Now with Fanconi, further definition,
generalized dysfunction of PCT due to cellular
energy metabolism might be lost. Remember
the PCT is the segment of the nephron that
requires quite a bit of ATP, doesn't it? Because
it requires that basolateral membrane, sodium-
potassium ATPase pumped to generate that
symport and antiport and so forth result in
impaired reabsorption of almost all of your substances,
and may result in all kinds of issues may
be idiopathic, maybe you have drugs that may
then cause toxicity. Multiple myeloma, which
we'll talk about this as being
paraprotein type of issue and multiple myeloma,
we will talk about Bence-Jones light proteins.
You have recap on them and we will talk
about that in great detail. This may then
cause damage to the PCT along with your myeloma
casts. Do not worry. All this is to come and
it might be inherited disorder. Now this is
interesting. Pay attention. The most common
is cystinosis. So in inherited disorder in
which it may cause damage to your PCT, inherited,
a cystinosis, a rare disorder of cysteine deposition
in tissue. So in an inherited disorder, cystinosis,
there might be generalized damage to the PCT.
All this is saying on this particular slide
is the fact that we have numerous causes of
Fanconi syndrome. What does this mean? It
means generalized dysfunction of the PCT.
What are you going to find in your labs? Pretty
much everything is decreased. Your pH is decreased,
why please? Because you cannot reclaim your
bicarb. What kind of RTA is that? Renal tubular
acidosis. May I ask you something? What if
you took that drug called acetazolamide? When did
we, you and I, give acetazolamide? Who is that
patient? High altitude. To do what? To facilitate
the renal compensation, to get rid of bicarb
in the patient that had respiratory alkalosis.
Are you with me? Good. If you are getting
rid of your bicarb in the patient, with acetazolamide,
technically speaking what are you creating?
A type II RTA. What if you had a patient, listen
to this one, the boards or the wards or whatever
will ask you such questions, think. What
if you have a patient who genetically was
missing carbonic anhydrase? If you are genetically
missing, autosomal recessive disorder, in which
your carbonic anhydrase is missing, what happens
to your renal threshold for reclaiming bicarb?
It is decreased. What kind of RTA is this?
RTA type II. You see that. So all that RTA
type II means to you is the fact that well
it is just a consequence of many diseases
of the proximal convoluted tubule. Be smart
about how you approach diseases. Keep
abreast of you, do not dive into the details
immediately without first understanding of
the big picture.
Next in Fanconi, you are going to lose everything.
Polyuria, polydipsia, dehydration, in other
words, there is a lot of solute in my urine.
You tell me what kind of diuresis. Osmotic
diuresis, pathologic of course. You give me
a diuretic provides osmotic diuretic or
as it works its osmotic diuresis. Mannitol.
Multiple metabolic issues. We talked about
metabolic acidosis, what kind please? RTA type II.
Your next step is this. You ready? So
you find your patient having metabolic acidosis.
What does that mean in terms of pH? Decreased.
What does that mean to you specifically? You
have your pH being less than 7.35 or so. I
will give you something significant like maybe
7.2. So for sure you know you're acidosis. You
take a look at your bicarb and it's less than
22, maybe 18, maybe 15. So now you have confirmation
of metabolic acidosis. Are we clear?
And so, therefore, how would you then compensate
well? The compensation would be immediate
with respiratory blowing off with hyperventilation,
are we clear? Good. Fanconi syndrome, RTA
type II. Hypophsophatemia, you are getting
rid of your phosphate. Remember you lost
homeostasis of phosphate in the PCT. Indirectly
you might end up losing your potassium, hypokalemia
and may result in hypocalcemia. Remember the
reason that we have bone next to calcium and
phosphate, how do you form bone? How do you
make your bone extremely strong? It is called
hydroxyappetite. Correct? Hydroxyappetite,
what does that actually mean? The combination
of calcium and phosphate, it's the proper mineralization
of your bone. End up losing the calcium and
you lose your phosphate, your bone is definitely
going to be affected or influenced. So you can see
Fanconi syndrome is a wonderful disease in
which we can integrate and bring in a lot
of issues all at the same time.
Major complication. We talked about the bone
formation resulting in growth impairment and
perhaps even failure to thrive. Let us talk
about a couple of other diseases here of the
PCT. We haven't left PCT yet. Now we have hartnup
because in hartnup you cannot properly reabsorb
tryptophan. Got that. P and P. Hartnup, tryptophan.
So these are neutral amino acids specifally
tryptophan, that is which you want to pay
attention to. The other one will be cystinuria,
inherited disease. You cannot properly take
up a basic amino acid and there is a nicely
know mnemonic here called COLA or whatever that you may want
to use in which apart from cystine
you may also not be able to properly take
up ornithine, lysine, and arginine. We shall
see. So PCT, you are not able to properly take
up your tryptophan
in hartnup and cystinuria with the mnemonic Cola.
Let us take a look.
Both diseases, you end up having issues in
the PCT. It is inherited autosomal recessive
and the defect in the fact that you cannot properly
take up these particular amino acids.