We begin with this slide as being quite important.
Filtration barrier is what we'll set up and before
you do any of that, I am going to give you
steps that you want to take every single time.
When you see a picture like this, that is then representing
electron microscopy. Now from a bird's eye of
view, what exactly is occurring and why would
you want to use such tools at your disposal?
Well you know that the patient is demonstrating
glomerular nephritis, how? Well as we go through
the particular diseases obviously I will give
signs and symptoms. Next, well what particular
type of biopsy and imaging studies subsequently
would you want to perform so that you can
actually find the pathology? So upon biopsy,
you might want to begin with light microscopy,
which is not what is being shown here. But
light microscopy is something that will give
you a bird's eyeof view of the glomerulus and
then say that you don't find your pathology
then perhaps you go into a little bit detail
and that, of course, brings us to our electron
microscopy and that is where we are at this
juncture. What I am going to show you first
would be the normal electron microscopy of
the exchange system or the filtration system
of your fluid from the plasma. Close your
eyes. You are in the tuft of capillaries, that's
your plasma. The first barrier that you are
going to hit is what? Is that an endothelial
cell or an epithelial cell? It is an endothelial
cell. Are we clear? Because it is lining
of the blood vessel. I will show you what
they are as you move through here, just I want
to conceptualize things first. Underneath
that endothelial cell is what? That is what
we're saying here. So this would be the first
paved road and by paved road, this is the
first thing that you want to identify in electron
microscopy so that you immediately get your
bearings. The bearings here would be this
paved road and this would then represent your
filtration or your basement membrane. A couple
of things about this basement membrane that
you have learned in anatomy and then reinforce in
physio and then we'll add some pathologies
here include the fact that well and as far
as chargers are concerned, it has a negative
charge. It has to. Now, let me tell you the objective first
so that you understand this. Albumin would
be on the blood side, wouldn’t it? May I
ask you a question? Do you want albumin to
pass through? Simple question, but yet effective.
No, you don't. If you don't want albumin to
pass through, you should know the protein
as a negative charge. We've talked about such
things with the double helix of the DNA. Our
protein has a negative charge in general.
In physics, when you have two likes and charges,
what do they do? Not relationships. These
are charges, when you have two likes, they
repel. So, therefore, albumin has a negative
charge, the basement membrane has a negative
charge. Thus, what about that albumin?
It is repelled. That is one form of defense.
A second form would be well you know filtration
is taking place. The pores, the fenestrations
that exist that allow for filtration to take
place. They are quite tiny. They have to be.
So these pores and fenestrations that are quite
tiny do not allow the large albumin proteins
to pass through. Two major natural defense
mechanisms or barriers that preclude albumin
from passing through. If at any point in time,
pathologically, there is abnormality with
that pore getting larger or the negative charge
has been lost, you have now introduced albumin
into the Bowman space and you have a true
pathology and we will walk through that. So
now what we are seeing here, the blood side
is what we will talk about in the fenestrations.
In the fenestrations here then allow for filtration
to take place. Now where the fenestration
here is in reference? Now we are going to
go step by step. On the right side of this
barrier would be the endothelial cell. There
would be the blood side. Stop there, identify.
That is your blood side. In between the endothelial
cells are technically called fenestrations
and that you must understand.
Next, while you have that glomerular basement
membrane and that glomerular basement membrane
is then going to be made up of a negative
charge. When we talked about the fenestrations being
extremely, well small enough, large enough
just right where electrolytes and small amino
acids will pass through filtration. But please
understand that large protein will not.
So it is a negatively charged. It has to be.
Next on the side of the urine is where we
are here. On the side of the urine well now
we have left the blood vessel. Is that clear?
When you’ve left the blood vessel and now
you are dealing with a cell of a tissue, that
cell of a tissue is then called an epithelial
cell, isn't it? The epithelial cell and specifically
take a look, this is the visceral epithelial
cell. What does that mean? The inner layer,
the visceral epithelial cell is then called
a podocyte. I would know about the names.
Why do we call this a podocyte? What is the
profession of podiatry? Who is a podiatrist?
A "foot" doctor right. Oh! Look at your feet,
I love them so much. Anyhow, that's the foot doctor,
podiatrist. The point is this is a podocyte
and so therefore what you will find are this
foot processes. In between the foot processes
are slit diaphragms and so therefore as your
filtration now you tell me which way filtration on this electron
microscopy? What are you doing when you filter? You are moving
from the plasma into the Bowman space. On this
picture is it left to right or is it right
to left? Good. It is right to left. That is
filtration. You are leaving the plasma on
the right side, passing through the basement
membrane, and then moving through your slit
diaphragms of your podocyte. Everything that
you are seeing here is perfectly normal. I
need you to get a firm grasp of what we are looking
at with electron microscopy. What is the first
thing that you want to do? Paved road. From
the paved road, you look for the feet, the
foot processes that automatically puts you
on the urine side. We are going to keep playing
around with this and until you get this firmly implanted.
Let's move on.