Nephrotic Syndrome

foreign what's up Ninja nerds in this video today we're going to be talking about nephrotic syndrome it's one of the types of glomerulonephritis it brings a lot of students a lot of fear and anxiety I'm going to do my absolute best to make sure that at the end of this video you guys understand it if you guys do like this video it makes sense it really does help you please support us one of the best ways that you guys can do that is by hitting that like button commenting down in the comment section and please

also subscribe if you guys do want to follow along with me we got some great notes some great illustrations that our team has worked together to make just some beautiful notes and illustrations for you guys to follow along with me and really understand this topic so go down in the description box below and it'll take you to our website where you guys can follow along with me but let's start talking about nephrotic syndrome so before we actually get into the you know the kind of the meat and potatoes of nephrotic syndrome I want to go

over the basic functions the anatomy of the glomerulo filtration barrier it's really important that we understand this because once we build on this Basics we can kind of really understand the pathophysiology so the first things first is when we talk about the glomerular filtration barrier it's really just three layers so I have it abbreviated I'm going to abbreviate it as gfb the glomerular filtration barrier if you will now there is three different components of this barrier the first one is going to be this red capillary here so you know you have the glomerular capillaries they're

supposed to be what's called fenestrated so it means that they're a little bit porous and they allow for things particularly selective things to be able to move from the the plasma of the blood into this actual bone in space so that's the first kind of component of this barrier here is you have what's called let's actually do this one here in Black this is called your fenestrated capillaries all right so these are porous and they are allowing particular things to leak through here but we want them to be very very selective though right so we

have fenestrated capillaries the second component is this blue structure here you see that one right there this is a really interestingly negatively charged kind of membrane if you will and it's really nicely sticking and adhering to the Finish rated capillaries but it's highly negatively charged you know what's really interesting uh proteins that run through our bloodstream they're very negatively charged so negative and negative charges should kind of repel each other we know like and like charges repel one another so it's really good at being able to block large proteins from exiting the blood and coming

into this capsule space so that'd be the second component of the barrier here which is going to be the glomerular basement membrane the glomerular basement membrane now again with this one you need to remember it's that negatively charged membrane so that's what's really cool about that so I'm going to put this here and like this thing here negatively charged just to remind you kind of that function the third component of the glomerular filtration barrier is going to be these like cells here you see these like little cells they're kind of like right next to the

glomerular filtration the glomerular basement membrane these are called your podocytes so this is the third and last component of this filtration barrier this is going to be the podocytes now the podocytes are really cool and what happens with the podocytes is they have like these little like you can't see them but you see like there's little divots there they're called their foot processes and generally there's some spaces between them called filtration slits and that's what's supposed to again allow for some degree of permeability across this filtration barrier so the third component here is going to

be the podocytes and again the real significant component of this is going to be what's called your filtration slits all right now you're probably wondering okay exactly we got a little bit of Basics here for nephrotic syndrome I get it why is this so important well the glomerular filtration barrier is supposed to be very very important and being able to regulate what leaves the blood and enters into this space here The Bowman space we really only want certain things filtering out of the bloodstream and into the actual bone in space we only want certain things

things like sodium things like water things like electrolytes and nutrients but you know we don't really want running through here well we don't want to be leaving is we want the glomerular filtration barrier to block the loss of red blood cells white blood cells and proteins and that's the job of this glomerular filtration barrier now imagine for a second you develop a damage to one of these three components of the glomerular filtration barrier are you going to be able to closely regulate what leaves the blood and enters into the Bowman space no and so that's

the important thing here is that this whole membrane here it's supposed to block the loss of red blood cells white blood cells and proteins there's two diseases that are part of the what we call glomerulonephritis one is called nephrotic syndrome so one is called nephrotic syndrome and that's what we're going to be discussing now nephrotic syndrome really how it breaks down the glomerular filtration barrier if you will is it really takes a hit to the podocytes so what this son of a gun does is is it really causes a lot of podocyte injury so it

caused a lot of podocyte injury and so whenever you damage these protocytes it's one of these actual particular components of the filtration barrier and then look what happens as a result of the podocytes that are actually being injured you lose the capacity to control what things are leaving the blood and entering into the Bowman's space now out of all of these three and we're going to hit on a little bit more the true one that actually ends up becoming the most affected is proteins and you're going to see a massive massive amount of protein loss

so protein loss is going to be the heavy heavy cause here that you're going to see in nephrotic syndrome so the big big Bare Bones things understand for the global filtration barrier is that again it's made with these three layers but which one of the layers is damaged to nephrotic syndrome it's the prototypes that are injured they are supposed to be controlling what leaves the blood and enters into the moment space particularly red blood cells proteins white blood cells but the most important one is going to be proteins and if you damage these podocytes you're

going to lose a lot of proteins so that leads us into the next component here which is nephrotic syndrome so we know the nephrotic syndrome the basic concept of this disease process which is again it's kind of an umbrella so when we talk about glomerular diseases or glomerulonephritis is the inflammation of the glomerulus and this can present in a couple different ways one of the ways that glomerulonephritis can present is in the nephrotic syndrome another way it can present is a nephritic syndrome which we'll talk about another video but nephrotic syndrome so what we know

is we know right away that there's some type of podocyte injury if you will and whenever you have this podocyte injury what it's really going to be doing is is going to cause these poor little cute podocytes to become damaged in some particular way and whenever you damage these podocytes you technically what you do is you kind of you face so you see these like little foot processes you actually efface them so you get rid of them and then you kind of like make them flat and they lose the ability to really control permeability and

so what happens is is you end up what's called podocyte effacement so you end up with some type of podocyte effacement and the problem with this is we already kind of mentioned it is this is going to lead to a heavy heavy degree of protein loss so what you're going to see is as a result of this potocity facement is you're going to see heavy heavy degrees of proteins being lost across the actual glomerular filtration barrier so here let's actually represent these as protein so here's all the proteins that I'm going to be losing here

Across The Bowman space and they're going to end up draining all up into the urine so what you're going to notice as a result of this protocytofacement is you're going to notice what's called heavy heavy protein area so we noticed something called protein urea and we have to be very very specific to the degree of protein you're at I keep saying heavy what I really mean is is that the amount of protein that's truly being lost is very significant we say it has to be greater than or equal to 3.5 grams of protein is being

lost in the urine per day so that's what I really want you to take away from this is It's 3.5 grams or more being lost per day in the urine that's one of the Hallmark signs of nephrotic syndrome secondary two podocyte injury in a basement one of the components of the again glomerular filtration barrier now when you lose protein in the urine what happens is you have less protein that remains within the blood right so we know that here's the proteins we're going to kind of represent here they're supposed to be circulating through the bloodstream

they go through the glomerulus generally it's not supposed to be getting filtered off my friends right so what should happen is that when we leave when the blood leaves this so this is what's called your afferent arterial and this is your efferent arterial when blood comes out here what should be the albumin level in normal people it shouldn't be very very low but in these patients who have nephrotic syndrome when the blood leaves guess what happens to their albumin levels in the blood it drops and so does other proteins so let's talk about that so

we end up with what's called hypo album anemia which is low albumin within the blood and this can cause a lot of problems but what are some of those problems so one thing is that we're going to have less albumin in the blood we can call that hypo album anemia so albumin within the blood now why is that a problem and what can that lead to well albumin is a really interesting type of protein it helps to regulate what's called osmotic or oncotic pressure if you will so let's say that here I show these albumin

proteins here that's in the bloodstream normally what it's supposed to do is there's water that sits in the cells and in the spaces and they should get kind of sucked in or drawn into that actual space there but as you lose albumin you lose this oncotic pressure and you lose the ability to draw water into the cells now as a result because of decreasing the osmotic pressure what's the end result here as you decrease the osmotic pressure or the oncotic pressure they're both kind of similar terms semantics really it leads to a lot of fluid

staying in these tissue spaces and what will that look like to the patient when you look at them you know in a person it's going to give them a lot of Edema so a lot of fluid sits in these spaces and the ways that these present patients will present is they present what it's called edema now the question arises what does edema look like it can look like a lot of peripheral edema on their legs they could have pulmonary edema fluid in their lungs they could have fluid in their belly ascites or sometimes they can

even sit around their eyes periorbital edema so a lot of different problems here that's one thing is they can definitely have a lot of Edema what's another problem though I'm going to write it here but I'm going to explain it up here another issue with low albumin is it increases your lipids so it increases your lipids you're like wait what the heck how the heck does it increase my lipids what you talking about Willis when there's low albumin albumin is made by the liver right and so your liver is like a little albumin sensor if

you will and it senses the albumin levels within the blood and it says oh shoot man albumin levels below well I'm going to have to compensate for this and I'm going to start trying to pump up my production of albumin so it tries to go and synthesize albumin as a result that's what it's trying to do you know what ends up happening it also ends up making some other proteins that are similar and these are called lipoproteins so we call these things like vldl and LDL and you know what these Sons of Guns do these

Sons of Guns increase your triglycerides they increase your cholesterol and you know what ends up happening these things get into the bloodstream so you have higher amounts of these these things move right into your bloodstream right so now look look at this you got increasing levels of these lipoproteins these lipoproteins will then circulate through your bloodstream they'll go to the kidneys and when they go to the kidneys they'll filter out look you're going to filter out a bunch of different lipids and some of these lipids will end up into the urine some of them will

actually passively move into these tubular cells and tubular cells just like other people they don't like you know getting all fat and so they decide to just die and Shed off into the actual urine and so then you get like some cells that are filled with a bunch of fat and you know what we call this what do we call this when you have tons of lipids within the urine oh that's not too crazy it's lipiduria so we can have what's called I'll actually write this down here you can have something called lipiduria and you

can have another one here so there's two terms that I want you guys to be familiar with one is what's called lipid urea and the second one which is these cells filled with all that fat these are called fat oval bodies how original right sometimes when you look at them under like microscopy and you really get a good look at them they kind of look like what they call a Maltese cross but I think this is the big things that you need to understand is that in response to low albumin your liver starts cooking up

a lot of other lipoproteins which unfortunately has an adverse effect increases your triglycerides your cholesterol you leak a lot of that into the urine you know another problem is what happens if you have high triglycerides and cholesterol in the blood you can't get up with all kinds of problems man so you'll see sometimes these patients unfortunately as a result of all of these things in the blood so if these things are like just cooking up in the blood you can see a lot of problems things like you might have heard these terms like xanthomas right

so these kind of like big things that form on tendons you can get these fatty like plaques around the like the eye so xanthelasma you know the worst case scenario is these things can plaque up the blood vessels and you can end up with what's called atherosclerotic cardiovascular disease right this can look like peripheral artery disease this can look like coronary artery disease or the worst case scenario you can develop a cerebrovascular accident so you see how having a lot of these nasty little molecules increase the risk of some lipid complications but also leads to

a lot of lipid loss within the urine okay what else well here's another thing you're like oh geez it causes renin Angiotensin aldosterone system activation okay all right man this albumin does some stuff doesn't it it's kind of odd so yes when you have less albumin it causes edema right because of this osmotic pressure so we know how this will cause edema but another thing is when you have less osmotic pressure not only does it cause edema but it decreases the amount of fluid that's in your vessels ah what's that called your effective arterial blood

volume drops so you have a drop in the effective arterial blood volume when you have a drop in the effect of arterial blood volume isn't that just like the circulating volume going around the body yeah you know why that's a problem the reason that's a problem is is that tells the kidneys that hey there is a very low perfusion there's low circulating volume can you do me a favor and can you pump up the renin Angiotensin aldosterone system and it does and you know what the result of the renin angiotense and aldosterone system activation is

is it causes your blood pressure to go up so what's the effects out of all of this well what we know is this can increase your blood pressure so let's actually make this nice and Purdy here so we'll have it can increase your blood pressure and it can activate sodium and water retention all right so it can cause an increase in blood pressure what's that whenever the blood pressure Rises hypertension so this is another common feature and it can cause sodium and water retention when you retain a lot of this not only does that increase

your blood pressure but what happens if you retain a lot of sodium water you get a puffy and they start developing features of Edema so they can get edema because of red angiotensinaldoctrine activation and because of low osmotic pressure son of a gun so these guys just can't take a break right so we know now that they're losing tons of protein the biggest one is albumin and we see all the negative consequences of that there's other proteins that can be lost another protein that can be lost and it's really important to differentiate this between nephritic

syndrome is it's called anti I'm going to abbreviate anti-thrombin three so if you guys remember from our hemostasis lecture antithrombin 3 is an anticoagulant what it's supposed to do is is it should naturally you know uh there's a molecules called factors 10 and another one called thrombin and these are supposed to what they want to do is these molecules want to go and and stimulate their procoagulants they want to stimulate a clot that is what they're designed to do they want to stimulate a clot to form all right that's their goal is to increase clot

formation well you know what antithrombin 3 is supposed to do anti-thrombin 3 is like uh-uh daddy you ain't gonna do that I'm going to inhibit you from being able to function and so anti-thrombin 3 naturally is supposed to inhibit these but if you have less antithromb than three are you going to be able to inhibit these proteins no and so what happens is you aren't able to do this particular function because of a decrease in this molecule and then these things go Haywire and they increase your clot formation what does that look like well you

get clots my friend and usually this is Venous clots and so it can form in the leg so watch out for those dvts they can break off get stuck in the lungs a PE and a weird one is what's called a renal vein thrombosis this is kind of rare but if you think about this in the context of nephrotic syndrome it is relatively common okay all right what else we lose one other protein and that's these little dudes these are supposed to be made by plasma cells but if you're losing more than your plasma cells

are able to produce these are called immunoglobulins or antibodies immuno globulins now you're jacking these things up these are supposed to go and fight off bacteria you know the very specific bacteria that for some reason patients with nephrotic syndrome are super super susceptible to it's called streptococcus pneumonia and what happens is you have less of these antibodies so are you able to bind up this bacteria enhanced oxidization complement pathway activation nope you lose this strep pneumonia starts going on the rise and if it gets on the rise guess who it likes to plague and increase

the mortality for these patients son of a gun it loves to hit the lungs and so you can end up with a nasty nasty pneumonia and so as you can see the complications of having less of these immunoglobulins is you're going to be at very high risk of infections so you're going to have infection risk that's going to be a little bit higher than most people and that's the problematic issue and I think the big boards question that you can see for this is It's streptococcus pneumonia and usually streptococcus pneumonia is the most common cause

of community acquired pneumonia so you want to watch out for that pneumonia in these patient populations so at this point we've talked about nephrotic syndrome what it really looks like when you damage those podocytes but the question that arises what's causing the injury to the podocytes let's talk about that all right my friends so now we have to talk about the reasons the podocytes are damaged or injured and we're losing all this protein so the first one that I want to talk about is called minimal change disease so before we even talk about that there's

there's three particular types of nephrotic syndromes that really are what we term primary meaning that we don't really know the reason why these are occurring they're what we call idiopathic there may be some genetics or autoimmune things but we just don't know then there's What's called the term secondary causes of nephrotic syndrome which you can see in every single one of these okay but just remember that the ones that we call primary nephrotic syndromes is minimal change membranous nephropathy and focal segmentoglomerulosclerosis I'll explain that a little bit more as we go along but first thing

is minimal change disease so a minimal change disease it can be primary we don't know the reason why it happens okay so when I say primary it did primary for these three accounts for 70 to 80 percent of the nephrotic syndromes that's insane so most of the time it's primary but the when I say primary we don't know why it happens so we'll use this term idiopathic meaning we don't know but there is secondary causes meaning that we've seen some Association of this disease with these particular things and what they've seen is for the secondary

causes they've seen things like infections like upper respiratory tract infections and Hodgkin's lymphoma the only other one is NSAID use so you can also add that one in as well so NSAIDs have also been kind of linked to this now how exactly these things do this next step we just don't know and I always feel bad for that but I don't have an answer but what we know is is that these particular things whether we it's idiopathic or it's secondary what they do is they stimulate T cells right and these specifically Target these T cells

to go to the kidney and release tons of these cytokines and what these cytokines do is is they go and they cause damage to the podocytes and really all they do is they rip the foot processes off so what you get is you get what's called podocyte effacement which we talked about and that's really the interesting thing with this and then as a result of the podocyte effacement what do you lose a lot of in the urine you lose a ton of protein in the urine how much just to test your knowledge greater than 3.5

grams per day and you also can lose a lot of lipids in the urine so you can get that lipid urea right now the big concept for this is again we're knowing that these cytokines by some particular means are injuring the podocytes they're getting effaced and these podocyte effacements are increasing the protein loss and then subsequently from a lot of albumin being lost a lot of lipideria so you're getting podocyte effacement from increased cytokines and here we'll just kind of draw this here so that you see you're damaging these protocytes now that's really the key

things when I say minimal change think about a young child all right and it's usually either primary idiopathic we don't know or secondary something else has been associated with it infections maybe even immunizations Hodgkin's lymphoma and NSAIDs all right that's enough said membranous nephropathy again can be primary but thank goodness we have something to link with it so in primary causes there's this weird antibody and it's called anti pla2 receptor antibody and it's for some reason loves one of the proteins in the podocytes it loves one of those proteins and it loves to attack it

in a face the podocytes if I were to say secondary causes then you're thinking about things that have been Associated to lead to antibody activation and this is things like Hepatitis B hepatitis C syphilis and there's one other kind of weird one there are these two weird medications one is gold and the other one is called penicillamine but these are the weird things that for some reason have been associated with membranous nephropathy now regardless of what that may be what happens is is you get some type of antibody that is actually going to be in

some way binding with one of these antigens or the antigens that are present here and so you're going to either get like these immune complexes and what they do is they go in and they deposit here right into the What's called the subepithelial layer all right and when they deposit in there look at this you get all these kind of like deposition here this could be the anti-pla2 antibodies or this could be all of the other antibodies from hepatitis syphilis Etc but you get a lot of antibody deposition so what's the result of this is

you get what's called subepithelial sub-epithelial immune complex deposition and when these suckers deposit into this area they trigger an inflammatory reaction and what they do is this sub-epithelial immune complex they activate complement proteins my friend so you're going to activate these complements you guys remember those the C3 C4 all those things that come in there and really trigger a lot of inflammation so what you're going to do is is you're going to stimulate the complement system and when the complement system gets in there it's going to jack everything up and then as a result you're

going to get podocyte effacement but you also get one more thing when that complement system gets in there and really starts revving up a lot of activity and getting super inflamed not only do you get a lot of podocyte effacement but you also start causing some other problems which is the glomerular basement membrane starts kind of having a reactionary thickening so the GBM will start thickening gonna get thick and when you get this GBM thickening it does something kind of like weird where when you actually kind of like zoom in and we'll talk about it

a little bit later here's your glomerular basement membrane all right and then what happens is you have your kind of podocytes that would be on this side here so we'll kind of give them a little bit of space here here's your podocytes look their foot process is gone all jacked up but what happens is right in here is going to be your immune complexes all these things that we're depositing you know what the GBM does when it thickens it does something weird where it kind of like thickens outwards and when it thickens outwards it gives

this weird type of appearance that we'll talk about later and it's called a spike and Dome pattern so we call it a spike and Dome type of pattern and that's really really interesting that you get with this GBM thickening okay all right so that's what we get from membranous nephropathy so when I say minimal change is these you think child idiopathic secondary you think like infections maybe NSAIDs Hodgkin's lymphoma membranostaropathy primary it's one weird antibody and if I were to say the primary if I put the primary here what would that primary antibody be it

would be anti pla2 receptor antibody this is the one that's the primary cause if it's not this antibody then you have to remember it's an immune complex where antibodies bound to one of these things and then deposited into that space okay all right let's come into the next one the next one here is focal segmental glomerulosclerosis now with this one the big thing to remember here is this can also be primary believe it or not it tends to be out of all of these like the primary causes this one is the most common to be

the primary type so if we talked about when we uh particularly all of these different types of diseases for nephrotic syndrome this is one of those that the primary causes is the most common there really isn't many secondary causes but we'll talk about those rare situations so primary I want you to associate with idiopathic right we don't know why something genetic we just don't know secondary there has been a couple things that have been linked to this HIV heroin use dang and also sickle cell disease there also has been an association with like obesity but

I think these are the ones that you're more likely to see on the exam now what happens with this one is again we don't know I I don't have an answer as to why these things happen but something occurs where you activate a lot of like sclerosis and hyalenosis of parts of the glomerulus that's why we call it focal and segmental it's not the entire thing so imagine like right here in this area I'm going to have a lot of sclerosis right here in this particular area there's going to be a lot of sclerosis and

then we'll use like a different color here maybe we'll do like a little bit of pink or something and this will represent the hyalenosis so you're going to get kind of like a hyalenosis and sclerosis of parts of the glomerulus weird right we don't know why but it just happens so you can get what's called hyalenosis and sclerosis of the glomerulus the glomerular filtration barrier if you will and what this does is this causes podocyte effacement so you're noticing a trend between these three primary types of disorders is that no matter what it may be

you're getting some degree of podocyte effacement and this one is going to be due to a lot of hyalenosis and sclerosis of that glomerular filtration barrier now that's the big thing to remember for these okay now here's the other the next thing with this particular disease with focal segmented glomerular sclerosis and membranous to fropathy because you can cause potentially over time a lot of damage to these kidneys it's important to remember that in situations where these patients have focal segmental glomerulus sclerosis and membranous nephropathy so in diseases such as membranous nephropathy and focal segmental glomerulus

sclerosis these can really plague the kidneys they can really do a lot of damage if they're not treated and what can happen is as you continue to plague these kidneys and injure them injure them and cause inflammation and fibrosis you can literally progress these kidneys into something called chronic kidney disease but these are really the only two that have that higher risk of end-stage renal disease or chronic kidney disease minimal change disease not so much all right we go on to the next one diabetic nephropathy so at this point we're now talking about only secondary

causes of nephrotic syndrome so what are the reasons the protocytes are being injured or damaged in some way shape or form for the primaries it was minimal change membranous nephropathy focal segmental if it's not primary which is usually the most common cause for those meaning it's idiopathic and we don't know why then there's some random secondary ones that we thought talked about but for these it's only secondary causes so it's some systemic disease that causes nephritic syndrome diabetes or amyloidosis so obviously in diabetic nephropathy the hint to knowing this one is you got a patient

with diabetes and what's the problem with diabetes what does it really do well you got that high glucose right and what that glucose does is it causes if you guys remember that non-enzymatic glycation of the efferent arterial oh shoot so you get what's called efferent arterial hyaline arteriolo oh my gosh so many words sclerosis and what that does is it makes it super impossible for blood to leave the glomerulus and then the glomerular blood pressure is like crazy high and you hyper filtrate we already talked about this before right but what happens is your intra

glomerular blood pressure Rises the glomerular filtration rate would rise and so you're going to have to compensate and protect the kidneys from that high pressure my friends and so what you do is you cause GBM thickening and you cause sclerosis and a nodular pattern and what this does is when you thicken up that GBM it causes the podocytes the food process is to be farther away from one another so it causes the podocyte foot processes to stretch out and it's the same way of causing podocyte dysfunction and if you do that you're going to get

the heavy protein area because you're causing prototype dysfunction so in this particular situation what we know is the increase in E for an arterial arterial sclerosis reduces blood flow out of the glomerulus increases the blood pressure increase the GFR thickens the glomerular base membrane causes sclerosis and then it faces those foot processes and that is how we end up with this heavy heavy degree of protein loss the other thing is that with this over time the sclerosis and nodules you can lead to what chronic kidney disease my friends what is the most common cause of

chronic kidney disease diabetes and this is because it's going to damage and cause tons and tons of sclerosis to the kidneys that they will progress to chronic kidney disease if I were to ask you what's the most common cause of chronic kidney disease you should say diabetic nephropathy if I were to say what's the most common cause of nephrotic syndrome you should say diabetic nephropathy and that is the important thing to remember for this one the last one here is just kind of a weird one we got to talk about it unfortunately because it's a

part of the nephrotic syndromes but it's amyloidosis and this deserves a quick discussion as to the two types of amyloidosis so there's what's called a l so a l amyloidosis that means light chain amyloid proteins you know there's a disease where you produce lots of these light chains unfortunately multiple myeloma so in patients who have multiple myeloma they're at high risk of injury to their kidneys we know that that's one of the features right multiple myeloma if you guys remember like that crab mnemonic the hypercalcemia the renal failure the anemia the bone pain that's one

very particular significant feature the other one is what's called secondary amyloidosis which means there's something that's causing chronic inflammation which is leading to a lot of these amyloid proteins to be produced you know what that disease is called it's really any disease that has chronic inflammation what's a big one ra rheumatoid arthritis causes a great degree of inflammation but the difference is in really just the protein kind of like structure and composition but either way the the same kind of thing exists between these which is your body is regardless of what the structure of them

is your body is producing an increased amount of abnormal proteins that's the whole point with this one is you're getting a lot of abnormal proteins my friends and when you get a lot of these abnormal proteins guess where they decide to go and the same situation here my friends they like to go here and they like to deposit into the glomerular filtration barrier and when they deposit what they do is they cause a lot of inflammation and guess what they do they do the same thing that this diabetes does they cause GBM thickening so they

thicken up that glomerular basement membrane so they cause GBM thickening and then they also cause a lot of inflammation and then sclerosis so they cause a lot of sclerosis of the glomerulus as well somewhat in a nodular pattern but if that happens what's the end result that we saw within diabetes same kind of thing you're getting the foot process effacement I'm sorry you're actually stretching out the podocyte foot process I apologize which is the same thing because you're causing podocyte dysfunction leading to the loss of the good filtration barrier and proteins to get lost the

other thing is with the sclerosis what can you also progress this thing to chronic kidney disease so you're noticing a trend with all of these nephrotic syndromes the only one that really won't really progress to renal failure is which one minimal changes of these the ones that can progress to renal failure that are primary is members of nephropathy and focal segmental sclerosis the ones that can progress to chronic renal failure is going to be diabetic nephropathy and amyloid nephropathy we've gotten the causes mental change membranous nephropathy focal segmental diabetes and amyloid the question then comes

because a lot of this is a lot of information how am I supposed to know which one it is off a patient who comes in with some vague symptoms like some edema right or maybe they have high lipids or maybe they have hypercoagulable States or maybe they have increased risk of infections they got a lipid in their urine they got a protein in the urine how am I supposed to know let's talk about that all right my friends so we have a patient that we think may have nephrotic syndrome so sometimes looking at the physical

exam features that we talked about kind of the effects of nephrotic syndrome really was looking for any features of Edema right so periorbital edema pitting lower extremity edema pulmonary edema ascites that could be one thing or if they come in with a history of recurrent dvts PES renal vein thrombosis if they have complications of hyperlipidemias xanthomas and thalasma cardiovascular events or if they come in with increased risk of infections like particularly streptococcus pneumonia now with this being said this is very vague right so oftentimes what ends up happening is if we have a patient who

has like some degree of Edema we may get a urinalysis and microscopy and the reason why this is kind of helpful is because this leads us into the next topic that we'll talk about another video called nephritic syndrome but I want to introduce it I want you guys to be able to compare contrast differentiate these two it's very important for your exams so a urinalysis of microscopy is really good it just doesn't it doesn't quantify the protein loss as much which is really really important but it gives you an idea hey there's a heavy amount

of protein there's some other weird stuff in here too this is where it's really good at being able to differentiate between nephrotic and nephritic syndrome so the basic basic thing for nephritic syndrome is it's inflammation of the glomerulus causing glomerular basement membrane damage whereas nephrotic syndrome was inflammation of the glomerulus causing podocyte damage all right both of them either way lead to loss of particular things into the urine nephrotic syndrome causes heavy proteinuria and lipiduria nephritic syndrome leads to everything being lost red blood cells white blood cells and protein would I be able to differentiate

that off of the urinalysis with microscopy absolutely I would so when I go look at nephrotic syndrome and I get a urinalysis one thing I'm going to notice is is I'm going to have two big things for nephrotic syndrome two big things I notice in the urine one is I'm going to have a massive massive amount of protein and I'm going to have a lot of lipids and if I look under microscopy I'll also see those weird fat oval bodies right so I have a lot of what's called lipid urea and if I look under

the microscope I can see those fat oval bodies right that we talked about in the lipiduria situation the other thing is I'm going to have a lot of protein problem is is I'm not going to be able to quantify this so the dipstick kind of gives you like a plus one plus two plus three amounts of proteins I'll have a lot of protein so plus three plus four protein area but it's not good at telling me the true amount that I need to know is it greater than or equal to 3.5 grams per day I

won't be able to get it off just a basic urinalysis all right so that's not crazy helpful but it's at least something here's another thing nephritic syndrome I told you so again this is podocyte damage podocyte dysfunction if you will whereas nephritic syndrome its glomerular basement membrane dysfunction is the basic pathophysiology they both lead to heavy leakage now the difference between this one is a little bit different so we're going to have protein but it's not going to be as much I'm only going to give it one Arrow we're going to have a lot of

red blood cells and we're going to have a lot of like white blood cells huh so what will I have lost here I'll have some protein but it won't be as significant of the protein maybe this is like plus one plus two it's like plus three plus four still not great but it's okay but here's what's the big difference between these I'm gonna have hematuria and when I look at this red blood the actual blood under the microscope I noticed something called red blood cell Cass and that's usually a buzzword term for nephritic syndrome the

other thing is I'll have what's called pyuria which is white blood cells but sometimes people would be confused and be like Oh white blood cells doesn't mean that there's an infection this is what we call sterile pyria so it means that there's actually no evidence of infection there's just a lot of white blood cells that leaked across the blood into the actual bone in space so that's kind of the basic differences it's not enough but it at least gives you kind of a basic beginning I could at least tell off to your analysis with microscopy

which one's likely nephrotic which one's likely nephritic but it's not Stone Cold kind of definitive so then what I would do is I would do what's called a 24-hour urine protein or what we call a urine albumin creatinine ratio so this you have to collect urine over 24 hour period that sounds very tedious very annoying probably not the most desirable thing to do this one is what we call a spot urinalysis we do it one time people like that a lot more and so they both are pretty good at giving you the amount of protein

that you're using and you're losing in your urine over a 24 hour period that's really helpful because I know in nephrotic syndrome which is podocyte dysfunction I'm going to have a lot of protein but how much protein how much do you have to have to truly be considered because you're going to get protein area here there's still protein loss but what is the big difference here so I'm going to have protein loss and both of these this one I already told you will be crazy high this one will just be a little bit high but

what's the true number over a 24 hour period that we need to have this has to be greater than 3.5 grams per 24 hour period and this has to be less than 3.5 grams per 20 volt four hour period that is the big difference and that will set this apart between the two so if you have heavy proteinuria with lipid urea no hematuria and no sterile pyria it's more likely to suggest nephrotic syndrome if you have hematuria pyuria and subnephrotic range protein area less than 3.5 grams per day it's more likely to be suggestive of

nephritic syndrome because they both can have edema which we'll talk about they both can have hypertension which we'll talk about and they both can lead to renal failure which we'll talk about it's really this that helps you another thing that can be somewhat helpful in differentiating nephrotic versus nephritic syndrome is in nephrotic you have a heavy amount of protein loss but I was very specific what was the most significant protein that was lost there was a lot of albumin there was a lot of albumin loss and what did we say we would be able to

determine off of the albumin in the bloodstream well I told you that because this disease there's podocyte dysfunction it causes a lot of here's our blue color here a lot of albumin to get lost there's gonna be a ton of albumin in the urine what happens to the albumin that leaves the glomerular capillaries and goes into the efferent arterial and into your circulation which one what is it going to be here it's going to be very low so if we were to check the serum albumin levels their albumin within the blood would be very low

right and so they would have very low albumin levels within the blood and we also can kind of make a little connection here that when he said that when the albumin levels in the blood are low what did that do to the liver stimulated the liver to pump what out into the bloodstream lots of lipids unfortunately as the result of trying to make more albumin right and so if I were to test the blood what would I find a lot of in the blood as a result of the heavy albumin loss I would find a

lot of vldls I would find a lot of ldls and maybe I would even find a lot of like high triglycerides as a result here so you're going to notice that these patients will have features of hyperlipidemia on their lipid panel okay and this again adds to the definitive shot of saying oh it's nephrotic syndrome so if I've done all of these I should be able to get to the point where I say I know it's nephrotic syndrome causing some type of podocyte dysfunction leading to heavy protein urea and lipid area then we got to

get to the next step which one is it which is the cause of the nephrotic syndrome is it minimal change memorence nephropathy focal segmental diabetes Emily Zach I don't know what to do I got you let's go now we move into the next step here which is we don't know which one it is it's a minimal change is it membranous is it Focus like mental is it diabetic is it amyloid how am I supposed to figure this out remember I told you that out of all of those causes it's likely going to be again primary

causes as one of those big things for minimal change or for membranous nephropathy or for focal segmental glomerulosclerosis on the rare occasion for those three diseases there could be secondary causes that we said have been associated with it those are things to think about and you could test for those things right because right now we've already just gotten to the point I know it's nephrotic syndrome I just don't know which one it is look for specific hints that may be suggestive so for minimal change disease I already said look for like a young child so

I think that's one of the big things to think about is a very young child because it's more common it's one of the most common nephrotic syndromes in children so right when you see that with nephrotic syndrome features you want to think about minimal changes that's one way that they'll try to get you the second one is we said that it could be associated in some way shape or form with secondary causes such as what infections it could also be due to Hodgkin's lymphoma or it could be seen in association with NSAIDs so look for

that look for Hodgkin's lymphoma in the vignette in a child which would be really sad look for NSAIDs in the vignette with a little child or look for some type of infection or even sometimes recent immunization for a child okay but out of all of these ones this is probably going to be the one that when you just Bings up off the exam it really will help you to make that differentiation okay now these are the secondary ones it doesn't account for the primary one which is we don't know why it happens right so that's

why sometimes these three can be difficult to diagnose because if it is primary these things won't come up as very helpful for membranous nephropathy what you really want to look for in the question stem is someone who is Caucasian right and this is usually an adult so it's some type of Caucasian adult and this is usually the epidemiological range where you can see this one the other things that you want to watch out for is those infections so you can test them for things like HIV right you can test them for things like hepatitis you

can test them for things like syphilis so I apologize this one specifically Hepatitis B virus hepatitis C virus you can test for that you can do the rpr right testing for syphilis if you believe that that could be a potential cause and then look for any medications in their history so look for those particular medications that I told you which was gold or penicillamine so look for gold or some type of penicillamine now this is for the secondary causes right I told you that there is one particular primary thing that we can test for and

I'll talk about it down here in a little bit but it was that anti-pla2 receptor antibody you can test for that but that's not a secondary cause that's a primary cause so again that would be the big thing that would kind of ping off here is maybe this or potentially some of these for the focal segmental glomerulosclerosis you want to look for some type of African-American horse Hispanic male Hispanic adult these are usually the big things for this so look for some type of African-American Or Hispanic adult so again what you're already noticing is that

this could be one way of helping you to kind of stratify and differentiate is the child versus the adults it'll automatically kind of like point to these two if it's adult it'll kind of like point to this one if it's a child so look for that the other thing is we did say that this could be associated with HIV so you can do HIV testing and this can also be associated with heroin use so looking for that potentially in their history as well as things like sickle cell and looking for obesity as another Factor now

these ones I think are probably going to be the easiest secondary cause and I again I stress this what's the most common cause of chronic kidney disease diabetes what's the most common cause of nephrotic syndrome it's diabetes so diabetes is an easy one that you can obviously elucidate look for a history of diabetes but one's what's one thing that I can do and I can test for to find if they have diabetes a hemoglobin A1c right so that's usually going to be the biggest diagnostic tool here is a hemoglobin A1c like you know generally we

like to say greater than seven percent to really be a true effect on the actual kidneys all right but you know generally by definition it's anything like greater than 6.5 but usually when you get to greater than seven you start seeing a lot of kidney damage all right for amyloidosis the big thing for this one is if you're really looking for amyloidosis you want to consider things for multiple myeloma right or a lot of this antibody deposition in other areas so we can do two other tests if you're ever concerned for it you can do

what's called an S pep or a u-pap and that's usually very very helpful for multiple myeloma but if it's not completely clear another one that you could do is you could do what's called a fat pad biopsy and that's also very helpful for being able to identify amyloidosis and that's why when you have a patient who has nephrotic syndrome and they have amyloidosis or diabetes it is very rare that you would ever get renal biopsies on these patients because diabetes is the likely cause and if they have a history of diabetes it's likely that and

if they have a history of amyloidosis or you think it's amyloidosis I can kind of go away from doing a renal biopsy and do a fat pad biopsy okay but for completeness sake for the lecture you could consider doing a renal biopsy if there's an unclear cause of the nephrotic syndrome in other words it's a primary type minimal change remember it's the property focal segmental and it's idiopathic I don't know why there's no cues there's no keys that really kind of buzz out and help me out very much that's where renal biopsy would really kind

of solidify this but again I need to make sure that you guys understand for diabetic nephropathy and for amyloid nephropathy It's relatively rare that we would obtain these particular studies even in minimal change disease it's kind of rare that you would obtain it just because this isn't children renal biopsies are relatively contraindicated in children less than 10 years of age so it would also be something that you might not be getting but if you did get the renal biopsy what they do is they take a chunk of tissue out and they take that tissue and

they look at it under three different types of ways one is they look at what's called light microscopy electron microscopy and immunofluorescence all right basic things for this one light microscopy gives you General details this is some general basic look at the glomerulus electron microscopy Zooms in on the podocytes that's what I want you to remember General look at the glomerulus Zooms in on the podocytes immunofluorescence looks for antibodies or some type of immune complex that are deposited in the glomerulus and lights it up a beautiful fluorescent green that's it General change zooms under the

podocytes looks for antibody or immune complex deposition and lights them up green that's what this is helpful for and already I can tell you which ones are beneficial minimal change is the beautiful name it's a beautiful name because really there's only one thing that's happening with this it's podocyte to facement so if I'm facing the podocytes what would be out of all of these the tests that would be very helpful electron microscopy so the electron microscopy is going to be the best particular test here because what it's going to show me is the podocyte effacement

the light microscopy and immunofluorescence will be completely normal that's why it's a very minimal change all right but membranous nephropathy I said that there was immune complexes they were depositing into this particular area here so they were depositing all up in this area here and really causing a lot of problems so if I were to do these I could actually see something in each one if I did light microscopy I may see something what would I see generally you see a lot of just thickening of the glomerular basement membrane if I did electron microscopy I

zoom in on the podocytes what would I see in the podocyte area I would see effacement of the podocytes but what else would I see I'd see a lot of these immune complexes deposited in that sub-epithelial layer and immunofluorescence it's the one that's going to be the most helpful why because I'm going to light this thing up beautifully green showing that there is these antibodies that are depositing and kind of this nice granular fashion in that area okay so this will show GBM thickening this will show that spike in Dome pattern with potosite effacement from

the subepithelial deposition and this will show a nice granular green pattern this one ah for this one if I did light microscopy it'll give a general look and what it will show is it'll show a lot of that hyalenosis and sclerosis so to show a lot of hyalenosis and sclerosis of segments and parts of the glomerulus on electron microscopy it'll zoom in on the podocytes and show podocytic basement so for each one of the electron microscopies what should you see protocyte effacement which one will only have immunofluorescent positive membranous nephropathy which will only have hyalenosis

and sclerosis focal segmental glomerulosclerosis and which one will have GBM thickening and the spike in Dome pattern due to the immune complex deposition membranous nephropathy that's it so that's why these are relatively easy if you do a biopsy to identify these ones you won't be doing it because it's really off their history and you can avoid biopsying these patients but if you did really you could get most of your information off of these because what you're going to notice from these patients is they're going to have a lot of that nodular sclerosis we call this

the camel steel Wilson nodules that's going to be pretty obvious off their kind of light microscopy so you can honestly just do like light microscopy for these patients and be able to notice those Kimmel steel Wilson nodules same thing for amyloid nephropathy you're going to be able to notice a lot of like that sclerosis of the actual glomerular filtration barrier and it can be nodular but here's the key thing they stain it right they they stain the actual the biopsy tissue and what you look for is this weird thing where the amyloid proteins when you

stain them with what's called a Congo red stain they light up like an apple green color so you go it's called apple green by pharynge on a Congo red stain of this biopsy all right so I know this is a lot but I just want you to get the basic idea that we would only go to the renal biopsy usually if it's a primary type of nephrotic syndrome so minimal change membrane's nephropathy focal segmental where it's idiopathic we don't know the cause rarely for amyloid and diabetic okay with these you can get a good amount

of findings to truly differentiate which type it is now at least in the last step here which is how do we treat nephrotic syndrome let's talk about it all right so we've come to the point where we've said okay it's nephrotic it's not nephritic we figured out the cause if it was minimal change focal segmental members nephropathy diabetic amyloid if we were really kind of uncon not sure we could do the biopsy if we need to to Really delineate it based upon electron microscopy light microscopy immunofluorescence we got to the point where we came I

know the patient has nephrotic syndrome it's easy to treat this because you're treating the complication and then you're treating the cause and the complications are very straightforward we should know this proteinuria you're losing tons of protein this is the only one when I want to Mark the kind of mechanism just quickly because a lot of these are straightforward it makes your treatment you know remembering these very easy this is the only one I got I want to go into a little bit more detail for so for proteinuria obviously kind of maybe controlling the diet so

not kind of restricting proteins but really trying to just limit excessive amounts of protein and then the other one is ACE inhibitors and arbs if their blood pressure tolerates and believe it or not these patients also have that hypertension from the Rand and angiotense and aldosterone system so they will likely tolerate it but I want to explain how this helps okay so we know that in this patients who have nephrotic syndrome their Angiotensin II levels are usually High because of the Raz activation right so if you have higher Angiotensin II what that does is it

basically causes efferent arterial vasoconstriction so watch this look how narrow this sucker is going to be whoop there's like no blood leaving that glomerulus all right and so because of this one of the problems is that whenever you have high Angiotensin II we said it increases the interglomerular blood pressure that increases the GFR and this increases the protein loss all right so this is kind of like that Downstream effect from high levels of Angiotensin II all right so this is kind of what we expect to happen is when there's Angiotensin II it causes this this

this and this what if I gave an Ace inhibitor or an ARB guess what they're going to do ah my friend it's very good you're going to take an Ace inhibitor or an ARB and you're going to shut down the Angiotensin II if you shut down the Angiotensin II you will prevent this increase in adrenal blood pressure you'll prevent the excessive filtration and you'll prevent the protein loss and so that's why this is so great is because you get a double whammy effect out of this thing you inhibit protein loss and you inhibit the renin

angiotensinaldosterone system the renin Angiotensin aldosterone system that is also causing the patient's blood pressure to be high so that's another beautiful effect out of this is that you also will block the random angiotensinaldoctrine system will prevent the patient from having that secondary hypertensive effect beautiful everything else is pretty easy for the complications hyperlipidemia diet and then statins if that doesn't work so diet changes so diet changes and then statins for edema it's fluid and sodium restriction try to minimize as much fluid and sodium that you're getting into the body that can help to reduce some

of the edema and then if that doesn't work you can progress to diuretics like Loop diuretics hypercoagulable state because these patients are at very high risk for dvts PES renal vein thrombosis if they have any of these incidencies you should really continue anticoagulation for these patients so anticoagulation should be on the table for these patients as well and because they have a high infection risk what was the particular bacteria streptococcus pneumonia you better make sure that these patients are heavily vaccinated against the pneumococcus all right so pneumococcal vaccination and just a quick little kind of

like cool tip um is that impatients who have nephrotic syndrome not only is pneumococcal vaccination and helpful but you know what else increases strep pneumonia type of infections edema so if we want to basically inhibit streptococcus pneumonia not only should you vaccinate these patients but also reduce the edema because edema provides a nitus for strep pneumonia infections so don't let them develop any of this edema the last thing for the treatment is treating the cause so we know the complications all those results that we went into great detail about loss of immunoglobulins decrease in antithrombin

three hypo album anemia that's causing this hyperlipidemia due to the hypoalbum anemia and proteinuria due to the podocyte damage this is the cause it's minimal change Focus like mental membrane sarfaropathy diabetic nephropathy everything what I want you to realize is that there's the secondary and primary causes so when I say this I'm talking about okay secondary causes of nephrotic syndrome this is basically everything that we went over for each one so in other words if it's not primary minimal change disease if it's not primary focal segmental glomerulus gross if it's not primary membranous nephropathy or

if it's diabetic nephropathy or if it's amyloid nephropathy you have to treat the underlying cause so if it's secondary minimal change disease it's secondary membranous nephropathy secondary focal segmental glomerulosclerosis and if it's diabetic nephropathy or amyloid nephropathy you have to treat the underlying cause so in other words getting rid of NSAIDs treating their infection treating their Hodgkin's lymphoma treating their Hepatitis B treating their hepatitis C their syphilis getting rid of the offending medications treating their HIV telling them to stop doing heroin and also trying to control their Sickle cells this one glycemic control using insulin

if needed and this one depending upon the type of amyloidosis may require further like chemotherapy but that's the important thing is you have to treat the actual secondary cause which is a little bit beyond we can't go through every single one of these but you have to treat the causes that we kind of highlighted what we can discuss and is important to discuss is if they have primary causes of nephrotic syndrome in other words we don't know why it's likely genetic it's likely some type of like autoimmune component but we just don't know why what

are those that is your primary minimal change disease your primary focal segmental sclerosis and your primary membranous nephropathy so primary minimal change disease primary membranous nephropathy primary focal segmental glomerulosclerosis how do we treat these all of them you're going to start them off on steroids so you're gonna start steroids because you're going to try to suppress their immune response this one was a T Cell response this one was some type of immune complex response this one we don't even know how it forms but steroids are going to be the first particular thing now here's what's

really helpful in Diagnostics of the Therapeutics if that makes sense if they have a good response to the steroids so let's put that here a really good response that's highly suggestive of minimal change disease and oftentimes you can avoid doing the biopsy that's why we don't always go to biopsy first if there's a poor response to the steroids guess who it likely is it's your nasty primary ones that are in adults your primary membranous nephropathy or your focal segmental glomerulosclerosis so and these what did I tell you was the scary thing I don't put primary

focal segmental glomerulosclerosis what did I tell you was a big thing with these that they cause that this one does not cause these can cause end-stage renal disease so if they do not respond to steroids and you don't treat them any further guess what these suckers can do they can cause chronic kidney disease so they can jack up those kidneys and lead to in-stage renal disease do we want that no so steroids won't working what can I do to reduce the risk of these patients developing chronic kidney disease then I can put them on long

term and this is where we do the biopsy so usually if you put a patient on steroids they have a good response it's likely mental change if they did not have a good response it's likely these two you probably should get a biopsy to confirm and then put them on long-term immunosuppressive therapy because you don't ever want to commit a patient to this if you don't really know and so this is where you would do things like long term immuno suppressants and there's so many of these I'm just going to mention the biggest ones the

biggest ones that you'd want to be able to remember here is going to be something called um so we use cyclophosphamide this is a pretty good one and another one is called tacrolimus these are other types of immunosuppressants that have been shown to be pretty beneficial in these patient populations so again think about long-term immunosuppressive therapy if they failed steroids to prevent the progression to chronic kidney disease my friends in this video we covered nephrotic syndrome I hope it made sense I hope that you guys enjoyed it as always until next time [Music] [Music]