Introduction to pathophysiology of skeletal muscle Flashcards
How can you describe skeletal muscle?
Plastic
How is skeletal muscle plastic?
Adapts to changes in functional demand
What does skeletal muscle respond to during endurance exercise?
Total contractile activity
What does skeletal muscle respond to during resistance training?
Loading and stretch
List some adaptations of skeletal muscle that makes it plastic
Structural eg. size and capillarisation
Contractile properties eg. fibre type transitions
When does adaptability occur?
From embryogenesis into maturity
Describe the structural adaptation of skeletal muscle
Total number of muscle fibres fixed at birth
Give the name of the process of muscle growth
Hypertrophy
Describe hypertrophy
Synthesis of myofilaments
Addition of sarcomeres
Satellite cell activation
Angiogenesis and vascularisation
How much do some muscles enlarge by?
15-50%
Give some examples of endurance exercise
distance running, cycling or swimming
(low force, high contractile frequencies)
What can endurance exercise cause in the muscle?
Increased fibre diameter Increased blood supply, increased oxidative capacity Increased mitochondrial content Increase in oxidative enzymes Slower fibres
What transformation of fibre type occurs with endurance exercise?
Gradual transformation of type IIX to type IIA
What transformation of fibre type occurs with non-endurance exercise?
Conversion of type IIA to type IIX
What does non-endurance exercise result in?
Increase type IIX fibre size due to increased number of sarcomeres and myofilaments
Results in larger muscles (bulk) and an increase in power
What is ice used for?
To reduce swelling by reducing perfusion
After an acute injury such as a sprain
After exercise in overuse injury
What is heat used for?
To relax and loosen tissues
Use before activities that irritate chronic injuries such as strain
Increases blood flow
What class of drugs is aspirin?
Non steroidal anti inflammatory
What does aspirin do?
Reduces pain and inflammation
Where is aspirin used for in musculoskeletal conditions?
Chronic diseases - osteoarthritis
Sports injuries - combined with ice often after exercise
How does aspirin work?
Inhibits COX
Reduces prostaglandin synthesis
Part of arachidonic acid pathway
What adverse effects do prostaglandins and arachidonic acids have?
Stomach bleeding
Gastric ulcers
List the anabolic effects of testosterone
Increases protein synthesis
Decreases catabolism (by opposing cortisol & glucocorticoids)
Reduces fat: increase BMR, increase differentiation to muscle (rather than fat cells)
Why are anabolic steroids abused?
used to increase muscle size and strength
Give the side effects of anabolic steroid abuse
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
What does space flight do to muscles?
Decreased weight bearing
Transition of type I fibres to type IIA/X fibres
Decreased relative muscle mass - all muscles undergo some atrophy - predominately weight bearing muscles
What does bed rest do to muscles?
transition of type I fibres to type IIA
weight-bearing muscle atrophy
- decreased muscle protein synthesis - myofibrillar breakdown - Decreased strength (due to decreased size) - loss of type I fibres
How do you treat the effects of bed rest?
treat by resuming minor activity early. Add physiotherapy to prevent contractures.
What is contracture?
Shortening of muscle
How does contracture occur?
if limb immobilised for long periods:
process of growth is reversed
sarcomeres are removed in series from myofibrils
How can contracture be prevented?
patients with paralysed limbs must have physical therapy to prevent contractures occurring
What word is used to describe the cellular structure of skeletal muscle
Multinucleate
Describe the development of skeletal muscle cells
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 usually impossible
How are skeletal muscles enlarged?
Fibre enlargement
Increased vascularisation
Describe muscle regeneration
During inflammation and degeneration of damaged muscle tissue
previous quiescent myogenic cells, called satellite cells, are activated
These proliferate, differentiate and fuse onto extant fibres
They contribute to forming multinucleate myofibers
What are myosatellite cells?
Progenitor cells in muscle Also called “satellite cells” NOT related glial satellite cells Essential for regeneration & growth Most are quiescent Activated by mechanical strain Activation —> proliferation & differentiation
What is myalgia?
Muscle pain
Give some causes of myalgia
Injury, overuse, infections, auto-immune
What can myalgia be associated with?
Rhabdomyolysis
What is myopathy?
Muscular weakness due to muscular muscle fibre dysfunction
Cf. neuropathy & neurogenic disorders
Failure to contract cause possibly muscle or nerve
Systemic vs. familial
What are dystrophies?
familial, progressive
Stuck in degeneration-regeneration cycle
Eventually regenerative ability is lost
What is paresis?
weakness of voluntary movement, or
partial loss of voluntary movement or
impaired movement
Usually referring to a limb
From Greek “to let fall”
What are fasciculations?
involuntary visible twitches in single motor units (neurogenic)
When do fasciculations occur?
commonly occur in lower motor neuron diseases such as damage to anterior horn cell bodies characteristic of ALS or polio
How do fasciculations appear clinically?
clinically appear as brief ripples under the skin
What are fibrillations?
involuntary spontaneous contractions of individual muscle fibres (myogenic) invisible to the eye but identified by electromyography
What is rhabdomyolysis?
Rapid breakdown of skeletal muscle
What is rhabdomyolysis a risk for?
Risk of kidney failure
Cellular proteins (esp myoglobin) released into blood can “clog” renal glomeruli
Urine is “tea coloured”, no urine produced 12 hours after injury
Leads to electrolyte changes: hyperkalaemia
How is rhabdomyolysis treated?
Intravenous fluids (to treat shock) possibly haemodialysis, etc
List some causes of rhabdomyolysis
Trauma: Crush injury Drugs adverse effects of: statins or fibrates Hyperthermia Ischaemia to the skeletal muscle Compartment syndrome, thrombosis
Give some symptoms and signs of rhabdomyolysis
muscle pains
vomiting and confusion
Dark urine
What is Creatine Phosphokinase (CK/CPK) and what is it used for clinically?
The enzyme
distinct forms of CPK found in different tissues
skeletal muscle CPK isoform is CK-MM
cardiac muscle CPK isoform is CK-MB
when tissue damaged and cells lyse there is a release of tissue specific CK from cells into blood
Elevations in CK-MM occur after skeletal muscle trauma or necrosis
muscular dystrophies, polymyositis and rhabdomyolysis
Test = “Total CK” (CK-MM is not a clinical test)
What is myoglobin and how is it diagnostic?
“Buffers O2” Protein + Haem group “tea coloured” In plasma indicates 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+
Nb: decreased serum K = cause of rhabdo,
increased K = result of rhabdo
What is myasthenia gravis?
progressive muscle weakness and fatigability
Often starts with eye muscles
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 leads to neuromuscular fatigue
symptoms include ptosis, diplopia,
with weakness in eyelid and extraocular muscles
proximal muscle weakness
Describe different treatment options for MG
AChE inhibitors
Neostigmine
Increase ACh activity at NMJ. ACh released from nerve terminals into synapse not rapidly catabolised but can bind to the remaining AChRs for longer time
Edrophonium (a/k/a tensilon): short-lived AChE inhibitor for diagnosis, temporarily improves symptoms eg ptosis
Other category of treatment is directed at immune system
Thymectomy – reduces symptoms in 70% of patients. Exact mechanism unknown. Rebalance immune system?
use of immunosuppressive drugs e.g. corticosteroids
plasmapheresis = removal of anti AChR antibodies from blood stream
What is spinal muscular atrophy?
a/k/a Floppy Baby Syndrome
One of most common genetic causes of infant death
Severity and time of onset can vary greatly
death of lower motor neurons in anterior horn of spine
Muscle atrophy —> hypotonia & muscle weakness
Via apoptosis
Fibre type grouping
Sensory system is spared (b/c not in anterior horn)
What causes spinal muscular atrophy?
Caused by genetic defect SMN1 gene Required for survival of anterior horn neurons Autosomal recessive Other genes cause similar syndromes
Describe 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
What is malignant hyperthermia?
Genetic (rare) susceptibility to gas anaesthetics
Eg sevoflurane
Mutation in RyR means gas anaesthetic - Ca2+ release
Autosomal Dominant
Channel is susceptible if any of subunits are
Result: SERCA works too hard (to pump Ca back into SR)
Increased O2 consumption, increased CO2, acidosis, tachypnea, muscles overheat, the body overheats, muscles are damaged (rhabdomyolysis), hyperkalaemia, muscles become rigid
Muscle cells open and leak their contents
Plasma CK-MM increases
Kidney failure possible: urine red from myoglobin
dantrolene sodium can stop the abnormal calcium release
Inhibits ryanodine receptor
Describe muscular dystrophies
group of inherited disorders severe and progressive wasting of muscle muscle weakness Due to myopathy, not neuropathy waddling gate contractures cardiorespiratory muscle involvement
What is duchenne muscular dystrophy?
x-linked disease affects 1:3500 live male births one third of cases arise spontaneously progressive loss of muscle tissue replaced by fibrofatty connective tissue Mutation: gene for dystrophin protein
