Pathophysiology of skeletal muscle Flashcards
Muscle plasticity: adaptations
Structural
- e.g. size, capillarisation
Contractile properties
- e.g. fibre type transitions
Adaptability occurs from embryogenesis into maturity
Capillarisation
The formation and development of a network of capillaries to a part of the body
Often occurs in muscle in response to long term exercise
Also occurs in cancerous tissue
Structural adaptation
Total number of muscle fibres fixed at birth
- e.g. 200,000 biceps brachii
Muscle growth: hypertrophy
- synthesis of myofilaments
- addition of sarcomeres
- satellite cell activation
- angiogenesis and vascularisation
Some muscles enlarge by between 15-50%
Effect of endurance exercise
Increased
- fibre diameter
- blood supply
- mitochondrial content
Will express increase in oxidative enzymes
Fibres become slower
Gradual transformation from type IIX to type IIA
Non-endurance exercise
Conversion to type IIX
- from type IIA
- greater muscle force and strength
Increase in type IIX fibre size due to increase in number of sarcomeres and myofilaments
Results in much larger muscles
Increase in power
Ice
Reduces swelling
- by reducing perfusion
After an acute injury
- sprain
After exercise in overuse injury
Heat
To relax and loosen tissues
Use before activities that irritate chronic injuries
- strain
Increases blood flow
Sprain
Injury to a ligament
Strain
Injury to muscle or a tendon
Aspirin
NSAID, reduces pain, reduces inflammation
Used for
- chronic diseases (osteoarthritis)
- sports injuries
Mechanism
- inhibits COX
- reduces synthesis of prostaglandins
- part of arachidonic acid pathway
Side effects
- stomach bleeding
- ulcers
Anabolic effects of testosterone
Increases protein synthesis
Decreases catabolism by opposing cortisol and glucocorticoids
Reduces fat: increases BMR, increases differentiation to muscle
Anabolic steroid abuse
Used to increase muscle size and strength
Large doses required- leads to damaging side effects (kidney, liver, heart, mood changes)
Male- testes atrophy, sterility, baldness
Female- breast/ uterus atrophy, menstrual changes, facial hair, deepening of voice
Effect of spaceflight
Humans- transition of type I fibres to type IIA/X fibres
Decrease relative muscle mass- all muscles undergo some atrophy, but predominantly weight bearing muscles
Effect of bed rest
Transition of type I fibres to type IIA
Weight bearing muscle atrophy
- decrease muscle protein synthesis
- myofibrillar breakdown
- decrease strength
- loss of type I fibres
Treat by resuming minor activity early
Contracture
If limb immobilised for long periods
- process of growth is reversed
- sarcomeres are removed in series from myofibrils
- resulting in shortening of muscle called a contracture
Patients with paralysed limbs must have physical therapy to prevent contractures occurring
Skeletal muscle cells are multinucleate
They develop as myoblasts
- which are mononucleate
- then the myoblasts fuse
The nuclei are peripheral
The multinucleate cells do not divide
- mitosis with multiple nuclei is usually impossible
Skeletal fibres are enlarged by
- fibre enlargement
- increased vascularisation
Muscle regeneration
During inflammation and degeneration of damaged muscle tissue
Previous quiscent myogenic cells, called satellite cells, are activated
- they proliferate, differentiate and fuse onto extant fibres
- they contribute to forming multinucleate myofibres
Myosatellite cells
Progenitor cells in muscle
- also called satellite cells
Essential for regeneration and growth
Most are quiescent
- activated by mechanical strain
Activation -> proliferation and differentiation
Myalgia
Muscle pain
Causes: injury, overuse, infections, auto-immune
Can be associated with rhabdomyolysis
Myopathy
Muscular weakness due to muscular muscle fibre dysfunction
- cf. meuropathy and neurogenic disorders
- failure to contract cause possibly muscle or nerve
Systemic vs familial
Dystrophies: familial, progressive
- stuck in degeneration- regeneration cycle
- eventually regenerative ability is lost
Paresis
Weakness of voluntary movement, or partial loss of voluntary movement or impaired movement
Usually referring to a limb
From greek ‘to let fall’
Fasciculations
Involuntary visible twitches in single motor units
Commonly occur in lower motor neuron diseases such as damage to anterior horn cell bodies characteristic of ALS or polio
Clinically appear as brief ripples under the skin
Fibrillations
Involuntary spontaneous contractions of individual muscle fibres invisible to the eye
Identifiable by electromyography
Rhabdomyolysis
Rapid breakdown of skeletal muscle
- not cardiac muscle, not myocardial infarct
Risk of kidney failure
- cellular proteins released into blood can clog renal glomeruli
- urine is tea coloured, no urine produced 12 hours after injury
- leads to electrolyte changes: hyperkalaemia
Treatment of rhabdomyolysis
Intravenous fluids
Possibly haemodialysis
Causes of rhabdomyolysis
Trauma: crush injury
Drugs
- adverse effects of statins or fibrates
Hyperthermia
Ischaemia to the skeletal muscle
- compartment syndrome
- thrombosis
Symptoms and signs of rhabdomyolysis
Muscle pains
Vomiting and confusion
Dark urine
Serum levels CPK: diagnostic
Creatine phosphokinase
- CK or CPK abbreviations used interchangeably
- the enzyme, not creatine phosphate
Distinct forms of CPK not found in different tissues
Skeletal muscle CPK isoform is CK-MM
Cardiac muscle CPK isoform is CK-MB
When tissue damage and cells lyse there is a relase of tissue specific CK from cells into blood
Elevations in CK-MM occur after skeletal muscle trauma or necrosis
Myoglobin: diagnostic
Buffers O2
Protein and haem group
Tea coloured
In plasma indicated rhabdomyolysis or MI
- can lead to renal failure
- urine tested for myoglobin
Diagnostic: hyperkalaemia
- when muscle cells lyse
- they release K+
- this increases serum K+
Myasthenia gravis
Progressive muscle weakness and fatiguability
- often starts with eye muscle
Caused by depletion of nAChR
Arises as the immune system inappropriately produces auto-antibodies against nAChR
Less depolarisation of muscle fibres
- many fibres do not reach threshold
Repeated stimulation -> neuromuscular fatigue
Symptoms include ptosis, diplopia
Proximal muscle weakness
Myasthenia gravis: treatment and diagnostics
AChE inhibitors
- neostigmine: increases ACh activity at NMJ
- endrophonium: short lived AChE inhibitor for diagnosis
Other category of treatment is directed at immune system
Spinal muscular atrophy
Floppy baby syndrome
- one of the most common genetic causes of infant death
- severity ant time of onset can vary greatly
Death of lower motor neurone in anterior horn of spine
- muscle atrophy -> hypotonia and muscle weakness
- fibre type grouping
- sensory system is spared
Fibre type grouping
During spinal muscular atrophy
Cycles of denervation are followed by collateral reinnervation
Surviving axons innervate surrounding fibres
Resulting in fibre type grouping
In healthy muscles, motor units are intermingled
During reinnervation, nearby surviving neurons re-innervate the denervated fibres, resulting in clusters
Malignant hyperthermia
Genetic (rare) susceptibility to gas anaesthetics
- e.g. sevoflurane
Mutation in RyR means gas anaesthetic -> Ca2+ release
- autosomal dominant
- channel is suceptible if any of subunits are
Results: SERCA works too hard
Increase O2 consumption, increase CO2, acidosis, tachypnoea, muscles overheat, the body overheats, muscles are damaged, hyperkalaemia, muscle become rigid
Muscular dystrophies
Group of inherited disorders
Severe and progressive wasting of muscle
- muscle weakness
- due to myopathy, not neuropathy
Waddling gait
Contracture
Cardiorespiratory muscle involvement - leads to death
Duchenne muscular dystrophy
X linked disease
Affects 1:3500 live male births
- 1/3 cases arise spontaneously
Progressive loss of muscle tissue
Replaced by fibrofatty connective tissue
Mutation: gene for dystrophin protein
Causes of spinal muscular atrophy
Caused by genetic defect
- SMN1 gene (required for survival of anterior horn neurones)
- autosomal recessive
- other genes cause similar syndromes
Dantrolene sodium
Can stop abnormal calcium release in malignant hyperthermia
Inhibits ryanodine receptor
