1
Q
purpose of the skeleton
A
- raises us from the ground against gravity
- determines basic body shape
- transmits body weight - even distribution
- forms jointed lever system for movement
- protects vital structures from damage
- houses bone marrow
- mineral storage (calcium, phosphorus, magnesium)
2
Q
what is the axial skeleton?
A
head, trunk, vertebrae
80 bones
3
Q
what is the appendicular skeleton?
A
The appendicular skeleton is composed of the upper limbs, lower limbs, pectoral girdle, and pelvic girdle.
126 bones
4
Q
bone types - classification by shape
A
- long bones
- short bones
- flat bones
- irregular bones
- sesamoid bones
5
Q
what are the 2 types of macro bone structure?
A
Cortical:
compact - dense, solid, only spaces are for cells and blood vessels
Trabecular
cancellous, spongy - network of bony struts (trabeculae) looks like sponge, many holes filled with bone marrow. Cells reside in trabeculae and blood vessels in holes.
6
Q
what are the 2 types of micro bone structure?
A
Woven bone:
made quickly, disorganised, no clear structure, temporary
Lamellar bone:
made slowly, organised, layered structure
7
Q
how does the structure of hollow long bones contribute to its functions?
A
- keeps mass away from neutral axis, minimises deformation
8
Q
how does the structure of trabecular bone contribute to its function?
A
gives structural support while minimising mass
9
Q
what role do flat bones generally have?
A
protective
10
Q
how do wide bone ends aid the function of the bone?
A
spreads the load over weak, low friction surface
11
Q
what is bone composed of? (adult)
A
50-70% mineral (hydroxyapatite, a crystalline form of calcium phosphate)
20-40% organic matrix - mostly type 1 collagen, 10% non-collagenous proteins
5-10% water
12
Q
Bone is a composite of collagen and mineral - why these 2 components?
A
mineral provides stiffness
collagen provides elasticity
13
Q
what are the 4 key cells of bone and how do they differ histologically?
A
osteoclast - multinucleated
osteoblast -plump, cuboidal
osteocyte - stellate, entombed in bone
bone lining cell - flattened, lining the bone
14
Q
what cells do osteoblasts differentiate from?
A
mesenchymal stem cells
15
Q
function of osteoblasts
A
- form bone - secrete osteoid
- produce type 1 collagen and mineralise the extracellular matrix by depositing hydroxyapatite crystal within collagen fibrils
- secrete factors that regulate osteoclasts
16
Q
what cells are precursors for osteoclasts?
A
haematopoeitic stem cells
- specialised macrophages
17
Q
function of osteoclasts
A
- resorb bone
- dissolve the mineralised matrix
- break down the collagen in bone
18
Q
what is the difference between bone modelling and bone remodelling?
A
modelling - gross shape altered, bone added/taken away
remodelling - all of the bone is altered, new bone replaces old bone
19
Q
what is the difference between bone modelling and bone remodelling?
A
modelling - gross shape altered, bone added/taken away. Occurs during growth to sculpt adult shape, involves formation and resorption.
remodelling - all of the bone is altered, new bone replaces old bone/damaged bone. Mobilise mineral for homeostasis.
20
Q
reasons for bone remodelling
A
- form bone shape
- replace woven bone with lamellar bone
- reorientate fibrils and trabeculae in favourable direction for mechanical strength
- response to loading (exercise)
- repair damahe
- obtain calcium
21
Q
what is interstitial growth? where does this mostly occur?
A
Happens in most tissues.
Nutrients move into the space to grow.
The cell material is soft in most tissues so can get bigger/swell without having to add to the surface.
(like a loaf rising)
22
Q
why is interstitial growth not possible in bone?
A
not possible for nutrients to move into solid bone matrix - cannot swell, so cells have to add to the surface in appositional growth
23
Q
which bones are produced by endochondral ossification?
A
Most bones in the body - long bone is most common example.
Embryonically begins as a hyaline cartilage model.
24
Q
describe the process of endochondral ossification?
A
- Collar formation: psteoprogenitor cells become osteoblasts, which secrete osteoid to form a body collar around the shaft (diaphysis)
- Cavity formation: cartilage in bone centre starts to ossify - known as the primary ossification centre. Inner cartilage cannot get nutrients so degrades and forms cavity.
- Vascular invasion: vessels bring blood, nutrients and osteoblasts/osteoclasts. Osteoclasts break down cartilage, osteoblasts secrete spongy bone.
- Elongations: increased cell numbers and the secretion of osteoid lead to elongation of diaphysis. Vessels bud into cartilage at ends of bone - secondary ossification centre.
- Epiphyseal ossification: ends of bone form spongy bone, articular cartilage on end of bone - growth/epiphyseal plate on other side
25
describe the process of endochondral ossification?
1. Collar formation: osteoprogenitor cells become osteoblasts, which secrete osteoid to form a body collar around the shaft (diaphysis)
2. Cavity formation: cartilage in bone centre starts to ossify - known as the primary ossification centre. Inner cartilage cannot get nutrients so degrades and forms cavity.
3. Vascular invasion: vessels bring blood, nutrients and osteoblasts/osteoclasts. Osteoclasts break down cartilage, osteoblasts secrete spongy bone.
4. Elongations: increased cell numbers and the secretion of osteoid lead to elongation of diaphysis. Vessels bud into cartilage at ends of bone - secondary ossification centre.
5. Epiphyseal ossification: ends of bone form spongy bone, articular cartilage on end of bone - growth/epiphyseal plate on other side
26
which bones are produced by intermembranous ossification?
Flat bones - skull, teeth, clavicle
27
describe the process of intermembranous issification
1. mesenchyme cells become osteoprogenitor cells which form osteoblasts - forming the primary ossification centre
2. osteoblasts secrete collagen and proteins to form osteoid (bony matrix)
3. osteoid is calcified, trapping the osteoblasts in their own matrix to form osteocytes
4. osteoblasts are on periphery. Osteoid is randomly laid down around blood vessels - trabeculated
5. peripheral osteoid becomes compact bone. Spongy bone contains bone marrow.
28
features of long bones
| e.g.
tubular hollow shaft
expanded ends for articulation
e.g. femur, humerus - most bones
29
features and e.g. of short bones
- cuboidal shape
| - e.g. carpal bones
30
features and e.g. of flat bones
- curved plates of bone
- protective function
- e.g. bones of the skull
31
features and e.g. of irregular bones
- various shapes
| - eg. vertebrae for spinal cord protection
32
features and e.g. of sesamoid bones
- round, oval bones embedded in tendon
| - patella - knee joint
33
what are primary osteons?
concentric circles of bone, form during rapid growth/apposition. Fill in from outside.
34
What is the distribution of calcium in the body?
skeletal - 1200g
extracellular - 1g
some intracellular
35
functions of calcium in the extracellular space?
- normal blood clotting
- muscle contractility
- nerve function
36
functions of intracellular calcium
- signalling
| - endoplasmic reticulum - calcium from sarcoplasmic reticulum is important for contraction
37
how is calcium distributed in the blood? (what forms)
- over half is protein bound/complexed - usually to albumin, and is not metabolically active.
- under half is ionised, metabolically active.
- small amount it complexed with citrate/phosphate and filtered by the kidney
38
what is the effect of alkalosis on serum calcium?
Alkalosis causes more albumin bound calcium to form.
39
How are calcium levels increased/decreased in the gut?
Absorption:
actively absorbed in duodenum and jejenum, passively absorbed in ileum and colon.
Excretion:
faecal Ca out
40
How are calcium levels increased/decreased in the kidney?
Reabsorption:
| majority passively reabsorbed in PCT and ascending loop, minority actively absorbed in DCT - under hormonal control.
41
How are calcium levels increased/decreased in the bones?
Resorption/exchange frees calcium, formation decreases levels.
42
describe the processes that release calcium from bone
- rapid release of exchangeable calcium on bone surface
| - slower release by osteoclasts during bone resorption
43
dietary sources of calcium
We absorb about 30% of dietary calcium
- milk, cheese and other dairy foods.
- green leafy vegetables
- soya beans
- tofu
- nuts
- fish where you eat the bones
44
what does the amount of calcium filtered by the kidney depend on?
- GFR
| - ultrafiltrable calcium - whether it is ionised or complexed
45
what % of Ca2+ filtered by the kidney is usually reabsorbed?
| when does this change?
98%
Increases when PTH is high.
Decreases when filtered sodium is high.
46
where in the nephron does reabsorption of calcium change according to need? why?
in the DCT - here calcium is actively reabsorbed.
| Most calcium is passively reabsorbed in the PCT.
47
what happens when serum calcium is low?
PTH is secreted from the 4 parathyroid glands.
48
what is the affect of high vitamin D on PTH?
stops PTH secretion
49
how sensitive is PTH to serum calcium?
very - small changes in serum calcium produce large changes in PTH levels
50
targets of PTH
- cells on bone, kidney
| - activates second messenger cAMP
51
actions of PTH on kidney
- increased active calcium reabsorption
- decreased phosphate reabsorption
- increased activation of vitamin D (calcitriol)
52
actions of PTH on bone
- increased bone remodelling
| - bone resorption > bone formation
53
actions of PTH on gut
- no direct effect
| - BUT increase in activation of vitamin D (calcitriol) from kidney indirectly increases calcium absorption from the gut.
54
how is vitamin D activated?
calcidiol (vit d) from the liver is hydroxylated to form calcitriol:
25-OH vit D --> 1,25-OH vit D
enzyme = 1a hydroxylase
55
what is calcitonin hormone?
- produced by... in response to..
- effect
- produced by C cells in the thyroid
- secretion stimulated by an increase in serum calcium
- lowers bone resorption - but importance is uncertain
56
Fast actions of PTH
- exchangeable calcium released from the surface of bone
| - decreased excretion of calcium from the kidney
57
Slow actions of PTH
- increased bone resorption
| - increased fractional absorption by the intestine via calcitriol from the kidney
58
sources of calcium
- dietary
- UV hits skin, converted by the liver to 25 hydroxy vitamin D
- kidney converts some to 1, 25 hydroxyvit D (more when low phosphate, calcium and calcitriol levels)
59
Osteoblasts have a PTH receptor - what happens when PTH binds?
- osteoblast proliferation
- RANK ligand expressed and inhibitory molecule removed, allowing binding and activation of osteoclasts
- osteoclasts are multinucleate when activate, and eat away at bone
this releases minerals from bone.
60
function of the RANK ligand
- signal released by osteoblasts, regulates/controls function of osteoclasts.
61
which cells in the parathyroid glands detect Ca levels?
chief cells
62
what are the 3 classifications of joints that are based on tissue type at articulation?
1. Synovial Joint
2. Fibrous Joint
3. Cartilaginous
63
Describe features of synovial joints
- discontinuous connection
- joint cavity filled with synovial fluid
- articular surface covered in hyaline cartilage
- joint capsule: inner layer is the synovial membrane
- reinforcing ligaments act as stabilisers
64
Describe features of fibrous joints
subdivisions and examples
- continous connection
- low to moderate mobility
Types:
a) suture - e.g. cranial sutures only
b) syndesmosis e.g tibiofibular
c) gomphosis e.g. peg in socket joint of tooth articulation only
65
describe features of cartilagenous joints
| subdivisions and examples
- continuous cartilage connection
- moderate mobility
a) synchrondoses - bones directly connect by hyaline cartilage e.g. costochondral (ribs and sternum)
b) symphyses - connecting cartilage is a pad/plate of fibrocartilage e.g. pubic symphysis/intervertebral disc
66
3 functional classifications of joints - by the degree of movement
what structural types are they mostly?
e.g.
a) synarthroses: immoveable joints, mostly fibrous - e.g. skull sutures
b) amphiarthroses: slightly moveable, mostly cartilagenous - e.g. intervertebral disc
c) diarthroses: freely moveable, mostly synovial = e.g hip
67
6 different types of synovial joints
1. Ball and socket
2. Hinge joint
3. Pivot joint
4. Condylar joint
5. Saddle joint
6. Plane/gliding joint
68
Example of a ball and socket joint
| movement allowed?
```
- polyaxial, rotational. Most mobile type of joint.
Ligaments restrict movement.
e.g. glenohumeral joint (shoulder)
acetabulofemoral joint (hip)
```
69
Example of a hinge joint
| movement allowed?
Uniaxial - flexion and extension.
| e.g. tibiofemoral, elbow joint
70
Example of a pivot joint
| movement allowed?
Uniaxial - rotational movement along the y axis.
| e.g. atlantoaxial joint, radioulnar joint
71
Example of a condylar joint
| movement allowed?
Biaxial
| e.g. radiocarpal joint
72
Example of a saddle joint
| movement allowed?
Biaxial
| e.g. carpometacarpal joint
73
Example of a plane/gliding joint
| movement allowed?
Gliding joints allow the bones to glide past one another in any direction along the plane of the joint
e.g. acromioclavicular joint
74
Functions of ligaments
- attach bone to bone
- augment joint's mechanical stability
- guide joint motion
- prevent excessive motion
75
Functions of tendons
- connect muscle to bone: a solid base on which muscles can pull
- transmit tensile loads from muscle to bone, in order to:
stabilise joint, act as restraint, interact with ligaments and joint capsule to mitigate load
- aid joint stability
76
what is the general composition of joints and ligaments?
vascularisation?
- dense connective tissue of mainly parallel fibres to sustain high tensile strains
Tissue is composed of:
fibroblasts (/tenocytes) which synthesise and remodel the extracellular matrix
- sparsely vascularised so poor capacity for healing
77
What is the distribution of ECM vs cells in the tissue of tendons/ligaments:
- only 20% of tissue volume is cells
| - ECM is 80% of tissue volume
78
what is the extracellular matrix of tendons/ligaments made up of?
70% water
30% solids - collagen type 1 and ground substance (proteoglycans and glycoproteins)
has hierachical structure
79
Histologically, longitudinal arrangement of collagen fibrils and fibres appears crimped - why is this?
Enables some increase in ligament length during tension
80
Describe the hierachical structure of a tendon:
Tropocollagen bound by endotenon membrane to form microfibril.
A few microfibrils bound by endotenon to form a subfibril.
Subfibrils form fibril
Fibrils form Fascicle.
Fascicles are bound by paratenon/epitenon membrane forming a tendon.
81
What is the purpose of endotenon membranes?
Help fibrils slide over each other, reducing friction.
82
What is the role of the small amount of collagen that is not type 1 in tendons/ligaments?
and proteoglycan?
Control fibril diameter to enable packing into hierarchical structure.
Proteoglycan regualtes fibre diameter in fibrillogenesis, and acts as a lubricant
83
Describe formation of hierarchical structure of tendons starting with collagen synthesis
Fibroblast is precursor - formes 3 polypeptide alpha chains in helix.
This is secreted into the extracellular space.
Assembly occurs outside the cell - terminal regions are cleaved, covalent (very strong!) crosslinks form in specific places.
Fibrillogenesis arranges the collagen fibrils in hierarchical order.
84
What is the role of elastin in tendons and ligaments?
increases elasticity
85
Example of a ligament with more elastin present in its structure?
Ligamentum flavum, between laminae of vertebrae.
| Protects spinal nerve roots and provides stability to the spine.
86
Key differences between ligaments and tendons
Ligament
- bone to bone
- 90% collagen type 1
- higher elastin
- random organisation
- blood supply from insertion points
Tendon
- muscle to bone (except eye)
- 95-99% collagen type 1
- very little elastin
- fibres highly organised in hierachical structure
- vascular have paratenon, avascular have thick vascular sheath
87
What are the 2 types of insertion points - enthesis - of a tendon/ligament into bone?
How do they differ?
1. Fibrous: formed through intermembranous ossification
| 2. Fibrocartilage: endochondrial ossification
88
example of a fibrous enthesis
distal medial collateral ligament
89
example of a fibrocartilage enthesis
proximal medial collateral ligament
90
What is an enthesis? Are they innervated?
- place of insertion of a tendon/ligament into bone
| - innervated: proprioception & pain
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