MSK💪🩻🦴 Flashcards
Why do we have bones?
- Raises us from the ground against gravity
- Determines basic body shape
- Transmits body weight
- Forms jointed lever system for movement
- Protects vital structures from damage
- Houses bone marrow
- Mineral storage (calcium, phosphorous,
magnesium
Types of bone classification by shape
Long bones
Short bones
Flat bones
Irregular bones
Sesamoid bones
Shape of long bones
Tubular shape with hollow shaft and ends
expanded for articulation with other bones
Shape of short bones
Cuboidal
Shape of flat bones
Plates of bone, often curved, protective function
Two areas of bones and how many in each
Apendicular skeleton- 126 bones
Axial skeleton- 80 bones
Shape of irregular bones
Various shapes
Shape of sesamoid bones
round, oval nodules in a tendon
Cortical bone structure
= Compact
Dense, solid, only
spaces are for cells
and blood vessels.
Trabecular bone structure
= 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
Woven bone microstructure
Made quickly
Disorganised
No clear structure
Lamellar bone microstructure
Made slowly
Organised
Layered structure
What do hollow long bones do?
Keeps mass away from neutral axis,
minimizes deformation
What do trabecular bones do?
Gives structural support while
minimizing mass
What do wide ended bones do?
Spreads load over weak, low friction
surface
What do flat bones do?
Condensed so protective
Composition of adult mammalian bone
50-70% mineral
(Hydroxyapatite, a crystalline form of Calcium Phosphate)
20-40% organic matrix
Collagen (type 1) – 90% of all protein
Non-collagenous proteins -10% of all protein
5-10% water
The collagen assembles in fibrils with mineral crystals situated in ‘gap’
regions between them
How does bone microstructure contribute to function?
Bone is a composite
Mineral provides stiffness
Collagen provides elasticity
What are the cells of the bone?
Osteoclast - multinucleated
Osteoblast- plump, cuboidal
Osteocyte- stellate, entombed in
bone
Bone lining cell- flattened, lining the bone
Origins of osteoblasts
Mesenchymal stem cell -> progenitor cells -> osteoblasts, adipocytes, myoblasts, chondrocytes, fibroblasts
Function/characteristics of osteoblasts
Form Bone - in form of osteoid
Produce Type I collagen and mineralize
the extracellular matrix by depositing
hydroxyapatite crystal within collagen
Fibrils
High Alkaline Phosphatase activity
Make non-collagenous proteins
Secrete factors that regulate osteoclasts
ie RANKL
Origin of osteoclasts
Haematopoetic stem cells -> determination -> proliferation, survival -> differentiation -> attachment, resorption
Function/characteristics of osteoclasts
Resorb Bone
Dissolve the mineralised matrix (acid)
Breakdown the collagen in bone
(enzymatic)
High expression of TRAP and
Cathepsin K
Bone remodelling process
Resorption -> reversal phase -> formation -> resting phase -> activation -> back to resorption
Bone modelling
Gross shape is altered, bone added or
taken away
Bone remodelling
All of the bone is altered, new bone
replaces old bon
Reasons for bone remodelling
- Form bone shape
- Replace woven bone with lamellar bone
- Reorientate fibrils and trabeculae in favourable direction for mechanical strength
- Response to loading (exercise)
- Repair damage
- Obtain calcium
- Dysregulated remodelling = disease!
Different stages of changes of bone
0-20 -> development -> modelling
20-50 -> maintenance -> remodelling
50+ -> osteoporosis -> acquired pathology
How do pathological fractures heal?
Periosteum tears
Haematoma
Adjacent bone cell death
Soft tissue damage
Callus
Osteoblasts -> new woven bone
Osteoclasts -> mop up dead bone, remodel strong bone
Osteoblasts lay down lamella bone
Two types of bone treatments
Anti-catabolic- stop osteoclasts (more)
Anabolic- stimulate osteoclasts
What is Gly-X-Y?
modular building block
(3 residues per turn) up to about 1000 amino acids
X and Y are often proline, hydroxyproline or hydroxylysine
Allows the formation of a helix (alpha-chain)
Outline tropocollagen
3 collagen chains – 2 x α1 + 1 x α2
Form the 3-stranded
tropocollagen molecule
How is tropocollagen arranged and what holds it together?
The tropocollagen modules are
then assembled into a collagen
fibril
The tropocollagen molecule and
the fibril are held together by
covalent crosslinks (both intraand intermolecular) derived from
lysine/hydroxylysine side-chains
Processing of type I collagen
N terminals and c-terminals are cut off the ends
N creates P1NP
C creates P1CP
Can be measured
What joins collagen together?
Covalent crosslinks
Hydrogen bonds
Intermolecular crosslinks
Outline covalent crosslinks in collagen
– Within and between the triple helix/tropocollagen molecule
= “intra/intermolecular crosslinks” – OH-lysine x2
lysyl oxidase needs copper
Outline hydrogen bonding in collagen
– Between hydroxyproline molecules, within tropocollagen
* OH-proline from proline requires Fe2+
* Fe3+ to Fe 2+ requires vitamin C
How are tropocollagen molecules bound together?
– = “intermolecular crosslinks” -
– OH-lysine x 3 = pyridinolines
Collagen breakdown
Via proteinases esp. collagenases and
cathepsin K (in bone)
Can be a normal process of repair and replacement
(breakdown is balanced by synthesis),
or pathological process
- examples: arthritis, osteoporosis, tumour invasion,
hypertrophic scarring, kidney fibrosis
Breakdown products of type I collagen
NTX and CTX
Can be measured to see breakdown
Outline the types of collagen
– Type I – bone, tendon, ligaments, skin
– Type II – articular cartilage, vitreous
– Type III – alongside Type I – wound healing
– Type IV - basal lamina
– Type V – cell surfaces
– Type X – growth plate
Outline bone matrix
- Synthesised by osteoblasts
- 90% collagen
- Other proteins
- osteocalcin, osteonectin, osteopontin, fibronectin, bone sialoprotein,
bone morphogenetic proteins (BMPs)… - Contribute to structure
- Regulate bone cell activity
Outline bone mineralisation
- Alkaline phosphatase hydrolyses pyrophosphate
- Inorganic phosphate complexes with calcium to form
hydroxyapatite - Hydroxyapatite crystals propagate along collagen
Where does intramembranous ossification occur?
*Skull
*Clavicles
Outline endochond
Chondrocytes become hypertrophic which attracts blood vessels and so osteoblasts which form the bones
Secondary ossification centres
Growth plate fusion
Driven by oestrogen
Appositional growth of bone
Outward growth of bone
Osteoblasts on osteocortical surface add on bone going outwards
Osteoclasts add on bone growing inwards
Age of peak bone mass
About age 25
Enzyme for bone mineralisation
Alkaline phosphatase
Outline distribution of calcium in the body
*Skeleton is main reservoir
o 1200 g
*Extracellular space has much smaller amount of
calcium (only 1 g), but it is key for
o Muscle contractility
o Nerve function
o Normal blood clotting
Total serum calcium usually about 2.4 mmol/L
Ionised serum calcium about 1.1 mmol/L
Outline the different types of calcium in circulation
*Ionised, metabolically active
*Protein-bound, not metabolically active
*Complexed, such as citrate, phosphate
Modulation of ionised calcium by pH
At higher pH, albumin binds strongly to calcium
Effect of low ionised/serum calcium
- Low ionised calcium is associated
with contraction of the small muscles
of the hands and feet
o TETANY
There is depolarization of the long nerves of the upper limb
Sources of dietary calcium
- Major sources
o Dairy products make up 2/3
− Milk, yoghurt, cheese - Minor sources
o Vegetables, e.g. broccoli
o Cereals, e.g. white bread
o Oily fish, e.g. sardines
Recommended intake of calcium
700 mg/day
Outline calcium absorption
*We absorb about 30% of dietary calcium
o Active absorption in duodenum and jejunum
o Passive absorption in ileum and colon
*Higher fractional excretion when low availability
o More active transport
o Mediated by calcitriol, the active form of vitamin D
Outline release of calcium from bone
- Calcium can be released rapidly from exchangeable
calcium on the bone surface
o We don’t know much about this mechanism - Calcium can be released more slowly by osteoclasts
during bone resorption
Outline calcium handling by the kidney
*The amount of calcium filtered by the glomerulus depends on
o Glomerular filtration rate
o Ultrafiltrable calcium
− Ionised
− Complexed
* 98% of this filtered calcium is usually reabsorbed
o Reabsorption increased by PTH
o Reabsorption decreased if the filtered sodium is high
Calcium and phosphate reabsorption and excretion
Fractional excretion of calcium- 2%
Fractional excretion of phosphate- 10%
Parathyroid hormone effect on serum calcium
4 parathyroid glands express
calcium sensing receptor
Decrease in serum calcium means increase in parathyroid hormone
Relationship between serum calcium and PTH
Small changes in serum ionised calcium
Big changes in PTH
Parathyroid hormone actions
Increase Ca2+ Reabsorption
Increase Phosphate reabsorption
Increase 1 α - hydroxylation of 25-OH vit D
Bone Remodelling
Bone resorption > bone formation
No direct effect
increase of ca2+ absorption because of increased 1,25 (OH) 2 vit D
Response to low calcium diet
Vitamin D overdose
Increased gut ab
Calcitonin
- Hormone produced by thyroid C cells (parafollicular cells)
*Secretion stimulated by increased serum calcium - Its effect is to lower bone resorption
*Significance in humans uncertain
o It is much more important in animals living in a high calcium environment,
e.g. fish
Outline creation of vitamin D
Forms from 7-dehydrocholesterol
Synthesised in the skin
To maintain vitamin D must expose arms for 20mins/day in good sunlight
Outline formation of vitamin D
7- dehydroxy cholesterol in skin ->
25 hydroxy D in liver->
1,25 hydroxy D in kidney
Calcitriol is the active form of vitamin D and it is
hydroxylated at positions 1 and 25
Outline the action of calcitriol (vitamin d)
- VDR, vitamin D receptor
- TRPV6, transient receptor
potential V6 - PMCA, plasma membrane
calcium pump ATPase
Role of phosphate in physiology
ATP
DNA
cAMP
Phospholipid bilayer
Bone mineral – calcium hydroxyapatite
Normal phosphate status
- Whole body phosphate 500 - 800g
- 1% total body weight
- 90% in bone mineral
- Serum phosphate 0.8 – 1.5 mmol/l
Presentation of low phosphate
- Poor bone mineralisation
- Rickets or osteomalacia
- Pain, fractures
Presentation of high phosphate
- Excessive formation of hydroxyapatite
- Deposition in tissues other than bone e.g artery calcification and tumoral calcinosis
Dietary sources of phosphate
- Protein
- Animal
- Dairy
- Soy
- Seeds and nuts
- Adult recommended daily intake = 700mg
Outline renal phosphate handling
In glomerulus unbound phosphate (about 90%) is filtered
80% reabsorbed in PCT- Na cotransporter
10% reabsorbed in the distal tubule
Maximum rate of reabsorption is limited, so excess is excreted
Regulation of phosphate metabolism
- Parathyroid hormone
- 1,25 dihydroxyvitamin D
- FGF-23
Impact of parathyroid hormone on phosphate
Main function is regulation of calcium
Also affects phosphate
Increases 1,25 vitamin D
Increases active gut absorption
Decreases tubular
reabsorption of phosphate
Increases renal excretion
Outline FGF-23 (fibroblast growth factor 23)
Now known to be the major regulator of phosphate metabolism
* Produced by osteocytes
* In response to:
* Rise in phosphate levels
* Dietary phosphate loading
* PTH
* 1,25 vitamin D
Outline inherited rickets
- Presents in childhood or adulthood
- Bone pain, deformity, fracture
- Low bone density
- Low serum phosphate
- High urine phosphate
- X-linked hypophosphataemic rickets (XLH)
- Autosomal dominant rickets (ADR)
Genetic investigation to identify gene for a disease
- Linkage analysis
- Fixed genetic markers
- Identify on which chromosome
and region the abnormal gene is
likely to be - Sequencing
- Identify where DNA differs
between affected and unaffected
people
White Nature Genetics 2000
Named FGF-23 because sequence similar to other FGFs
Outline tumour induced osteomalacia
- Rare form of osteomalacia with low phosphate
- Seen in patients with small benign mesodermal tumours
- Osteomalacia heals when tumour removed
FGF-23 actions
- Decreases expression of Na transporter in the renal
tubule - Increases renal excretion of phosphate
- Decreases 1α-hydroxylation of vitamin D
- Decreases gut absorption of phosphate
- Decreases whole body phosphate
Comparing calcium and phosphate pathways
- Calcium mostly regulated by hormones that increase
serum calcium - PTH, vitamin D
- Phosphate mostly regulated by hormones that decrease
serum phosphate - FGF-23, PTH
Regulation of bone turnover (remodelling)
- Osteoblasts and osteoclasts must be able to communicate with each other.
- Coupling
o Bone formation occurs at sites of previous bone resorption - Balance
o Amount of bone removed by osteoclasts should be replaced by osteoblastic activity
Derivation of osteoclasts
Macrophages (“big eaters”, makros
= large, phagein = eat)
Involved in chronic inflammation
Phagocytose (ingest) pathogens
Osteoclasts are specialised
macrophages
Outline cytokines as inflammatory mediators
o A group of proteins and peptides that are used to allow one cell to
communicate with another.
o Released by many types of cells (both haemopoietic and non-haemopoietic)
o Particularly important in immune responses (immunological, inflammatory
and infectious diseases).
o Sometimes these effects are strongly dependent on the presence of other
chemicals and cytokines
* The cytokine system demonstrates great redundancy and great
pleiotropism.
What is redundancy in relation to cytokines?
Redundancy means that most functions of cytokines can be performed
by many different cytokines.
o Blocking or genetically ablating (“knockout” transgenic technology) a particular
cytokine rarely has widespread or dramatic effects
What is pleiotropism in relation to cytokines?
- Pleiotropism means that a single cytokine has many different functional
effects, on many different cell types or even on the same cell.
o Overexpression or exogenous administration of a single cytokine frequently has
several diverse effects.
Endocrine and paracrine mediators of osteoclast differentiation and activity
- Hormones (endocrine) including
o 1,25 dihydroxyvitamin D
o PTH/PTHrP
o Oestrogen
o Leptin - Paracrine/autocrine including
o Prostaglandins
o Interleukin-1 (IL-1)
o Interleukin-6 (IL-6)
o Tumour necrosis factor (TNF)
Impact of mediators of osteoclast differentiation activity
- None of them appeared to have significant effects through receptors on
osteoclasts! - They didn’t work in pure osteoclast cultures
- They only worked in the presence of osteoblasts or other bone marrow
stromal cells (mesenchymal lineage)
Outline osteoprotegerin (OPG)
- Also known as osteoclastogenesis inhibitory factor (OCIF)
- A member of the tumour necrosis factor (TNF) receptor superfamily.
- Inhibits the differentiation of myeloid precursors into osteoclasts
- Decreases resorption by osteoclasts in vitro and in vivo.
- Works by binding to RANK-ligand, thus blocking the RANK-RANK
ligand interaction between Osteoblast/Stromal cells and Osteoclast
precursors
Derivation of osteoblasts
Mesenchymal stem cells
* Can give rise to
o Osteoblasts
o Adipocytes
o Chondrocytes
o Myocytes
* As we age, more mesenchymal
progenitors are directed down
the adipocyte pathway
Impact of prostate cancer on bone
Increases rank ligand and OPG
Increased osteoblast activity in prostate cancer
Outline the Wnt pathway
- Sclerostin (Scl), like Wnt, is a
secreted glycoprotein. - Sclerostin deficiency associated
with increased Wnt signalling - Increased bone formation
- Decreased bone resorption
- Anti-sclerostins should have
anabolic effects on bone
Functions of skeletal muscle
Produce movement
Support soft tissues
Maintains posture and body position
Communication
Control openings and passageways
Control of body temperature
Breathing via diaphragm
Universal characteristics of muscles
Responsiveness (excitability)- capable of responding to stimuli
Conductivity- local electrical change triggers a wave of excitation’
Contractability
Extensibility
Elasticity- returns to resting position
What are T tubules?
Sarcolemma invaginations that help propagating an action potential
Myofibre size
Length 5cm
Diameter 100um
Outline the light band and the dark band
Light band- I-band, actin, divided by Z-disc
Dark band- A-band, overlapping of actin and myosin, divided by M-line
Thin filament
Contains F-actin capped by alpha actinin and CapZ and tropomodulin. Nebulin consists of 35aA acting binding motifs and acts as a molecular ruler
Thick filament
Contains myosin filaments maintained by Titin which acts as a molecular spring. Titin is the largest protein in our genome with >34000aA
Heads of the myosin
Each thick filament contains approx 300 myosin heads
Each head cycles 5 times/second
- ATP binds to the myosin head cauring the dissociation o f the actin myosin complex
- ATP
How is contraction initiated?
Motor neurones send an impulse to muscle which communicates via a neuromuscular junction
Motor unit
A motorneuron and all fibres innervated by it
A motor unit always contains fibres of the same type (slow/fast)
ACH stimulates acteylcholine gated cation channels w
Troponin structure and function
Troponin C binds to Ca2+
Troponin I is an inhibitory subunit
Troponin T binds to tropomyosin
Tropomyosin
Rods cover 7 myosin binding sites on the actin and prevents binding
Binding of Ca2+ to the troponin binding sites which pulls it away from the binding sites
Slow oxidative
Fatigue resistant
Red- myoglobin
Low glycogen content
Oxidative
Aerobic atp synthesis
High mitochondria
SOleus
Fast glycolytic
Fatiguable
White
Glycolytic metabolism
High glycogen content
Anaerobic stp
Slow vs fast fibres
Slow- half the diameter of fast fibres take longer to contract and
Creatine is ingested from the diat and transported to tge muscles biva the bloodstream
95% of creatune present in mysdls as P-creatine (60%) or creatine (40%)
CAtalyst for conversion of creatine to phosphocreatine
Creatube c=kinase- cytoplasmic and mitochondrial isoforms
Fatigue
progeressive weakeness of the muscle#
ATP shortage due to shortage of glycogen
Lactic axid leveks rise and lover the PH which prevebnts normal workingin the sarcoplasm
Failure of the neuromuscular junction
Do skeletal muscles have stem cells?
yes
Do skeletal muscles have pain receptors?
No
Classification of joints
Structural classification
Functional classification
Types of joint- structural
fibrous
Cartilaginous
Synoial
Synarthroses- immovabkle and mostly fibrius
Amphiarothese- slightly moveabke mostly carti
Diarthroses- synovial k
Fibrous joints-suture
Only sutures of skull
Adjacent bines interdigitate
Junction with very short tissue fibres
Fibrous - Syndesmosis
Bones connescted by a cord(ligament or interosseous membrane ofn ifbrous tissue
Amount of mvmt permited is proportional to length of fibre
E.g between radius and ulns
Fibrous- Gomphoses
Peg in socket joint only found in tooth articulation
Syncondroses- cartilagenous
Bones connected bu hyaline cartilage
Usually amphiarthroses e.g
sympheses- cartilagenous joint
Here the connecting cartilage is a pad or plate of fibrocartilage e.g pubic symphysis and intervertebral disk
Synovial joints
Atriculating bines are separated by a fluid filled cavity
most body
- articular (hyaline cartilage
- Joint capsule- inner layer is synovial membrane
Joint synovial cavvity
synovial fluid
reinforcing ligamnets
Additional components associated with some synovial joints
Bursae- fluid filled sacs lined by synovial membrane
Menisci- discs of fibrocartilage allow for friction free memt
Articular (hyslaune cartiklaeg
Almost fricitionless
resistes compressibve loads
high water contednt
low dcell contrent
no blood supply
Synovial fluid
civers articykaitg surfaces with a thin fillm
Modifird from pkasma by synovual membrana( synoviocytes)
Fluid, proteins, charges sugars that bind water e,g hyaluronic acid
Result: slimy fluid (loke eggwhite)
Reduces friction during articulation
Sits on inside f joint capsule and encloses synivual cavity’inky a dw cels thich
may have villi to increase SA
Types of synovial joints
Ball and socket joint- knee
Condyloid joints- metacarpal and phalanges
Glifing joint- between carpals
Hinge joint- elbow
Pivot joint- between c1 and 2
Saddle joint-base of the thumb
Attatch bone to bone
prevent excessive motion
goide joint motion
augemnt mechanical stbilty
Connect muscle to bone
Transmit tenske loads form muscle to bone
Prosuce joint torqu
Stabilisis joint during oisometric contration
ensbles joint motion siring isptonic
stabilises
Dense connective tissue
Clls fibroblasts 20% od tussye synthesis anr enremodle the ecm
80% ectracelllular matrix- 70% wet 30% solid
spparselu vascularised
Collagen type 1 90-95% dry weight
proteoglycan and ither types od collagen
how does ligament have slight mvmt
fibres slighlt crimoed together allowing fir sime movement
influences elsasitn in tendons and ligaments
little in tendons
mroe in liagamebtum flavum
lower colagen content 90% of dry weight
more elastin
bllodd supply from isertion point
fibres less organisd
Entheses
Places of insertion of thendon or ligament into bone
pain and proprioceptive receptors
Important for disease
e.g epicondyles of elbow
achillies tehn
load bearing
transmit forces
tendos aee viscoelsasic- voth viscous and elastic can treform hsape
themilw loads cause elongathom
Typical elongation load
1- toe regiom small loas and crimped fibres straighten
2. linear curve as fibres straigten and stifness increases rapide
3. pmax - maximal deformation ant tensile tstrength
4. yeild point- after which is complete failure to support structures
Golgi tendon organ
encapsuleated sensory recepotis proprioceptirs activated by stretch or active mucle contraction
Associated intendons near insertion (mostly but also a nit in orougun’consists if thin capsule
enclosing cillahem gibres
Inverse myotatic reflex protective reflex
factors affec
- maturation and ageing- up to 20 years
aging preganancy and postpartuk
physical training- increase tendon tensile strenght
immobilisation decrease thensile strength
Size of the problem of inactivity
Only 59% of adults in England meet DoH
recommended levels of PA
▫ 28% meet all aspects of guidelines
* Drops to <10% in over 85s
* 23% do <30 min exercise TOTAL per week
* 5.3million 25-64 yo would find 3mph walk
“vigorous” activity
* Total cost of inactivity in UK >£20 billion/year
What is cardiorespiratory fitness?
The ability of the circulatory and respiratory systems
to supply oxygen to skeletal muscles and the muscles’
ability to absorb and utilise the oxygen, during
sustained physical activity”
What is fitness?
The condition of being physically fit and healthy
What is gout?
High uric acid levels in the blood cause urate/uric acid crystals to deposit in the joints.
The crystals cause inflammation, which then causes the swelling, pain & redness.
Toe is the most commonly affected joint
Key features of uric acid
Poorly soluble in plasma
The lower the pH the less soluble it becomes
Where does uric acid come from?
Purines are in the blood (e.g Adenine and guanine + hypoxanthine and xanthine)
Sources of purines
Diet
Breakdown of nucleotides from tissues
Synthesis in the body
Where does uric acid leave the body?
Excreted in the urine
Breakdown in the gut
Why is gout not common in children and pre-menopausal women but is more common in older men?
Oestrogen helps to promote excretion of uric acid
Dietary purines
Meat
Offal – heart, liver & kidney
Seafood - muscles
Fish – herring and sardines
Also – oatmeal, soya & yeast extracts
Fructose – found in soft drinks
Risk factors for gout
Metabolic syndrome
Obesity
Raised triglycerides
Raised blood pressure
Coronary heart disease
Diabetes
WHat is metabolic syndrome
Increases risk for CHD and gout
combination of obesity raised triglycerides, raised blood pressure
How does alcohol affect uric acid conc.?
Synthesis increased and excretion decreased
Mainly beer, spirits and port wine
Wine in moderation doesn’t increase risk of gout
Medications that have an effect on uric acid
Thiazide diuretics
Low dose aspirin
Ciclosporin
Levodopa
Ethambutol
Pyrazinamide
How does reduced kidney function lead to increased uric acid conc.?
Reduced kidney function can lead to reduced excretion of uric acid
Key steps in uric acid formation
Purines —–xanthine oxidase—> xanthine —- xanthine oxidase —–> Uric acid
Complications of gout
Damage to the joint (degenerative arthritis)
Secondary infections
Nerve damage
Outline kidney stones
Consequence of high uric acid
Urate crystals can form in the kidneys
Causes damage to the kidneys & reduces kidney function
How does increased turnover of nucleic acids increase uric acid conc.?
Increased tissue nucleotides and body purine nucleotides so increased purines and increased uric acid
What causes an increased turnover of cells
- Rapidly growing malignant tissue
- Leukaemia
- Lymphoma
- Polycythaemia rubra vera
- Increased tissue breakdown
- Tumour lysis syndrome
- Trauma
- Starvation
- Psoriasis
Outline salvage of purines
Hypoxanthine & guanine are recycled back to precursors by enzyme HPRT.
If enzyme missing leads to increased production of uric acid.
Functions of bone
Bones protect the vital soft organs
– brain, heart, lungs etc
Bones allow muscles to work to move us around
Bones store mineral and house marrow cells
How do bones respond to loading?
Loading increases bone mass
Off-loading decreases bone mass
Is loading all over or site specific?
Loading response is site-specific and localised
What happens to bones when they are loaded?
Deformation and strain
Force (F) causes deformation ( change in length)
Change in Length / Length
femur: 600mm
Deformation= 0.6 mm
Strain = 0.6/600= 0.1%
Strain variables
Magnitude
Rate (up and down)
Frequency
Dwell (hold/rest periods)
Number of cycles
Non-direct things that affect bone formation
- Sex and age
- Age
- Hormones, cytokines
- Drugs/medicines/nutraceutical
What is mechanostat theory?
- There is not a single mechanostat
- Our skeletons contain vast numbers of small units of
bone, each of which has its own dynamically regulated
mechanostat
Maximising response to loading
- Bone responds maximally to only a few loading cycles each
day - Exercise in the previous 4 hours increases the response to
subsequent loading - Bone responds to very brief mechanical events
(milliseconds) - Rest periods between single loading events (~10 seconds)
increase their effect
How do osteocytes sense loading?
Fluid flow shear stress
Deformation of bone cause movement of fluid which signals the osteocytes
The osteocytes then signal the other bone cells- extends processes to cells
Outline changes in trabecular architecture with ageing
Trabecular loss more pronounced for
non load-bearing horizontal trabeculae
Definition of a fracture and when do they occur
breach in continuity of bone
Fractures occur when:
non-physiological loads applied to normal bone
Physiological loads applied to abnormal bone
Diseases that can lead to abnormal fractures of bone
Tumour
-Benign
-Malignant
-Metastatic
Metabolic bone disease
-Osteoporosis
-Paget’s Disease
-Osteogenesis Imperfecta
How to describe fractures to colleagues?
Site
Pattern
Displacement / angulation
Joint involvement
Skin involvement
How to describe site of bone fracture
WHich bone
Part of bone (prox., mid., or dist.)
Patterns of fractures
Transverse
Oblique
Spiral
Comminuted
Segmental
Avulsed
Impacted
Torus
Greenstick
Describing displacement/angulation
Displacement (%)
Angulation – of distal part
Outline joint involvement in fracures
Extra-articular
Intra-articular
Outline skin involvement in fractures
Open / closed
Open fracture = breach in skin communicates with #
Orthopaedic emergency
Requires urgent treatment
Soft tissue injury determines outcome
Fracture patterns unique to children
Epiphyses open and bone more ‘plastic’
∆ fracture types
Heal quickly
deformity remodelling
Fracture healing stages
Haematoma (hours)-> inflammation (days) -> repair (weeks)-> remodelling (months to years
Haematoma after a fracture
Bleeding
endosteal and periosteal vessels, muscle etc
Decreased blood flow
Periosteal stripping
Osteocyte death
Inflammation stage of fracture healing
Fibrin clot organisation
Platelets rich in chemo-attractants
Neovascularisation
Cellular invasion
Haematopoietic cells
clear debris
express repair cytokines
Osteoclasts
resorb dead bone
Mesenchymal stem cells
building cells for repair
Repair stage of fracture healing (callus formation)
‘Callus’ formation
Fibroblasts produce fibrous tissue (high strain)
Chondroblasts form cartilage (strain <10%)
Osteoblasts form osteoid (strain <1%)
Progressive matrix mineralisation
High vascularity
Soft callus 2-3 weeks
Hard callus weeks to 5 months
Remodelling stage of fracture healing (months to years)
Woven bone structure replaced by lamellar bone
osteonal remodelling
Increased bone strength
Vascularity returns to normal
Healing without scar - unique
Principles of fracture management
Reduce fracture-> Immobilise the part-> rehabilitate the patient
Types of fracture fixation
Slings
Casts and splints
Extra-medullary devices
plates and screws
Intra-medullary devices
nails
External Fixation
Rigidity of primary bone healing
Strain <2%
Intramembranous
Haversian remodelling
Occurs with rigid fixation e.g plates and screws
Secondary bone healing
Strain 2%-10%
Responses in the periosteum and external soft tissues
Endochondral healing
Occurs with non-rigid fixation-casts
Combined secondary/primary bone healing
Semi-rigid fixation- i.m nail
Fibrous response
Strain >10%
Results in non-union
Factors that influence fracture healing
Patient
Age
Nutrition
Smoking
Drugs – NSAIDs, steroids
Tissue
Bone type: cancellous vs. cortical
Bone site: upper limb vs. lower limb
Vascularity / soft tissue damage
Bone pathology - # in metastatic deposit does not heal
infection
Treatment
Apposition of fragments
Stability (ability to resist force without deforming)
Micromotion (<1mm)
Early complications of fractures
Local-
Vessel damage
Nerve damage
Compartment syndrome
infection
General-
Hypovolaemic shock
ARDS
VTE
Fat embolism
Late complications of fractures
Local
Malunion
Non-union
Avascular necrosis
Ischaemic contractures
Joint stiffness
Myositis ossificans
Complex regional pain syndrome
Osteoarthritis
General
Poor mobility
Functional disability and social isolation
Pressure sores
Disuse osteoporosis
Loss of income / job
Which nerve is affected by shoulder dislocation and fracture of the humeral head?
Axillary nerve
Which muscles do the axillary nerve supply?
Deltoid and teres minor
What area of skin does the axillary nerve supply?
Area at the top of the shoulder
Nerve most likely to be affected by a mid shaft femur fracture?
Radial nerve
What does radial nerve do?
Wrist extension
Nerve at risk from elbow dislocation
Ulnar nerve
How to test ulnar nerve?
Altered abduction and adduction of fingers
sensation to little finger and that part of hands
