Nephrotic Syndrome: Etiology

by Amy Sussman, MD

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    00:01 Before moving on, I think it's important to review the resident glomerular cells.

    00:05 So let's look at our schematic over here to the right.

    00:08 The glomerular endothelial cell is represented in yellow and it lines are capillary lumen.

    00:16 The masangial cell, outlined in blue, is what provides structural support and makes extracellular matrix.

    00:23 The podocytes or glomerular epithelial cell is represented in red, and it lines the outer aspect of the capillary loop and I want to take just a moment for you to really appreciate where that podocyte is.

    00:35 Is look at the cell body and how it's really just hanging in the urinary space and what's actually attaching that podocyte to the underlying glomerular basement membrane are those foot processes.

    00:46 If you look now at my electron micro graph over here, you can see on the left is our actual cell body and then on the right are those foot processes and look how beautiful they are and how they line up just like a picket fence.

    00:59 They actually interdigitate with each other and there's a slit diaphragm between them and that really is critical to maintaining that glomerular capillary wall and that ability to keep that filtrate in macromolecules from escaping.

    01:14 So the podocyte has a couple of different jobs it maintains loop shape.

    01:19 It provides the size and charge barrier to filter protein.

    01:24 And it synthesizes and maintains glomerular basement membrane.

    01:28 So what I have represented over here is a scanning electron micrograph.

    01:31 And what I want you to appreciate is how those foot processes interdigitate with each other and you can see how that's so critically important in order to be that ultimate barrier to keep those macromolecules from filtering out.

    01:45 Okay, so we've discussed the resident cells let's talk now a little bit more about nephrotic syndrome and what the ideologies are.

    01:52 When we think about that we can group them into primary glomerular diseases and secondary glomerular diseases and before moving on what I'd like you to appreciate is that anytime we're talking about glomerular diseases there's a couple of different things that go into it.

    02:06 Number 1, our patients tend to have a genetic predisposition we know this because when we do genome-wide association studies, there are things about our patients that are that predispose them.

    02:15 Number 2, there's some kind of environmental trigger that happens.

    02:19 In number three, our patients have the tendency towards autoimmunity and then manifests with these glomerular diseases.

    02:25 So again, when I'm thinking about primary glomerular diseases, these are diseases where there's an immune mediated injury to the podocyte.

    02:33 We also call them immune podocytopathy.

    02:35 So I want you to think of it in a sense that the podocyte really is the star of the show.

    02:40 These are diseases like membranous nephropathy, minimal change disease, and focal segmental glomerulosclerosis.

    02:47 It's a mouthful. So often times we just say FSGS.

    02:50 Remember no proliferative glomerularnephritis this is also included in this category.

    02:55 When we think about secondary systemic diseases, This is where the podocyte injury really is a consequence to an old underlying systemic disease.

    03:03 So it's kind of an innocent bystander that gets injured during this process of other disease process.

    03:09 This includes amyloidosis, diabetic nephropathy, and systemic lupus erythematosus or lupus nephritis.

    03:16 Now as you can see, I've bolded both membranoproliferative glomerulonephritis and lupus nephritis.

    03:21 And the reason being is that these two diseases can present both with nephrotic syndrome and with nephritic syndrome, but because they have more of an inflammatory etiology, we're going to be talking about them in the nephritic syndrome lecture.

    About the Lecture

    The lecture Nephrotic Syndrome: Etiology by Amy Sussman, MD is from the course Nephrotic Syndrome.

    Included Quiz Questions

    1. Membranoproliferative glomerulonephritis
    2. Amyloidosis
    3. Membranous nephropathy
    4. Diabetic nephropathy
    5. Focal segmental glomerulosclerosis
    1. Diabetic nephropathy
    2. Minimal change disease
    3. Focal segmental glomerulosclerosis
    4. Membranous nephropathy
    5. Membranoproliferative glomerulonephritis

    Author of lecture Nephrotic Syndrome: Etiology

     Amy Sussman, MD

    Amy Sussman, MD

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