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hello and welcome back
today in our nephrology curriculum we're
going to be talking about nephrotic
syndromes which are part of the
glomerular diseases and one of my
personal favorites
let's start out with a clinical case we
have a 45 year old gentleman
who presents to the hospital with weight
gain and worsening lower extremity edema
over the past two months
his laboratories are significant for a
serum creatinine of 1.2 milligrams per
deciliter
his albumin in the serum is low at 2
grams per deciliter
his urine analysis shows 4 plus protein
on the dipstick
but there are no white cells or red
cells by microscopy and he has
about 8 grams of protein estimated on a
urinary spot protein to creatinine ratio
so the question is is this nephritic or
is this nephrotic syndrome
let's look through our case and see if
we can arrive at that diagnosis
so what we can see is that our patient
had worsening lower extremity edema
and this is because of that low albumin
or hypoalbuminemia
why does he have a low albumin because
he's spilling a lot of protein in his
urine we have eight grams of protein in
the urine
that's a large quantity he has a normal
serum creatinine relatively
and he has no red blood cells or no
white blood cells in his urine
so taken together this really is more
indicative
of nephrotic syndrome and something to
really help us think about
is that nephrotic contains the letter o
and podocyte which is the superstar of
nephrotic syndrome
has the letter o in it when we think
about nephritic
it has an eye in it when we think about
nephritic diseases they're more
inflammatory so i think that can help us
distinguish between nephrotic and
nephritic syndrome
so of course in our answer this is
nephrotic syndrome
so let's talk a little bit about what
nephrotic syndrome is
it's actually characterized by the
clinical presentation of four different
things
number one our patients have to have
nephrotic range proteinuria
that means they have greater than 3.5
grams of protein in their urine over a
24-hour period of time
our patients also manifest with
hypoalbuminemia in the serum
those serum albumin levels are less than
3 grams per deciliter remember
normal is 4 grams per deciliter
sometimes with certain nephrotic
syndromes we can see
even a 0.8 grams per deciliter the serum
albumin is so low
our patients also have edema as shown
here in our schematic in the diagram
we've got pitting edema as our patient
is actually
so volume overloaded because of that
sodium and water retention due to their
nephrotic syndrome
and of course we have hyperlipidemia and
lipiduria
so let's talk about these a little bit
more closely so we can better understand
the pathophysiology of nephrotic
syndrome
so proteinuria we talked about high
grade proteinuria greater than 3.5 grams
we know that this is glomerular
proteinuria because the principal
component is going to be albumin
so what exactly does that mean patients
who have nephrotic syndrome will have an
increase in filtration of
macromolecules across the glomerular
capillary wall
because of abnormalities in the
glomerular epithelial cells the
podocytes
as i mentioned albumin is kind of the
star player here it's the principal
protein
that makes up that urinary protein and
that's what's lost in glomerular
proteinuria
we can lose other things like clotting
inhibitors transferrin
and vitamin d binding protein as well
but we really think about our patients
as losing a lot of albumen
now if you look at our schematic over
here we actually have the glomerular
capillary wall
so to the right of the slide we have
that capillary lumen
the red cells are the endothelial cells
that are lining that lumen
the yellow is the glomerular basement
membrane and then those little picket
fences or those little fingers that are
standing up are our podocyte foot
processes
and those are incredibly important
because their job
as they interdigitate together they form
these elekin slit diaphragms
and that job is to keep all of the good
stuff those macromolecules like albumin
and clotting inhibitors and
vitamin d binding protein in the serum
and let the filtrate go through
when we have problems with glomerular
proteinuria
there's something wrong with the
integrity of those podocytes in those
slit diaphragms so they can't
interdigitate the way they should
and then therefore we have escape of
macromolecules into the urinary space
so we mentioned that our patients have
hypoalbuminemia
and that's simply due to the consequent
loss of albumin in the urine
our liver tries its best to synthesize
as much protein as possible so
we have hepatic albumin synthesis but
it's not able to keep up to replete
those serum levels
sometimes our patients can manifest with
45 grams of proteinuria
so you can imagine how hard the liver is
working to try and to
sufficiently replete the serum levels
and sometimes that just can't happen
and then oftentimes our patient's
albumin levels will drop to less than
two grams per deciliter
we also mentioned edema and this is
consequent to the hypoalbuminemia that
causes egress of fluid into the
interstitial space because we have a
decrease in plasma oncotic pressure
we don't have albumin there to hold on
to that vascular fluid
into the vascular space we also get
stimulation of the renin angiotensin
system
so in the end we end up with aldosterone
release causing market sodium retention
that's working at that principle cell
we have sympathetic stimulation to
increase sodium retention
and we also have reduced natural peptide
release
all of this together causes that soft
pitting
dependent edema that we see in our
patients
finally we have hyperlipidemia remember
that decrease in oncotic pressure is
also going to stimulate hepatic
lipoprotein synthesis so the liver will
be producing a lot of lipid that's going
to manifest as hypercholesterolemia
or hypertriglyceridemia
we can also see lipiduria that's when
lipid actually becomes entrapped
in the urine in these cellular casts or
in casts
so you can see that also in the plasma
membrane of a degenerative tubular
epithelial cell
so as we have a lot of lipid remember in
protein those proximal tubular
epithelial cells
are trying to absorb as much as possible
and sometimes they detach from the
underlying basement membrane they become
engorged with lipid
and they turn into these oval fat bodies
that you can see right here in our slide
so it almost has a little bit of a
brownish hue with these refractive
elements those are lipid
oval fat bodies now if you're lucky
enough to have a polarizer on your
microscope
these guys can actually turn or show
maltese crosses
where that uh where those lipid elements
are they're actually fun to look at
underneath the
urine underneath the microscope
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