- [voiceover] diabetic nephropathyis one of the most common and serious chronic complications associated with diabetes mellitus. in this tutorial, let'sdiscuss how the mechanisms underlying diabetic nephropathy
correlate with the clinical presentation as well as the treatment of the disease. now fortunately the mechanisms underlying diabetic nephropathy,
directly correlate withthe clinical presentation. and the first clinicalfinding of the disease is somewhat paradoxicallyan increased kidney filtration rate orglomerular filtration rate. so, diabetic nephropathy,if you break down the term into nephro and pathy literally means kidneydisease caused by diabetes. now typically kidney disease is marked by a decreased filtration rate,
so why is it that the first clinical stage of diabetic nephropathy is that of an increased glomerularfiltration rate? well recall that the earliest mechanism contributing to diabetic nephropathy is an increased pressurestate, over here in blue. and this is due to hypertension and efferent vasoconstriction. so let's use a common garden hose
to help illustrate how thisincreased pressure state will ultimately result in an increased glomerular filtration rate. so, imagine you have this garden hose and it has a small holein the middle of it. so first you're gonna open up the spigot and increase the pressureand flow through the hose. intuitively, this isgoing to increase the rate at which water is leakingfrom the hole in the hose.
next, you partially kink off the end of the hose distal to the hole, and once again this isgonna further increase the rate at which waterleaks from the hose. this is essentially what'soccurring in the glomerulus with the hypertension representing the opening up of the spigot and increasing the pressurebefore the glomerulus, in front of the glomerulus,
and the efferent vasoconstriction representing the kinking off of the hose, which causes this back pressure. both of which are going toincrease the filtration rate. this stage of diabetic nephropathy is most commonly asymptomatic, so it goes typically unnoticed. however, it's going to set the stage for the next clinical stepof diabetic nephropathy;
and that is detectable proteinuria. and what proteinuria isis protein in the urine. so this increased pressure state causes trauma on the mesangium, in the middle of the glomerulus here and it results in mesangial expansion, which is this second mechanismof diabetic nephropathy. now as the mesangium expands, this also increases thesize of these fenestrations
or spaces between thepodocyte foot processes, so let's go back and look real closely at these fenestrations andwatch how they increase in size. now, these podocytefenestrations are a component of the glomerular filtration mechanism. so, let's think of thesepodocyte foot processes as a coffee filter. a proper coffee filter is porous enough to allow for the water to flow through,
but will retain the coffeegrounds within the filter. this is because the molecules of water are much smaller than thesize of the coffee ground, so over time the coffee pot is gonna fill just with the coffeebut no coffee grounds. now imagine if the coffee filter was replaced with a cooking strainer, which has considerably larger pores. if you were to try anduse a cooking strainer
as a coffee filter, when youpour the hot water through, it's not gonna work because the pores of this cooking strainer are much larger. both the coffee as well as the grounds are gonna start to spill through and you're gonna end up withcoffee grounds in your coffee. so in the glomerulus, the fenestrations between these podocyte foot processes are kind of like coffee filters
and normally in the filtration of blood no proteins or largemolecules are allowed though. however, with mesangial expansion these fenestrations become much larger and when filtrationoccurs they become leaky, and they allow formolecules, such as proteins, to be spilled out into the urine. so this is what causesthe detectable proteinuria in diabetic nephropathy.
one of these proteins is albumin. urine tests are available to detect the presence of albumin in the urine, so frequently individuals with diabetes will have routine screening to test for this albumin or forprotein in their urine, which is a sign that they may be developing diabetic nephropathy or kidney disease due to diabetes.
then the next clinical stageof diabetic nephropathy is that of a decreasedglomerular filtration rate. so you can see that we've gone from an increased glomerular filtration rate, then to a decreasedglomerular filtration rate. so what exactly causes this? well, recall that part of the reason for this mesangial expansion is the release of cytokineswhich cause inflammation
and oxygen free radicals. now, these cytokinesand oxygen free radicals damage the mesangium, resultingin the mesangial expansion. however, they don't justdamage the mesangium. they damage the cellsthroughout the tubules as well as the vasculaturethat supports the nephron. now in addition to the cytokinesand oxygen free radicals, this vasculature is further damaged by this efferent vasoconstriction here.
which is one of the causes ofthat increased pressure state. and this combination of damage from decreased blood flow and cytokines and oxygen free radicals results in ischemia andatrophy of this vasculature. as this vasculature kind of dies off, it no longer can supportthe tubules of the nephron, so the nephron itselfbegins to die off as well, and so there's a decreasedability to filter the blood.
now initially this occursin just a small percentage of the nephrons in the kidney, and the kidney's able to compensate, but eventually over time ifthis diabetic nephropathy is not treated, a large enough number of nephrons throughout thekidney are gonna die off, and it's gonna be detected asa decreased filtration rate. the kidney's no longer able to keep up with the dying off of nephrons.
if this is present, thisdecreased filtration rate is present for more thanthree months in a row, then it's known as chronic kidney disease. as it continues to progress, eventually it will becomea permanent decrease, which is then known asend-stage renal disease. now that we have a better understanding of the mechanisms thatcause diabetic nephropathy and how they correlate withthe clinical presentation,
let's just briefly touch on how diabetic nephropathy is treated. this is, once again, gonnabe directly correlated to the underlying mechanisms. so, the most important thingin diabetic nephropathy is to treat the underlying diabetes. this is because the hyperglycemiaassociated with diabetes is the cause of thisincreased pressure state, so if you can treat the diabetes,
you can prevent theincreased pressure state, which will then preventthe cascade of effects leading to diabetic nephropathy. however, if this increased pressure state does start to occur, the next step is to treat the pressure. and what i mean by thatis treat the hypertension. so if you can decrease the blood pressure, that goes into theafferent arteriole here,
you'll decrease thisincreased pressure state. in addition, one of themost common medications to treat blood pressure areknown as ace inhibitors. now ace inhibitors stands for angiotensin converting enzyme inhibitor and angiotensin is one of the hormones in thatrenin-angiotensin-aldosterone system that results in theefferent vasoconstriction. so by treating the bloodpressure with an ace inhibitor,
you're also going to decreasethis vasoconstriction to further decrease this pressure state within the glomerulus. these two treatments should be occurring regardless of whether or not an individual with diabetes is in any of these clinical stagesof diabetic nephropathy. so these are not only treatments, but they're also good for preventing
the progression of diabetic nephropathy before someone even entersthis first clinical stage. however, if someone doesdevelop diabetic nephropathy and it unfortunately progresses far enough to have this decreasedglomerular filtration rate and they end up inend-stage renal disease, unfortunately then there areonly two treatment options. the first is dialysis, in which the blood is filtered outside the body by a machine
to kind of replace theeffect of the kidney. and the other is a kidney transplant. fortunately though, likemost of the complications
Diabetic Retinopathy Icd 9,of diabetes mellitus, ifthe underlying disease and its comorbidities,such as hypertension, are properly treated, diabetic nephropathy can be a preventable complicationof diabetes mellitus.
Now you understand how to handle your condition, you will be far better ready to make your proper choices and alterations in your life. Remember that these tips are only pertinent if you use as the majority of them as is possible, and for that reason you should commence right now to see quick final results.
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