Minimal change disease

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Minimal change disease

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USMLE® Step 1 style questions USMLE

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A 13-year-old male with a history of non-Hodgkin lymphoma presents to the primary care physician with leg swelling. He states that “My shoes won’t fit anymore, and I feel like I’ve gained weight too.” The patient last received treatment for non-Hodgkin lymphoma 1.5 weeks ago. Temperature is 37.0°C (98.6°F), pulse is 80/min, respirations are 18/min, and blood pressure is 105/64 mmHg. On physical exam he is noted to have bilateral periorbital edema and 2+ pitting edema of the lower extremities. Urinalysis demonstrates 4+ protein and is negative for blood. The patient subsequently undergoes a kidney biopsy. Which of the following findings is most likely to be observed on electron microscopy?  

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Minimal change disease p. 612, 613

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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.

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.

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.

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.

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.

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?

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.

Sources

  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine" McGraw Hill Education/ Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "The Treatment of Minimal Change Disease in Adults" Journal of the American Society of Nephrology (2013)
  6. "Minimal Change Disease" Clinical Journal of the American Society of Nephrology (2016)
  7. "Management of Childhood Onset Nephrotic Syndrome" Pediatrics (2009)
  8. "The Treatment of Minimal Change Disease in Adults" Journal of the American Society of Nephrology (2013)
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