Glomerular Filtration Barrier (Part - 4) Video Lecture - MBBS

so this is the lecture number four for
the glomerular filtration barrier and we
have talked about the context we have
talked about the glycosaminoglycans we
have talked about the collagen four and
the formation of it in our previous
lectures so today we will be talking
about the components of the glomerular
filtration barrier so the first
component is endothelium so really
remember filtration barrier on the
vascular side has a capillary and the
capillary are usually single cell thick
structures which have endothelial cells
lining them so like other capillaries
the the glomerular capillaries are also
fenestrated now I hope you know that the
capillaries could be fenestrated or the
may or may not be fenestrated so like
other fenestrated capillaries thicker
murder the police are also fenestrated
the important thing to notice that the
glomerular capillary fenestrations
do not have a diaphragm on them so they
do not have any company so if you look
at this fenestration over here this when
fenestration does not have a covering on
it there is no diaphragm or the low
membrane covering these holes so that is
one important thing the other thing is
that the fenestrations or these holes in
the endothelial cells these are physical
holes in the cell their size is larger
than the fenestrations in the other part
of the bodies capillaries so their size
is usually 8200 nanometers if you see
the other fenestrated capillaries their
size where the fenestrations are 30 to
60 nanometers then as we have been
building up a context these endothelial
cells here they have glycosaminoglycans
and proteoglycans attached to them so
these cells they have glycosaminoglycans
attached to them cell of glycoproteins
other glycosaminoglycans of course when
they are attached to them that would
cause negativity and the negatively
charged proteins they cannot pass
through this so please remember this
thing that we have talked about it in
our context now the albumin size is
about 3.5 nanometer and this hole over
here defenestration these fenestrations
are about 100 nanometers so albumin can
very easily pass through them and
usually it does pass but this negativity
which is present here the glycocalyx or
the glycosaminoglycans of the
proteoglycans which are present here
with this negativity they will try to
repel the protein away so that is one
defense that is why we say that the
barrier itself is size and charge
barrier so here if you see the size is
not doing a lot of function here because
it would allow the albumin to pass
through it but the charge is what would
repel the LP mean away now continuing on
with the endothelium the other thing to
notice that we have VEGF signals from
the poorer sites which are really the
outer layer so outside the capillary we
have the epithelial cells called the
poorer sites so these photo sites
release VEGF which then causes the
development of the fenestrations so the
fenestrations are a desert of VEGF
signal so you can ask me here that why
am i talking about a VEGF signal here
well the importance is this that in
certain clinical settings these photo
sites they get damaged such certain
pathological settings and when they are
damaged they cannot form the VEGF
signals and so in turn the the
fenestrations in the capillaries they
reduce and so the Mariner function
reduces the other interesting thing is
that these cells have water channels in
them you know just like the nephrons
they also have water channels through
them and so they have aquaporins the
and these cells have integrins which
allowed them if you see here in this
diagram this is a and bacterial cell and
outside the cell there is a basement
membrane so this cell is bound to the
basement membrane we are the integral
proteins so integral proteins are also
present which connect these cells to the
basement membrane outside now clinically
this is a very important piece of
information
because the in diabetics the glucose can
come and be attached to these cells so
remember that we already have glycocalyx
over here so we already have glucose
attached here but in certain cases in
diabetic cases when the glucose amount
is more inside the blood that forces the
glucose to sit on the surface of the
endothelium this is this process is
called non and non enzymatic
glycosylation or it is also called
glycation so when glucose is attached to
some structure through a through an
enzyme that means a normal attachment we
call it to be glycosylation but if
glucose is forced onto a surface and
just attaches there without any enzyme
that means it attaches there abnormally
that is called glycation so of course in
case of diabetes there is enough glucose
running around in the blood which goes
and settles on the surface of the
endothelium and that causes the age and
Raw's and these are the advanced
glycation end-products
these are the aged andross are the
reactive oxygen species so what happens
is that when glucose settles on the
endothelium it damages the endothelium
plus it creates the intracellular
signals which creates the reactive
oxygen species the end result is that
this cell would get damaged and then we
would replace it with a scar cell where
a damaged cell would not be able to
perform good good function for a
glomerular
filtration so now we understand the
characteristics of the endothelium these
are these this is fenestrated in
endothelium but the fenestration does
not have a diaphragm on them the
fenestration size is from 80 to 100
nanometer that is larger than the usual
which is 30 to 60 these fenestration of
these cells have glycosaminoglycans
attached to them which allow the
negative proteins to be repelled away
from them then the fenestrations appear
in these endothelial cells because of
the VEGF signals these VEGF signals are
actually brought in or sent by the
epithelial cells or the porta sites and
then we also have the aqua purines which
are the water channels and we have
integrins
remember the water channel are here
because this is a filtration system and
the water has to be moving from the
vascular system outside into the
Bowman's space so presence of the
aquaporin only increases the movement of
the water and then we also talked about
that in clinical or that in pathological
settings for the diabetics we get the
glycation and we try to clear up that
what is the difference between glycation
and glycosylation glycosylation is the
normal glucose attachment via an enzyme
to a surface so that isn't like
oscillation for example glycocalyx and
proteoglycans as the result of
glycosylation but if glucose is just
abundant around and that just forces
itself on a surface of a cell that is
called glycation or now non and somatic
glycosylation the result of the
glycation is the advanced glycation
end-products
and the reactive oxygen oxygen species
both of them are damaging to the cell
and the cell can be broken and in this
particular case GFR will be affected so
this is about the endothelium next
lecture we'll talk about GBM