Question on Acid Base Balance - Urgent and Desperate!!! (1 Viewer)

[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!

 

[suess]

Dear monstersaurous, sorry for the late reply. I hope you did well on your exam.

I thought I'd reply and answer your questions even though I am a bit late, just in case you still don't understand. I've typed my responses in bold.


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.

You must first understand that although vomiting of the gastric contents alone, without vomiting of the lower GI contents, causes loss of HCl and the net result is loss of acid from extracellular fluid and development of metabolic acidosis. However, vomiting large amounts from deeper in the GI tract causes loss of bicarbonate and results in metabolic acidosis in the same way that diarrhoea causes acidosis.

Now to answer your question:

During prolonged vomiting, there is a loss of H+ (due to loss of HCl) and also contraction alkalosis from release of aldosterone and subsequent reabsorption of HCO3. The equation is moved to the RIGHT to compensate. However, hypoventilation is often seen in patients with metabolic alkalosis. This is because there is an increase in pCO2 (respiratory acidosis) is to compensate for the loss of H+. A typical textbook case is be:

Patient with intermittent profuse vomiting, tachycardic, reduced tissue turgor and hypotension (other clinical signs may be present depending on aetiology of vomiting, such as abdominal succussion splash). Blood pH 7.55, pCO2 48mmHg, bicarbonate concentration 35mmol/L.

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.

There will be hypoventilation (you were on the wrong track before). Although pH (H+ concentration) does have an impact on peripheral chemoreceptors, its main action is on the respiratory centre in the brain stem.

To answer your question, H+ is vital in stimulating the central chemoreceptors (inspiratory area located bilaterally in the medulla). CO2 passes the blood brain barrier (as it is not very permeable to hydrogen ions) and then reacts with the water of the tissues to from carbonic acid, which dissociates into hydrogen and bicarbonate ions. The H+ has a potent direct action on this chemosensitive area. The reason a change in pH (without a significant change in pCO2) does not result in a major change in alveolar ventilation is due to the fact that hydrogen ions cannot cross the blood brain barrier to stimulate the central chemoreceptors.

H+ and CO2 do have a role in peripheral chemoreceptor stimulation, however O2 is the most potent stimulator. The effect of H+ and CO2 on peripheral chemoreceptors is only about 1/7 of their effect on central chemoreceptors.

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+)

No, you were on the wrong track with “effect A” and hence your conclusion is incorrect. CO2 is always the more powerful in triggering ventilation (although it is mediated via H+ once it passes through the blood brain barrier).

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).

Refer to the above explanations and re-think this – you should be able to work it out.


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?

The dissolved CO2 reacting with H2O to form carbonic acid occurs very rapidly in erythrocytes due to the presence of carbonic anhydrase (the catalyst of the reaction). In the plasma, without the carbonic anhydrase, the reaction still occurs. The reaction is significantly (approximately 5000-fold) slower though, taking seconds or minutes to occur.

You have to remember that a catalyst speeds up a reaction, but the reaction will still occur without it, albeit much slower.

Just for your information:

CO2 is transported as:

• CO2 = 7%
• Haemoglobin CO2 = 23%
• HCO3- = 70%