nodules are a feature of diabetic nephropathy and are described as nodular hyaline deposits in glomeruli.
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A 50-year-old man comes to the office because of foamy urine for 6 weeks. He states that he used to get a little foam in the past when rapidly emptying a full bladder, however recently he has been getting foam whenever he urinates, regardless of amount or time of day. His medical history includes osteoarthritis, gout, and type II diabetes mellitus. His temperature is 36.8°C (98°F), pulse is 87/min, respirations are 18/min, and blood pressure is 152/89 mm Hg. Examination shows decreased fine sensation on both feet bilaterally. There is also a skin ulcer on the left hallux which appears to have been there for some time. Laboratory investigations show there are no erythrocytes on urinalysis, and that the albumin/creatinine ratio is 42 mg/mmol. Which of the following is the most likely diagnosis?
Each kidney has millions of nephrons, each of which is served by a tiny capillary bed called a glomerulus.
The tiny arteriole that approaches the glomerulus is called the afferent arteriole - a for approaching, and the arteriole that exits the glomerulus is called the efferent arteriole - e for exits.
The glomeruli are a tiny cluster of capillaries that are physically supported by mesangial cells.
So when blood is filtered it moves through the endothelium lining the capillary, then through the basement membrane, and then through the epithelium lining the nephron, and finally into the nephron itself - at which point its called filtrate.
The endothelium has pores that keep cells from entering the filtrate, and the basement membrane is negatively charged and repels other negatively charged molecules and proteins, like the protein albumin.
The epithelium has of special cell type called a podocyte which looks like an octopus because it has foot processes that wrap around the basement membrane, leaving tiny gaps between its octopus-like projections called filtration slits.
In diabetes mellitus, there’s an excess of glucose in the blood, because it can’t get into cells, and when blood gets filtered through the kidneys, some of that excess glucose starts to spill into the urine, called glycosuria.
In addition, when there’s a lot of glucose in the blood, it also starts sticking to proteins in the blood — a process called non-enzymatic glycation because no enzymes are involved.
Because glucose can get through the endothelium, this process of glycation can also involve the basement membrane of small blood vessels making it thicken. The process particularly affects the efferent arteriole causing it to get stiff and more narrow - a process called hyaline arteriosclerosis.
This creates an obstruction that makes it difficult for blood to leave the glomerulus, increasing pressure within the glomerulus. At the same time, the afferent arteriole dilates, allowing more blood flow into the glomerulus and increasing pressure further.
High pressure in the glomerulus leads to an increase in the glomerular filtration rate--which is simply the amount of blood filtered through per minute. This is the first stage of diabetic nephropathy, called hyperfiltration.
In response to this high-pressure state, the supportive mesangial cells secrete more and more structural matrix expanding the size of the glomerulus. This matrix deposition and mesangial expansion happen uniformly, or it can result in little nodules within the mesangium called Kimmelstiel-Wilson nodules - which are tiny little balls of protein.
The thickening of the basement membrane counterintuitively makes it more permeable—allowing proteins like albumin through that otherwise would have been filtered out.