Nephrotic Syndrome: Pathophysiology with Case

by Amy Sussman, MD

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    00:01 Hello and welcome back.

    00:03 Today in our nephrology curriculum, we're going to be talking about nephrotic syndrome, which are part of the glomerular diseases and one of my personal favorites.

    00:11 Let's start out with a clinical case.

    00:13 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.

    00:21 His laboratories are significant for a serum creatinine of 1 .2 milligrams per deciliter.

    00:26 His the albumin in the serum is low at 2 grams per deciliter.

    00:31 His urine analysis shows four plus protein on the dipstick, but there are no white cells are red cells by microscopy and he has about 8 grams of protein estimated on a urinary spot protein to creatinine ratio.

    00:44 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.

    00:54 So what we can see is that our patient had worsening lower extremity edema, and this is because of that low albumin or a hypoalbuminemia.

    01:01 Why does he have a low albumin? Because he's spilling a lot of protein in his urine we have 8 grams of protein in the urine.

    01:08 That's a large quantity.

    01:10 He has a normal serum creatinine relatively and he has no red blood cells or no white blood cells in his urine.

    01:17 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 podcyte which is the superstar of nephrotic syndrome has the letter O in it.

    01:34 When we think about nephritic, it has an I on it.

    01:37 When we think about nephritic diseases, they're more inflammatory.

    01:41 So I think that can help us distinguish between nephrotic and nephritic syndrome.

    01:45 So of course in our answer, this is nephrotic syndrome.

    01:50 So let's talk a little bit about what nephrotic syndrome is.

    01:53 It's actually characterized by the clinical presentation of four different things.

    01:58 Number 1.

    01:59 Our patients have to have nephrotic range proteinuria.

    02:02 That means they have greater than 3.5 grams of protein in their urine over a 24-hour period of time.

    02:09 Our patients also manifest with hypoalbuminemia in this serum.

    02:14 Those serums albumin levels are less than 3 grams per deciliter.

    02:17 Remember normal is four grams per deciliter.

    02:20 Sometimes with certain of radek syndromes, we can see even a 0.8 grams per deciliter.

    02:26 The serum albumin is so low.

    02:28 Our patients also have edema as shown here in our schematic in the diagram.

    02:33 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.

    02:42 And of course, we have hyperlipidemia and lipidurea.

    02:47 So let's talk about these a little bit more closely so we can better understand the pathophysiology of nephrotic syndrome.

    02:53 So proteinurea, we talked about high-grade proteinuria greater than 3.5 grams.

    02:58 We know that this is glomerular proteinurea because the principal component is going to be albumin.

    03:03 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 to podocytes.

    03:16 As I mentioned albumin is kind of the star player here.

    03:19 It's the principle protein that makes up that urinary protein and that's what's lost in glomerular proteinuria.

    03:25 We can lose other things like clotting inhibitors, transferrin, and vitamin D binding protein as well.

    03:31 But we really think about our patients as losing a lot of albumin.

    03:34 Now, if you look at our schematic over here, we actually have the glomerular capillary wall.

    03:39 So to the right of the slide we have that capillary lumen.

    03:42 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 podocytes foot processes.

    03:55 And those are incredibly important because their job as they interdigitate together.

    04:00 They form these elegant 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.

    04:13 When we have problems with glomerular proteinuria, there's something wrong with the integrity of those podocytes in those slit diaphragm so they can't interdigitate the way they should and then therefore we have escaped of macromolecules into the urinary space.

    04:28 So we mentioned that our patients have hypoalbuminemia, and that's simply due to the consequent loss of albumin in the urine.

    04:35 Our liver tries it's best to synthesize as much protein as possible.

    04:39 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.

    04:48 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.

    04:55 And then often times our patient's albumin levels will drop to less than 2 grams per deciliter.

    05:01 We also mentioned edema, and this is consequent to the hypoalbuminemia that causes egress so fluid into the interstitial space because we have a decrease in plasma oncotic pressure.

    05:11 We don't have album in there to hold on to that vascular fluid into the vascular space.

    05:16 We also get stimulation of the renin-angiotensin system.

    05:20 So in the end, we end up with aldosterone release causing marked sodium retention that's working at that principle cell.

    05:26 We have sympathetic stimulation to increase sodium retention and we also have reduce to natriuretic peptide release.

    05:33 All of us together causes that soft pitting dependent edema that we see in our patients.

    05:40 Finally, we have hyperlipidemia.

    05:43 Remember that decreasing oncotic pressure is also going to stimulate hepatic lipoprotein synthesis.

    05:48 So the liver will be producing a lot of lipid that's going to manifest as hypercholesterolemia or hypertriglyceridemia.

    05:58 We can also see lipiduria.

    06:00 That's when lipid actually becomes in trapped in the urine in the cellular casts or in cass so you can see that also in the plasma membrane of a degenerated tubular epithelial cell.

    06:11 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 to become engorged with lipid and they turn into these ol fat bodies that you can see right here in our slide.

    06:26 So it almost has a little bit of a brownish hue with his refractory elements.

    06:30 Those are lipid oval fat bodies.

    06:32 Now, if you're lucky enough to have a polarizer on your microscope, these guys can actually turn or show multis crosses where that where those lipid elements are.

    06:43 There actually fun to look at underneath the urine underneath a microscope.

    About the Lecture

    The lecture Nephrotic Syndrome: Pathophysiology with Case by Amy Sussman, MD is from the course Nephrotic Syndrome.

    Included Quiz Questions

    1. Hypoalbuminemia
    2. Proteinuria of <2.5 g/24 hours
    3. Inhibition of the renin-angiotensin system
    4. Hematuria with RBC casts
    1. Increased hepatic lipoprotein synthesis
    2. Decreased renal excretion of lipoprotein
    3. Increased activity of lipoprotein lipase
    4. Laboratory error because of hypoalbuminemia
    1. Glomerular proteinuria leads to loss of clotting inhibitors.
    2. Nephrotic syndrome is the result of inflammation affecting the glomeruli.
    3. The edema in nephrotic syndrome is mainly due to increased hydrostatic pressure.
    4. Nephrotic syndrome is characterized by sodium and water depletion.

    Author of lecture Nephrotic Syndrome: Pathophysiology with Case

     Amy Sussman, MD

    Amy Sussman, MD

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