PHYS: Neuromuscular Junction & Disease Flashcards
What are the 3 skeletal muscle fibres types? How are they determined?
- Type 1 - slow contracting, fatigue resistant
- Type 2a - fast contracting, fatigue resistance
- Type 3b - fast contracting, fast fatigue
Nerve tells muscle fibre which type to become.
Altering nerve activity patterns changes slow muscle -> fast muscle.
What would we expect to see on a histochemical stain? What would neurogenic and myopathic disease look like?
Normal
- salt and pepper
- relatively spherical
- connective tissue
Neurogenic disease:
- Sensorimotor polyneuropathy
- death motor neuron, surrounding survive = fibre type clustering
- Fibre atrophy from LMN disease
- death motor neuron, lost innervation = atrophy all muscle fibres, hypertrophy adjacent muscle fibres to compensate
Myopathic disease:
- Duchenne muscular dystrophy
- damaged and necrotic muscle fibres
- lots of inflammatory cells release oxidative chemicals destroy muscle fibre membranes
What are the graded effects of skeletal muscle denervation?
- Paralysis (immediately)
- Fasciculation (immediately) - spontaneous firing of injured axon
- Fibrillation (days) - spontaneous firing of individual muscle fibres due to changes in muscle excitability
- Supersentivitiy to ACh (days) - increased AChR in muscle membrane
- Muscle atrophy (>1 week) - loss muscle protein
- Receptiveness to innervation
What clinical differences between neurogenic and myopathic disease?
Neurogenic will exhibit fasiculations, sensory loss and hyperreflexia
(Myopathic and neurogenic will show weakness, wasting and reflex loss)
What are Myasthenic Disorders?
-
Myasthenia Gravis: Produce autoantibodies to nicotinic acetylcholine receptors
- clinically: hypertonic cranial muscles, limb muscles
- no sign of denervation (atrophy, loss of relexes)
-
Lambert-Eaton syndrome: produce autoantibodies that block release mechanism (voltage gated Ca2+ channels) of ACh
- clinically: proximal limb muscles, respiratory muscles
Both produce:
- Severe muscle weakness
Treatment with immunosuppresion: prednisolone
What are signs of muscular dystrophies?
Fragility –> ongoing rounds of degeneration/regeneration with progressive loss of muscle function.
Microscopic signs:
- variation myofibre size
- necrosis
- internal nuclei and regenerating myofibres
- hypercontracted, split and whorled fibres
What is Duchenne Muscular Dystrophy?
- Caused by mutations in dystrophin gene
- X-linked, recessive inherited disease
- Awkward gait, frequent falls, scoliosis
- Progressive muscle degeneration -> wheelchair bound by 10-12 years
- Death from cardiac/respiratory failure around 20-30 years
What is dystrophin?
Subsarcomal cytoskeletal protein - provides mechanical stability to muscle cell surface membrane
Dystrophine mutation results in absent or defective dystrophin and associated proteins
What is the difference between Duchenne and Becker MDs?
Duchenne:
- absent dystrophin
- lethal
- out-of-frame dystrophine mutation
Becker:
- alterzied size & decreased amount dystrophin
- much less severe phenotype
- big chunk in middle missing - still have both ends
Difference in where mutation occurs.
What is Myotonia?
Slow or delayed relaxation after contraction.
Difficulty releasing grip
Caused by mutation in chloride channel - don’t rectify flux anions after undergone action potential
What is motor neuron disease/amyotrophic lateral sclerosis?
- Progressive degeneration of CNS motor neurons
- Cause unknown
- Affects upper and lower MNs
- Uniformly fatal
Discuss polio
Paralytic poliomyolitis = viral invasion of the motor neurons
- Inflammation of nerve cells - damage/destruction of motor neuron.
- Phrenic nerve -> diaphragm -> iron lung
For 25-50% of those who recover:
- Post-polio syndrome
- Undamaged nerve begin to remodel
- Oversized motor units fail, failing synapses = degeneration
- Muscle weakness
- extreme fatigue
- paralysis
