Lecture 2- Pathophysiology of skeletal muscle Flashcards
what is known as the plasticity of the skeletal muscles?
exercise
what does muscle plasticity mean?
adapting of changes in functional demand
what does the endurance exercise respond to ?
total contractile activtivty
What does resistance exercise respond to?
loading and stretching
what are the muscles adaptations that allow plasticity?
structural- eg size and capillarisation
contractile properties- e.g. fibre type transitions-
when does adaptability occur?
from embryogenesis into maturity
what is the total number of muscle fibres of bicep brachii at birth?
200,000
what does muscle growth mean?
hypertrophy- (growth due to enlargement without cell division)
synthesis of myofilaments
satelite cell activation
angiogenesis and vascularisation
what are the effects of endurance exercise on the muscles?
- Slight increase in Fibre diameter
- blood supply-increased oxidative capacity
- mitochondrial content
- will express Increased in oxidative enzymes
- Fibres become slower
what happens to the fibre types during endurance exercise>
gradual transformation of type :
IIX —–> IIA
what happens to the muscle fibres types during non-endurance exercise?
conversion to:
IIA—-> IIX
Greater muscle force and strength
what causes increase in power in type IIX fibre?
- Increase in IIX fibre size due to increased numbers of sacromeres and myofilaments
- results in LARGER muscles (BULK)
what is the role of ice in acute muscle injury?
-reduce swelling- reduces perfusion
what is the role of heat in muscle injury?
- to relax and loosen tissue
- to use before activities that irritate chronic injury
- INCREASES blood flow
why is aspirin/NSAIDs use in MSK pain?
-Reduces pain/inflammation
Describe the mechanism of action of NSAIDS?
- Inhibits COX
- Reduces the synthesis of prostaglandins
- Part of the archidonic pathway
Name a chronic disease which NSAIDs are used?
Osteoarthritis
what are the possible SEs of using NSAIDS (inc aspirin)?
-STomach bleeding
-ulcers
amongst others
what effects does the testosterone have?
anabolic and androgenic
Describe the anabolic effects of testosterone?
- Increased protein synthesis
- decrease catabolism- opposes cortisol and glucocorticoids
- reduces fat- increases basal metabolic rate
- Increases differentiation to muscle rather than fat
what is the purpose of anabolic steriod use?
increase muscle size and strength
why do the anabolic steroids lead to damaging SE’s?
-Large doses required
what are the some of the SE’s of using anabolic steriods?
Male- testes atrophy, sterility and baldness
Female- breast/uterus atrophy, menstrual changes, facial hair and deepening of voice
what is the effect of spaceflight on muscle fibre transition?
From type I—->IIA/X
what happens to the muscles during spaceflight?
- due to decrease weight bearing–>all muscle undergo some atrophy-
- weight bearing muscle show greatest atrophy
what is the effect of bed rest on muscle fibre types?
From Type I—–>type IIA
what is the effect of bed rest on the weight bearing muscles?
- Atrophy due to:
1. decreased muscle protein synthesis
2. myofibrillar breakdown
3. decreased strength due to decreased size
4. Loss of type I fibres
What are the possible treatment options for muscle atrophy?
- Resume minor activity early
- physiotherapy
what is a contracture?
-If a limb is immobilised for long periods then:
-process of growth is reversed
(sacromeres are removed in series from myofibrils)
-results in shortening of the muscle
Describe the nucleation process for the skeletal cells?
-Multinucleate
develop as myoblasts which are mononucleate
these then fuse
-Nuclei are peripheral
Why does multinucleate cells do not dividie?
mitosis cells do not divide
How are the skeletal muscles enlarged?
- fibre enlargement
- increased vascularisation
What causes muscle degeneration?
inflammation
How is this damage repaired?
- Satellite cell- activated by inflammation
1. proliferate, differentiate and fuse onto extant fibres
2. contribute to forming multinucleate myofibers
what is the role of myosatellite (satellite cell)?
- Progenitor cells in muscle
- essential for regeneration and growth
What activates the satellite cell?
mechanical strain
what is myalgia and what are the possible causes?
-muscle pain
causes:
injury, overuse, infection and autoimmune
Can be associated with rhabdomyolysis
What is myopathy?
muscular weakness due to muscular fibre dysfunction
What is muscle dystrophy and what are the causes?
dystrophy- stuck in degeneration and regeneration cycle- until regenerative ability is lost
Causes- familial/progressive
What is paresis?
weakness of the voluntary movement- partial loss of voluntary movement or impaired movement
What are fasciculations?
- Involuntary visible twitches in a single motor unit
- commonly occur in lower motor neuron disease such as ALS
- clinically appear as brief ripples under the skin
what are fibrillations?
Involuntary spontaneous contractions of individual muscle fibres invisible to the eye
what is rhabdomyolysis?
rapid breakdown of skeletal muscle
what are the signs and symptoms of rhabdomyolysis?
- Risk of renal failure due to:
1. cellular proteins (esp myoglobin) release into the blood- clog renal glomeruli
2. Dark urine- usually no urine produced after 12 hours after injury
3. leads to electrolyte changes- Hyperkalemia
4. muscle pain
5. vomiting&confusion
what are the treatment options for rhabdomyolysis?
- IV fluids- to treat shock
- haemodialysis
what are the possible causes of Rhabdomyolysis?
occurs when cell membrane loses integrity due to:
- Trauma
- Drugs- statins/fibrates
- hyperthermia
- Ischaemia to skeletal muscle- thrombosis and compartment syndrome
what are the diagnostics of rhabdomyolysis?
- Total serum level creatine phosphokinase (CK)
- When tissue damaged- release CK into blood
-CK increases after skeletal muscle trauma/necrosis - Myoglobin in plasma indicative of Rhab or MI- can lead to renal failure
- Hyperkalaemia-
when muscle cell lyse they release K+=increase in in serum K+
what is the cardiac form of CK?
CK-MB
What is rigor mortis?
ATP depleted after death.
muscle cells does not requester Ca2+ into SR thus Increase cytosolic Ca
Ca2+ allows crossbridge cycle contraction
Until ATP & creatine-P run out
W/o ATP —-> myosin stops just after power stroke
With myosin still bound to actin.
Rigor mortis ends when muscle tissue degrades after 3 days
What is myasthenia gravis and its causes?
progressive muscle weakness and fatigability- often starts with eye muscle
caused by:
depletion of nAChR- due to the immune systme inappropriately producing antibodies against nAChR
How is the myasthenia gravis caused?
- Due to less depolarisation of muscle fibres- many fibres do not reach the threshold
- Repeat stimulation causes neuromuscular fatigue
what are the symptoms of Myasthenia gravis?
ptosis and diplopia- weakness in the eyelid and extraocular muscles
- proximal muscle weakness
- fatigue
what are the main treatment options for Myasthenia gravis?
- AChE inihibitors: pyrodostigmine: increases ACh activity at NMJ- prevents breakdown of Ach in the synapse
- Edrophonium- short acting AchE- inhibitor- used mainly for diagnosis-
What are the other treatment options for Myasthenia gravis?
Treatment directed at Immune system:
- Thymectomy- reduces symptoms in 70% of the patients
- Corticosteriods- immunosuppresive effects
- Plasmapheresis: removal an anti AChR antibodies from the blood
what is spinal muscular atrophy(SMA) and who does it affect?
SMA is degeneration of lower motor neurons-
Most common cause of genetic infant death
what is the cause of SMA?
genetic defect-
autosomal recessive
what does the death of lower motor neuron in the anterior horn of the spine cause?
- Muscle atrophy: hypotonia and muscle weakness
2. Fibre type grouping
Why is the sensory system spared?
due to anterior horn is not affected
What is 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
what is malignant hyperthermia?
Genetic (rare) susceptibility to gas anaesthetics
Eg sevoflurane
what is the cause of malignant hyperthermia?
Mutation in RyR means gas anaesthetic —-> Ca2+ release
Autosomal Dominant:
Channel is susceptible if any of sub-units are
Result: SERCA works too hard (to pump Ca back into SR)
What are the signs and symptoms of MH?
Increased O2 consumption, Increased CO2, acidosis, tachypnea, muscles overheat, the body overheats, muscles are damaged (rhabdomyolysis), hyperkalaemia, muscles become rigid
Explain malignant hyperthermia in simple term?
Muscle cells open and leak their contents
Plasma CK-MM increases
Kidney failure possible: urine red from myoglobin
what are the treatment options for Malignanat hyperthermia?
dantrolene sodium can stop the abnormal calcium release-
Inhibits ryanodine receptor
what are muscular dystrophies?
- Group of inherited disorders
- Severe and progressive
- muscle weakness due to myopathy
- Waddling gate
- Contractures
- Cardio-respiratory muscle involvement
what is Duchenne muscular dystrophy?
- x-linked disease-gene for dystrophin protein
- affects 1:3500 live male births
- progressive loss of muscle tissue
- replaced by fibrofatty connective tissue
what is Gower’s sign?
indicates weakness of hip and thigh muscles associated with muscular dystrophy. The patient has to use hands and arms to “walk” up his own body from a squatting position
