In this course, students learn to recognize and to apply the basic concepts that govern integrated body function (as an intact organism) in the body's nine organ systems.
Balance, Disturbances, and Analysis
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Duke University의 강좌에서
Introductory Human Physiology
1833개의 평가
수업에서
The Urinary System
Welcome to module 11 and the last organ system to be covered in this course! In this module, we turn our attention to the urinary system and specifically to the functions of the kidney, a filter of the blood. The kidney is a complicated organ whose actions integrate with those of the cardiovascular system to maintain blood pressure and with the respiratory system to maintain acid-base balance. As we progress through this module, we consider the mechanisms by which the kidney regulates the water content and the electrolyte content of the body. We focus on the roles of the normal kidney but also consider changes in homeostasis due to either disease or drugs. The last lesson of this module considers the role of the kidney in regulating acid-base balance of the body and its integration with the respiratory system.
The things to do this week are to watch the 6 videos, to answer the in-video questions, to read the notes, and to complete one problem set (urinary system). In this module, the sequence of videos is important. As you proceed through the videos and notes, try to correlate the specific region of the renal tubule with its function. Often this is best achieved by drawing the renal tubule and labeling the specific changes in structure and function. Again, the notes will provide a more detailed summary of the material presented in the videos. Please note that the first two videos correlate with the first set of notes and the third video with the second set of notes. We encourage you to complete the problem set. The problem set is not graded and is for your personal feedback. Both your understanding and retention will increase with application of the new learned information.
강사 만나기
Jennifer CarbreyAssistant Research Professor
Department of Cell Biology
Emma JakoiAssociate Research Professor
Department of Cell Biology
Greetings. Okay, so this is the last lecture of our
course, and so what we want to talk about is the acid-based disturbances and how
you analyze these disturbances. So the learning objective then is first,
we want to explain how new bicarbonate is generated from from ammonium ions, and
are eliminated then by the body. And second the, and secondly we want to
explain how new bicarbonate is generated by the kidney when fixed acids or
titratable acids are eliminated from the body .
And third, we want to explain the classifications of four acid-base
disorders. And you've already heard about these from
the respiratory system lectures. But we're going to revisit them.
And then fourth we want to describe how metabolic acidosis Is differentiated from
respiratory acidosis and, and we want to consider a specific case.
Okay, so there's a lot of things to do. So again, why are we worrying about mass
balance and pH? And, and as we said in the last lecture,
there's a net intake of acids from the diet, and there, and the generation of
acids from metabolism. So the body's responses are that we have
to buffer these protons immediately. And we buffer them by binding it to
proteins. And the proteins specifically that we're
going to use is hemoglobin. That's one of the major proteins.
But, as soon as the protons are generated, they move into the cells and
they bind to proteins within the cells. So, this is an immediate protection.
The second that we, that occurs is that there's going to be a change in
ventilation and this will occur within minutes.
And that is, is that we have a change in our minute ventilation.
They, if the lung needs to remove a the acid, then it will increase the the
ventilation rate and so they'll blow off the CO2 and by blowing off the CO2, we
lose acid from the body. And the last is we're going to change the
amount of bicarbonate and protons that are going to be lost into the urine, and
this is going to be the job of the kidney.
And this can take hours. So, the kidney is our slow, our slow
responder. And the last time we were in here, we
talked about how the kidney was, was moving all of the filtered bicarbonate,
or the majority of it, back into the body through the proximal convoluted tubule.
But that in the distal collecting duct and in the distal convoluted tubule, that
it could use this last 10% of the filtered bicarbonate to adjust the pH of
the blood. But as you go through your day and you're
ventilating your breathing, you're blowing off CO2, you are losing
bicarbonate from the body. And the job of the kidney then is it has
to replenish this. It has to replace the lost bicarbonate
and then reabsorption is simply not sufficient.
So how does it make new bicarbonate? So it does it in two different places and
does it by two different mechanisms. So let's consider the first.
So the first is it's going to make the ammonium ion.
And it does that in a proximal convoluted tubule.
So here in the proximal convoluted tubule, which is the very first region of
the, of the renal tubule. We have glutamate, which is freely
filtered. This is an amino acid.
It's freely filtered and it enters into the filtrate.
We also can have glutamate which can enter into these cells from the blood.
And this of course our paratubular capillary.
So the glutamine, the amino acid, can enter into the cells and it either does
it by simple diffusion, facilitated diffusion coming in from the blood or
having a code transporter a sim porter with sodium.
Once the glutamine is within the cells, these proximal convoluted cells, the
amine group is removed from them and that then becomes NH4+, the ammonium ion.
And the ammonium ion is extruded from the cells at what using an antiporter when
sodium enters the cell. In addition to making the ammonium ion we
also are making bicarbonate. And that bicarbonate then this is new
bicarbonate. That new bicarbonate then is extruded
from the cells using the chloride bicarbonate antiporter.
And that's what shown here. Now, the ammonia that has been removed
from these, that's been generated by these cells, now enters into the renal
tubule, and the ammonium ion is not able to go across the epithelial of the renal
tubules. The ammonium ion is delivered to the thin
ascending loop, or the thick ascending loop of Henle, and when it gets into this
region it then in this area it can in fact move across this, across these
cells, and and enter into the interstitial space.
Once it enters into the interstitial space, it's converted from NH4 plus to
NH3, to ammonium. And ammonium can move across the
collecting duct epithelial cells. And so it can enter the lumen of the, of
the collecting duct. Once it's within the lumen of the
collecting duct, that NH3 combined to a proton, a free proton that's present
within the filtrate, within this region and it then reforms NH4 plus and it traps
that proton. And now that proton is no longer free,
and is no longer adding to the to decreasing the pH in this region.
The ammonium ion is excreted into the urine, and this is and this is one of the
ways that we can lose a proton from the body, and at the same time, we generate a
new bicarb. Okay, so why have I tortured you with
this? This is actually an interesting situation
because if the, if the kidney is not working correctly, if for some reason the
collecting duct is not working then what happens is that this NH4 plus.
Which is present in the thick ascending loop of Henle could move into NH3 and
then it can enter into the blood and is delivered to the liver.
And once it's delivered to the liver, it's converted to urium.
And the, by the liver, and the liver then is generating what's called bun or blood
urea nitrogen. So, the urea that enters into the, into
the cells of the liver, it forms this urea and then the urea is moved back into
the blood. And so what you find then is a hallmark
of a sick kidney, or kidneys whose collecting duct doesn't work correctly as
a rise in BUN within, within the, the blood.
So this second way, that the kidney can make new bicarb is, in the distal
convoluted tubule and collecting duct itself.
And here it's using the fixed acids, it's excreting, those are their sulfates, the
phosphates, and so forth, that came in from the diet, that we couldn't blow off,
through through the respiratory system. These cells have, again, luminal surfaces
here, and the blood surface is here. So we have our pair of tubular capillary
surrounding these cells as well. In this particular case, now, we are
going to be delivering to these cells CO2 from the blood and the, the blood the CO2
can enter into the cell. And in the presence of carbonic
anhydrase, we can generate bicarbonate. And this is new bicarbonate.
The new bicarbonate is then delivered to the blood using our chloride bicarbonate
antiporter on the basal surfaces of these cells.
The proton is going to be extruded into the lumen of the tubule in this region.
And that proton, that free proton can now bind to phosphor the phosphate or the
sulfate and so forth. And to, and once it's bound of course
then it's no longer contributing to pH, okay, it's no longer a free proton.
And so we trap then this proton and it is extruded into the urine.
There is one other way that we can move the, the free proton that we've generated
from these cells. and that is through using that proton
potassium ATPase, and that's what's shown here.
So the proton can leave the cells and move into the lumen, get trapped by the
titratable acid, and in exchange we have our potassium ion then that can move into
the cells. So for mass balance then,[COUGH] what we
want to do is to balance the amount of acid input to the amount of acid output.
And as we said the last time we were in here that the acid input for a 70
kilogram individual is about 70 milli-equivalents per day.
And this is from diet and from metabolism.
Our acid output, however, free protons is, has a pH of about 7.4 so it's 40
nano-equivalents per day. So, we're putting out very, very, very
small amounts of free free protons. So what, what we are putting out in
addition to that, is fixed acids, up to the, to the amount of 34 mEq per day, and
the amount of amin, of the ammonium ions, and that's about 35 mEq per day.
And as you notice, this adds to approximately 70 milliequivalents per
day. So, 69 milliequivalents per day.
And so the free protons then within, within the urine is, is almost
negligible. So that the pH of the urine, then is is
close to neutral, and for those of you who want to calculate this, the
calculation is here at the bottom, which is the net acid excretion is the, the
concentration of the ammonium ion within the urine, in the volume of the urine.
This is a time sample. And then we have the concentration of the
titratable acid, and the volume of the in the urine, and the volume that's within
the urine. And the amount of bicarbonate that was
lost from the body. And this is usually, under normal
conditions, is usually about zero. Okay, that's in a normal person, and
that's in normal condition. But we can have conditions where, where
there's acid-base disturbances. Such as, you've been vomiting.
Okay, if you're vomiting, what happens? You're losing acid from the body.
And if you're vomiting for several days. Then, then, it can affect the pH of the
body, and that is you're losing protons, and so the blood then becomes, more and
more alkaline. So we're having higher and higher
amounts, of of, higher and higher pH with circulation.
So if we look then at these acid-based disturbances, we, we can categorize them
on the basis of the primary disorder. So in the case where we have a
respiratory in the case of metabolic acidosis, which, which which is where
we're retaining our protons. So if we're retaining the protons for
some reason within the body, then we're decreasing the blood pH.
And as we decrease the blood pH, it's due to an inadequate amount of bicarbonate.
In compensation, the lung is going to try to blow off the PaCO2.
And so we are going to decrease the PaCO2.
This is in contrast to respiratory acidosis.
And in respiratory acidosis, again, the blood pH decreases because we have an
acid condition. But under this condition it's due to
holding the P, the, the CO2 within the blood.
So the arterial blood then has a higher CO2.
And that, by increasing that we then become acidic.
And the cause then, is a decrease in ventilation.
It is not, it is it is the cause, it is not the compensation.
So you can differentiate between a respiratory acidosis and a metabolic
acidosis in that the in the amount of PaCO2 which is within the blood.
If the PaCO2 is higher than normal, then it's a respiratory acidosis, we're
holding the CO2 ventilation is inadequate.
If the PaCO2 is low, lower than normal, then we're trying to blow off the CO2,
and we're trying to balance trying to compensate for a metabolic acidosis.
Things to remember is that we have the CO2 levels which are within the arterial
system, the PaCO2 is going to be 40 millimolars of mercury.
And the amount of bicarbonate, it will be 24 milliequivalents per milliliter and
that's going to be the concentration of the bicarbonate within the blood under
normal, under normal conditions. Okay, so how should you analyze these
acid-base disorders and as I said this is sort of review for you because we have
done this already once in the respiratory system, but let's go through it.
So the first is, the first question you ask is, what is the pH of the arterial
blood? This determines the state, and remember
we said we could have a normal state, that's going to be pH of 7.4.
Acidemia, means that it's going to be less than 7.35, and if it's alkalemia,
it'll be greater than 7.45. The second is, you want to know is it
metabolic or is it respiratory, is that, that's the underlying cause?
And you want to know, is it an acidosis or an alkalosis?
And in this particular class we're not going to deal with mixed.
Next would be an individual who is, retaining CO2 because he has emphysema.
So he's not ventilating his CO2 adequately, and at the same time he's
got, he's vomiting, so he's losing, he's losing his proton, and he could have a
neutral pH. But he's got two different different
disorders going on. But in this particular class we're not
going to deal with mixed with a mixed disorder, only acidosis or the alkalosis,
and it's a simple acidosis or alkalosis. So the thing that you want to do then is
to examine the amount of bicarbonate in you to see whether or not it's normal.
So it should be 24 mEq per liter and in the, and in the PaCO2 you want to see
whether or not it's normal and that's 40 millimeters of mercury.
The thing to remember is the compensations never going to bring you
back to an exact pH of 7.4. And so it's always going to reflect the
disorder so you'll bring it back close but it's not going to bring you back to
exactly neutral. And then, the last thing we want to deal
with is, what is the compensate, the compensation?
In the metabolic disorders, the compensation will be a change in the
PaCO2, the vent, the ventilation rate is going to change.
We'll either be blowing off our CO2, because we have an acid condition, or
we're holding our CO2 because we have a basic condition.
And in respiratory disorders then, compensation's going to be in our bicarb.
And that's when this collecting duct, the intercalated cells, are going to be
moving bicarbonate, back then to if we have an acidosis then it's going to be
trying to move bicarbonate back into the blood.
And so under those conditions, the type A cell is going to be working, because it's
making acidic urine. It's getting rid of protons.
But if we have an alkalosis, or alkaline condition, then we want to be secreting,
the bicarbonate into the urine, and we'll be bringing back, protons into the blood.
So, let's just go over a case together, so you can see what I'm talking about.
So, Mary is dehydrated from two days of severe diarrhea and her labs are she has
a blood pH of 7.3 and her blood sodium is 143.
Her proton, her bicarbonate is 16 millequivalents per liter.
and her PaCO2 is 33 millimeters of mercury.
So what's her acid-base status? So the first thing we look at is pH.
And the pH is 7.3, so that's less than 7.4.
7.4 is normal. So, that means that she has acidemia.
The second question is what's the underlying process.
So, if she has acidemia, we can immediately rule out alkalosis and
respiratory. Whether is metabolic or respiratory, the
alkalosis doesn't apply. And, so, now you have to decide, is it
the respiratory that's the cause or is it meta-, metabolism that's the cause.
And if you look at the PaCO2, it's 33 millimeters of mercury and the normal
PaCO2 should be 40. So we have a low PaCO2.
So, low PaCO2 means that it cannot be the lung that is the problem.
The, the lung is trying to compensate, the lung is blowing off as much CO2 as it
can to try to correct for the pH. And so that means that the, that the lung
is compensating and so the underlying cause has to be metabolic acidosis.
It's acidosis, because we already determined that it has a low, pH, and and
metabolic acidosis, it does correlate with severe diarrhea.
So what happens with severe diarrhea, is that we're losing bicarbonate up the
wazoo. And by losing bicarbonate from the body
then the, the, the blood pH is going to become more acidic.
Okay, so, see how easy that was? Alright?
So, all you have to do is sort of think through these things and look at your
numbers and then decide what is, what's normal.
and, and what's abnormal. All right.
What's our key concepts? The key concepts, then, are, one, we have
a daily diet and metabolism generates a net increase in acids; two, that the
kidney maintains an acid-base homeostasis by reabsorbing filtered bicarbonate,
forming titratable fixed acids and then excreting the ammonium ion.
Three, there are four types of acid based disturbances that the body can be
presented with and four that the acid based disturbances are classified as to
the direction of change of the pH. So it's acidosis or alkalosis, and by our
underlying problem which is ventilation or metabolism.
Okay, so that's the last of our lectures. So it's the end of the course and we hope
that you've enjoyed it. It's been a fun time for us.
And so, perhaps you'll join us again next year.
Bye bye.
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