Muscles and the Neuromuscular Junction Flashcards
(43 cards)
What symptoms and signs are usually present in a lower motor neuron disorder?
Weakness
low muscle tone
fasiculations
What symptoms and signs usually present in an upper motor neuron disorder?
Stiffness
Spasticity
Increased tone
Neuromuscular junctions (NMJ) join which two parts of the peripheral nervous system?
Motor neuron + muscle
What name other than NMJ is given to the synapses formed between motor neurons and muscle?
motor end plate
Describe how Acetylcholine is released into the NMJ?
AP at presynaptic membrane Ca2+ influx Vesicles of ACh released This diffuses across synaptic cleft Picked up by ACh receptors Opens Na/K channels to depolarise post-synaptic membrane AP generated
What toxin is known to cause complete failure of muscular contraction and what are the consequences of this?
Curare
- causes respiratory failure
Give examples of pre-synaptic causes of NMJ dysfunction
- abnormality of Ca2+, Mg2+ or Na+ channels
- Clinical botulism
- lambert-eaton syndrome
How does botox affect the pre-synaptic terminal involved in muscle contraction?
- block vesicle docking in presynaptic membrane
=> Rapid onset weakness without sensory loss.
How does Lambert-Eaton syndrome affect the NMJ, and what could be an underlying cause for this?
- antibodies to pre-synaptic Ca2+ channels
=> less vesicle release
Strong association with small cell carcinoma
Is Myasthenia Gravis a pre-synaptic or post-synaptic disorder of the NMJ?
Post-synaptic
Explain the pathophysiology of Myasthenia Gravis
Autoimmune - antibodies to acetylcholine receptors
=> Reduced number of functioning receptors
=> muscle weakness and fatiguability
What percentage of receptors remain to be working when symptoms start in myasthenia gravis?
symptoms start when ACh receptors reduced to 30% of normal
Why do patients with myasthenia gravis often have a “Square smile”?
They have bilateral facial weakness
Why may patients with myasthenia gravis appear to have excessive wrinkles on their forehead?
They have ptosis of the eyelids
=> are holding their eyebrows up high to keep eyes open
What percentage of myasthenia gravis patients are found to have antibodies against ACh?
80-90%
What other structure in the body can contribute to myasthenia gravis?
Thymus => 75% patients have hyperplasia or thymoma
- removing thyroid can often reverse disease in these cases
What is the female:male ratio of patients with myasthenia gravis and at what age does incidence of the disease in each gender peak?
female:male ratio - 3:2
females in 30s
males in 60s-70s
What symptoms do patients with myasthenia gravis usually notice?
- Weakness - gets worse through the day
=> give up chewing food, keeping eyes open - extraocular, facial and bulbar weakness
- Limb weakness typically proximal
How is myasthenia gravis treated acutely?
ACh inhibitor - Pyridostigmine
IV immunoglobulin to mop up Antibodies
Thymectomy
What long-term treatment is available for myasthenia gravis?
- immunomodulating
- steroids (prednisolone)
- Steroid sparing agents (these take 12 weeks for peak action to occur) e.g. azathioprine, mycophenelate
- Emergency treatment = plasma exchange or IV Ig
What clinical features of myasthenia gravis are most likely to cause morbidity?
respiratory failure and aspiration pneumonia
What drug can potentially precipitate myasthenic crisis
Gentamicin
What is a fasiculation of muscle?
Visible, fast, fine , spontaneous twitch
When are fasiculations of muscle usually seen?
Physiologically => in healthy muscle – precipitated by stress, caffeine, fatigue (after exercise etc)
Occur in denervated muscle which become hyperexcitable
=> more a problem with motor neuron than muscle
