AssessmentsNephrotic syndromes: Pathology review
USMLE® Step 1 style questions USMLE
A 62-year-old woman comes to the clinic due to progressive fatigue, weight loss, and ankle swelling for the past two months. Physical examination shows 2+ pitting edema around the ankles. Cardiovascular and respiratory examinations are non-contributory. Laboratory results show a serum creatinine level of 3.1 mg/dL, albumin of 2.2 g/dL, and total cholesterol concentration of 290 mg/dL. Urinalysis results show 3+ proteinuria without hematuria or red cell casts. Renal biopsy is performed, and the results are shown below:
Reproduced from: Wikipedia
Which of the following is the most likely explanation for this patient’s condition?
On the Nephrology ward, two people came in with the same symptoms: peripheral and periorbital edema.
One of them is a 10 year old caucasian boy named Brian who had recently been stung by a bee, and the other one is a 55 year old Hispanic individual named Gregory.
A 24-hour protein collection was done which showed massive proteinuria with more than 3.5 grams of protein lost through urine per day.
Nephrotic syndrome happens when the glomeruli are damaged and they become more permeable, so they start letting plasma proteins pass from the blood to the nephron and then into the urine.
This leads to proteinuria, which is when more than 3.5 grams of protein is excreted through the urine per day.
One of the proteins lost through urine is albumin and this leads to hypoalbuminemia.
This causes peripheral and periorbital edema since there’s less oncotic pressure in the blood vessels and the fluid leaks out.
The reason for this is that the person is also losing antithrombin III proteins which is the body’s anticoagulant.
Immunoglobulins are another type of proteins lost through urine, which means that there’s a higher risk for infection.
Now, apart from proteins, lipids are also lost through urine, which gives the urine a frothy or foamy appearance.
It’s also important to remember that one of the secondary changes in individuals with nephrotic syndrome is that the liver will increase lipoprotein synthesis, which results in hyperlipidemia.
Now, nephrotic syndrome can be primary, due to direct sclerosis of podocytes on the glomerulus.
Let’s begin with minimal change disease and a commonly tested fact is that this is the most common cause of nephrotic syndrome in children.
The cause is most often idiopathic and it can be triggered by a recent infection, recent vaccination, or by an immune stimulus, like a bee sting.
It’s also important to remember this disease is caused by T cells in the blood, releasing cytokines-glomerular-permeability factor, that specifically damages the foot processes of the podocytes, making them flatten out, a process called effacement.
Damaged foot processes lose their negatively charged coat, eventually allowing negatively charged molecules, like albumin, to slip into the nephron.
Even though albumin goes through, other larger proteins like immunoglobulins don't.
So for your exam it’s important to remember that in minimal change disease there’s selective proteinuria; in contrast to other causes of nephrotic syndrome which are characterized by non-selective proteinuria.
On light microscopy, the glomeruli look completely normal.
Immunofluorescence is negative.
The only changes are seen on electron microscopy, where there’s effacement of podocyte foot processes.
The last high yield fact is that idiopathic minimal change disease is the only nephrotic disease that can be consistently treated with corticosteroids.
Next is focal segmental glomerulosclerosis, which is the most common cause of nephrotic syndrome in individuals of African or Hispanic descent.
Focal segmental glomerulosclerosis is more common in adults and can be idiopathic, but the most common clues test makers give is a history of heroin abuse,
The cause of focal segmental glomerulosclerosis is not exactly known yet, but you need to know is that just like minimal change disease, there’s effacement of podocyte foot processes.
Additionally, with focal segmental glomerulosclerosis, there’s also hyalinosis that’s caused by deposition of lipids and proteins in the glomerulus.
Over time, hyalinosis further develops into sclerosis or scar tissue.
On light microscopy, there’s sclerosis and hyalinosis among the glomeruli.
For your tests, it’s important to understand that in focal segmental glomerulosclerosis, segmental means that only a segment, or part of the glomeruli is affected, and focal means that only some of the glomeruli are affected.
Immunofluorescence is often negative, but can sometimes be positive for deposits of C3, C1 or IgM.
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