In this section, we’ll take a
look at muscle pathology,
and at first, I’m going to make sure that
we walk through organization
of a few things that I feel as though are
important from anatomy and physiology
that the pathology will make
perfect sense. Let’s begin.
Classification of muscle itself—cardiac,
of course, being involuntary.
Cardiac also then being striated
intercalated discs so and so forth.
Keep that in mind.
With the cardiac muscle, the fundamental
unit is going to be the sarcomere
from Z line to Z line,
and then you have the actin,
and you have the myosin.
That is all intercellular
and this then will communicate with
the extracellular matrix
and what may then happen, since
we’re doing muscle pathology,
are some of the anchors that are
in the extracellular matrix
to keep the intracellular components
intact, might disappear.
Not only would it affect
the cardiac muscle,
but then it would also affect the skeletal
muscle when we start talking about issues
that we categorize as muscular dystrophies.
Smooth muscle also involuntary,
but the smooth muscle is a little
bit different, isn’t it?
We don’t necessarily call it from Z line
to Z line, we have these dense bodies.
Think about smooth muscle then
you need to have relaxation,
in other words, when a blood vessel
relaxes, we’ll talk about
vasodilation or if the bronchi,
then you call it bronchodilation,
and vice versa of course when it’s
contracting in other words constriction.
The skeletal muscle, and the
fundamental unit here would be
similar to that of the cardiac and therefore
when we comment to muscular dystrophies,
our discussion will not only
be relevant for the heart
but then also for the skeletal muscle.
Quickly here, to review, our muscle
and the types of muscle that you should b
referring to when you see Z line to Z line,
would then be your cardiac muscle
and skeletal muscle, correct?
What you’re seeing here on the left
is electron microscopy.
It is important that you’re
able to identify
your sarcomere on electron microscopy.
You will then focus upon the Z line
which is on the ends here
and then the Z line will then
have your titins and such
without going into too much
into anatomy and physio
which will then bond your myosin to
myosin represents a dark feature here.
You see the dark aspect of the dark band
that you see here is your myosin.
And the light, of course,
would then represent the actin.
And what you have there in the middle is
the M line and you have the H band.
Now you must know of course
that from Z line to Z line,
when the length of it becomes shorter,
obviously you’re in the process of
contracting. And when you’re contracting,
the A band will not change in length.
Because the A band will
strictly then only be
representing the myosin.
Whereas the I band, if you take
a look at the I band,
you have Z line to Z line,
which will then contract
and the I band and the H band
will indeed change in length.
Keep that in mind. The one of the
left is electron microscopy,
once you see over to the right,
focus on the A band please.
The A band is only representing
that of the myosin;
therefore, upon contraction.
The sarcomere terminology,
while the actin is important
that you know
and this will then play a role
as we begin pathology.
To review actin real quick,
it is the light portion of the electron
microscopy that I just showed you.
And the actin is the one that has
the tropomyosins and the troponins.
Once calcium ________
it will untug the tropomyosins
so that it can then bind to the
myosin heads if you remember.
The A band will then represent the dark,
in other words, only represents the
myosin and therefore will not
change in length upon contraction.
The H band was heavy chains only
and the Z line from Z line
represents the sarcomere.
The sarcomere terminology continues, the
Z line things that change with contraction
and the light bands shorten,
and this then represents the I band.
Refer to the fact that it only
represents the myosin
and does not change in length
There are particular proteins that I
want to make sure that you’re
extremely familiar with and that your focus
specifically is called to dystrophin.
Please note that dystrophin is the
one of the largest proteins
that is coded for in our bodies.
That would mean that if you have
a protein that is highly coded,
it would also mean that it’s
susceptible to mutations.
Good. So when we later on
have our discussion
of muscular dystrophies
it’s a fact that either have complete
absence of your functional
dystrophin or you might have partial
retention of your dystrophin
as we shall see.
Where is your dystrophin?
Well once you hit your dystrophin
let me set up this picture here—you have
the membrane, the transmembrane,
and we’ll be focusing
upon those subunits
specifically the beta and alpha.
They’re called your dystroglycans.
The alpha and beta dystroglycans,
the transmembrane protein
is the bridge between the
dystrophin which is
facing the extracellular
intercellularly you will then have your,
what we call, actin and company.
A combination of the two of after
dystrophin, the anchor has been lost
and you can imagine things that will take
place and that will be a discussion later,
but I want to make sure
that you’re in or updated
to what I need you to know for pathology.
Here, why do you want to know the different
types of muscle fibers real quick?
Well, it’s important.
For example, if you have a lady,
less than 37 years of age
and she wakes up in the morning and she
feels okay, but then around
let’s say 11 or 12 she works
in front of a computer all day
and she’s an assistant what have you,
and she says that she’s
having a hard time seeing,
and now you ask yourself, what’s going on?
And then later on at 4 o’clock
maybe she has a hard time just moving,
having a hard time just
getting out of her chair.
So you do need to ask yourself of what
kind of muscle fibers are being affected
and why is the patient then having
difficulty seeing at 11 or 12 o’clock
The reason for that is the eyelids
are your fast-twitch
fibers—over to the right
Type II muscle fibers are fast twitch.
The first type of muscle fiber
to be affected in the lady
with the type of diagnosis that she
has is called myasthenia gravis.
Myasthenia gravis syndrome as
we shall also discuss later,
the eyelids which are, in general,
the fast-twitch muscle fibers
will be affected first.
Now before I move on, the opposite
of your fast twitch
obviously would be slow twitch,
and a cute little mnemonic that I like using,
and you can use whatever you wish,
is I—Type 1—red, or RED
or RED meaning aerobic
glycolysis hemoglobin being
supplied to that muscle slowly.
In other words, Type I muscle
fiber is a red muscle fiber,
, it is slow muscle fiber.
If it’s not Type I, it’s Type II.
If it’s not red then it’s white.
If it’s not slow then it’s fast.
Welcome to Type II.
Without going into further detail,
I just want you to once again to
have a comparative table
to review between Type I and Type II
without getting into too much physiology
so that you’re clear and understanding that
that you have Type II muscle
fibers that are fast twitch,
lots of ATPase activity,
and so therefore can fatigue
very, very quickly
such as the eyelids; therefore, are one
of the first type of muscle fibers
that are affected in condition.
Now muscular dystrophies
is what we look at first.
It’s a genetic issue most of them
tend to be exocrine related.
Characteristically degeneration of not
just skeletal muscle but then also
cardiac muscle because of the similar,
as I showed you earlier,
microscopic features of Z line
to Z line sarcomeres.
Now, because the muscles then are being
broken down, obviously the enzyme
that you’re expecting to then see to be
elevated would be creatine kinase.
A differential, or how it’s differentiated,
would be based on the age of the patient
and when the onset of the disease was,
what kind of muscles are involved, and what
is the mode of inheritance is important.
Now you will have deletions
that take place in both,
and by both, we will be focusing on two
major muscular dystrophies
and then we will end by looking
at myotonic dystrophy.
And as the order in which we will walk
through muscular dystrophies,
the nonspecific degenerative
changes in biopsy include
replacement of that muscle
with what’s known
as fibro fatty tissue. We then
call this pseudofat.
So you have the, let’s say
or the calves in which
it is then replaced by
fibro fatty changes, in other words,
is what it’s referred to.