USMLE® Step 1 style questions USMLE
A 52-year-old female comes to the primary care physician due to worsening weight gain. She has gained approximately 20 lbs over the past six weeks. In addition, the patient has been experiencing lower extremity edema and has noticed her urine appears more cloudy than usual. Past medical history is notable for hypertension and hyperlipidemia. Temperature is 37.3°C (99.1°F), pulse is 76/min, respirations are 18/min, blood pressure is 137/84 mmHg, and O2 saturation is 97% on room air. Physical exam is notable for bilateral pitting edema of the lower extremities. A urinalysis is notable for 4+ protein and oval fat bodies but no hematuria. A renal biopsy is performed, and the following is visualized on light microscopy:
Reproduced from: Wikipedia
Which of the following is most suggestive of this patient’s underlying diagnosis?
Membranous nephropathy exam links
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Tanner Marshall, MS
Membranous glomerulonephritis, also known as membranous nephropathy, is where the glomerular basement membrane, or GBM, which lines the glomeruli in the kidney, becomes inflamed and damaged, which results in increased permeability and proteins being able to filter through into the urine, causing nephrotic syndrome.
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 makes 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 lipid in the blood, called hyperlipidemia.
Just like the proteins, these lipids can also get into the urine, causing hyperlipiduria.
And those are the hallmarks of nephrotic syndrome—proteinuria, hypoalbuminemia, edema, hyperlipidemia, and lipiduria.
Alright, so with membranous glomerulonephritis, the basement membrane becomes damaged which causes nephrotic syndrome. How does this happen, though? Well, ultimately this damage is caused by immune complexes—complexes composed of an antigen with an antibody bound to it.
One way these complexes can form is as a result of autoantibodies directly targeting the glomerular basement membrane.
Two major antigen targets that’ve been identified are the M-type phospholipase A2 receptor and neutral endopeptidase, which are both expressed on the podocyte surface—the cells that line the basement membrane, and we know this because a large proportion of cases, people with membranous glomerulonephritis have antibodies against these autoantigens in their bloodstream.
Immune complexes, though, might also form outside of the kidney, and then get carried through the bloodstream to the glomerulus and deposit in the basement membrane.
One potential circulating antigen that’s been identified is cationic bovine serum albumin, which is present in cow’s milk and beef protein, and can escape the intestinal barrier, cause immune complex formation, and deposit in the GBM.
Whether they bind directly to the GBM, or come from somewhere else, these immune complexes are called subepithelial deposits because they’re sandwiched right between the epithelial cells or podocytes, and the GBM.
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