoarthritis

A

Most common joint disease

Loss of articular cartilage +/- bone leading to synovitis

70
Q

List some risk factors for OA

A

Genetics

Age

Female sex

Trauma

Obesity

High/low bone density

71
Q

What causes primary OA?

A

Genetic factors, no precipitating insult

72
Q

What causes secondary OA?

A

Joint pathology e.g. trauma, infection, joint defects

73
Q

Draw out the pathophysiology of OA

A

See slide 36 of joint disease lecture and footnotes

74
Q

What 4 pathological changes would you see on an X ray in someone with OA?

A

Joint space narrowing - asymmetric

Subchondral cysts and sclerosis

Osteophytes

Malalignment

75
Q

List some signs and symptoms of OA

A

Joint stiffness

Joint pain

Functional limitation

Rest/night pain

Restricted movement

Crepitus

76
Q

What are the nodes called on the hands that are visible in OA?

A

Herberden’s nodes

Block 4 (11 decks)

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