week 2 - joints, connective tissue and the vascular tree Flashcards
health benefits of exercise
beneficial in prevention and treatment of disease
social and recreational benefits
feeling of healthy self awareness and reduction in smoking and alcohol
risks of physical activity
sudden death during exercise
risk of death due to nature of the sport
risk of injury
most common anatomical sites of injury from sport
lower leg - 32%
upper limp - 30%
head and neck - 17%
chest, upper leg and knee all less common
two types of sport injury
microtrauma (overuse) and macrotrauma
sports injuries to bone
acute - fracture and periosteal contusion
overuse - stress fracture, osteitis, periostitis
sports injuries to articular cartilage
acute - osteochondral fractures and minor osteochondral injury
overuse - chondropathy
sports injuries to joints
acute - dislocation and subluxation
overuse - synovitis and osteoarthritis
sports injuries to ligament
acute - sprain/tear
overuse - inflammation
sports injuries to muscle
acute - strain/tear, contusion, cramp, acute compartment syndrome
overuse - chronic compartment syndrome, delayed onset muscle soreness, focal tissue thickening/fibrosis
sports injuries to tendonn
acute - tear - complete or partial
overuse - tendinopathy including tendinosis and tendinitis
sports injuries to bursa
acute - traumatic bursitis
overuse - bursitis
sports injuries to nerve
acute - neuropraxia
overuse - entrapment, minor nerve injury, adverse neural tension
sports injuries to skin
acute - laceration, abrasion and puncture wound
overuse - blister, callus
traumatic sports injuries
fractures and dislocations
major muscle - ligament - tendon injuries
head and spinal injuries
chest and abdominal injuries
factors leading to overload - injury due to overuse
intrinsic factors - anatomical, muscle imbalance
increased participation in sport
increased intensity and duration of training
extrinsic factors - training errors, poor technique, incorrect equipment, poor conditions
clinical features of bone injury
pain, tenderness, localised bruising, swelling, deformity, restriction of movement
management of bone injury
anatomical and functional realignment
may need reduction
plaster cast or surgical stabilisation
classification of fractures
transverse
oblique
spiral
comminuted - harder to treat due to multiple fragments
avulsion - piece of bone attached to tendon or ligament is torn away
complications of bone injury
infection - most likely in open fractures
acute compartment syndrome
associated injury - nerve or blood vessel
DVT/pulmonary embolism
delayed union/non-union
malunion
acute compartment syndrome
secondary swelling in a muscle compartment with non-distensible fascial sheath
severe pain, pain on movement, numbness, absent pulses
treated by fasciotomy
problems with injury to bone
immobilisation - can result in muscle wasting and joint stiffness
growth plate fractures in children - danger of interruption of bony growth - distal radius at wrist, elbow, distal femur, tibia and fibula
soft tissue damage - commonly with fracture and can result in more severe problems than fracture
periosteal injury - uncommon but painful - nerve supply in periosteum
articular cartilage
lines the ends of long bones
absorbs shock and compressive forces and permits almost frictionless joint movement
does not show on x-ray
diagnosis and treatment of articular cartilage injury
diagnose on MRI
arthroscopy to confirm and remove loose fragments
may predispose to premature osteoarthritis
do not usually heal fully - treatment to improve healing: perforation, alteration of joint loading, cell transplantation
dislocation v subluxation
d - trauma produces complete dissociation of the articulating surfaces
s - some contact of articulating surfaces remains
all result in damage to surrounding joint capsule and ligaments
complications of dislocation and subluxation
associated nerve or blood vessel damage - axillary nerve in shoulder, brachial artery at elbow
treatment of dislocation and subluxation
reduction muscle relaxants protect to allow soft tissue to heal early protected mobilisation rebuild muscle strength to prevent reoccurance
grades of ligament injury
1 - fibres stretched but normal range on stressing
2 - more fibres involved, laxity on stressing but definite end point
3 - complete tear, excessive laxity and no end point - may be pain free as nerve fibres torn
management of ligament injury
initial management is to minimise bleeding and swelling
grade 1 and 2 - promote tissue healing, prevent joint stiffness, protect against further damage, strengthen muscle to provide additional joint stability
grade 3 - surgical - direct repair or reconstruction
when do you get a strain/tear to muscle
when demands exceed muscles capacity
common - hamstring, quadriceps and gastrocnemius
common during sudden acceleration or deceleration
grades of muscle strain/tear
1 - few fibres, localised pain and no loss of strength
2 - significant no of fibres, swelling, pain on contraction, reduced strength and limitation of movement
3 - complete tear - most common at musculotendinous junctions
management of a muscle strain/tear
first aid to minimise bleeding, swelling and inflammation electrotherapy eg ultrasound soft tissue therapy stretching strengthening
predisposing factors of muscle injury
inadequate warm up insufficient joint range of motion excessive muscle tightness fatigue/overuse/inadequate recovery muscle imbalance previous injury poor technique altered biomechanics
cause of quadriceps rupture
direct impact against contracted muscle or sudden vigorous contraction
myositis ossificans
occurs when haematoma calcifies
most resolve spontaneously
describe achilles tendonopathy
chronic repetitive overload injury pain especially uphill local swelling and tenderness crepitus on ankle movement complications - rupture, chronic tendonitis, achilles bursitis
bursa
small fluid filled sacs usually situated between a tendon and bone
role is to reduce friction
hips, knees, feet, shoulders and elbow
neuropraxia
nerve injury
if severe may result in paralysis and weakness of muscles innervated with associated sensory loss
tendon structure
dense connective tissue
high proportion of collagen
closely packed parallel arrangement in direction of force
sparsely vascularised
fibroblasts/tenocytes
ECM - water 80% - 30% collage 1, ground substance, elastin and collagen 3
phases of tendon healing
inflammation - day 0-7
repair - day 3-60
organisation and remodelling - day 28-180
regulators of tendon healing
PDGF and TGF-beta
inflammation phase of tendon healing
inflammatory cells migrate from epitendinous tissues (sheath, periosteum, soft tissues) and epitendon and endotendon
defect is rapidly filled with granulation tissue, haematoma and tissue debris
matrix proteins laid down as scaffolding for collagen synthesis
repair stage of tendon healing
fibroblast/tenocyte migrate to zone of injury and begin to synthesise collagen by day 5
initially collagen type 3 produced which is laid down in a random orientation
4th week - intrinsic fibroblasts proliferate and these cells take over the healing process both synthesising and reabsorbing collagen
switch to production of type 1 collagen which is increasingly orientated along line of force
vascular ingrowth via collagen/fibronectin scaffolding
organisation stage of tendon healing
final stability acquired by the normal physiological use of tendon
accompanied by cross linking between fibrils further increasing tendon tensile strength
complete regeneration never achieved - defect remains hypercellular - thinner collagen fibres
patient rehab for tendon injuries
early controlled mobilisation can reduce scare adhesions and facilitate healing by stimulating remodelling
excessive loading will disrupt repair tissue
optimal healing requires - surgical apposition and mechanical stabilisation, minimal soft tissue damage, optimal mechanical environment for healing
causes of rotator cuff tears
age - >65 multifactorial - smoking, diabetes, manual labour tendinopathy leading to tear bone spurs acromion shape trauma genetics
rotator cuff tear treatments
physio, injection for pain
operative - repair tendon to bone - arthroscopic/open surgery
platelet rich plasma injection
4 compartments of tendinopathy
stromal
immune
neural
vascular
stromal compartment of tendinopathy
includes tissue-resident tenocytes and matrix components
tendons acquire altered surface markers and pertubed intracellular signal pathways that have functional consequences
immune compartment of tendinopathy
t cells, dendritic cells, mast cells and macrophages respond to initial tissue insult through damage associated molecular patterns or PAMPs
neural compartment of tendinopathy
plays a role in propioception, interacts with mast cells to modulate adaptive responses in the normal tendon
in tendinopathy, excessive stimulation leads to tissue breakdown, degeneration and neoinnervation involving glatamatergic and autonomic systems
release of neuropeptides such as substance P stimulate mast cell degranulation, releasing a variety of agents which modulate a variety of cellular activities in the matrix
vascular compartment of tendinopathy
most tendons are poorly vascularised but respond to hypoxia by secreting angiogenic factors that induce growth of neovessels, which compromise vascular compartment of tendinopathy pathogenesis
fibrin-rich exudates leak from neovasculature resulting in fibrinoid degeneration
three layers of an artery or vein
tunica intima
tunica media
tunica externa
tunica media structure and function
smooth muscle
activated by sympathetic NS
vasoconstriction and vasodilation
elastic fibres stretch and then passively recoil
tunica intima structure and function
single layer of flat epithelial cells with a supporting layer of elastin rich collagen
provides a smooth, friction-reducing lining for the vessel
tunica externa structure and function
outermost layer, made of fibrous connective tissue and vasa vasorum
protective and supporting layer
anastomoses
arteries communicating with each other or veins communicating with each other form anastomoses
can be anatomical or functional
describe peripheral pulses
contraction of left ventricle results in volume of blood ejected into arterial tree
systolic heart contraction results in pressure wave
pulse represents palpable arterial palpation after each heartbeat
felt where artery can be compressed against bone
femoral pulse
mid inguinal point - halfway between anterior and superior iliac spine and pubic symphysis
popliteal pulse
above knee in the popliteal fossa - hold knee bent to find
dorsalis pedis pulse
top of the foot, immediately lateral to the tendon of the extensor hallucis longus
posterior tibial pulse
medial side of ankle, 2cm inferior and 2cm posterior to medial malleolus
axillary pulse
inferior on the lateral wall of axilla
brachial pulse
medial aspect of arm near elbow
ulnar pulse
medial aspect of wrist
radial pulse
lateral aspect of wrist and also anatomical snuff box
carotid pulse
medial to anterior border of sternocleidomastoid muscle
above hyoid bone and lateral to thyroid cartilage
ABPI - ankle brachial pressure index
measures systolic pressure of arteries in upper and lower limb - allows comparison
buergers test
assesses arterial sufficiency
when leg is elevated or drops it goes pale from the red state
are the iliac arteries easy to find
no - only felt if the person is skinny or has an aneurysm
atherosclerosis
arterial disease characterised by calcification and plaque formation
arterial wall thickening, elasticity loss
can be blockage of artery
risk factors for atherosclerosis
increasing age, sex (male), family history
hyperlipidaemia, hypertension, cigarette smoking, diabetes, obesity and pro-thrombotic tendencies
atherosclerosis hypothesis
chronic inflammation response of the vascular wall to endothelial injury or dysfunction
activation of endothelial cells
recruitment of monocytes/macrophages (chronic inflammatory cells)
formation of foam cells and fatty streaks
proliferation of smooth muscle cells
deposition of ECM proteins
major components of plaque
cellular - SMCs, macrophages, WBCs
ECM - collagen, elastin and prostaglandins
lipid - cholesterol
major process of plaque formation
intimal thickening - SMC proliferation and ECM synthesis
lipid accumulation
altered vessel function in athersclerosis and their consequence
plaque narrows lumen - ischaemia, turbulence
weakening of wall - aneurysms and rupturing
thrombosis - narrowing, ischaemia, embolisation
plaque disruption - athero-embolisation
intermittent claudication
“leg angina”
exertional leg pain - typically in the calf
assessment includes - walking distance, level of disability, risk factors, medical comorbidity - imaging after
critical limb ischaemia
rest pain, ulceration, gangrene
limb-threatening and life-threatening
arterial reconstruction methods
endovascular - balloon angioplasty or stent to keep artery open
open surgery - endarterectomy or bypass
angioplasty procedure
needle into lumen
wire into artery
balloon over the wire is inflated
lumen is widened
endarterectomy
open artery, remove plaque and close artery
peripheral bypass
bypass graft added to artery - blood flows around and separate to blockage
blockage too lengthy for other methods
two types of peripheral bypass
reroutes blood supply from blockage in artery
anatomical - bypass alongside
non-anatomical - blood supply from a completely different site eg. arm to groin
embolism
blockage of blood vessel by a solid, liquid or gas at a site distant from its origin
>90% of emboli are thrombo-emboli
carotid artery stenosis
internal carotid artery supplies brain
common carotid bifurcation is a common site of atherosclerosis - causes luminal narrowing and potential embolisation to brain
subsequent cerebral ischaemia can result in transient ischamic attack of thromboembolic stroke
ECM change from embryo to adult
early embyro - 80% cells, 20% ECM
adult - 20% cells and 80% ECM
ECM functions
provides a scaffold for tissue development
provides a mechanical basis for cell attachment and movement
transmits force eg. tendon, ligament cartilage, bone
can withstand compression in cartilage and intervertebral disc
provides survival signals to cells and differentiation signals to stem cells
reservoir for growth factors
ECM components
water, proteins, glycoproteins, proteoglycans, glucosaminoglycans
glycoproteins
protein with carbohydrate side chains
attached by glycosylation in golgi by glycosyltransferase
proteoglycan
subclass of glycoprotein
heavily glycosylated protein with GAG side chain
acid group provides negative charge
attracts water and protection against compressive forces
is collagen always arranged in the same way
organisation is related to the function
tendons, skin and a cornea all have different collagen fibril arrangement
types of collagen and the disease their mutant phenotype
type 1 - severe bone defects, fractures
2 - cartilage deficiency, dwarfism, vitreous humor of the eye
3 and 5 - fragile skin, loose joints, blood vessels prone to rupture
4 - kidney disease, deafness
6 - myopia, blindness
9 - osteoarthritis
12 and 17 - skin blistering
18 - myopia, detached retina, hydrocephalus
describe triple helix structure of collagen
types I, IV, V, IX and XI have 2 or 3 types of alpha chain (hetrotrimer) whereas II, III, VII, XII and XVIII have only one type of alpha chain each (homotrimer)
collagen structure
glycine-x-y repeating unit - glycine residue located at the centre of the triple helix - x is sometimes proline and y can be hydroxyproline
triple helical structure - 3 alpha polypeptide chains - each chain is a polyproline helix
intracellular steps of collagen maturation
transcription of mRNA in the nucleus, translation, post translational modification
extracellular steps of collagen maturation
propeptide cleavage
collagen fibril assembly
describe transcription and translation in collagen maturation
transcription - genes for pro-a2 and pro-a2 chains are transcribed
translation - mRNA moves into the cytoplasm and interacts with ribosomes for translation
it is now referred to as a pre-pro-polypeptide and it travels to ER
post translational modification in collagen maturation
pre-pro-polypeptide undergoes post translational processing - 3 major modifications for it to become pro-collagen
1. signal peptide on N terminal is removed
2. lysine and proline residues get additional hydroxyl groups added to them via hydroxylase enzymes which require vitamin C as a cofactor - catalysed by prolyl-4-hydroxylases, prolyl-3-hydroxylase and lysul hydroxylases
3. glycosylation of the selected hydroxyl groups on lyosine with galactose and glucose b
three of the hydroxylated and glycosylated pro-a-chains fold into a triple helix and are then secreted into vesicles
propeptide cleavage in collagen maturation
enzymes known as collagen peptidases preform propeptide cleavage and remove the ends of the procollagen molecule and the molecule becomes tropocollagen
collagen fibril assembly
lysyl oxidase acts on lysine and hydroxlysines
covalent bonding between tropocollagen molecules forms a collagen fibril
describe c-proteinase and n-proteinase
the C-propeptides of the fibril-forming collagen, and the N-propeptides of type I and II, partially also of type III collagen are cleaved by these proteases
c-proteinases are of the BMP1 type
n-proteinases are ADAMTS family members - a disintegrin and metalloproteinase with thrombospondin repeats
describe the collagen turn-over-half life
in adulthood - no collagen turnover in healthy state
about 120 years meaning collagen will stay for life - even defective proteins will stay for life
describe osteogenesis imperfecta
brittle bone disease
range of clinical severity from fractures to lethality
autosomal recessive and dominant forms
collagen type 1 related disorder - mutation in COL1A1 or COL1A2
describe the structure of collagen type 1
major fibrillar collagen
COL1A1 and COL1A2 heterotrimeric protomer - 2 alpha 1 chains and 1 alpha 2 chain
OI type 1
less severe, no symptoms at birth
early onset osteoporosis, few fractures
null mutations - gene not being transcribed into RNA and/or translated into a functional protein
reduced collagen
how does mild OI impact procollagen
normally 8 molecules of pro-alpha1 chains and 4 molecules of pro-alpha2 chains which combine to make 4 procollagen proteins
OI means you only have 4 molecules of pro-alpha1 chains and so only 2 procollagen proteins are produced
mutations in mild OI
stop codons
promoter mutations - impacts amount of collagen being produced
mRNA instability
consequences always the same - not enough collagen made - quality of collagen is fine
role of HSP47 in collagen maturation
prevents aggregation of collagen by coating the procollagen
HSP47 can be recycled
mutations in severe forms of OI
80% glycine missense mutations - quality of the protein is impacted
dominant negative
effect on modification due to delay in folding - disruption of gly-x-y sequence slows rate of folding resulting in overmodification of the chains N-terminal to the disruption
mutant chains are secreted
potential effects on protein binding
3 joints of the elbow
humeroulnar
humeroradial
proximal radioulnar joint - not involved in flexion/extension - passively moves
where does the humerus articulate
with two forearm bones - laterally with radius at the rounded capitulum and medially with ulna bone at the trochlea
epicondyles on distal end of humerus
medial and lateral epicondyles
located proximal to capitulum and trochlea
they site muscle attachment
describe the proximal end of ulna
trochlear notch
2 processes:
larger processes is called olecranon and is posterior - elbow prominence
smaller process is the coronoid process which is anterior
both processes together receive the trochlea of humerus
describe the distal end of ulna
head is anterior and articulates with radius
styloid process is posterior and medial - wrist ligaments
ulnar does not articulate with carpal bones - fibrocartilaginous ligament prevents this
ulnar articulates with radius instead
