Wikipedia:VideoWiki/Minimal change disease
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Minimal-change disease, sometimes called nil disease, affects the millions of the kidney’s glomeruli, which are the specific parts of the kidney where small molecules are first filtered out of blood and into the urine. Specifically, it’s a type of nephrotic syndrome, in fact, the most common nephrotic syndrome seen in children.
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But what exactly is nephrotic syndrome? Well usually the glomerulus only lets small molecules—like sodium and water—move from the blood into the kidney nephron where it eventually make its way into the urine. But with nephrotic syndromes, the glomeruli are damaged and they become more permeable, so they start letting plasma proteins come across from the blood to the nephron and then into the urine, which causes proteinuria—typically greater than 3.5 grams per day.
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An important protein in the blood is albumin, and so when it starts leaving the blood, people get hypoalbuminemia—low albumin in the blood. With less protein in the blood the oncotic pressure falls, which lowers the overall osmotic pressure, which drives water out of the blood vessels and into the tissues, called edema.
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Finally, it’s thought that as a result of either losing albumin or losing some protein or proteins that inhibit the synthesis of lipids—or fat—you get increased levels of lipids in the blood, called hyperlipidemia.
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Just like the proteins, these lipids can also get into the urine, causing lipiduria. And those are the hallmarks of nephrotic syndrome—proteinuria, hypoalbuminemia, edema, hyperlipidemia, and lipiduria.
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Okay, so minimal change disease is a type of nephrotic syndrome—got it, but how exactly do those glomeruli start letting plasma proteins like albumin through?
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Well, usually, in the glomerulus, you’ve got your endothelial cells lining the capillaries, then the basement membrane, and then the podocytes, which are the cells that have these long tentacle-like projections, called foot processes, and this is also why they’re called podocytes since podo refers to the foot. The foot processes have a negatively charged coat that helps repel negatively charged molecules—like albumin, thereby acting as a charge barrier.
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With minimal change disease, although not completely known, it’s thought that the T cells in the blood release cytokines that specifically damages the foot processes of the podocytes, making them flatten out, a process called effacement. This means that there’s less of a charge barrier, right? And albumin is allowed to slip through from the blood into the nephron. Even though albumin goes through, other larger proteins like immunoglobulin aren’t allowed through, and so with minimal change disease there’s selective proteinuria. The exact identity and mechanism of these ominous T-cell cytokines, though, still remains a mystery.
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As far as causes of minimal change goes, in most cases it’s idiopathic, meaning the cause is unknown, although one interesting clue is that it’s associated with Hodgkin’s lymphoma, possibly because of the general increase in cytokine production in that disease.
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For diagnosis, minimal-change disease can be kind of tricky. With only light microscopy and H&E stain, you can’t see the foot process effacement, so it seems as if there’s no change to the glomerulus, hence the names “minimal-change” and “nil” disease. With electron microscopy, though, you can see effacement of foot processes. Also, immunofluorescence with minimal-change disease is usually negative, since the damage is due to cytokines, not immune-complex deposition.
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Treatment of minimal-change disease is typically corticosteroid therapy, of which about 90% of children respond very well. Adults also respond well to corticosteroid therapy, but their response is generally slower. In both cases, though, there’s a potential for relapse.
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Alright, so as a short recap, minimal change disease is a nephrotic syndrome thought to be caused by cytokine damage to the foot processes of the podocytes in the glomeruli of the kidney.
References edit
Pathoma (text)
Robbins Basic Pathology (text)
First Aid USMLE Step 1 (text)
http://emedicine.medscape.com/article/243348-overview#a5
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163769/