7/6/2011 9:01:00 AM

Physiology Lecture 24

Beginning of our acid base lec, 2 things we do today, look at how

K is handled by the kidney and also how bicarb is handled by the
kidney
Spec bicarb is going to play a big role, how lungs and kidneys
work together to influence pH and also bicarb.
Today how kidney controls bicarb formation and excretion.
4 learning objectives
to see how Kidney handles K and how it gets regulated
Some things that may get in the way of regulating K.
How bicarb is actually reabsorbed, and something new is that
kidney can actually generate additional bicarb and put that into
the blood, under conditions of increased acid or bicarb that the
kidney may actually want to be making additional bicarb to help
things along, that plays a big role.
Well start w/ K handling by the kidney, guy just had K meal so
we take in K, we eat cells, we dont eat ex space, we eat int
space.
All the cells you take in have high K, K high inside cells, low
outside cells, so whether youre a vegetarian or a carnivore, your
taking in cells, so your taking in K all the time, you should know
as a number that normal plasma K is around 4mmol, so relatively
thats low. Na is 140mmol. K is low and thats because the Na K
ATPase on all cells is continuously moving K into the cells. And we
talked about how that was important because we use K to
generate a membrane potential to help repolarize the cells, to
help w/ conduction, so maintaining a low extracellular K is
essential and the kidney helps w/ keeping that extracellular K
low.

So we eat food that has K, so we need to excrete that K from the

body. The kidney plays a big role in that and along w/ K that
leaves in undigested food in the feces.
Magic wheel describes how on avg we take in 100meq/day and
thats distributed then btwn K outside the cells where there is
approx 70mEq/day and the large amount remaining inside the
cells 3500 mEq is in the sense in balance because the Na K
ATPase is constantly keeping the intracellular K high and as K
leaves the pump puts it back in again. So if we bring in 100, we
better excrete 100 so that we stay at K balance , and so the
majority of that 100 that gets excreted its shown in this diag is
getting exreted through the kidney (90) and the remainder is
getting excreted in the stool (10).
So the body watches it wants the K to remain constant because if
we have hyperkalemia or hypokalemia, we talked about how that
changed membrane potentials and how that affected conduction.
Mostly changes abnormal fluctuations, or abnormal levels of K are
going to affect cardiac excitation and will result in arythmias, will
result in changes in the ECG pattern, whether its an elevation of
K or a fall in K, doesnt make any difference, if it goes a mmol or
2 away from normal, it goes up to 6,7,8 or goes down to 3,2,
then either of those will cause problems.
K is sensed by body in the adrenal cortex, so K there will
influence aldosterone secrtion. An elevation of K, leads to an
elevation in aldosterone secretion. And well see in a little bit
that when aldosterone reaches the collecting duct of the kidney it
stimulates K secretion. So in that way it helps to balance to
maintain a constant plasma K levels. If plasma K goes up,
aldosterone goes up , aldosterone acts on the collecting duct to
stimulate K secretion , K is then excreted and were back in
balance. If plasma K falls then aldosterone secretion from the
adrenal cortex is reduced, less K is secreted by kidney, less K is

excreted and this helps to keep the K levels from falling any
further.
Simple relationship btwn Aldosterone and K.
With a meal we also release insulin, whch helps us process
glucose, insulin in addition acts on the Na K ATPase in all cells,
skeletal muscle for ex, insulin stimulates the NaKATP ase.
stimulation of the NAKATPase drives K into the cells and helps
keep K low. In association w/ your meal that has high K, your
alos realeasing insulin and that insulin helps you bring some of
that K into the cells preventing extracellular K from rising
dramatically in association w/ the meal so theres already a
process that helps balance that right as soon as your begin to
ingest high K. And then finally there is a relationship btwn the
plasma H ion conc. and extracellular K, will come back when we
talk about acid base balance. So lets see what that relationship is
btwn the H ion conc and K.
So this is a diag of any cell in the body and so you know that K is
high inside cells and low outside cells. When there is an increase
in H ions in the extracell space, thats the same thing as a
decrease in pH. When H ion conc goes up, the pH goes down.
H ion conc goes up, what happens then is H goes into cells. Goes
downhill when it goes downhill , K leaves the cell. And its not an
exchange process or carrier mediated process, you can look at it
as just trying to just balance the charge, as this +H ion goes into
the cells, a +K ion leaves just to keep charge neutrality. So with
acidemia, that is acid in the blood, with acidemia you get
hyperkalemia. So w/ Acidemia you get hyperkalemia. We have H
ions that are greater than normal they have a tendency to go into
the cells that will bring K ion out, and so in association w/
acidemia you have hyperkalemia.

Now the opposite happens, if we have low H ions outside which

we call alkalemia, then H will want to leave and K will want to
enter. And we will therefore get Hypokalemia.
Since K is an ion it can only go through channels, there are
always leaky K channels that can allow K go either direction.
Idea is that K moving through those channels because we have
changes in H outside.
Acidemia you get Hyperkalemia , lots of acid, get lots of K.
Little acid, little K.
pH of 7.4 = 40 nmol of H ions , not many H ions were talking
about when we have acidemia/alkalemia its still enough to
produce changes in K, but not enough to upset membrane
potential.
If K levels change sufficiently then you will get changes in
membrane potential and leads to conduction problems within
heart, yes changes in acid base balance severe enough, sever
changes in K to get arythmias.
Changes in pH are enough through changes in K to alter the
membrane potential to cause arythmias.
If this is good enough for H ions, that is if high acid makes high
K. Why cant it be the other way around also? If for some reason
or another we have hyperkalemia, then K will want to go into the
cell, when that happens H comes up, and we get acidemia.
Hyperkalemia leads to acidemia just like Hypokalemia will lead to
alkalemia. Works in both directions
When we talk about acid base disturb on frid, well point out
situations where we have concomitant changes in K, or if we have
situations where there is excess K secretion. Aldosterone

influences K secretion, if we have too much Aldosterone around ,

hyperaldosteronism, then we would be secreting a lot of K. What
would the blood look like? If we secrete lots of K, we are having
hypokalemia and we would have alkalemia. So excess K secretion
can lead to alkalemia and produce an acid base inbalance. Their
tied closely together , they go back and forth.
In your handout little diagram by this + high K acts directly on
the adrenal cortico cells, it does not need angiotenin 2, block it
out.

Table 5-5
Causes of shift of K+ into cells Hypokalemia
1.List in this table, a variety of things that cause K to either leave
the cells or go into the cells. Mentioned things that could cause K
to come out of the cells producing hyperkalemia and that might
be no insulin, because insulin remember stimulates the
NaKATPase to push K in. Insulin causes it to go in.
2. Beta agonists like epi and NE stimulate the Na pump and they
also cause K to enter the cells
3. Alkalosis does that.

Hyperkalemia shift of K out of cells

Hyperosmolarity K and water sorta go together across the cell
enough to cause changes in K. Water flows out of the cell, K
diffuses out w/ water.

Exercise does it because your cuasing lots of mem APs so K is

being released from the cells, skeletal muscle cells, during
repolarization in order to have another contraction. So exercise
causes K to shift out of cells and
Obviously cell lysis , if you break the cells, K will leak out.

Whats happening in kidney, where K is moving

Nephron 60-70 percent in proximal tubule!
K reabsorption in the proximal tubule and in the loop of henle,
K is secreted in the collecting duct by a passive process through
ion channels.
Reabsorbed in the collecting duct in association w/ H ions
(coupled to H+).
Most of the reabsorption of K is happening in the proximal tubule.

Details about each of these cells.

K is high inside all of these cells because of the NaK ATPase so
theres always a gradient for K to leave cells and this diag shows
yes , there is some K oozing out of these cells. So you could say
that yes, here in the proximal tubule there might be some
secretion going on , but the net movement of K is from the
tubular fluid into the IS, and therefore ultimately into blood. And
most of that is happening through intracellular spaces. Remember
proximal tubule cells are fairly permeable to water, and as they
reabsorb salt, water is drawn and follows along. A lot of water will

just go riht throught the cell but some of that water is able to
pass btwn the cells because the proximal tubule epithelial cells do
not have firm tight junctions, theyre kind of leaky, and so there
is just what is called bulk flow of liquid through these spaces btwn
the cells and because K is here in this tubular fluid it is carried
along in bulk flow from the tubular lumen into the IS. Also whats
happening is that there is a change in the charge on the
epithelium as you from higher up in the proximal tubule to further
towards the end of the proximal tubule. And that change in
charge making it more positive towards the end of the proximal
tubule , acts as a charge gradient favoring K reabsorption.
So we have 2 things, we have a charge difference btwn the lumen
or the apical surface of the epithelial cells and the basolateral
surface and then we have process of bulk flow, both of those
things then cause net reabsorption of K in the proximal tubule
and thats why we get 60-70 percent reabsorbed there. Again
were only talking about 4-5mmol, not like Na where we have
huge amount that are reabsorbed, we are trying to reabsorb 6070 percent of 4 mmol.
Change in charge helps because if it becomes more positive on
the luminal surface , it repels K and making K want to go to the
more negative side in the IS.
K is a passive process . No transporter. No NaK ATP ase on the
apical side, they are on the basolateral side. Nothing bringing K
in, so thats why most of it going through. And passive leak
channels down the conc. gradient.
Kidney reabsorbing NaCl, in the very beg of proximal tubule, were
getting a lot of Na reabsorbed because of Na glucose, Na a.a,
Na-H, so the reabsorption of Na exceeds the reabsorption of Na
exceeds the reabsorption of Chloride thats what makes it
negative, then as we get further down the proximal tubule that Cl
is picked up and it shifts from being negative to more positive
because we still have Na gone.

So now we get to thick ascending limb.

we have the tritransporter so of course K is being reabsorbed by

that tri transporter and then goes out the basolateral side
through ion channels. A fact is that K then backdiffuses and again
is secreted here in the thick ascending limb but this cycling of K is
really important to help that tritransporter do its thing. It needs
this K, there has to be some K coming back to fit in with this
tritransporter to enable that process to go on. So some of the K is
just sort of cycling here, some of it though moves out of the cell
across the basolateral side through these ion channels, and of
course we have some K that is beign reabsorbed again through
these paracelullar p/ws . So the NET process is reabsorption, so
we had reabsorption in the proximal tubule, we had net
reabsorption in the TAL.
And now we get to the principal cells, these are wherever
principal cells live, and generally we think of them living in the
collecting duct, collecting tubule, whatever we call last little piece.
Here are principal cells we have Na channel the one that Aldo
works on, and there are K channels on the apical side.
On the basolateral side, there are K channels that allow K to
escape. But its the principal cells, where the principal action of
Aldo is on. You can already Na channels but also on K channels.
So this is the site at which K SECRETION (here is where you get
net secretion). This is where Aldo regulates our blood K. So if we
have too much K , then well increase Aldo secretion from the
adrenal cortex, it will go to the collecting duct, and work on
principal cells to open up these K channels, it will also stimulate
the synthesis of additional channels and their insertion into the
membrane and then it will also stimulate the Na K ATP ase so
that it brings more K into the cell so that more can be secreted.
PRINCIPAL CELLS = NET SECRETION
****Aldosterone opens K channels in the collecting duct
(principal cells) and stimulates synthesis of additional channels

and their insertion into membrane. Also stimulates Na K ATPase

pump
So its these ion channels in the collecting duct principal cells that
are responsible for K secretion.
Now you know in the collecting duct there is another group of
cells called INTERCALATED CELLS and these cells reabsorb K,
they REABSORB K in an ACTIVE transport mechanism, so here we
have an ex of an H-K ATP ase, so these intercalated cells
reabsorb K through a H-K ATP ase, so H is secreted as that K is
reabsorbed. And as far as I know, aldosterone does not work on
those cells.
But they will be affected by changes in availability of H ions.
Reabsorption of K in the proximal tubule & TAL
Secretion of K in the principal cells by just passive diffusion
through those ion channels
Reabsorption by intercalalted cells through the H-K ATPase.
So if we have that info , how can we possibly change or what
situation will change the ability of principal cells to regulate K.
So were look at principal cells of the distal tubule collecting duct,
so this is a bigger diag of one of those principal cells w/ Na
channels, K channels. And our Na-K ATP ase over here on the
basolateral side, so here is blood , here is tubular lumen on left
side.
1st thing if plasma K conc goes up, if we have just hyperkalemia
that means over here in the blood we have more K, more K
stimulates the pump because this enzyme here is sensitive to the
extracellular K conc. As this conc goes up the pump is stimulated
it raises the conc of K within these principal cells and favors then

the downhill diffusion of K out of the cells into tubular lumen and
therefore enhances secretion. So increased plasma K leads to
increased K secretion directly through these processes.
Hyperkalemia elevates the K conc in the principal cells because
it stimulates the Na K ATP ase that elevated intracellular K conc
then is able to diffuse out through those channels on the apical
side and increase secretion.
Oviously aldosterone will open up more of these channels, so
whatever the intracellular K conc is , having more channels open
will enable more K to leave.
So increasing aldosterone leads to increase K secretion.
Now since K secretion is passive, means it depends on a conc
gradient, high inside, low in the tubular fluid, if we stopped
tubular fluid from leaving the collecting duct, more and more fluid
will keep coming in and K will be continuously secreted and at
some point we might actually get enough K here in the tubular
fluid to balance the K within the cell and passive secretion passive
diffusion would stop.
So the speed with which fluid is moving through the tubule is
important because its constantly moving this K that has been
secreted downstream further , so the faster the tubular flow rate
, the lower will be the K conc. here in tubular fluid and therefore
the better will be the secretion or more the secretion will be.
So diuretics that are acting up at the proximal tubule, in the LH,
in the distal tubule all cause increased tubular flow because they
are interefering w/ usually Na reabsorption in one of those
segments. If Na reabsorption is interfered with , water
reabsorption is interfered with , so there is more volume there is
more flow.

Elevated tubular flow causes K to be constantly washed away and

so that enables continuous K secretion. So one of the side effects
of most diuretics is hypokalemia because they enhance K
secretion in the collecting duct leading then to hypokalemia. If
you have hypokalemia, what might be your acid base status?
Alkalemia. So diuretics if aggressive enough can cause
hypokalemia and secondarily lead to alkalemia, so you have to be
very careful w/ your use of diuretics to monitor plasma K levels
so that K doesnt fall and therefore lead to alkalemia and make
things even worse.
So reduced tubular flow, a decrease in GFR for example, so that
flow is slow will retard K secretion and lead to retention of K in
the body.

If you drank a ton of water will that cause hypokalemia and

alkalemia? That high volume will dilute extracellular K to start
with so that will make hypokalemia and then because liquid
excreted rapidly that wil exacerbate the problem so youll get lots
of K secretion and arythmias.
Plasma pH
If we had increased H ions , H will want to go into cells, we talked
about how it will go into any cell, like principal cells. So increased
H will mean some K would leave the principal cells and go back
into the blood , and therefore the K inside principal cells would go
down and therefore secretion would go down. So increased acid
would put H in and cause K to leave across the basolateral side
and therefore there will be less K inside the cell, less for secretion
and so acidemia inhibits K secretion which exacerbates the direct
effect of the hyperkalemia.

If we decrease H ions then H will leave the cells, K will go into

cells and that will enhance secretion and ehance the hypokalemia
associated w/ alkalemia.

Using the exchange of H and K across the basolateral side of

these principal cells to give us a handle on what the intracellular
K conc might be and therefore what the rate of secretion might
be.
Luminal charge obviously there is lots of + charge left behind
here , depends on how much + is left here, we could attract or
repel K. If the tubular fluid is charged that will enhance K
secretion.
Certainly H K and secretion *** Important
IF we have volume depeletion we have increased aldosterone
release, more Na reabsorption, will make lumen more negative
because were removing + charges, that will enhance K secretion
just because of that charge diff, on top of that we have aldo
acting to open these channels, so well get 2 things enhancing K
secretion.
It isnt the mag of charge, its the polarity of charge. Since K is +
, if the lumen more that will attract K and enhance secretion . If
lumen more + , that will repel K and reduce secretion.
So if we removed a lot of + charge through stimulated Na
reabsorption lumen will be more neg and enhance K secretion.
Diuretics,
An anion that might have not been reabsorbed will also attract K
and lead to secretion so not just removal of a + charge, but
introduction of some anion, nonreabsorbable anion can do that.

Now we have to finish w/ Bicarb.

Lets just look at ex of volume depletion.

The kidneys response to volume depletion, a fall in MAP, release
alsosterone frm the adrenal cortex because we activate the renin
angiotensin aldosterone system and therefore we get more aldo
secretion which increases Na reabsorption and increases K
secretion.
Would you expect hypokalemia following volume depletion?
No!
What else happens when MAP falls that could influence K
secretion, a fall in GFR. A fall in GFR impacts K secretion, tubular
flow. If GFR goes down tubular flow goes down, if tubular flow
goes down, K secretion decreases, less secretion. Even though
with volume depletion or fall in MAP we would expect increase K
secretion because of the increased aldosterone, concomitant with
that is reduction in tubular flow which inhibits secretion, so those
two things balance and generally with volume depletion,
decreased MAP, you do not get hypokalemia because they
balance!

Now severe cases then other things happening lots of aldo around
you might get K depletion then but generally your run of the mil
fall in MAP does not lead to excess K secretion.
Lets look at how body reabsorbs bicarbonate.
Fig 38-23 Diagram on far left that shows the diff segments of the
neprhon where most of the bicarb is reabsorbed. 60-70 percent is
reabsorbed in the proximal tubule (80), we get rid most of the
bicarb, close enough to 60-70. We get rid of here is the
relationship btwn proximal end loop and we reabsorb a little more
in the collecting duct.

Regardless of wher we are the same sort of process works.

Middle diag. Shows proximal tubules but this is happening pretty

much everywhere, take it as main mechanism, and this accounts
for 80 percent of the reabsorption, so this is the main mechanism
we need to look at.
Lumen, tubular fluid is coming in, were in the prox tubule, fluid
freshed out of the bowmans space, the intersitium supplied by
the peritubular capillaries. So Bicarb is filtered as Sodium
Bicarbona, so in comes Sodium Bicarbone, they dissociate , you
have a bicarb molecule and Na molecule, Na gets reabsorbed
through this Na H exchanger. Na goes in, H comes out.
The H combines w/ the bicarb in the tubular fluid to form
Carbonic acid (H2CO3) . In the presence of carbon anhydrase
that is stuck on the surface of these epithelial cells , the Carbonic
acid is converted to water and co2 , that is all happening wihin
the lumen. The CO2 then very permeable to cell membranes as
your remember from pulmonary lectures it easily diffuses into the
epithelial cells of the proximal tubule where it combines w/ water
where there is Carbonic anhydrase again, and so that forms
carbonic acid which rapidly dissociates into hydrogen ions and
bicarb ions inside these epithelial cells. The H exchanges for Na ,
combines w/ bicarb in the tubular fluid and off we go again.
The bircarb that was generated within the epithelial cell is then
removed from the epithelial cells through a Na bicarb
cotransporter (both going to I), so the bicarb that was originally
in the tubular fluid was converted to Co2 which went into the
epithelial cells which was eventually converted into bicarb which
went out the basolateral side. So unlike a lot of the molecules
that weve looked that began on the luminal side and had some
carrier ion channels that move them intact from the luminal side
to the interstitla side, bicarb undergoes a chemica rxn that
requires carbonic anhydrase. So thats how bicarb is reabsorbed ,
thats how body reabsorbs all the bicarb that it has, and it tries to
keep bicarb normal.

Now one of the very weak diuretics is a CA inhibitor. So why

would inhibiting that enzyme cause diuresis (excessive urine
production)?

If we dont have CA were not generating H ions to exchange w/

luminal Na, so this process within the epithelial cells is reduced so
that retards slows down Na reabsorption, if you reduce Na
reabsorption in the proximal tubule, no water is reabsorbed
,therefore tubular flow downstream goes up and you get diuresis.
So by inhibiting the CA , you are blocking *** MC**reducing the
Na-H exchanger, you reduce its activity therefore not as
reabsorbing as much Na and therefore Na remains in tubular fluid
and you have diuresis.

Bottom left diagram

This diag over here goes along with that a little bit in that here is
plasma bicarb conc and then bicarb , and then shows bicarb
filtered excreted and reabsorbed.
It looks like normal bicarb is around 24*** It looks like most of
the bicarb is reabsorbed because filtered and reabsorb are
coincident and very little if any bicarb is excreted, a little bit but
not very much.
But as we higher higher conc , we eventually get some excess
bicarb excreted. One way body can get rid of bicarb, if it gets
high in blood it will just excrete that excess and tend to get rid of
it. Notice that if we have volume exansion, now this says
exaggerated , big, volume expansion we actually cause more of
bicarb to get excreted and thats because were messing w/ Na
reabsorption there.
So with large volumes that are coming in we have high filtration
and that affects the ability to reabsorb Na which is going to affect
the ability of kidney to reabsorb bicarb, so were going to get w/

volume expansion , and increase in bicarb excretion over what we

would expact normally at these high levels.
We have to be able to reabsorb Na in order to reabsorb bicarb.
Increased volume , which makes more filtration, makes it harder
to reabsorb Na.
2 imp things.
Bicarb is not reabsorbed intact, its turned into CO2 which then is
used to generate bicarb inside the epithelial cells which are then
ultimately reabsorbed. This reabsorption requires Na-H exchange
and if we inhibit the process to CA we inhibit Na, and therefore
we cause diuresis.
Now this diag shows w/ intercalated cells, but process were going
to talk about happens anywhere along the tubule, so lets dont
focus too much on intercalated cells but process is as follows:
Not only do we filter Na Bircarb, but we filter other weak acids
such as phosphates or sulfates. So here is our tubular lumen and
here is I. So lets say we have Na phosphate (Na2HPO4). Na
phosphate filtered, and you end up w/ 2 Na , plus Phosphate -- .
Dissociation molecule and so we have our Na H exchanger so
one of these Na gets reabsorbed, one of these H takes the place
of Na and what we get excrete is NaH2PO4, so this is what is
excreted. Now this H came from carbonic acid and so here is a
bicarb that is in excess of the bicarbs that were filtered, so this is
a bicarb that didnt come from the lumen, it came from the
consumption of this H ion , when we combined it with this
phosphate. So the kidney has actually generated one bicarb.

Now we call this substance here in the urine, we call that

titratable acid => NaH2PO4, generally thats because the urine
sample that you send to the lab the technician then combines this
with NaOH and titrates it back to Na2 HPO4 and the amount of
NaOH that is added is equal to the amount of bicarb or the
amount of H that combined w/ the phosphate. So by titrating this
acid we can calculate how much bicarb has been generated.
Other way you can look at it is this Sodium phosphate within the
tubular fluid is being titrated w / the Hydrogen ion that is being
secreted there. So this H combines w/ the phosphate and titrates
that weak acid.
But if there is an increase in titratable acid excretion that means
that you have added more bicarb to the body. The kidney has

actually made generated a bicarb ion and it does tat when the
body has acidemia and needs to raise the amount of bicarb thats
there. Generation of titratable acid needs to occur to help the
kidney buffer changes in blood pH. So youll see that titratable
acid will go up when we have acidemia in order to raise the bicarb
conc and help to bring pH back to normal.
Now in situations where we have lots of acid around , lots of H ,
plenty of H to titrate w/the phosphates and so we can makes lots
of bicarb. But its limited by your ingested phosphate, you cant
titrate more than you got. So this is a very quick way for kidney
to make bicarb but it doesnt have a big capacity because it
depends on whatever it is youve been eating , and how much
phosphates is in your blood, generally we dont have much
phosphates a few mmol, but it is a quick way for kidney to add
some more bicarb because this is just chemistry and it can
happen very quickly w/ acidemia.
If there was alkalemia, little H ion lying around, well there is no H
around to titrate the phosphates and therefore you wont
reabsorb this Na and it wont come out as titratable acid, it will
just be Na2HPO4 which is the way it went in. So the formation of
titratable acid is a way for kidney to generate additional bicarb
and it does that by titrating sulfates and phosphates that are
normally present in the blood.
Lets go back to reabsorbing bicarb under normal circumstances
Proximal tubule secretes a lot of H ions, normally there are
24mmols of NaBicarbonate in the blood. If 80 percent of that
bicarb has to be reabsorbed, thats 16 or more mmol of bicarb,
everyone of those mmol of bicarb has to have a H ion, so were
secreting 16 mmol or more of H ions (stronger than Hcl), so this
is a huge amount of acid being excreted, but every one of these
H ions is buffered or combines w/ a bicarb so there is no pH
change. A lot of acid is being secreted but everyone of these H is

picked up by a bicarb and so the pH of the tubular fluid does not

change.
Just like it came in isotonic, its coming in at 7.4 and leaves at 7.4
even though were secreting a very large amount of acid. So the
greates amount of acid secretion is occurring in which segment of
nephron , proximal tubule.
Under normal conditions, and even in abnormal conditions,
kidney good job at absorbing all of the filtered bicarb and keeping
it at normal level of 24mmol, lots of H ions secreted in the
proximal tubule but its all buffered by bicarb , if we have excess
H then that H begins to titrate the sulfates and phosphates
forming titratable acid thats excreted, and for every mmol of
titratable acid thats formed theres one mmol of bicarb that is
added. One to one relationship.
When we were taling about bicarb, secreted acid is being buffered
by this bicarb. So essentially this is not generating any acid, no
acid excreted.
Reason we excrete titratable acid, reason is we want more bicarb
in blood. This isnt reabsorbed bicarb because this bicarb did not
come from filtered fluid, it is generated within the epithelial cells
from CO2 that is everywhere your breathing CO2, CO2 around to
generate carbonic acid or hydrogen , this bicarb is put into the
blood, this is one of the ways that kidney can make additional
bicarb and it does that when there is lot of acid around, it is a
compensatory mechanism to buffer H ioins, So if lots of H ions
around , there is plenty of H for the secretory process and it will
titrate any phosphates.
The reabsorption process has already done its thing , all the
bicarb that was filtered is gone already been reabsorbed,
normally there is plenty of H to do that , and so if we have excess
H we cant reabsorb anymore and so the next thing to do is make
more, and so this is one of the ways through formation of
titratable acid to make more bicarb.

CARBONIC ANHYDRASE MAKES CARBONIC ACID!!!!

One more
Second way that the kidney has for making new bicarb is a
method that is more effective than forming titratable acid, it
results in large amounts of bicarb being generated but its slower
to take effect.

Second way is through a more complicated process, is through

formation of ammonium ions.
The epithelial cells of the kidney have glutamine and they can
break down glutamine and in the process form ammonium ions or
ammonia. In the process, when we have lots of acid around , the
acid stimulates the enzymes responsible for the metabolism the
breakdown of glutamine into ammonium ions and bicarb ions. The
bicarb ions go into the blood , the ammonium ions are excreted.
And so you can measure ammonium ion excretion and there is a
1 for 1 relationship btwn the amount of ammonium ions excreted
and the amount of bicarb put back in the blood. So this is the
second way for kidney to generate new bicarb, it takes a little
while, it takes a sustained increase in H ions to stiumulate these
metabolic enzymes to break down glutamine and form
ammonium ions. It has a very large capacity because there is
plenty of glutamine around and if your running low , liver will
share some of its glutamine , has blood supply that can deliver
more glutamine to the tissues . So this is a process that can
generate lots of bicarb over a long period of time but it takes a
while to kick in.
The sequence would be the 1st thing the kidney does when acid is
high is reabsorb all bicarb to make sure we dont lose any.

Then 2nd thing is form titratable acid which generates some new
bicarb.
Then as acidemia lasts long enough it kicks in glutamine
metabolism and the generation of ammonium ions and that will
cause even more bicarb to form and help correct the acid base
problem.
And were going to use titratable acid, ammonium formation, and
bicarb reabsorption on Friday when we look at how lungs and
kidney work together to keep acid base constant.
You have to have several hours of acidemia before last process
kicks in.

Titratable acid in urine, we have to have at least excreted

60meq/day.
Remember H ions combine w/ phosphates and sulfates so those
are H ions that are leaving , 60meq of H ions leaving in
association with those phosphates and sulfates.
NH4+ is NH3 + H+, that looks like acid leaving the body as
NH4+.
If we put bicarb back in, if were losing bicarb thats the same as
adding acid back into the body , so we have H and we have
bicarb. If we excrete H , if we excreted bicarb, then that leaves H
behind so the excretion of bicarb, is the addition of acid to the
body so we got 60 + 100 = 160 but we added 10meq of acid
back when we lost the bicarb , so we have to take away 10 and
we end up w/ 150meq acid excreted each day in that way.

Acid excreted = bicarbonate reabsorbed - bicarbonate excreted

Bicarbonate reabsorbed = 60 + 100; bicarbonate excreted = 10

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