T2 l6 :intro to pathophysiology of muscle Flashcards
difference between endurance exercise and resistance training
endurance: responds to total contractile activity
resistance training: responds to loading and stretch
what are the muscle plasticity adaptations
- structural; size, capillarisation
- contractile properties: fibre type transitions
if the total number of muscle fibres are fixed at birth how do they grow
Hypertrophy:
-synthesis of myofilaments
- addition of sacromeres
- satellite cell activation
- angiogenesis & vascularisation
list the effects of endurance exercise
fibre diameter
blood supply
mitochondrial content: express an increase in oxidative enzymes
fibres become slower-2x and 2a and type 1 eventually
describe the changes that occur to non-endurance exercise
conversion to type IIX
- from type IIA
- greater muscle force & strength
increase in type IIX fibre size due to increase in numbers of sarcomeres & myofilaments
results in much larger muscles (bulk) and leads to an increase in power
what type of injuries is ice used to reduce
To reduce swelling By reducing perfusion After an acute injury Sprain After exercise in overuse injury
what type of injury is heat used to reduce
To relax and loosen tissues
Use before activities that irritate chronic injuries
Strain
Increases blood flow
describe the class, function and diseases that aspirin can be used on
Aspirin is an NSAID:
- Reduces pain
- Reduces inflammation
Mechanism:
- Inhibits COX
- Reduces synthesis of prostaglandins
- Part of arachidonic acid pathway
Used for musc-skel pain:
- Chronic diseases
- –Osteoarthritis
- Sports injuries
- –Combined with ice
- –Often after exercise
Arachidonic acid and prostaglandins
Gastro-intestinal adverse effects of chronic aspirin
Stomach bleeding
Ulcers
what are the effects of testosterone :
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)
what occurs in anabolic steroid abuse
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
what is the effect of spaceflight on humans
- Theres a decrease in weight bearing that the muscles have to undertake
- Humans transition from type 1 to 2A/X fibres
- decrease in the relative muscle mass- all muscles undergo some atrophy, but predominately weight-bearing muscles
what is the effect of bed rest on muscle
transition of type I fibres to type 2a
this causes weight bearing muscle atrophy
- decrease in muscle protein synthesis
- myofibrillar breakdown
- decrease strength due to smaller size
- loss of type 1 fibres
how do you treat the effect of bed rest
Add physiotherapy to prevent contractures.
describe contracture
-if limb is immobilised for a long period of time
-process of growth is reversed
sarcomeres are removed in series from myofibrils
-resulting in shortening of muscle called a contracture
describe the multinucleate nature of skeletal muscles
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
- Skeletal muscles are enlarged by:
- Fibre enlargement
- Increased vascularisation
how does muscular regeneration occur
previous quiescent myogenic cells, called satellite cells, are activated:
- These proliferate, differentiate and fuse onto extant fibres
- They contribute to forming multinucleate myofibers
describe myosatellite cells
Progenitor cells in muscle
- Also called “satellite cells”
- NOT related glial satellite cells
activated by mechanical strain on muscle
activation leads to proliferation and differentiation
what are the causes of muscle pain
injury
overuse
infections
auto-immune
associated with rhabdomyolysis
describe the aetiology of myopathy
Muscular weakness due to muscular muscle fibre dysfunction:
- Cf. neuropathy & neurogenic disorders
- Failure to contract cause possibly muscle or nerve
can be systemic or familial
describe dystrophies
Dystrophies: familial, progressive:
- Stuck in degeneration-regeneration cycle
- Eventually regenerative ability is lost
describe paresis
weakness of voluntary movement, or
partial loss of voluntary movement or
impaired movement
Usually referring to a limb
describe fasciculations
: involuntary visible twitches in single motor units (neurogenic), which 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
describe fibrillations
: involuntary spontaneous contractions of individual muscle fibres (myogenic) invisible to the eye but identified by electromyography
describe rhabdomyolysis
Rapid breakdown of skeletal muscle
-Not cardiac muscle, not myocardial infarct
is there An organ risk with rhabdo
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
what is the treatment for rhabdo
- Intravenous fluids (to treat shock)
- possibly haemodialysis, etc
what can cause rhabdomyolysis
- Trauma: Crush injury
- Drugs
- -adverse effects of: statins or fibrates
- Hyperthermia
- Ischaemia to the skeletal muscle
- -Compartment syndrome, thrombosis
what are the signs and symptoms of rhabdo
Symptoms & signs (depending on severity):
- muscle pains
- vomiting and confusion
- Dark urine
different forms of CPK
skeletal muscle CPK isoform is CK-MM
cardiac muscle CPK isoform is CK-MB
what occurs to CPK levels when tissue damage occurs
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)
how can you use myoglobin as a diagnostic test
“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: decrease serum K = cause of rhabdo,
increase K = result of rhabdo
how is rigor mortis caused
ATP depleted after death
Muscle cell does not resequester Ca2+ into SR
increases Cytosolic Ca2+
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 occurs in 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
pathophysiology of myasthenia gravis
less depolarisation of muscle fibres
many fibres do not reach threshold
repeated stimulation neuromuscular fatigue
symptoms include ptosis, diplopia,
with weakness in eyelid and extraocular muscles
proximal muscle weakness
what is the treatment 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 occurs in 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)
Caused by genetic defect SMN1 gene Required for survival of anterior horn neurons Autosomal recessive Other genes cause similar syndromes
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
In healthy muscles (Figure A), motor units are intermingled. During reinnervation, nearby surviving neurons re-innervate the denervated fibres, resulting in clusters (Figure B)
study slide 32
what occurs in 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)
O2 consumption, 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
what occurs in 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 occurs in 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
what sign is associated with Duchenne muscular dystrophy
Gowers sign -is a medical sign that indicates weakness of hip and thigh muscles associated with muscular dystrophy. The patient that has to use his hands and arms to “walk” up his own body from a squatting position.
