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Intercal - Adaption in physiology > Skeletal Physiology and Adaptation > Flashcards

Skeletal Physiology and Adaptation Flashcards

1
Q

Functions of bones

A

Protection
Movement
Support
Metabolic
Mineral storage
Hearing

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2
Q

3 factors of the metabolic role of bone

A

Haematopoiesis, blood production
Homeostasis of Ca2+
Defence against acidosis

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3
Q

What is bone the main mineral reserve for

A

Calcium
Phosphorus

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4
Q

5 classifications of bones

A

Long
Flat (sternum, cranium)
Irregular (vertebrae)
Sessamoid (patella)
Short (talus, carpal etc)

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5
Q

5 features of long bones

A

Highly vascularised
Enclosed by fibrocartilagenous periosteum
Articular cartilage at joint surfaces
Red bone marrow (metaphysis)
Yellow bone marrow (diaphysis)

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6
Q

What does red bone marrow contain

A

RBCs

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7
Q

What does yellow bone marrow contain

A

Fat cells

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8
Q

Two types of bone material

A

Cortical - hard outside (80%)
Trabecular - marrow site (20%)

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9
Q

How does intramembranous ossification form

A

A fibrous plate then bone cells differentiation from fibroblasts and haemopoietic precursors

NO cartilaginous phase

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10
Q

Example of a bone type that undergoes intramembranous ossification

A

Flat bone

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11
Q

How does endochrondral ossification form

A

Bone cartilage forms at 13 months
Bone vessels invade the cartilage
Cartilage remains at the growth plates but bone forms elsewhere by osteogenic cells.
Growth plates fuse at the end of puberty.

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12
Q

Composition of bone

A

Water (20%) - heat to get dry weight
Mineral (hydroxyapatite) (50%) - burn to get ash weight
Organic (proteins e.g. collagen) (30%) - dry - ash

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13
Q

What is the bone mineral name and its role

A

Hydroxyapatite forms rigidity

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14
Q

Features of older bone

A

More mineralised
Further from the surface

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15
Q

What happens to bone when only mineral present when weight is dropped on it

A

Disintegrates completely

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16
Q

Collagen type 1 features

A

Triple helix protien
Combine to make fibrils
Fibrils combine to make fibers and then the gaps are filled with mineral bone.

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17
Q

If the bone is only organic what would happen if a weight is dropped on it

A

Would be extremely elastic as no mineral content to give it its rigidity.

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18
Q

Types of bone water

A

Pore water - in haversian canals
Bound water - works with collagen to give elasticity

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19
Q

What happens to water with age

A

Pore increases and bound water decreases

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20
Q

What machine is used for bone composition

A

Spectroscopy

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21
Q

What is the function of osteoclasts

A

Multinucleated cells formed by the fusion of mononuclear precursors - responsible bone degradation

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22
Q

What is the function of osteoblasts

A

Synthesis of new bones

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23
Q

What is the function of osteocytes

A

Osteoblasts who have become embedded within the bone - function as sensors of mechanical load.

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24
Q

Which cells does osteoblasts and osteocytes come from

A

Mesenchymal stem cells

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25
Q

Where do osteoclasts come from

A

haemopoietic stem cells

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26
Q

What is osteoid

A

Uncalcified bone matrix - formed by osteoblasts

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27
Q

How do osteoclasts degrade bone

A

Form an F-actin ring to secret acid and cathepsin K (enzyme) to break down bone.

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28
Q

How long does the bone remodelling cycle take

A

3 months

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29
Q

The 4 stages of bone remodelling cycle

A

Quiescence - bone linning cells (at rest)
Resorption - osteoclasts working to remove one
Reversal - synthesis of new bone matrix formation as osteoblasts are recruited
Formation - synthesis of new non-mineralised bone and is then mineralised overtime

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30
Q

When is bone formation more than resorption in humans

A

Younger
Opposite for older

31
Q

Factors that influence bone mass

A

Genes
Exercise
Nutrition
Smoking

32
Q

How does osteoporosis affect the bone

A

Decrease in bone mass
Normal mineral and organic content

33
Q

How does osteoarthritis affect bone

A

Increase in bone mass
Decrease in mineral content
Increase in organic content

34
Q

Drugs that inhibit bone resorption

A

Bisphosphonates
SERM
HRT

35
Q

How do bisphosphonates work

A

Induce osteoclast death

36
Q

How do SERM work

A

Acts as oestrogen in bone to reduce osteoclast activity

37
Q

How does PTH stimulate bone formation

A

Activated Vit D
Increases Ca uptake in the gut
Increases bone formation

38
Q

How are osteocytes mechanosensitive

A

Number of cycles
Strain magnitute
Load distribution
Dynamic stimulus is better for bone formation than static load

39
Q

What is released by osteocytes with increased loading

A

Sclerostin (Decrease of connectivity with age)

40
Q

How to optimise the bone formation

A

Increase dynamic strain magnitude
Increase number of strain cycles/rate
Have rest/refractory periods

41
Q

Define Wolffs law

A

Bone is a dynamic tissue that will adapt to the loads placed on it.

Put wolffs law into exam answer

42
Q

What does a DXA scan do

A

Measure bone density

43
Q

What imaging technique to see trabeculae in vivo

A

HRpQCT

44
Q

What imaging technique to see trabeculae ex-vivo

A

Microscopy

45
Q

Why are larger bones less likely to break when bending

A

The further the bend is from the centre of the bone the greater the strength

46
Q

Why do bones grow more anteriorly-posteriorly and not mediolaterally

A

Bones grow wider via periosteal formation - this is not symmetrical and there is usually more present anteriorly and posteriorly due to this is where the most forces are present - this keeps them strong but also light

As X4 amount of bone would be needed if it grew anteriorly-posteriorly AND mediolaterally.

47
Q

What is disuse osteoporosis

A

Lack of loading leads to bone loss -
Bed rest
Space flight
Spinal cord injury

48
Q

What is just as important as bone density to its strength

A

Bone shape

49
Q

What are the two stages of osteoblast formation

EXTRA READING - DIRCKX and MAES

A

Stage 1 - matrix producing osteoblasts - secrete collagen type 1

Stage 2 - mineralizing osteoblasts - secrete osteocalcin (OCN)

50
Q

3 fates of osteoblasts

EXTRA READING - DIRCKX and MAES

A

1 - Apoptosis
2 - matrix-embedded osteocytes
3 - bone lining cells

51
Q

2 markers that form osteoprogenitor cells

EXTRA READING - DIRCKX and MAES

A

RUNx2
Osterix

52
Q

How do stable fractures heal

EXTRA READING - DIRCKX and MAES

A

Intramembranous ossification - osteoprogenitor cells are recruited and differentiate into osteoblasts.

53
Q

How do unstable fractures heal

EXTRA READING - DIRCKX and MAES

A

Endochondral ossification - haematoma releases cytokines which recruit progenitor cells.

54
Q

What controls the formation of collagen and mineralisation

EXTRA READING - BRADLEY

A

ALK Phosphate
Osteocalcin
etc

55
Q

Other than strength what is another role of hydroxyapitite

EXTRA READING - BRADLEY

A

Can hold on to toxins e.g lead before forming in bone

56
Q

What is the chemical that affects osteocyte connection via its cytoskeleton

EXTRA READING - bonewald

A

Fimbrin - commonly found in high conc at the edges of osteocytes

57
Q

What do osteoblasts do to activate osteoclasts

EXTRA READING - bonewald

A

RANKL expression when feel areas of microfractures –> recruits monocytes to form osteoclasts

58
Q

Where are progenitor stem cells found
EXTRA READING

A

Periosteum inner layer

59
Q

What enzyme do osteoclasts secrete
EXTRA READING

A

Collagenase and hydrochloric acid

60
Q

What does hydrochloric acid form
EXTRA READING

A

Dissolves hydroxyapatite -
Calcium and phosphate

61
Q

How do osteoclasts get controlled to prevent excess bone breakdown

A

Osteoprotegerin binds to RANKL to slow down osteoclasts

62
Q

How does parathyroid hormone affect bone remodelling

A

PTH released when low Ca so causes bone resorption so decrease bone mass

63
Q

When does bone shape change

A

Menopause and age to combat the effects of bone loss - to keep bone strength for as long as possible.

64
Q

How does long term bisphosphonates affect bone strength

A

Decreases fibril and mineral strain therefore –> followings wolffs law –> decreases bone strength

65
Q

How do corticosteroids affect bones

EXTRA READING - BRIOT AND ROUX

A

Impairement of bone formation as they significantly decrease P1NP and ostecalcin (markers for bone formation)

66
Q

How do corticosteroids affect osteoblasts

EXTRA READING - BRIOT AND ROUX

A

Decrease growth hormone and IGF1 so decreases osteoblast function

67
Q

How do corticosteroids affect osteoclasts

EXTRA READING - BRIOT AND ROUX

A

Increase RANK-ligand and decrease osteoprotegerin (inhibitor for osteoclasts) –> longer time for osteoclasts to be active so more bone degradation

68
Q

How does glucocorticoids cause an increase in falls

EXTRA READING - BRIOT AND ROUX

A

Causes GC-induced myopathy which makes muscles weaker

69
Q

Define osteoporosis

EXTRA READING

A

osteoclastic bone resorption not compensated by osteoblastic bone formation

70
Q

3 causes of osteoporosis

EXTRA READING

A

Oestrogen, vitamin D defciency and hyperparathryoidism

71
Q

How does gut biome and age increase the risk of osteoporosis

EXTRA READING

A

With age, disease anf fraility - the gut microbiome changes rapidly. This can cause a a distruption in short chain fatty acids which are used to regulate osteoclast differentiation causing a dysregulation in the abundance of osteoclasts

72
Q

How does the menopause affect bone remodelling

EXTRA READING - MENG XIA JI

A

Menopause causes decrease in oestrogen which affects bone by -

1 - lowering bone sensitivty to PTH
2 - Increasing calcitonin thus inhibiting bone resorption
3 - accelerating calcium resorption from intestine
4 - reducing calcium excretion from kidney
5 - direct affects on bone as there is oestrogen receptors there

A loss of oestrogen means a loss of these protective functions

73
Q

What endocrine conditions can cause oseoporosis

EXTRA READING - MENG XIA JI

A

Cushings
Menopause
Hyperparathyroidism

74
Q

How does oestrogen directly affect bone

EXTRA READING - MENG XIA JI

A

Ostreogen receptors found on osteoclasts and their progenitor cells.

When ostrogen decreases this inhibition is lost.

Intercal - Adaption in physiology (11 decks)

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