Question regarding Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome

[sylhet]

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In a myasthenia gravis patient, the weakness does not improve with exertion. why so? And why in Lambert-Eaton myasthenic syndrome patient it does improve with exertion? 😕

 

[Phlame217]

Typical Myasthenia Gravis = antibodies to muscarinic ACh receptors; therefore the Abs act as a noncompetitive inhibitor and no matter the ACh release, the message isn't getting through.

Lambert-Eaton myasthenic syndrome is a syndrome of not releasing enough ACh. By exerting more effort, you will get up-regulation of post-synaptic receptors so it takes less ACh to trigger the proper response; you may also get some reversal of the low ACh release.

 

[norealname]

In Myasthenia, you have antibodies blocking the ACh-ligated Na channels of the muscle. No matter how much effort you spend, the ACh released from the nerve terminal cannot bind its active site on the channel. Eventually, the amount of ACh vesicles in the nerve terminal will decrease from the repetitive effort, and the muscle contractions will gradually weaken.

In Lambert-Eaton, the antibodies prevent calcium entry into the nerve terminal and therefore inhibit the release of ACh vesicles. The more effort you spend here however, the more calcium will start to accumulate inside the nerve terminal and the easier it will be to release the ACh vesicles. This is why the contraction force gradually strengthens in Lambert-Eaton.

 

[OveractiveBrain]

In a myasthenia gravis patient, the weakness does not improve with exertion. why so? And why in Lambert-Eaton myasthenic syndrome patient it does improve with exertion? 😕

The point both explanations have missed is that you have a preset, determined number of ACh vesicles at the presynaptic terminal.

In Myasthenia, to order to overcome the antibodies on Ach-R on the other side of the terminal, you have to have an overwhelming amount of Ach. You can get that. But only on the first contraction. Subsequent contractions that rapidly sucede one another do not give the presynaptic neuron ample time to reform, rebuild, or synthesize new Ach vesicles. All the neuron can do is try to keep up with the stimulus, dumping less and less Ach into a synapse that requires large amounts.

Take a look at this: You need 4 blocks of Ach to get a contraction to work. This is what happens on subsequent contractions.

1st.....2nd.....3rd.....4th
_
|.|......._
|.|......|.|......._
|.|......|.|......|.|......._
|.|......|.|......|.|......|.|

Less blocks, less contraction

OK. Now lets talk about Eaton-Lambert. Still a fixed number of Ach vesicles. Only this time, there is no Antibody to overcome. The normal amount of Ach in you and me will also induce a contraction in these people. The problem is, they've got no "RELEASE!" signal. This is because the calcium channels that conduct the action potential are blocked. With repeated contraction, you open more and more calcium channels. Eventually, WHAM! action potential propagates, Ach-vesicles fuse, Ach is released, and Ach-R (which are normal) induce a contraction.

Now, you only need 2 blocks to get a contraction (since there aren't any antibodies to compete with). But look at the ordering (ASCII made the mirror image look like garbage, so I had to renumber only). The LATER stimuli have enough to induce the contraction, and the last is the STRONGEST. The exact OPPOSITE of Myasthenia.

4th.....3rd.....2nd.....1st
_
|.|......._
|.|......|.|......._
|.|......|.|......|.|......._
|.|......|.|......|.|......|.|

Both of the posts above mine are correct, but they are just the definitions. The same definitions that likely led the OP to ask in the first place. Hope this helps illustrate WHY.

 

[sylhet]

The point both explanations have missed is that you have a preset, determined number of ACh vesicles at the presynaptic terminal.

In Myasthenia, to order to overcome the antibodies on Ach-R on the other side of the terminal, you have to have an overwhelming amount of Ach. You can get that. But only on the first contraction. Subsequent contractions that rapidly sucede one another do not give the presynaptic neuron ample time to reform, rebuild, or synthesize new Ach vesicles. All the neuron can do is try to keep up with the stimulus, dumping less and less Ach into a synapse that requires large amounts.

Take a look at this: You need 4 blocks of Ach to get a contraction to work. This is what happens on subsequent contractions.

1st.....2nd.....3rd.....4th
_
|.|......._
|.|......|.|......._
|.|......|.|......|.|......._
|.|......|.|......|.|......|.|

Less blocks, less contraction

OK. Now lets talk about Eaton-Lambert. Still a fixed number of Ach vesicles. Only this time, there is no Antibody to overcome. The normal amount of Ach in you and me will also induce a contraction in these people. The problem is, they've got no "RELEASE!" signal. This is because the calcium channels that conduct the action potential are blocked. With repeated contraction, you open more and more calcium channels. Eventually, WHAM! action potential propagates, Ach-vesicles fuse, Ach is released, and Ach-R (which are normal) induce a contraction.

Now, you only need 2 blocks to get a contraction (since there aren't any antibodies to compete with). But look at the ordering (ASCII made the mirror image look like garbage, so I had to renumber only). The LATER stimuli have enough to induce the contraction, and the last is the STRONGEST. The exact OPPOSITE of Myasthenia.

4th.....3rd.....2nd.....1st
_
|.|......._
|.|......|.|......._
|.|......|.|......|.|......._
|.|......|.|......|.|......|.|

Both of the posts above mine are correct, but they are just the definitions. The same definitions that likely led the OP to ask in the first place. Hope this helps illustrate WHY.

wow! this is excellent explanation. i am extremely sorry for my late reply , i just lost my hope that i wont get any ans that would satisfy me. but i got it now. thanks very much!!