light microscopy H&E, we have immunoflurorescence,
and number 3 electron microscopy. Let's move on.
Here in a cartoon form, we are showing you pathogenesis
of glomerular disease and I will show you
two major issues. The first one that you are seeing here,
let me just set up this picture. This picture
that you are seeing is the glomerulus.
Next, what you are seeing there in blue, purple?
That is going to be your podocyte. How can
you confirm that? A podocyte should have food
processes. You see that box around that podocyte
in that blue cell. We are going to take that section
and we are going to blow it up over anterior
right. So now we have amplified it or blow it
up, and that dark blue structure or the violet
structure that we are seeing is a huge podocyte
with a nucleus. And then we are seeing food
processes. Identify those first. Next, you
see that orange line. It looks like paint
or if you take a brush looks like you paint
it with an orange brush. Well, that's your glomerular
basement membrane, isn't it? So now what we
do is along with that orange line, which is
your glomerular basement membrane and the
epithelial cell, are you either going to deposit
some of these immunoglobulins either underneath
the epithelial site or you are going to deposit
it where? Underneath endothelial site. And what
you are clearly seeing here, ladies and gentleman
is immune complexes that are being deposited
underneath the endothelial cell. Between the
endothelial cell and the basement membrane
on that first picture where it's circulating, you
noticed that that is a subendothelial deposit.
First and foremost, would light microscopy
show you this? No. Would electron microscopy
show you this? Absolutely. And number 3, immunofluorescence,
but then recognizes beign what kind of pattern?
Granular. Let us now move
into the membrane a little bit. The one in
the middle that you see there is you have
immunoglobulins and what do these immunoglobulins
do? These immunoglobulins are literally only
attacking the glomerular basement membrane.
That is it. We will call this in situ. What
does in situ mean? Membrane. Doesn't it?
So literally here all you have is immunoglobulins
that are attacking some antigen of my glomerular
basement membrane. This is a type II hypersensitivity.
This is antiglomerular basement membrane diseases.
There are no complexes that are being formed
and no deposits. So, therefore, on let us
say electron microscopy, maybe you find changes within
the membrane. Great, but then here, immunofluorescence.
Immunofluorescence will show you, you see that
orange basement membrane are completely containing
immunoglobulins. So, therefore, the entire
basement membrane is going to be "laid up."
So this gives us our linear pattern. Then,
moving over to the far right, the two things
that are occuring here. Take a look at the
difference between the one on the middle and
the one on the right. The one on the right,
not only are you attacking the membrane, but
where else are you depositing? It is depositing
underneath what is that blue cell that we
called earlier? That is a visceral epithelial
cell. That is a podocyte and so, therefore,
the fact that you have involvement of the
membrane and you have deposits underneath
the epithelial cell. This is no doubt membranous
glomerulonephritis, involvement of the membrane
in what kind of hump or deposit? A subepithelial
deposit. So therefore, electron microscopy
would be relevant here and immunofluorescence
will show you what? A granular pattern.
Through these pictures on immunofluorescence
will then give you granular pattern, which
two? The one on the left with subendothelial,
the one on the right with subepithelial and
the one in the middle immunofluorescence would
be what pattern? Linear. Just
to make sure we have complete our discussion.
If you take a look at the big picture on your
left of the entire glomerulus or a section
of the glomerulus, the middle there that you
are seeing in green is a mesangium. And then
just to make sure we're clear that orange cell
that we're seeing with subendothelial is the
endothelial cell and so therefore that would
be your capillary lumen. Everything is in
properly annotated here. Spend a little time.
Make sure that you take a look at the text
from the previous discussions, arrive here,
take a look at the picture and let's now
continue forward with more pathology.
So real quick, let me just have your highlight subepithelial
deposit. Take a look at it. Underneath the
epithelial cell maybe immune complexes, what
would you then call this? Immunofluorescence.
This would be granular. On the bottom, subendothelial.
Underneath the endothelial cell, immune complexes
once again granular. Everything else has been
properly annotated here for you. These are
circulating in immune complexes. Let me give
you an example now. Let us build down a little
bit of foundation. Subepithelial, I will give
you PSGN, which one? Post-streptococcal glomerularonephritis,
subepithelial. Subendothelial would
be something like a SLE prototype known as
DPGN, diffuse proliferative glomerularonephritis.
How did I know that? Years and years and years
of learning and practicing. You will get this
done as well in which at that point you might
have to memorize a little bit. Here strictly
what are you doing? The immunoglobulins are
attacking the basement membrane only. May
I ask you something? Do you find any immune
complexes here? No. So therefore, on immunofluorescence,
what kind of pattern would you call this?
Very good. Linear. Welcome to Goodpasture,
type II hypersensitivity. And then finally
a picture here is showing you not only involvement
of the membrane. Take a look, but then also
what kind of deposit would you call that underneath
that epithelial cell? Obviously, it is subepithelial.
What would be my diagnosis here? Take a look. This
is membranous glomerulonephritis. Further
exapanding upon the overview picture that
we began with and then further dissecting
into each individual pathologies.
Type III hypersensitivity, immune complexes.