Here we’ll take a look at muscle pathology
but the focus here will be
the neuromuscular junction.
So please picture neuromuscular junction.
So we have a nicotinic receptor, and in
your head, you should be thinking about
the presynaptic terminal of the nerve
which is then communicating with
the motor end plate. In other words,
the skeletal muscle.
In that presynaptic termina l, we have a
vesicle and in that vesicle we have
So the 2 major neuromuscular junction
diseases that we’ll take a look at,
myasthenia gravis and myasthenia
So here’s a young lady, maybe 37 or so,
and I told you that
at about 8 o’clock in the morning, she’s
getting ready for work and she feels okay,
but about 11 o’clock or 12 o’clock,
she walks in—she’s a secretary for
for an executive what have you—and
she works in front of a computer,
and she has a hard time seeing because
the first type of muscle fibers
to be affected in myasthenia gravis
are of what type again?
The fast-twitch called type 2.
So if those type 2 muscle fibers
are becoming weakened
then this patient is having a
hard time seeing the screen.
Then at about 3 o’clock or 4 o’clock,
she is having a hard time getting out
of her chair,
and you ask yourself, why? Why am
I giving myasthenia gravis in the lady?
Well, give me one second.
Say you have proximal muscle weakness
and such that is taking place.
The proximal muscles are affected first
in myasthenia gravis—difficulty getting out
of chair. That’s your presentation.
Now, this lady comes in with this
presentation, do a chest x-ray,
and oh my goodness! You find in the middle
of the chest of a 37-year-old female,
an enlarged thymus. Excuse me,
but you and I as an adult—as a thymus—it
should be involuted. It should be gone
The education of your T cells has been
completed when you are a child.
So our thymus should be involuted.
[Inaudible 00:01:55] gone.
You have a lady adult who has a thymoma
no doubt, you’re thinking autoimmune disease.
Hence, I’m giving you a young lady.
Now could that be a male? Sure, absolutely,
but more commonly in a young lady.
Now thymoma—let me give you
another rule of thumb.
Whenever you hear thymoma, then you should
be thinking about autoimmune diseases,
One would be myasthenia gravis,
but if there is thymoma and
susceptibility to infection,
and there’s hypogammaglobulinemia,
that’s called Good Syndrome.
Or let’s say that you have a thymoma
in which the patient now presents
with fatigue and tiredness,
that’s called pure red blood cell aplasia
the only cell to be effected is RBC.
From now on, in general,
you hear about thymomas,
you should be thinking
Now what happens now in myasthenia gravis,
and why there’s this pattern
that I just gave you
of tiredness and weakness,
is the fact that it is these autoantibodies
that are attacking
and trying to destroy the
on the postsynaptic terminal which is
located on the skeletal muscle.
If acetylcholine receptors
are being destroyed,
like target practice—boom!
Boom! Boom! Boom! Boom!
The more number of receptors that you’re
destroying and then you are, cannot
then form an end plate potential. In other
words, you can’t have a depolarization.
If you cannot have a depolarization, how
in the world are you supposed to have
an action potential? Right?
So what are things that you’re
going to do to identify
[Inaudible 00:03:39] doesn’t mean all
receptors have been destroyed.
But what if there was a method
that you could test
and you activate those receptors?
If you activate those receptors, then maybe
perhaps you will find movement.
Keep that in mind. So the weakness
has intensified by use.
That’s important because you’re going to be
comparing myasthenia gravis with what?
Lambert-Eaton myasthenia gravis syndrome.
So here, in myasthenia gravis, with use,
it’s the patient that is feeling tired
and recovers upon rest
3 in 100,000 would be the epidemiology.
The prevalence, as I’ve told you, would
be much more in women
because of its autoimmune
nature—less than 40 years.
If it is a male, by chance,
affected greater than 60.
Pathogenesis. You have the
that are then attacking the
and surgically, there’s a possibility that
the thymus may then be removed
resulting in a thymic remnant.
And by doing so,
you are now actually improving the
patient’s signs and symptoms.
So the thymus is [Inaudible 00:04:47]
to type 2 hypersensitivity,
[Inaudible 00:04:51] toxicity,
try and go after those
The pathology here [Inaudible 00:05:04]
that the type 2 muscle fibers
will be affected first.
What kind are these? Fast, white
ATPase—lots of it.
For example, the ocular muscles.
There is absent simplification
of the motor end plate,
what does that mean?
It means that the acetylcholine receptors
are being knocked out,
and depending as to the severity
of the disease,
you will still have residual
[Inaudible 00:05:33] simplified.
Let’s go ahead and take a look at
that neuromuscular junction.
On the left, is normal.
So what is that that you see here?
The bulb which is coming down?
The bulb that you see coming down or the
flask, or whatever you want to call it,
it’s the presynaptic terminal,
and at the presynaptic terminal, you’ll
then notice you have these vesicles.
Inside those synaptic vesicles, of course,
is your acetylcholine.
What then allows for the vesicle to fuse
with your presynaptic membrane?
Help me out here.
Good. Voltage-gated calcium channels.
So the voltage-gated calcium channels
where are they located?
Not on the bottom structure—the bottom
structure, what is that?
That’s your motor end plate.
What does that mean?
That’s your skeletal muscle .So we’re
trying to have movement—motor end plate.
So the voltage-gated calcium
channels are on the
the presynaptic terminal, on the flask,
but then opens up the calcium channel.
Voltage coming from where?
The axon up above.
So the action potential is going to
come down the axon,
come down through the
presynaptic terminal and then open up
that voltage-gated calcium channel.
The calcium, of course, rushes in
allowing for fusion of the synaptic
vesicle that you see there.
With the membrane, and out then comes whom?
That acetylcholine is then going to bind to
the acetylcholine receptor and
open up what kind of channel?
[Inaudible 00:07:14] sodium channel.
The [Inaudible 00:07:16] acetylcholine
and the receptor, of course,
being on the skeletal muscle.
You have now created what?
An end plate potential,
and once it hits threshold and
have an action potential,
it is then going to travel across the wings
[Inaudible 00:07:32] that you see here.
You have an action potential
that is then going across
or propagate across the sarcolemma.
That’s normal on the left.
So what happens in myasthenia gravis
syndrome on the right?
You’ll notice autoantibodies
with the thymic hyperplasia
thymoma that is indicated
and these are antibodies are then going
to attack acetylcholine receptors,
making it very difficult
for acetylcholine to bind
o the receptors,
making it almost downright impossible
for sodium to come in so that you
can have an action potential.
If you don’t have an action potential,
does action potentials that should
be moving across the flask
through the sarcolemma.
In physio, remind me, where
should it be entering?
Obviously, that picture is not seen
here—we’re doing pathology.
And once it enters the T-tubule, it is
then going to communicate with,
remember the [Inaudible 00:08:35] receptors,
and we’re going to then bring
about a contraction.
So that, all important.
Junction in communication between
when it’s not happening, you’re
not having a contraction.
What type of muscle fibers
will be affect first?
Type 2, your fast-twitch. I gave you
the ocular muscles.
And what to test that you
may want to provide
or administer so you can find
increase in strength?
Do you have any problems with
The problem is it can’t bond
to the receptor.
What if you were able to give a drug
in which you inhibited the
enzyme in that cleft?
Remind me what the name of that enzyme and
that cleft that breaks down acetylcholine?
So what if you were able
to give a short-acting
such as edrophonium
in which you increased the concentration
of acetylcholine in that cleft?
It’s possible that the acetylcholine
might then linger around
and find a receptor that may
Then giving you for that
brief moment in time,
when you’re given that drug,
an increase in strength,
and by doing so, you’ve confirmed
myasthenia gravis. Haven’t you?
Here’s your full picture of
normal on the left
and on the right what’s happening
with a hypersensitivity
called myasthenia gravis syndrome.
One other thing that I wish to bring to
your attention before we move on,
what are the names of the receptors on
the presynaptic terminal again?
Voltage-gated calcium channels.
Give me pathology in which those voltage-gated
calcium channels will be affected
and we’ll discuss coming up?
That would be Lambert-Eaton
myasthenia gravis syndrome.
You will be spending time there.