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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 thekidney

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 intspace.

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 togenerate 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.

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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 andthats 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 ofK 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 itstimulates 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

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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 processglucose, 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 Hions 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.

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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 arealways 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

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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. Theirtied 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 cellsHypokalemia

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.

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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 saythat 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

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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 carriedalong 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 60-

70 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 itnegative, 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.

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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 isreally 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 ofAldo 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 sothat 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

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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.

1stthing if plasma K conc goes up, if we have justhyperkalemia

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

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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.

Hyperkalemiaelevates the K conc in the principal cells becauseit 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.

Oviouslyaldosteronewill 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.

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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 pHIf 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 directeffect 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.

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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 mightbe.

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 Kand lead to secretion so not just removal of a + charge, but

introduction of some anion, nonreabsorbable anioncan do that.

Now we have to finish w/ Bicarb.

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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 aldosecretion 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 aroundyou 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 thebicarb, 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.

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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 CO2then 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 sideto 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.

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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 arecoincident 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/ Nareabsorption 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/

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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 harderto 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). Naphosphate 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 thisphosphate.So the kidney has actually generated one bicarb.

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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

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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 bicarbconc 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 oftitratable 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 thatbicarb 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

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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 ofnephron , 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 cellsfrom 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.

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CARBONIC ANHYDRASE MAKES CARBONIC ACID!!!!

One more

Second way that the kidney has for making new bicarb is a

method that is more effectivethan 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 excretedand 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 cangenerate lots of bicarb over a long period of time but it takes a

while to kick in.

The sequence would be the 1stthing the kidney does when acid is

high is reabsorb all bicarb to make sure we dont lose any.

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Then 2ndthing 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 willcause 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.

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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 inassociation 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

bodyso 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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