Wikipedia:Osmosis/Membranous nephropathy
Author: Tanner Marshall
Editor: Rishi Desai, MD, MPH
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. These subepithelial deposits are thought to activate the complement system, which is a cascade of enzyme activation that ultimately produces the membrane attack complex, which directly damages both the podocytes as well as mesangial cells, which are the cells that work to remove trapped residue and debris. The immune reaction also recruits inflammatory cells that release proteases and oxidants, which damage the basement membrane and cause it to become “leaky”, allowing proteins to filter through into the urine, which causes the signs and symptoms of nephrotic syndrome.
Over time, as a reaction to the immune deposits, GBM matrix is deposited in between the immune complexes, which makes the GBM appear thickened on histology. If you take a closer look on electron microscopy, you’ll see that this pattern of GBM matrix on the subepithelial deposits creates a characteristic “spike and dome” pattern, and you also see effacement or flattening of the foot processes of the podocytes. Finally, on immunofluorescence you’ll see deposits of immune complexes, which appear as granular or sort of sprinkled throughout the GBM.
Membranous glomerulonephritis most commonly affects caucasian adults, and it can be primary, or idiopathic, meaning it’s not quite clear why these complexes form, and this accounts for the vast majority of cases. The rest of cases, though, are secondary, and seem to arise from autoantibodies that are generated in response to another process like an infection, malignancies, autoimmune conditions, or medications. If it is secondary to some other disease, then usually treatment starts by treating the underlying disease. If it’s primary or idiopathic, then steroids are sometimes used, but they’ve been shown to have mixed results. If it goes untreated or the treatment is not successful, then membranous glomerulonephritis can progress to chronic renal failure.
Alright, quick recap—membranous glomerulonephritis is where immune complexes deposit in the GBM, causing a thickening of that GBM and a “spike and dome” appearance that leads to nephrotic syndrome.
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Sources
[edit]Robbins basic pathology (text)
Pathoma (text)