Question on Acid Base Balance - Urgent n Desperate!!!

[monstersaurous]

Hi everyone, Im having my physiology exams in 3 day's times n Im desperate for some help in this question, will someone please give me some advice on these questions? Im desperate! I have coloured my questions blue and placed them alongside my reasoning, so that you can better understand the context of my questions:

Question 1
Continuous and severe vomitting may lead to metabolic alkalosis due to hypochloremic alkalosis and hypovolemic alkalosis. I understand the physiology of these 2 causes. However, this also occurs:

CO2 + H20 <=> H+ + HCO3-

During prolonged vomitting, excess HCO3- is released into the blood stream, thus pushing the equation to the left, decreasing [H+] and increasing PCO2.

Here's what Im confused about:
Wouldnt the increased PCO2 cause increased ventilation, and in so doing cause the equation to shift left even more, aggravating the alkalosis? Does transient alkalosis and hyperventilation and this occur in this patient in real life? I shall call this effect A.

However, if we were to look at it the other way, any increased [HCO3-] and pushing of the equation to the left will also cause plasma [H+] to drop, which will stimulate peripheral chemoreceptors at the aortic and carotid bodies, causing hypoventilation, thus increasing PCO2 and correcting the situation. (Is H+ in the plasma important at all in stimulating the central chemoreceptors in the brain to cause ventilation? Or is [H+] mainly, if not only, detected at peripheral chemoreceptors only?) I shall call this effect B.

Relating back to real life scenarios in the hospital, patients suffering from prolonged vomiting thus metabolic alkalosis usually hypoventilate, not hyperventilate, to correct the alkalosis. Does this mean that effect B is more significant than effect A, which implies that the triggering of hypoventilation by plasma [H+] is more powerful than the triggering of hyperventilation by excess CO2? (I find this wierd, as I was taught that CO2 is always the more powerful stimulant in triggering off ventilation, not H+)

Effects A and B are my self-formed hypotheses. Now, what I was taught in uni was this: As long as the lungs are functioning well, PCO2 in our blood is always kept very constant (with a very rapid response time, usually within seconds) despite changes in CO2 production in our body. As long as the kidney is working fine, [HCO3-] is also kept constant despite changes to its rate of metabolic production or external ingestion, although the response time is longer (days to weeks - am I correct to say this?). With this in mind, I was told that during prolonged vomitting, the excess HCO3- produced by the stomach will be quickly removed by the kidneys (doesnt it take days to weeks for the kidneys to compensate for any [HCO3-] imbalance in the body? I dont find point very valid), and the excess CO2 produced as a result of effect A (see above) will also be removed quickly by hyperventilation. Thus, only [H+] will drop, with little change in [HCO3-] or PCO2. This drop in [H+] will then push the equation to the right, decreasing PCO2, trigger hypoventilation and correct the alkalosis. I find this explanation rather wierd, because of the question I raised above (the previous question regarding HCO3- compensation by the kindeys).

Question 2
Again, we look at this equation:
CO2 + H20 <=> H2CO3 <=> H+ + HCO3-

It is commonly said, for example, that if PCO2, [H+] or [HCO3-] changes, the equation shifts left or right to buffer the changes etc. However, isnt it true that the components of this equation cannot freely equilibrate in the plasma (as the reversible reaction does not take place readily without carbonic anhydrase), but only do so where there is abundant carbonic anhydrase to catalyse the reversible equation, such as in RBCs? Why then can we still assume that the equation is freely equilibrating in the plasma, allowing for rapid or almost instantaneous right-left and left-right shifts in the plasma during buffering reactions? Is it because RBCs are so abundant in the plasma that any excess HCO3-, H+ or CO2 in the plasma will be rapidly acted upon by carbonic anhydrase in RBCs, allowing for rapid equilibration in the plasma?

I know that the questions are long, but would someone please please help me out? I really dont want to fail my exams 🙁 but as you can see, I may just be on my way to it. I would greatly appreciate your help!

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[megadon]

hypoventilate. Lost a lot of H, therefore more free HCO3. Therefore alkalotic, therefore breath less to increase CO2 to bring back to 7.4 Also, you reabsorb and make less bicarb in the kidney.

That's what the grid book says, however, I also throw in, if its 1-2 hours after you eat, HCO3 has been secreted to neutralize H, so all bets are off, maybe counteract effects.

 

[joe6102]

Question 1
Continuous and severe vomitting may lead to metabolic alkalosis due to hypochloremic alkalosis and hypovolemic alkalosis. I understand the physiology of these 2 causes. However, this also occurs:

CO2 + H20 <=> H+ + HCO3-

During prolonged vomitting, excess HCO3- is released into the blood stream, thus pushing the equation to the left, decreasing [H+] and increasing PCO2.

Here's what Im confused about:
Wouldnt the increased PCO2 cause increased ventilation, and in so doing cause the equation to shift left even more, aggravating the alkalosis? Does transient alkalosis and hyperventilation and this occur in this patient in real life? I shall call this effect A.

Excess HCO3- (bicarb) is not released into the blood. 2 things happen from vomiting:
1. H+ is lost
2. fluid is lost

When the H+ is lost, the equation shifts to the right (not the left), increasing bicarb and H+, but not enough to offset the H+ that was lost.

When fluid is lost, it activates the renin-angiotensin-aldosteron system. Aldosterone increases H+ excretion in the proximal tubule, exacerbating the alkalosis.

The metabolic alkalosis causes hypoventilation to increase PCO2 and push the equation to the right.

 

[monstersaurous]

Therefore alkalotic, therefore breath less to increase CO2 to bring back to 7.4 Also, you reabsorb and make less bicarb in the kidney.quote]

Alkalotic and breath less:
CO2 <=> H+ + HCO3-
More HCO3- means that [H+] drops and PCO2 rises. So you are telling me that it is the low [H+] that triggers hypoventilation. In this case, where exactly is the low [H+] detected? Is it only at the peripheral chemoreceptors (carotid and aortic body) or also at the central chemoreceptors (in brain medulla)? Does plasma H+ even cross the BBB to be detected in the brain medulla chemoreceptors (i dont know this)?

Then what about the problem of increased PCO2 (due to shifting of eqn to the left) and the resultant stimulus to cause hyperventilation? Why does hyperventilation not take place?

Also, while stimulus for ventilation is mainly PCO2, what is the main stimulus for regulating the formation of and secretion of HCO3-/H+ by kidney epithelial cells?

 

[Tired]

Excess HCO3- (bicarb) is not released into the blood.

Well, there is the bicarb/chloride exchanger in RBCs. Not a significant source of circulating bicarb, but there is uptake and release between the RBC and plasma.

 

[dynx]

Therefore alkalotic, therefore breath less to increase CO2 to bring back to 7.4 Also, you reabsorb and make less bicarb in the kidney.quote]

Alkalotic and breath less:
CO2 <=> H+ + HCO3-
More HCO3- means that [H+] drops and PCO2 rises. So you are telling me that it is the low [H+] that triggers hypoventilation. In this case, where exactly is the low [H+] detected? Is it only at the peripheral chemoreceptors (carotid and aortic body) or also at the central chemoreceptors (in brain medulla)? Does plasma H+ even cross the BBB to be detected in the brain medulla chemoreceptors (i dont know this)?

Then what about the problem of increased PCO2 (due to shifting of eqn to the left) and the resultant stimulus to cause hyperventilation? Why does hyperventilation not take place?

Also, while stimulus for ventilation is mainly PCO2, what is the main stimulus for regulating the formation of and secretion of HCO3-/H+ by kidney epithelial cells?

Respiratory drive is governed by central chemo receptors. It is driven by pH which ussually reflects CO2 conc. (which can cross the BBB while H+ HCO3 cannot) Review your resp physiology.

 

[monstersaurous]

Excess HCO3- (bicarb) is not released into the blood. 2 things happen from vomiting:
1. H+ is lost
2. fluid is lost

When the H+ is lost, the equation shifts to the right (not the left), increasing bicarb and H+, but not enough to offset the H+ that was lost.

When fluid is lost, it activates the renin-angiotensin-aldosteron system. Aldosterone increases H+ excretion in the proximal tubule, exacerbating the alkalosis.

The metabolic alkalosis causes hypoventilation to increase PCO2 and push the equation to the right.

Isnt the release of HCO3- from the parietal cells following the release of H+ into the stomach lumen (AKA alkaline tide) a well documented phenomenon in the stomach? In this case, why is it that you claim that during vomitting, when excess HCl is secreted, no excess HCO3- is released into the interstitium? Or is it that the amount of HCO3- released into the intersititum is insignificant? If it is insignificant, how then can the amount of H+ depleted from the interstitium be significant, since the amount of HCO3- released into the interstitium is equal to the amount of H+ released into the stomach lumen?

 

[joe6102]

Isnt the release of HCO3- from the parietal cells following the release of H+ into the stomach lumen (AKA alkaline tide) a well documented phenomenon in the stomach? In this case, why is it that you claim that during vomitting, when excess HCl is secreted, no excess HCO3- is released into the interstitium? Or is it that the amount of HCO3- released into the intersititum is insignificant? If it is insignificant, how then can the amount of H+ depleted from the interstitium be significant, since the amount of HCO3- released into the interstitium is equal to the amount of H+ released into the stomach lumen?

When thinking about acid/base disorders, only consider H+/bicarb/CO2 that leaves the body. The role of the digestive system in regulating acid/base balance is negligible. The only two systems you have to worry about are renal and respiratory.

The H+ that is secreted by the parietal cells to replace the H+ that is lost through vomiting is not significant because just as much bicarb is secreted in the small intestine to neutralize it. Very little H+ is lost in the feces.

 

[dynx]

When thinking about acid/base disorders, only consider H+/bicarb/CO2 that leaves the body. The role of the digestive system in regulating acid/base balance is negligible. The only two systems you have to worry about are renal and respiratory.

The H+ that is secreted by the parietal cells to replace the H+ that is lost through vomiting is not significant because just as much bicarb is secreted in the small intestine to neutralize it. Very little H+ is lost in the feces.

dear god. This may be the stupidest post ever. this is not a hard concept people.

 

[monstersaurous]

When thinking about acid/base disorders, only consider H+/bicarb/CO2 that leaves the body. The role of the digestive system in regulating acid/base balance is negligible. The only two systems you have to worry about are renal and respiratory.

The H+ that is secreted by the parietal cells to replace the H+ that is lost through vomiting is not significant because just as much bicarb is secreted in the small intestine to neutralize it. Very little H+ is lost in the feces.

Do you mean that even if there is an alkaline tide at the stomach due to the secretion of H+ into the stomach, this alkaline tide will not significantly alter the pH of the interstitium, because any HCO3- released into the interstitium at the stomach (alkaline tide) will be secreted at the small intestines, pancreatic ducts and bile ducts to neutralize the H+ that was secreted into the stomach lumen (which gave rise to the alkaline tide), thus in actual fact, net addition of HCO3- into the interstitium at the GIT = almost zero?

In other words, the alkaline tide at the stomach is almost exactly balanced out by the acid tide at the pancreatic duct, bile duct and small intestines, due to a need to neutralize the stomach acid in the small intestines.

However, the secretion of HCO3- into the small intestines may occur only some time after HCl is secreted into the stomach, as it takes several hours for food in the stomach to pass into the small intestines. So, in the meantime, the body attempts to remove any excess HCO3-by first increasing secretion into the urine at the kidneys. I believe this is what megadon meant in his earlier post:

hypoventilate. Lost a lot of H, therefore more free HCO3. Therefore alkalotic, therefore breath less to increase CO2 to bring back to 7.4 Also, you reabsorb and make less bicarb in the kidney.

That's what the grid book says, however, I also throw in, if its 1-2 hours after you eat, HCO3 has been secreted to neutralize H, so all bets are off, maybe counteract effects.

However, I believe that the above are not the most important explanations as yet. Take a look at what joe6012 said:

When thinking about acid/base disorders, only consider H+/bicarb/CO2 that leaves the body.

Thanks so much joe, I think this made clear something to me: The equation
CO2 + H20 <=> H+ + HCO3-
uses values of total PCO2, [H+] and [HCO3-] in our entire body, which is an aggregate of their total content in all sites of our body.

If we were to look at, for example, the formation of H+ and HCO3 by stomach parietal cells with the using up of CO2, assuming that (but this is not what really happens) all the H+ or HCO3- formed was returned back to the interstitium, there is actually no net change in PCO2, [H+] or [HCO3-] values that we input into our henderson hasselbach equation, because the shifting right of the equation at the stomach will be balanced out by the shifting left of the equation somewhere else in the body where equilibration takes place readily, perhaps in RBCs. (i.e. there is no net shift in direction of the equilibrium equation)

Now, it is only when we change the net values of PCO2, [H+] and [HCO3-] by adding in or taking out amounts of those items, such as by
1) Increasing CO2 production due to increased respiration
2) Increasing H+ loss through vomiting
3) Increasing HCO3- loss through diarrhoea
etc etc...
that we will be able to change the values we apply to the henderson hasselbach equation, thus causing a net shift of direction of the equilibrium equation (compared to no net shift in direction as explained above). This is exactly what happens during vomiting:

CO2 + H20 <=> H+ + HCO3-
1) Hyperchloremic alkalosis caused by Cl loss in vomitus: Net loss of H+ at the renal tubular cells, not net gain of HCO3- (an increased reabsorption of HCO3- promotes excretion of H+ into the renal tubular lumen), thus shifting direction of equation to the right.
2) Alkaline tide during vomiting: No net HCO3- is gained, but instead H+ is lost from the parietal cells into the stomach lumen.
3) Hypovolemic alkalosis - net loss of H+ in the intercalated cells of the collecting duct

The net result of the above is that net PCO2 decreases, causing hypoventilation, which will increase PCO2, shift equation to the right, increase [H+] and correct the alkalosis.

Is this correct?

 

[joe6102]

dear god. This may be the stupidest post ever. this is not a hard concept people.

If it's not a hard concept, then explain it yourself instead of bashing someone else for trying to help. The stupiest post ever is the one that adds NOTHING to the conversation.

 

[joe6102]

However, I believe that the above are not the most important explanations as yet. Take a look at what joe6012 said:

When thinking about acid/base disorders, only consider H+/bicarb/CO2 that leaves the body.

Thanks so much joe, I think this made clear something to me: The equation
CO2 + H20 <=> H+ + HCO3-
uses values of total PCO2, [H+] and [HCO3-] in our entire body, which is an aggregate of their total content in all sites of our body.

Great! It's good to know that the "stupidest post ever" actually helped somebody.

If we were to look at, for example, the formation of H+ and HCO3 by stomach parietal cells with the using up of CO2, assuming that (but this is not what really happens) all the H+ or HCO3- formed was returned back to the interstitium, there is actually no net change in PCO2, [H+] or [HCO3-] values that we input into our henderson hasselbach equation, because the shifting right of the equation at the stomach will be balanced out by the shifting left of the equation somewhere else in the body where equilibration takes place readily, perhaps in RBCs. (i.e. there is no net shift in direction of the equilibrium equation)

Now, it is only when we change the net values of PCO2, [H+] and [HCO3-] by adding in or taking out amounts of those items, such as by
1) Increasing CO2 production due to increased respiration
2) Increasing H+ loss through vomiting
3) Increasing HCO3- loss through diarrhoea
etc etc...
that we will be able to change the values we apply to the henderson hasselbach equation, thus causing a net shift of direction of the equilibrium equation (compared to no net shift in direction as explained above). This is exactly what happens during vomiting:

CO2 + H20 <=> H+ + HCO3-
1) Hyperchloremic alkalosis caused by Cl loss in vomitus: Net loss of H+ at the renal tubular cells, not net gain of HCO3- (an increased reabsorption of HCO3- promotes excretion of H+ into the renal tubular lumen), thus shifting direction of equation to the right.
2) Alkaline tide during vomiting: No net HCO3- is gained, but instead H+ is lost from the parietal cells into the stomach lumen.
3) Hypovolemic alkalosis - net loss of H+ in the intercalated cells of the collecting duct

The net result of the above is that net PCO2 decreases, causing hypoventilation, which will increase PCO2, shift equation to the right, increase [H+] and correct the alkalosis.

Is this correct?

Yeah, but don't worry about what happens in the parietal cells. I don't know how long it takes the stomach to secrete acid to replenish what it lost, but it doesn't matter. We were taught that parietal cell secretion of acid/small intestine secretion of bicarb have no effect on acid/base disorders. Renal and respiratory are the only systems that have any real effects.

 

[monstersaurous]

We were taught that parietal cell secretion of acid/small intestine secretion of bicarb have no effect on acid/base disorders. Renal and respiratory are the only systems that have any real effects.

Yes that's right, because only the renal and respiratory system has the ability to cause net excretion/addition of H+ and HCO3- respectively, from/into the body's system. This was a great conversation with you guys, thanks a million to those who helped! Thanks joe!

 

[dynx]

Yes that's right, because only the renal and respiratory system has the ability to cause net excretion/addition of H+ and HCO3- respectively, from/into the body's system. This was a great conversation with you guys, thanks a million to those who helped! Thanks joe!

I'm serious here, your explanation and reasoning is so far off base I would not know where to begin...ASK YOUR PHYSIOLOGY PROFESSIOR TO HELP YOU WITH THIS. The balancing to the alkaline shifts from the stomach are not matched if the patient is throwing up, thats only one problem with your line of thinking...it actually goes down hill from there. I'm not trying to be an dingus, but if you go into a test using this sort of logic to try to figure out different problems you're going to get slaughtered.

 

[monstersaurous]

Aright i will. Thanks for tt dynx, appreciate tt.

 

[ridirkulous]

h

 

[ridirkulous]

h