around with this and until you get this firmly implanted.
Let's move on.
The structure of the glomerulus, we talked
about the fenestrations. The fenestrations
if it is on the side of the endothelial side
well that allows for filtration to take place,
these holes. If it is a glomerular basement
membrane, what is the basement membrane always
made up of? Four the floor, collagen type.
Collagen type IV, collagen makes up the floor.
In other words basement membrane. Why is that
important? You know pathology or you will
know pathology in which that collagen type
IV ends up being deficient, is that clear?
Which one would that be? Something like output.
You have heard of that before. An output syndrome
you are literally missing type IV collagen.
Obviously, we will discuss all this and I
don't think we are going to have issues with
the basement membrane of your kidney, but
then you also have basement membrane issues
in the ear, don't you? With output. Of course,
you do. Kidney and deafness, that is output.
Let's us continue. Size and charge we talked about
earlier. What is the charge please at the
basement membrane? Negative, has to be.
What is it that contributes to the negative
charge? Called heparan sulfate. You noticed
that I dramatically pronounced heparan and the
reason for that, don't confuse this with heparin.
So heparan. Sometimes I just crack myself
up just because of learning purposes.
But anyhow this is heparan sulfate, not the drug
heparin. What does it do? It contributes to
the negative charge. Let us continue. Cationic,
protein, low molecular weight are permeable.
Is that clear? It has to
be. You can get little proteins through there,
but not large proteins like albumin. Next
question obviously is going to be the following.
If by chance albumin does pass through the
filtration barrier into the Bowman space,
would you tell me what Starling's force has been affected?
Question number 1. Oncotic pressure.
Good. Next, if oncotic pressure has been affected,
is it increased or decreased into the Bowman
space? Good. It is an increase in oncotic
pressure. Good. And normally you shouldn't have
oncotic pressure in your Bowman space. You
see the terminology there. I was asking about
the Bowman space and not the glomerular capillaries.
Let us continue.
Structure. Albumin, strong negative, not permeable.
Loss of the negative charge allows for maybe
albumin to get through. Now what I need to
be clear here as well is nephritic or nephrotic
if there is glomerular damage, obviously,
there would be. Then albumin would be passing
through both the nephritic and nephrotic.
But the abundance would be much greater in
nephrotic. Hence, you will focus upon the letter
O, and nephrotic referring to protein.
Well, selective proteinuria and that, of course,
would be something like minimal change disease
being the most common cause of nephrotic and
glomerular nephritis in children. Glomerular
basement membrane could be permeable to water.
Why is it permeable to water? And as far as
low molecular rate, hypertension, amino acids.
Amino acids as you know can be filtered through,
but not albumin. Causes of glomerular basement
membrane, thickening is what the next step
is and so close your eyes. I showed you on
the previous discussion of electron microscopy
with that glomerular basement membrane. It
is thickened. How do that occur? Maybe it
is immune complex deposition. And when you have
immune complex deposition, it might either
be underneath that epithelial cell. What is
the name of that epithelial cell? A podocyte.
What kind of epithelial cell technically?
A visceral epithelial cell. If it is underneath
that epithelial cell, what is? An immune complex.
Let me give you an example such as post-streptococcal
glomerulonephritis secondary to perhaps a
pharyngitis or maybe even a skin infection.
We've talked about all this, just process of reinforcement,
but I need to give you a clear story as to
what we are headed. Anyhow when you have
post-streptococcal glomerulonephritis, you
have these immune complexes that are then going
to deposit where? Underneath the epithelial
side. Epithelial, you call that subepithelial
deposit. I will show you pictures. How
else can you thicken your glomerular-based membrane?
Literally collagen type IV ends
up undergoing proliferation. Example, diabetes
mellitus. Would you expect your type IV collagen
to be thickened? Sure. Could you have involvement
of mesangium? Sure. What is that called when
you have light microscopy at diabetic nephropathy?
It is called a Kimmelstiel-Wilson nodule.
I will show you pictures there as well. Says
you can see here it is the clinical anatomy
that you start off with being normal and then
the physiology that we have talked about prior
and then bit by bit by bit, we are going to
stop plugging in our pathologies as we have
been doing the entire time.
Let us talk about the podocyte, shall we?
What does that call? A visceral epithelial
cell. Close your eyes or go back to that picture
of electron microscopy where you can clearly
see that podocyte. That podocyte has foot
processes. What about these foot processes?
If they get fused, a couple of differentials.
Couple? That was only one, Dr. Raj. No,
they are a couple. The first major fusion of foot
processes that you know is minimal change
disease in that child. At some point in time,
when our discussion takes us into focal segmental
glomerulonephritis, could you perhaps find
a fusion of your foot processes? Yes, you
can. What if the foot process would become,
the pores get larger in between the foot processes?
That's you are thinking about along the lines of
glomerulonephritis. The slit pore between
the podocyte allow for passage of water and
small amino acids, electrolytes serves as
a distal barrier preventing protein loss
in the urine. That is important. Fusion of
foot processes could be seen in nephrotic
syndrome such as minimal change disease. Let's talk
about the mesangium. What does mesangium mean?
You know that tissue in between the glomerular
capillaries and the tuft of capillaries, all
that tissue in the glomerulus. Think of this
as being smooth muscle, please. This is called
mesangium. The mesangium just like you would
talk about any type of tissue in an organ,
such as the interstitium. Here we will provide
support to the structures surrounding the
tissue. This would then include the glomerular
capillaries. Mesangium can release inflammatory
mediators and proliferate. This then brings
us to once again the discussion of diabetic
nephropathy. So apart from your glomerular
basement membrane, which undergoes thickening,
the mesangium could also get involved and forms
that huge Kimmelstiel-Wilson nodule. In the
mesangium, you could also deposit immunoglobulins
pathologically. The most famous of them all
would be IgA. So this then brings us to a
diagnosis of IgA nephropathy. You might have
heard of this in your medical education as
Henoch-Schonlein purpura or you might have
heard of this being Berger. What is the difference?
You have think to yourself that both pathologies are involved
with IgA? Sure. So what is the difference between
Berger and Henoch-Schonlein purpura? Hence,
nowadays, we have got rid of the
eponym, the names per se, and we are strictly
going into the pathology, which I love because
then the pathology gives you exactly what
you need to know for diagnosis without any
confusion. But the difference is the following.
When you have Henoch-Schonlein
purpura, could you have IgA deposition in
mesangium? Yes. If it is Henoch-Schonlein
purpura, what does purpura represent? You
have heard of palpable purpura and that palpable
purpura is referring in the lower extremity,
most likely a child, in the buttocks or in the
lower extremity in which blood vessel undergoes
inflammation and so therefore may result in
a little bit of hemorrhage. That is called
purpura, palpable. So Henoch-Schonlein purpura
is referred to as IgA vasculopathy technically.
Is that clear? In addition though, you could
also have IgA deposition in your mesangium,
that must be understood. We will talk about
that again later reinforcement, but if it
is strictly only IgA deposition in the mesangium
of the kidney, without IgA deposition anywhere
else. This is Berger. Hence, now we call
this or have been calling this IgA nephropathy.
Do you want to know that? Yes, you do. The most
common worldwide glomerulonephritis is your
IgA nephropathy. Let's move on.
We are going to the parietal cell. What does
that mean to you? Parietal always means outer.
Visceral means inner. What was the other name
or the most infamous name of the visceral
epithelial cell? Well, it is more commonly called
or popularly called your podocyte at your
visceral? So which one is your parietal? Well, let me
give you the example of your diagnosis.
In that way you clearly see what the heck
a parietal epithelial cell is. If you had
a patient that has pharyngitis in a child
that was inadequately treated, two to four
weeks later ends up developing hematuria, and
you would tell me at this point high in your differential
would be post-streptococcal glomerulonephritis.
Oh! my goodness. Within 12 weeks, the kidney
is dead. Twelve weeks is only four months.
That is not a chronic renal failure. It is
not an acute renal failure. It is rapidly
progressive glomerular nephritis. We will
talk about this again. The reason I bring
this up is the following. If you would take
a look at light microscopy of your rapidly
progressive glomerulonephritis, can you close
your eyes or conceptualize to tell me as
to what is proliferated within the glomerulus?
You've heard of crescentic cell, haven't you? Thus
crescentic cells are these, the parietal epithelial
cells that are proliferating causing massive
damage to the Bowman space. So it lines the
Bowman's capsule. Imagine that proliferating.
You have obliterated the Bowman space. What
happens to your kidney? Dead, really quick.
The proliferation causes crescents that encroach
upon and destruction of the glomerulus.
How quickly can the kidneys die of RPGN? Within
12 weeks. That is not a lot of time. It is
only about three months. Let us talk further
about our glomerular anatomy, that is relevant