MSK Flashcards
Purpose of the skeleton:
* Raises us from the ground against [a]
* Determines basic body [b]
* transmits body [c]
* Forms joint lever system for [d]
* [e] vital structures from damage
* Houses [f]
* [g] storarge
[a] gravity
[b] shape
[c] weight
[d] movement
[e] protects
[f] bone marrow
[g] mineral
How many apendicular bones do adults have?
126
how many axial bones do adults have?
80
how many bones does a newborn baby have?
350 - they then fuse
describe long bones.
example?
long tubular and hollow.
expanded at ends for articulation
femur, ulnar
what shape are short bones.
example?
cuboidal.
carpal bones.
describe the shape of flatbones.
flat, often curved, protective.
eg skull and ribs
give an example of an irregular bone
vertebrae
where are sesamoid bones found?
in the tendon
eg thumb, knee cap
where would a trabecular bone structure be found?
in the metaphysis of bone
where would compact bone structure be found?
in the diphysis of bone
which type of bone structure is made quickly?
woven bone
- disorganised
- no clear structure
which type of bone structure is made slowly?
lamellar - like tree rings
organised and layered
function of hollow long bone?
keep weight away from neutral axis
minimises deformation
function of trabecular bone?
give structural support while minimising weight
function of wide ends of bone?
to spread load over weak, low friction surface
what percentage of bone is made up from mineral particles?
50-70% mineral
- hydroxyapatite
what is hydroxyapatite?
crystalline form of calcium phosphate
what percentage of bone is made from organic matrix?
20-40% organic matric
-90% Type I Collagen
10% Non collagenous protein
what percentage of bone is water?
5-10% water
what is the purpose of collagen and minerals in bone?
minerals = stiffness
collagen = elasticity
label the cells of the bone
function of osteoclast?
to resorb bone
how does an osteoclast resorb bone?
dissolve mineralised matrix = acid
breakdown collagen in bone = enxymes
TRAP and Cathepsin K
what does an osteoclast derive from?
hematopoietic stem cells
(uses MCSF)
function of osteoblasts?
form bone - in form of osteoid
how do osteoblasts form bone?
produce type I collagen
mineralises extracellular matrix by depositing hydoxyapatite crystal within collagen fibrils.
high alkaline phosphatase activity
what do osteoblasts derive from?
mesenchymal stem cell
what is the function of osteocytes?
conductor of cells in bone - tell other cells what to do
5 steps of bone remodelling?
what is bone modelling?
adaptation (ie to sport)
gross shape of bone is altered, bone added or taken away
what is bone remodelling?
repair
all of the bone is altered, new bone replaces old bone
a human fully replaces its entire skeleton every…
10 years
explain what happens during trauma to a bone?
- periosteum tears = haematoma
- adjacent bone cell death
- soft tissue damage
- osteoblasts = new woven bone
- osteoclasts = mop up dead bone; remodel strong bone
- osteoblasts = new lamella bone
current treatments of osteogenesis issues?
anti-catabolic = stop the osteoclasts (more because easier)
anabolic = stimulate ostoblasts
function of collagen in bone?
allows elasticity in bone
creates structure for hydroxyapatite crystals
which enzyme is needed for bone mineralisation?
alkaline phosphate -
hydrolysis pyrophosphate
at what age is peak bone mass reached?
about age 25
what are collagen fibres made up from?
AA –> tropocollagen —> collagen fibrils –> collagen fibres
collagen molecule structure:
Molecular building block =
which forms
[a] Collagen chains =
which forms
[b] molecule
which is assembelled into a [c] via
collagen molecule structure: TRIPLE HELIX
Molecular building block = Gly-X-Y
which forms
[a] Collagen chains = 2 x 𝛂1 and 1 x 𝛂2
which forms
tropocollagen molecule
which is assembelled into a collagen fibril via covalent crosslinks
what are two biproducts of collagen synthesis?
P1NP and P1CP
biomarkers of collagen synthesis
osteogenesis imperfecta is a genetic disease causes by?
defects to Collagen chains = 2 x 𝛂1 and 1 x 𝛂2
joining collagen together requires many cofactors.
what is the role of vitamin C in joining collagen together?
Hydrogen bonds within tropocollagen require FE2+
Vitamin C reduces Fe3+ to Fe2+
what enzymes break dwon collagen?
proteinases: collagenases and cathepsin K
can be normal or pathological
what are the biomarkers of collagen breakdown?
NTX and CTX
what happens in bone mineralisation?
where does intramembranous ossification occur?
skull
clavicles
begins in utero, continues to adolescence
happens by remodelling of mesenchymal connective tissue.
where does endochondral ossification occur?
more common ossification - in long bones
bone forms by replacing a hyaline cartilage precursor
when does growth plate fusion occur?
around 16 (f)
18 (m)
how does outward growth of bones occur?
a woman who started her period late would have what bone proportions?
long legs and short torso
sine elongates most in puberty
how much calcium do we have in our body?
where is the main resevoir?
1200g
skeleton main resevoir
how much calcium is stored in exracellular space?
what is its functions?
only 1g
key for: muscle contractility; nerve function; normal blood clotting
normal total serum calcium levels?
how much is metabollically active?
Total Serum Calcium 2.4mmol/L
Ionised serum calcium about 1.1 mmol/L (metabollically active)
calcium is not metabollically active when?
Ionised = metabolically acrtive
Protein bound (albumin) = not metabolically active
what happens to calcium levels if you hyperventilate?
hyperventilate = alkalotic
at high pH, albumin binds more strongly to calcium
LESS ionised (metabolically active) calcium
hypocalcaemia = tingling in fingers
where in the body does calcium regulation/kinetics take place?
Gut = absorbtion/excretion
Bones = formation/resorbtion
Kidneys = reabsorbtion/excretion
recommended daily calcium intake/day?
700 mg/day
main sources of dietary calcium?
dairy products
how much dietary calcium do we absorb?
30%
where and how is clacium absorbed in the gut?
duodenum and jejunum = active absorbtion
ileum and colon = passive absorbtion
when there is low dietary calcium availability, which type of calcium transport increases?
mediated by?
active transport
mediated by calcitriol
what is calcitriol?
active form of Vit D
What are the two processes in which calcium can be released from the bone?
Rapidly - from exchangeable calcium of the bone surface
Slowly - by osteoclasts during bone resorbtion
the amount of calcium filtered by the glomerulus depends on?
glomerular filtration rate
ultrafiltrable calcium = ionised and complexed (not bound)
what percentage of filtered calcium is reabosribed in the kidney?
98%
what can increase the amount of calcium reabsorbed in the kidney?
Reabsorbtion increased by PTH
what can decrease the amount of calcium reabsorbed in the kidney?
Reabsorbtion decreased by high Na+ levels
calcium follows the sodium to be excreted
saline can be used therapeutically in hypercalcaemia
where in the nephron is calcium reabsorbed?
PCT = 65%, passive
Thick limb = 25%, passive
DRT = 8%, active
a decrease in serum calcium has what affect on PTH?
Increases PTH
small decrease in Ca++, BIG increase in PTH
how does PTH affect serum calcium levels?
Bones:
-increased bone resorbtion
-exchangeable calcium released from surface of bone
Kidney
-increased calcium reabsorbtion from kidney
↓
-increased 1,25(OH)2 vit D
↓
Gut
-increased calcium absorbtion in gut
Calcitonin:
where is it produced?
what stimulates its secretion?
what is its action?
- produced by thyroid c cells
- secretion stimulated by increases serum calcium
- effect to lower bone resorbtion
- significance in humans uncertain
vitamin D is a [?] of calcium
long term regulator
Vitamin D synthesis:
[a] is converted into vitamin D3 under the influence of [b].
In the liver, vitamin D3 is converted into [c] by [d]. This is relatively inactive.
In the kidney, [e] converts [f] into [g], otherwise known as calcitriol. This is metabolically active.
7-dehydrocholesterol is converted into vitamin D3 under the influence of UV radiation.
In the liver, vitamin D3 is converted into 25-hydroxyvitamin-D by 25-hydroxylase. This is relatively inactive.
In the kidney, 1-α-hydroxylase converts 25-hydroxyvitamin-D into 1,25-dihydroxyvitamin-D, otherwise known as calcitriol. This is metabolically active.
role of calcitriol on calcium?
- stimulates intestinal epithelial cells to increase the synthesis of calbindin-D proteins.
- Calbindin-D proteins increase the intestinal absorption of calcium by facilitating the transport of calcium from the intestinal brush border to the basolateral membrane, where it is released into the bloodstream.
If levels of calcitriol become excessive, it is converted to
24,25-dihydroxycholecalciferol
how much phosphate is usually present in a healthy body?
where is it mostly found?
500-800g = 1% of total body weight
90% found in bone mineral
what is a normal serum phosphate level?
0.8-1.5 mmol/l
what can low phosphate level lead to?
Poor bone mineralisation
- rickets/ osteomalacia
- pain, fractures
what can high phosphate levels lead to?
excessive fomratiom of hydrocyapatite –>deposits in places other than bone eg arteries
recommended adult daily intake of phosphate?
700mg
dietary sourced of phosphate?
proteins
anima, seeds, dairy soy
fairly ubiquitous
what percentage of unbound phsophate is filtered in the kidney?
where in the nephron?
90%:
80% in PCT (Na cotransport)
10% DCT
name three things that regulate phosphate metabolism
parathyroid hormone
1,25 dihydroxyvitamin D
FGF-23
what is FGF 23?
fibroblast growth factor 23
- the mahor regulator of phosphate metabolism
where is FGF-23 produced?
osteocytes
what stimlates osteocytes to prodcued FGF-23
rise in Pi levels
PTH
1,25 vitamin D
action of FGF-23?
DECREASES PHOSPHATE:
* decreases expression of Na transported in renal tubule = increase renal excretion of phosphate
* decreases 1𝛂-hydroxylation of vitamin D = decreases gut absorbtion of phosphate
an FGF mutation can lead to ?
Inherited rickets
Tumour Induced Osteomalacia
summarise phosphate homeostasis
calcium mostly regulated by hormones that [?] serum calcium =
calcium mostly regulated by hormones that increases serum calcium = PTH and VitD
phosphate mostly regulated by hormones tha [?] serum phosphate =
phosphate mostly regulated by hormones tha decrease serum phosphate = FGF-23 and PTH
outline the process of bone remodelling
leabel the cells if the bone remodelling unit
3 conditions that must be met for successful regulation of bone trunover (remodelling)
- osteoblasts and osteoclasts must be able to communicate withe eachother
- coupling
- balance
what is coupling?
bone formation by osteoblasts occus at sites of previous bone resorbtion by osteoclasts
same place
what is balance (in bone remodelling)
amount od bone removes by osteoclasts should be replaced by osteoblastic activity
same amount
this is impaired with age (osteoclasts>osteoblastic activity)
osteoclasts are derived form?
hemopoietic progenitor
the cytokine system demonstrates great redundancy and great pleiotropism.
what is meant by redundancy?
redundancy - if you remove/knock out the cytokine, nothing much happens
the cytokine system demonstrates great redundancy and great pleiotropism.
what is meant by pleiotropism?
pleiotropism - if you move the cytokine to a different area, they have a different function due to the presence of other cells
what is OPG?
osteoprotegrin, also known as
osteoclastogenesis inhibitory factor
Mediators of oseoclast differentiation and actvity?
Hormones (PTH, vit D, etc.)
Paracrine/autocrine (prostaglandins)
**OSTEOPROTEGERIN **
what is the function of OPG?
inhibits the differentiation of myeloid precursors into osteoclasts
= decreases resorbtion by osteoclasts
how does OPG inhibit the differentiation of myeloid precursors into osteclasts?
binds to RANK-ligand
thus blocking the RANK-RANK ligand interaction between osteoblasts and osteoclast precursors. (blocks the digging)
OPG knockout –> ?
thin bones
OPG overexpression —>?
overly dense bones
osteoblasts derive from?
mesenchymal cells
why does our bone marrow yellow as we age?
as we age, more mesenchymal progenitors are directed down the adipocyte pathway = yellow
what is the WNT pathway?
enhances differentiation of precursors into osteoblasts
what is sclerostin?
regulates bone remodelling in osteocytes
