Now, in the PCT, we are going to wrap
this conversation up in the PCT by looking
at important pathologies of the PCT. Begin
by looking at hartnup disease and then we will
walk through cystinuria, Fanconi syndrome,
obviously I am emphasizing syndrome on purpose,
and type II RTA. With heavy metal poison,
we will take a look at lead or mercury. Lead
we will spend a lot of time with. You tell
me sideroblastic anemia, why? Quick review.
It inhibits two enzymes. One is called ALA,
it's a synthase or it is going to be dehydratase?
Good. Dehydratase. Take the D in lead and do dehydratase.
Look for that enzyme, not synthase, is that clear?
The other enzyme would be ferrochelatase.
We will use that information later on when
we do our sideroblastic anemia, but you should
know in the meantime the lead also causes
what? Lead nephropathy. They cause damage
to the PCT. The proximal convoluted tubule
will undergo a second example of coagulation
necrosis. Second, what was the first? Obviously,
know about the heart. Isn't that the prototype
when we talk about coagulation necrosis? What
does that mean? Take the g in the coagulation
and you may want to call it ghost town. What
happens when you walk into a ghost town? No
people, but the architecture is preserved.
Look at all the buildings. You see them. It
is the ghost town. That is what the organ
looks like. The architecture is preserved,
but there is nobody home. Who is nobody? The
nucleii. The nucleii are up or dead? How do
you know? It is called necrosis. What does
that mean? Cell death. So, therefore, proximal
convoluted tubule or tubular epithelial cells,
if they undergo ischemia, they then result
in coagulation necrosis. Let me take you one
step further. If you did have death of the
PCT and the two epithelial cells are dead,
they're falling into the urine. Everything
is crumbling. It is falling into the urine. They are being
sloughed off. They might then aggregate together. What is
an aggregation of cells known as in the urine? It's called
a cast, good. What am I referring to right now?
It is called acute tubular necrosis. What
is in my hand? A cast. What kind of cast?
It is called a multi brown granular cast. We
will talk about that later with ATN. Make
sure that you are able to integrate all this.
Move on. Now produce a nephrotoxic acute tubular
necrosis. Heavy metal poisoning specifically
focused upon lead, please. Now all the normal
PCT functions are destroyed when you have
damage. So think of Fanconi syndrome, think
about acute tubular necrosis may be due to
lead poisoning so on and so forth. If that
PCT is dead, oh! my goodness, I cannot reabsorb
66 percent of my sodium. Welcome to hyponatremia.
I cannot reabsorb my 99 percent of glucose,
hypoglycemia. And I cannot take up my uric,
literally it's hypourecmia. Remember with
uric acid that will be an important component
when we have our discussion and further explained
upon gout and such. But in general, if your
PCT is dead, you are losing a lot of things.
Emia means blood. Hypo means lack that of because
you are losing it. Also, if you have destruction
of your PCT, you have completely lost the
homeostatic mechanism for phosphate. Remember
that vitamin D and PTH work opposite. Listen.
Vitamin D and PTH work opposite when it comes
to phosphate. Vitamin D is going to cause
reabsorption of phosphate, whereas PTH wants
to get rid of it. But when your PCT is dead,
please understand the homeostatic mechanism
has also been lost. What else? Well you are
not able to properly reabsorb bicarb, amino
acids and those have been lost. Now hold on for
one second here. If you have destruction of
PCT, stop. I am not able to reabsorb bicarb.
Are we clear? No chance of carbonic anhydrase
working properly. Bicarb gets lost. What about
in the plasma? I don't have as much bicarb
because things are being lost. So, therefore,
tell me about the renal threshold for bicarb
with reclaiming it. It is decreased, isn't
it? There is decreased renal threshold for
bicarb reclaiming. Do you understand the English
and the terminology that I just put forth?
So if there is decreased renal threshold for
reclaiming bicarb, what happens to your bicarb?
What is your normal plasma level? 22 to 26.
If you are losing your bicarb here in the
urine, then my bicarb drops down to maybe
15. What is my pH in your plasma? Decreased.
What do we call this clinically? What is your
diagnosis? It is called renal tubular acidosis.
What kind and where am I? Proximal. See that
X please. See the X. How many lines did it
take to form that X? One, two. Oh! yeah, two.
So type II renal tubular acidosis is in the
or is of the proximal renal tubular acidosis.
Is that clear? Type II RTA is of the proximal
convoluted tubule. Do not ever forget that.
It is the inability of your PCT to reabsorb
the bicarb. I don't care how it happens, destruction
of the PCT, you decrease renal threshold of
bicarb reclaiming. Let's move on.
Now ultimately when you have generalized dysfunction
of the entire PCT, maybe it is due to lead
poisoning maybe it is heavy metals, what have
you, but then generally speaking this is called
Fanconi syndrome. So what is Fanconi syndrome?
Do not confuse this with, those of you that
might have heard of the diagnosis Fanconi
anemia. One has nothing to do with the other.
Do not confuse the two. Fanconi syndrome is
only dealing with the PCT. It is generalized
dysfunction and so, therefore, you are going
to end up losing everything that we just talked
about. You have hyponatremia. You will end
up losing a calcium, end losing a phosphate,
end up losing your bicarb, get my point. But
this is only in the PCT, only. Fanconi syndrome
will not affect the DCT or collecting duct,
but the only difference between syndrome and
anemia in Fanconi anemia, you want to think
of that as being bone marrow disease and it is
an aplastic anemia. Think about where are you at,
bone marrow. Leave that seperate. That
is anemia. This is Fanconi syndrome. Is that
clear? Please do not get the two confused.