Now, renal failure.
Everything we talked about in that table, objective measures,
the second order testing, and where you are,
and why it’s taking place with the kidney,
all begins with the understanding of what we’re looking at here.
Pathophysiology of renal failure is huge.
Let’s begin at the top.
Let’s say now your patient has diabetic nephropathy.
How do you know?
Well, there’s microalbuminuria that was found
and your patient now has the symptoms of chronic renal failure.
First, the hypertension that we talked about earlier
was the fact that the GFR is decreased, you’re holding on to your fluid, hypertension.
Second, with the creatinine that will be increased as well as your potassium as well.
Now, if your kidney is dying,
then, I want you to go to the proximal convoluted tubule, PCT, it’s not functioning properly.
A very important enzyme that will activate your vitamin D.
That’s called 1-alpha-hydroxylase.
That is not functioning properly or it is inadequately functioning.
So for all intent and purposes,
you cannot form the active form of vitamin D which is calcitriol.
Now, you begin there and for the most part,
you’ll almost get all of the symptoms that should require
to diagnose your patient with the chronic renal failure
or at least will give you the symptoms of uremia.
Keep in mind the only other time that uremia could come into play,
apart from chronic renal failure would have to be with acute renal failure,
and you are dealing with the - good,
initiation or more importantly, the maintenance phase.
But I told you with that though, there is going to be
this whole thing about prerenal reestablishment
and perhaps going into recovery phase.
No such luck here.
Also, another important point that I wish to make here
is that we discussed glomerulonephritis -
when we discussed your glomerulonephritides,
but one of the important nephrotic syndrome was Focal segmental glomerulosclerosis.
So in renal failure, as you go through the various stages
and it’s important ladies and gentlemen, that you refer to that table
with the various stages of chronic renal failure.
Does it go - as your stages increase in severity and you get into stage four,
please understand that the glomeruli are starting to die
and so therefore, the existing glomeruli wanna undergo the process of compensation.
That compensatory hypertrophy that the existing glomeruli are undergoing
is then referred to as being your focal segmental glomerulosclerosis,
extremely common in our society.
That you cannot forget as being an important conversation,
an important pathologic point of view from renal failure.
Now, let’s get back to vitamin D.
If you’re an adult, remember, if with the diabetic nephropathy,
most likely an adult, and if they don’t produce or have enough vitamin D or Calcitriol,
for all intents and purposes, they are calcium depleted, aren’t they?
Next, if you’re deficient of vitamin D as an adult, what’s the technical diagnosis?
Not rickets, but good, osteomalacia.
So 1-alpha-hydroxylase is not working properly in the PCT.
You have decreased calcitriol,
so therefore, you have decreased calcium absorption
both from the kidney and also from the GI system.
If you are now rendered hypocalcemic, you are then going to recruit who?
Good, PTH, parathyroid hormone is then going to be recruited.
We will come into that and that is then referred to as being your
In the meantime, would you tell me the normal function of PTH with phosphate?
PTH works in the PCT.
Yet once again, apart from trying to activate 1-alpha-hydroxylase and that ain't happening.
Number two, it’s trying to do what?
It’s trying to inhibit the reabsorption of phosphate
so you flush your phosphate out, normally you can’t do that.
And the PCT once again, your PTH isn’t working properly,
you end up having hyperphosphatemia.
So whenever you see hyperphosphatemia in your patient
in a clinical vignette, you know, high in the differential,
you should be suspecting, is my patient having some type of renal failure?
Now, what is hyperphosphatemia? We’ve got a problem.
Phosphate can never go by itself, it’s completely dependent.
It’s one of those partners where you can’t live with them and you can’t live without them.
And by that I mean, the hyperphosphatemia is going to highly complex with calcium.
You already know that as being part of formation of bone.
It’s called hydroxyapatite, don’t you?
So therefore, the hyperphosphatemia is going to rob the free calcium.
It robs all the single calcium, so now, what happens?
You have decreased free calcium, clear? Don’t forget that.
And if your hypocalcemia are free,
then you may have issues with things like tetany and company.
The hyperphosphatemia further inhibits more 1-alpha-hydroxylase.
Therefore, only makes matters worse about hypocalcemia.
Point number two, this compensation, we have decrease in calcium
leads you into compensatory or secondary hyperparathyroidism.
Now, why is the PTH coming out?
The PTH is coming out in droves
because it wants to try to reabsorb the calcium from the kidney.
The kidney’s dead.
Where else does PTH work? Good, it works in the bone.
And what is its primary job on the bone, to build or to resorb?
Resorb, we’ve got a problem.
If you have too much, secondary hyperparathyroidism.
In all of this PTH, an army of PTH is now turning to the bone.
Destroy the bone, what do we call this? Renal osteo bone destruction.
Welcome to renal osteodystrophy, is that clear?
You walk into a dialysis clinic, you’ve got plenty of them
probably in your town, and that’s not funny actually.
But he walk into that dialysis clinic, every single one of those patients
sitting on their thrones have dialysis
are receiving either calcium or vitamin D supplement, aren’t they?
But at the same time, you know that patient who’s on a dialysis
is also getting a chelating agent for the hyperphosphatemia.
You have to because the more that you feed calcium
without removing the phosphate, what are you doing?
Oh my goodness, I’m forming a complex.
You don’t want that, you definitely don’t want that
may result in something like metastatic calcification even, keep that in mind.
So renal failure, continue, we have renal osteodystrophy,
now this should make perfect sense.
Hypocalcemia, secondary hypoparathyroidism,
we then go into the bone and remove it.
Work through the action of osteoblasts, osteoclasts,
resorption, resorption, resorption of your bone, renal osteodystrophy.
Now, in our society, it’d be very rare for this to go into worst case scenario
and the worst case scenario, you might ever heard of something like
Von Recklinghausen, right, or osteofibrosis cystica.
That would be worst case scenario
but that would be more of a symptom that you would find with primary hyperparathyroidism,
not so much secondary, renal osteodystrophy is.