Myasthenia gravis
How a nerve signal normally crosses the neuromuscular junction with a margin to spare, why antibodies against acetylcholine receptors erode that margin, and how this causes weakness that worsens with use, often starting in the eyelids and eye muscles.
By the end, you can
- Describe transmission at the neuromuscular junction and the safety factor.
- Explain how antibodies against acetylcholine receptors or MuSK impair transmission.
- Explain why weakness is fatigable and why eye and bulbar muscles are often affected first.
- Describe the role of the thymus.
- Explain myasthenic crisis and the rationale for acetylcholinesterase inhibitors.
- Recognise the thymic and end-plate appearances, the Osserman and MGFA grades and the antibody and electrical tests of myasthenia, and explain how each main treatment acts on its mechanism.
What it is
Myasthenia gravis is an autoimmune disease of the neuromuscular junction. In most patients, antibodies against the acetylcholine receptor reduce the number of working receptors on the muscle, so nerve signals fail to trigger muscle contraction reliably. The result is fatigable weakness: muscles tire abnormally with use and recover with rest. Sensation is unaffected.
3 types to tell apart
- Ocular
- Limited to the eyelids and eye muscles; some cases later become generalised.
- Generalised
- Also involves bulbar, neck, limb and breathing muscles.
- By antibody
- Acetylcholine receptor antibodies (about 85% of generalised cases), MuSK antibodies, or no detectable antibody.
Normal function
Crossing the junction with a margin to spare
When an action potential reaches the of a motor neurone, calcium enters and vesicles release acetylcholine into the narrow cleft.
Acetylcholine binds nicotinic receptors, clustered on the crests of folds in the . The receptors open, sodium enters, and the end-plate potential triggers a muscle action potential. Acetylcholinesterase in the cleft then breaks acetylcholine down within milliseconds.
Each nerve impulse normally releases more acetylcholine, and the end plate holds more receptors, than are needed to reach threshold: the safety factor. With repeated firing, release falls a little, but transmission still succeeds every time.
Underlying change · Step 1 of 5
Antibodies against the receptor
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Underlying change · Step 2 of 5
The thymus connection
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 3 of 5
Why weakness grows with use
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 4 of 5
Eyes first, then bulbar and limbs
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Consequences · Step 5 of 5
Myasthenic crisis
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Symptoms and signs
Symptoms, signs and findings
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Exam detail
Exam detail
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Treatment
How treatment works
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Recap
Recap
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Self-check
Check your understanding
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .