1
Q
list some purposes of the skeleton
A
- raises us up from the ground against gravity
- determines basic body shape
- transmits body weight
- forms jointed lever systems for movement
- protects vital structures from damage
- houses bone marrow
- mineral storage
2
Q
list the 5 different types of bone
A
- long
- short
- flat
- irregular
- sesamoid
3
Q
describe long bones
A
- tubular hollow shaft
- expanded ends for articulation
eg femur and humerus
4
Q
describe short bones
A
- cuboidal in shape
eg carpals
5
Q
describe flat bones
A
- (often curved) plates of bone
- protective function
eg bones of the skull
6
Q
describe irregular bones
A
- various shapes
eg vertebrae
7
Q
describe sesamoid bones
A
- round, oval bones embedded in a tendon
eg patella
8
Q
what are the 2 types of macro bone structure?
A
cortical and trabecular
9
Q
what is cortical bone?
A
(macro) COMPACT
- dense and solid
- only spaces are for cells and blood vessels
10
Q
what is trabecular bone?
A
(macro) CANCELLOUS/spongy
- network of bony struts filled with bone marrow
- cells reside in trabecular, blood vessels reside in holes
11
Q
what are the 2 types of micro bone structure?
A
woven and lamellar
12
Q
what is woven bone?
A
(micro)
- made quickly
- disorganised
- no clear structure
13
Q
what is lamellar bone?
A
(micro)
- made slowly
- organised
- layered structure
14
Q
what is bone composed of?
A
50-70% = minerals (hydroxyapatite, a crystalline form of calcium phosphate) 20-40% = organic matrix (90% T1 collagen, 10% non-collagenous) 5-10% = water
15
Q
what % of bone is minerals?
A
50-70%
16
Q
what is the main mineral in bone?
A
hydroxyapatite
17
Q
what is hydroxyapatite?
A
a crystalline form of calcium phosphate (reservoir for calcium and phosphate)
18
Q
what % of bone is organic matrix?
A
20-40%
19
Q
what is organic matrix composed of?
A
90% of protein = t1 collagen
10% = non-collagenous proteins
20
Q
what % of bone is water?
A
5-10%
21
Q
how is collagen assembled in the bone?
A
in fibrils with crystals situated in the ‘gap’ regions between them
22
Q
what does collagen provide bones with?
A
stiffness
23
Q
what do minerals provide bones with?
A
elasticity
24
Q
what are the 4 main bone cells?
A
- osteoclasts (multinucleated)
- osteoblasts (plump, cuboidal)
- osteocytes
- bone lining cell
25
what's the difference between osteoblasts and osteoclasts?
```
osteoBlasts BUILD bone
osteoClasts CHEW (break down)
```
26
what do osteoblasts do?
- derived from haematopoietic stem cells
- form bone - in form of osteoid
- produce t1 collagen
- act by secreting collagen into matrix (mineralise the extracellular matrix by depositing hydroxyapatite crystal within collagen)
- high alkaline phosphate activity
- make non-collagenous proteins
- secrete factors that regulate osteoclasts eg RANK ligand
- once collagen becomes calcified (mineralisation), osteoblasts become osteoCYTES
27
what is osteoid?
unmineralised, organic portion of bone matrix that forms prior to bone maturation
28
what do osteoclasts do?
- resorb bone
- dissolve the mineralised matrix
- break down collagen bone
- secrete collagenases and proteinases
- high expression of TRAP and cathepsin K
29
what do osteocytes do?
- form tight junctions with neighbouring osteocytes
30
what are the 2 ways in which bone shape can be renewed?
- MODELLING = gross shape is altered, bone is added/taken away
- REMODELLING = all of bone is altered, new bone replaces old
31
list some reasons for bone remodelling
1. forms bone shape
2. to replace woven bone with lamellar
3. to reorientate fibrils and trabecular in favourable direction for mechanical strength
4. in response to loading (exercise)
5. to repair damage
6. to obtain calcium (eg in times of stress such as pregnancy)
7. dysregulated remodelling = disease
32
what is the skeleton divided into?
axial and appendicular
33
what is the difference between the axial and appendicular skeleton?
```
axial = bones of head/trunk
appendicular = upper and lower limbs and girdles (shoulder/pelvis)
```
34
discuss primary bones
primary bones are the 1st bones that appear in embryonic development and fracture repair
it undergoes bone building in 1st trimester
- poorly organised structure
- synthesised from mesenchyme/cartilage
- bone is often heavy and weak
primary bone is REMODELLED
35
discuss secondary bones
the result of remodelling by osteoblasts/clasts
- occurs around age 17-18 (after growth stops)
- well organised structure
- bone is lighter
36
what are the 2 main types of ossification (and the difference between them)?
- endochondral ossification (produces LONG bones, cartilage is present)
- intramembranous ossification (produces FLAT bones, cartilage not present)
37
how are collagen fibrils formed?
3 collagen molecules --> tropocollagen --> collagen fibril
38
what joins collagen together?
covalent cross-links within the tropocollagen molecule and hydrogen bonds between hydroxyproline molecules (within tropocollagen) [requires vit c]
39
how is collagen broken down?
by proteinases - especially collagenases and cathepskin K (in bone)
40
why is vitamin C important in bone and what condition is associated with this?
vitamin c is involved in collagen formation
scurvy = severe vitamin c deficiency
41
what disease is as a result of not enough collagen?
osteogenesis imperfecta aka brittle bone disease
not enough collagen to support minerals in bone thus making bone weak
42
list 6 diff types of collagen and where they're found
type I = bone marrow, tendon, ligaments, skin
type II = articular cartilage
type III = alongside type I, wound healing
type IV = basal lamina
type V = cell surfaces
type X = growth plate
43
describe the stages in endochondral ossification
remember, it produces long bones
mnemonic: Boys Can't Pee During Erections
1. Bone collar formation
2. Cavitation
3. Periosteal bud invasion
4. Diaphysis elongation (diaphysis is the middle portion)
5. Epiphyseal ossification (epiphyseal = 2 round bits at ends)
44
describe stage 1 of endochondral ossification
BONE COLLAR FORMATION
- osteoprogenitor cells --> osteoblasts
- osteoblasts secrete osteoid
- bony collar formed around shaft (diaphysis)
45
describe stage 2 of endochondral ossification
CAVITATION (cavity formation)
- cartilage in bone centre begins to ossify [primary ossification centre]
- inner cartilage can't get nutrients --> degrades and forms cavity
46
describe stage 3 of endochondral ossification
PERIOSTEAL BUD INVASION
- vessels in periosteum invade cavity through nutrient foramen
- vessels bring blood, nutrients and osteoblasts/clasts
- osteoclasts break down cartilage and osteoblasts secrete spongy bone
47
describe stage 4 of endochondral ossification
DIAPHYSIS ELONGATION
- increased cell numbers + osteoid --> elongation of diaphysis
- vessels bud into cartilage at ends of bone [secondary ossification centre]
48
describe stage 5 of endochondral ossificaiton
EPIPHYSEAL OSSIFCATION
- when completed, hyaline cartilage remains only in epiphyseal plates and articular cartilages
- ends of bone form spongy bone
- articular cartilage on end of bone - growth/epiphyseal plate on other side
49
describe intramembranous ossification
(produces flat bones)
1. ossification centre forms
- mesenchyme cells --> osteoprogenitor cells --> osteoblasts --> primary ossification centre
2. calcification
- osteoblasts secrete collagen/proteins --> forms osteoid (bony matrix)
- osteoid is calcified --> engulfs osteoblasts to form osteocytes
3. trabecular formation
- osteoid is randomly laid down around blood vessels --> trabeculated (osteoblasts are on periphery)
4. periosteum development
- peripheral osteoid becomes compact bone --> spongy bone contains bone marrow
50
what are the 4 hormonal influences on growth?
growth hormone
- increases growth
thyroid hormone
- increases metabolic rate
- required for growth
sex hormones
- stimulates growth at puberty by stimulating GH
cortisol
- inhibits growth
51
how is calcium distributed?
mainly in skeleton - 1200g
52
what is calcium like in neonates?
they have only 30g thus need lots of milk during development
53
what are the levels of calcium intra/extracellularly? (and why is it needed there)
extracellularly - 1g
- needed for blood clotting, muscle contraction and nerve function
intracellularly - trace
- calcium in the ER
- major in muscle (SR)
- important for signalling
54
what is the total serum calcium?
2.4 mmol/L
55
what are the 3 forms of calcium in serum?
1. ionised (free)
2. complex eg citrate/phosphate
3. protein-bound
56
discuss ionised calcium
- just under half of serum
- metabolically ACTIVE
- if serum pH increases (alkalosis) = less ionised calcium
57
why is there less ionised calcium if serum pH increases?
- albumin is neg charged and a buffer
- H+ taken away from neg albumin
- Ca2+ has to take place of excreted H+ to balance charge
- thus, less circulating ionised calcium
58
discuss complexed calcium
- metabolically INACTIVE
| - filtered by the kidney
59
discuss protein-bound calcium
- metabolically INACTIVE
- mainly bound to albumin
- cannot be filtered by the kidney
60
what condition is low ionised calcium associated with?
tetany
associated with contraction of small muscles of hands/feet
61
discuss calcium kinetics (3 types of absorption)
calcium can be:
- ABSORBED from gut (excreted in faeces)
- REABSORBED from kidney (secreted into kidneys)
- RESORBED from bone (lost in bone formation - helping to mineralise)
62
name some major and minor dietary sources of calcium
- major: dairy prods (2/3) - milk, yoghurt, cheese
| - minor sources: veg (broccoli), cereals, oily fish
63
what % of dietary calcium is absorbed?
30% (actively or passively)
64
where does active calcium absorption occur?
in the duodenum and jejunum (majority)
65
what is active calcium absorption mediated by?
calcitriol (activated vitamin d)
- low calcium diet = increased calcitriol = increased calcium absorption in duodenum/jejunum
66
where does passive calcium absorption occur?
ileum and colon (to a much lesser extent)
67
what are the 2 processes in which calcium can be released from the bone?
1. can be released RAPIDLY from exchangeable calcium on bone surface
2. can be released from osteoclasts during bone resorption which is much SLOWER
68
what does calcium filtration through the glomerulus depend on?
1. GFR
| 2. ultra filtrable calcium (ie calcium which is either ionised or complexed to phosphate)
69
if the GFR is high, is there more or less calcium filtration?
more
70
what % of calcium filtered by the kidneys is reabsorbed back into the blood?
98%
71
if PTH levels are high, does reabsorption of calcium increase or decrease?
increase
72
if filtered sodium levels are high, what effect does it have on calcium filtration?
calcium filtration decreases (based on share of channels)
73
is calcium movement out of the nephron active or passive?
passive
74
what % do diff parts of the nephron excrete calcium?
65% @ PCT
25% @ LOH
10% @ DCT
75
is reabsorption of phosphate mostly active or passive?
active
76
what is the difference between calcium and phosphate reabsorption at the kidneys?
calcium = mostly passive WHEREAS phosphate = mostly active
77
what are the 3 hormones involved in regulation of calcium metabolism and what type of feedback is this?
1. PTH
2. calcitriol
3. calcitonin
negative feedback
78
what is calcitriol?
activated vit d
79
how is PTH secreted?
- decrease of serum Ca2+
- sensed by 4 parathyroid glands
- PT glands then secrete PTH
80
how is PTH inactivated?
- PTH made of 84 amino acids
- structure needs to be intact for it to be active
- once Ca2+ levels rise again, PTH is broken down thus inactivated
81
what does PTH do?
- acts on its target cell (bone, kidney)
| - activates 2nd messengers eg cAMP, intracellular calcium
82
does PTH increase or decrease phosphate reabsorption at PCT?
decreases
hence, it increases phosphate reabsorption at DCT
83
what are the 4 main ways of increasing Ca2+?
- increase calcitriol prod @ kidney
- increase calcium reabsorption at DCT
- increase calcium leeching out of bone
- decrease phosphate reabsorption at PCT (allow more calcium reabsorption at DCT)
84
what % of vit d is from diet?
20% - this is D2 (ergocalfierol)
85
where does 80% of vit d come from?
breakdown of cholesterol in the skin - this is D3 (cholecalciferol)
86
where does vit d get activated?
liver then the kidney
87
which form of vitamin d does the liver produce?
25(OH)vit d (calcidiol)
88
which form of vitamin d does the kidney produce?
1,25(OH)2vitamin D (calcitriol)
89
what determines how much of the 25(OH)vitD is converted into 1,25(OH)vitD?
kidney hormones
- these hormones are stimulated by PTH or if levels of 1,25(OH)vitD are low
- low levels of FGF23 also stimulates more
90
what is 1,25(OH)vitD also known as?
calcitriol
91
what is 25(OH)vitD also known as?
calcidiol
92
which hormone is secreted in response to an increase in serum calcium?
calcitonin
93
what is the difference between fast and slow actions in calcium homeostasis?
fast: exchangeable calcium is released from bone surface and decreased calcium excretion from kidney
slow: incr bone resorption, incr fractional absorption by intestine via activated vitD
94
how much phosphate is there in the body (and how is this distributed)?
500-800g
1% total body weight
90% in bone mineral
95
what is the normal range for serum phosphate?
0.8-1.5 mmol/L
96
what does high phosphate result in?
excessive formation of hydroxyapatite and deposition in tissues other than bone
97
what does low phosphate result in?
poor bone mineralisation ie low hydroxyapatite
rickets/osteomalacia, pain/fractures
98
name some dietary sources of phosphate
animal, dairy, soy, seeds/nuts
99
what is the adult daily recommendation of phosphate?
700mg
100
where is phosphate absorbed?
in the small intestine
passie diffusion @ hich conc
active transport @ low conc (sodium dependent)
101
what % of phosphate is reabsorbed into the blood at PCT & DCT?
80% @ PCT
| 10% @ DCT
102
what is phosphate metabolism regulated by?
- PTH
- calcitriol
- FGF-23
103
what is FGF-23?
fibroblast growth factor 23
- a major regulator of phosphate metabolism
- produced by osteocytes
- increases renal excretion of phosphate
- decreases gut absorption of phosphate
104
what is the main and secondary regulator in phosphate metabolism?
main: FGF-23
secondary: PTH
105
what % of body is made of collagen?
30%
106
what is a fracture?
breech in continuity of bone
107
what are the 4 fracture healing stages?
1. haematoma (hours)
2. inflammation (days)
3. repair (months to years)
4. remodelling (months to years)
108
what happens during fracture healing stage 1?
HAEMATOMA (hours)
- bleeding from endosteal and periosteal vessels/muscles
- decreased blood flow to fracture site = leads to perinatal stripping and osteocyte death
109
what happens during fracture healing stage 2?
INFLAMMATION (days)
- fibrin clot organisation bc of platelets
- neurovascularisation
- cellular invasion (osteoclasts resorb dead bone, mesenchymal stem cells stimulate new bone etc)
110
what happens during fracture healing stage 3?
REPAIR (months to years)
- callus formation (fibroblasts prod fibrous tissue, chondroblasts prod cartilage, osteoblasts prod osteoid)
- progressive matrix mineralisation
- high vascularity provides nutrition and blood supply
111
what happens during fracture healing stage 4?
REMODELLING (months to years)
- woven bone structure from repair stage is replaced by lamellar bone
- increased bone strength
- vascularity returns to normal
- healing w/o scar tissue
112
list 3 functions of joints
1. allow movement in 3D
2. to be weight-bearing
3. to transfer load evenly to MSK system
113
what are the 2 classifications of joints?
structural (by degree of movement) and functional (by the components which hold the joint together)
114
what are the 3 types of joints according to structural classification?
- fibrous eg teeth sockets
- cartilaginous eg IVD
- synovial eg metacarpophalangeal
115
what are the 3 types of joints according to functional classification?
- synarthroses eg skull sutures
- amphiarthroses eg IVD
- diarthroses eg hip
116
what are synarthroses?
immovable joints, mostly fibrous
eg skull sutures
117
what are amphiarthroses?
slightly moveable joints, mostly cartilaginous
eg IVD
118
what are diarthroses?
freely moveable joints, mostly synovial
eg hip joint
119
what are fibrous joints connected by?
a cord (ligament) or sheet (interosseous membrane) of fibrous tissue
120
what are cartilaginous joints connected by?
hyaline cartilage
| usually amphiarthroses ie slightly moveable eg costal cartilage
121
list the 5 characteristic features of synovial joints
1. articular cartilage
2. joint capsule (inner layer = synovial membrane)
3. joint (synovial) cavity
4. synovial fluid
5. reinforcing ligaments
122
what are bursae?
fluid filled sacs lined by synovial membrane
123
what are menisci?
discs of fibrocartilage
124
what is cartilage composed of?
water, proteoglycans, collagen
125
what is the diff between tendons and ligaments?
- tendons connect bone to muscle
| - ligaments connect bone to bone
126
which group of muscles help in stabilisation of the shoulder joint?
rotator cuff muscles
1. subscapularis
2. supraspinatus
3. infraspinatus
4. teres minor
127
what type of joint is the shoulder joint?
ball and socket (synovial)
128
what does synovial fluid do?
increases lubrication of the joint
129
are tendons/ligaments well vascularised?
no, so generally have poor capacity for healing
130
what are tendons and ligaments mainly composed of?
collagen (mainly type I)
131
what is the precursor of collagen?
procollagen
132
how do ligaments and tendons differ in their elastin content?
ligaments have a higher elastin content
133
what is the place of insertn of a tendon or ligament into bone called?
enthesis
134
what effect does physical training have on ligaments?
they become stronger/stiffer
| collagen fibres incr in diameter
135
what does ACL of the knee do?
provides rotational stability and resists anterior translation of the tibia
136
what does PCL of the knee do?
resits post translation of femur
137
what does MCL do?
resists valgus (inwards) force on the knee
138
what does LCL do?
resists varus (outwards) force
139
what causes gout?
high uric acid levels cause uric acid crystals to deposit in joints. these cause inflammation which causes swelling, pain n redness
140
how does pH affect uric acid solubility?
the lower the pH, the less soluble it becomes
141
what does uric acid come from?
purines (adenine/guanine)
142
list some sources of purines
diet (meat, offal, seafood, fish), breakdown of nucleotides from tissues, synthesis in the body
143
how does uric acid leave body?
70% excreted in urine
| 30% broken down in gut
144
what impact does oestrogen have on uric acid excretion in urine?
promotes it
145
list 4 purines
adenine, guanine, hypoxanthine, xanthine
146
what is the metabolic end prod of purine metabolism?
uric acid
147
what is hyperuricaemia as a result of?
- over production or under excretion of uric acid
148
list 3 functions of bone
- protect vital soft organs eg brain
- allow muscles to work to move us around
- store mineral and house marrow cells
149
what are the 3 types of muscle?
skeletal
smooth
cardiac
150
describe skeletal muscle
- multinuclated
- long, unbranched fibres
- voluntary contraction
- transverse tubules
- sarcoplasmic reticulum
151
describe smooth muscle
- uninucleate
- unbranched fibres
- involuntary contraction
- unstriated
152
describe cardiac muscle
- branched fibres
- intercalated discs
- purkinje fibres
- fairly striated
- inherent rhythm
153
list some types of synovial joints
- plane joint eg wrist/ankle
- hinge joint eg elbow/knee
- ball and socket joint eg shoulder
154
what enhances the strength of collagen molecules?
cross-linking between alpha chains (remember, 3 alpha chins are coiled in the left hand helix and same with right)
155
where are collagen molecules synthesised and then assembled into fibrils?
- collagen molecules are synthesised inside the cell
- they are then secreted into extracellular space
- outside the sell, collgaen fibrils self assemble
156
how are ligaments and tendons formed?
tropocollagen --> microfibrils --> sub fibrils --> fibrils --> fibres --> fascicles --> tendon
157
what is an enthesis?
place of insertion of tendon or ligament into bone
158
what are the 2 types of insertion (entheses)?
fibrous and fibrocartilagenous
159
what does enthusis insertion depend on?
cellular processes involved during their formation
160
what are entheses innervated by?
proprioceptive and pain receptors
161
what is the main difference between fibrous and fibrocartilage insertion at entheses?
fibrous: formed through intramembranous ossification
fibrocartilage: formed through endochondral ossification
162
describe fibrous insertion (entheses)
calcified anchorage is by calcified collagen fibres (Sharpey's fibres) into bone
163
describe fibrocartilage insertion (entheses)
gradual change from collagenous ligament --> fibrocartilage --> mineralised cartilage --> bone
164
how can you describe fractures?
- site
- pattern
- displacement/angulation
- joint involvement
- skin involvement
165
what is coupling?
bone formation occurs at sites of previous bone resorption
166
what is balance?
amount of bone removed by osteoclasts should be replaced by osteoblastic activity
167
what are osteoclasts derived from?
macropage
168
what activates osteoclasts?
RANK ligand
169
what is RANK ligand secreted by?
osteoblasts
170
what is bone remineralisation also known as?
calcification
171
what is calcitonin produced by?
c cells of thyroid gland
172
what does calcitonin do?
lowers calcium levels
- suppresses calcium release from bones, dampens calcium absorption in intestine and discourages kidney reabsorption of calcium
173
what is osteopenia?
decreases bone density but not to extent of osteoporosis
174
what is osteoporosis?
osteopenia to a greater degree
| decreased bone density
175
what is osteomalacia?
decreased mineralisation of newly formed bone (caused by severe vit D deficiency or cold that cause low blood phosphate levels)
(SALMA) Physiology
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