Myasthenia Gravis Flashcards
What is myasthenia Gravis?
An autoimmune disease characterised by the weakness of skeletal muscle
What causes the weakness of skeletal muscle?
Autoantibodies to the nicotinic acetylcholine receptor in skeletal muscle
Therefore transmission through neuromuscular junction is decreased
State some symptoms of Myasthenia Gravis
Ocular symptoms- droopy eyelids, double vision, restricted eye vision
May also have lack of facial expression, slurred speech, difficulty chewing, weakness in limbs, SOB - if severe myasthenic crisis
What tests can be done to detect MG
-Ice test- cooling muscles improves symptoms
-Blood test for autoantibodies
-Neurophysiology- electromyogram will detect decrease in muscle response
-Edrophonium- a short acting cholinesterase inhibitor. Causes increase in muscle strength (rarely used)
Treatment for MG
Acetylcholinesterase inhibitors: (anticholinesterases)
eg: pyridostigmine
Immunosuppressives: eg steroids or azathioprine
IV immunoglobin or plasma exchange:
for rapidly deteriorating MG or myasthenic crisis
Thymectomy
What usually happens in the NMJ to create muscle contraction? (Pathophysiology)
Action potential in,
causes voltage gated calcium channels to open,
influx of Ca2+,
Ca2+ goes into synaptic terminal,
causes exocytosis of acetylcholine, acetylcholine diffuses across synaptic cleft and interacts w/ receptors (nicotinic acetylcholine receptors),
Ligand gates ion channels open allowing SODIUM into cell,
End plate potential - stimulates action potential which then results in a muscle contraction
What is different to the pathophysiology of muscle contraction in MG?
Autoantibodies cause loss of nicotinic acetylcholine receptors therefore loss of transmission across synapse
Explain how acetylcholinesterase inhibitors help MG
Acetylcholinesterases located on post-synaptic membrane.
These break down acetylcholine to terminate contraction.
Want to BOOST transmission not lose it.
So inhibit acetylcholinesterases to stop break down of acetylcholine.
More acetylcholine which stays around in synapse, allowing increase of activity, causing increase contraction of muscle.
What is acetylcholine made from
Choline and cholineacetyl transferase
What is acetylcholine broken down into
Choline and acetate
What does acetylcholine esterase do
Uptakes choline into presynaptic terminal where it can be reused
What do cholinesterase inhibitors do
Block cholinesterase -> inc. acetylcholine and prolongs action therefore increase in contraction
What are the 2 types of cholinesterase
Acetylchoinesterase
butyrylcholinesterase
Where are nicotinic acetylcholine neurotransmitters found
In skeletal muscle in the somatic efferent system
In blood vessels in the sympathetic system
In salivary glands in the parasympathetic system
What nervous system do cholinesterase inhibitors mimic
parasympathomimetic
Mimic parasympathetic NS
(rest and digest, dec. HR, constrict bronchi, gland excretion, inc. GIT motility)
