Oxygen solubility and half times

[Piscean]

Hello Paul,

So, I think we agree. Thanks for filling in the bit about the CO2 buffering, I didn't know why execise increases the susceptibility to Ox Tox, but it sounds like that could be one of the reasons. Do you know where I could look up the pH dependence of the haemoglobin dissociation curve?

You are right of course about the oxygen in the tissues:

You say " If we breathe ppO2 at 3 bar then I suggest the ppO2 in our tissues will be 3-2.6 = 0.4 bar. (The 2.6 difference comes from the 6 ml of O2 that gets metabolised.) " I am not sure this is strictly true. While this may reflect what is seen in the blood, all tissues have a lower oxygen tension than seen in venous blood. In addition there are the confounding variables of differing tissue metabolic rates, variable blood supplies to those tissues and in addition the auto-regulation of blood supply to the brain. (CNS oxygen toxicity is not seen outside the brain!)

I meant to say in the blood in the capillaries in the tissues but I just got lazy and inaccurate in my writing.
So what else? I think we get back to your earlier mathematical gymnastics if we start on the MOD diluent question. Maybe I'll do that later, but I'm at work at the moment so maybe I should concentrate on that, but basically, I agree with you.

In the meantime shall look forward to your next poser.

Ciao,
Piscean.

 

[The Iceni]

Hi Piscean,

2nd year college biochemistry students spend a lot of time on the structure and function of haemoglobin. I did little research and came upon John Patterson's lectures on this very subject at;

http://www.smd.qmul.ac.uk/biomed/kb/cardioresp/CRstage2lectures/JP1GasCarriage/

The effect you ask about is known as the Bohr effect. Carbon dioxide competes with oxygen for sites on the haemoglobin molecule. The effect is shown on the following neat program

http://www.manbit.com/hbdiss.htm

In a nutshell it makes a great deal of sense for carbon dioxide to displace oxygen in the blood. Where there is a lot of carbon dioxide - in the tissues where oxygen is being used and therefore needed - the haemoglobin molecule looses its affinity for oxygen and releases it as molecular oxygen for use in those tissues.

Acidity has the same effect.

The more I look in to this the more I am convinced Carbon dioxide is the key to oxygen toxicity. We have all heard of the Haldane therories of decompression but he described an important feature of haemoglobin activity, known - surprise, surpise - as the Haldane effect.

"Venous blood can carry more carbon dioxide than arterial blood"

If you now understand the behaviour of haemoglobin the reason for this should now be obvious. Carbon dioxide is carried in the blood by haemoglobin in exactly the same way as oxygen . The more carbon dioxide the less oxygen can be bound to Hb and visa versa!

 

[Piscean]

... for the info. I like the program. Haven't read the other stuff yet.

Piscean.

 

[padiscubapro]

Originally posted by Dr Paul Thomas
Hi Piscean,

2nd year college biochemistry students spend a lot of time on the structure and function of haemoglobin. I did little research and came upon John Patterson's lectures on this very subject at;

http://www.smd.qmul.ac.uk/biomed/kb/cardioresp/CRstage2lectures/JP1GasCarriage/

The effect you ask about is known as the Bohr effect. Carbon dioxide competes with oxygen for sites on the haemoglobin molecule. The effect is shown on the following neat program

http://www.manbit.com/hbdiss.htm

In a nutshell it makes a great deal of sense for carbon dioxide to displace oxygen in the blood. Where there is a lot of carbon dioxide - in the tissues where oxygen is being used and therefore needed - the haemoglobin molecule looses its affinity for oxygen and releases it as molecular oxygen for use in those tissues.

Acidity has the same effect.

The more I look in to this the more I am convinced Carbon dioxide is the key to oxygen toxicity. We have all heard of the Haldane therories of decompression but he described an important feature of haemoglobin activity, known - surprise, surpise - as the Haldane effect.

"Venous blood can carry more carbon dioxide than arterial blood"

If you now understand the behaviour of haemoglobin the reason for this should now be obvious. Carbon dioxide is carried in the blood by haemoglobin in exactly the same way as oxygen . The more carbon dioxide the less oxygen can be bound to Hb and visa versa!

Hearing it from another doctor reinfoces what I have been taught and have been teaching.. I have been preaching CO2 as that primary catelist for Otox in the Nitrox class I teach for several years now.. Two of the ANDI programs I teach CSU and their o2 admnistration go into this as the primary cause. I teach students otox should be atributed to the PO2 + TO2 (time) + PCO2, if one is missing otox is less likely but not impossible...

I also bet smokers are at a higher risk also since the CO molecule bonds to hemoglobin much stronger than anything else, and would limit both CO2 and O2 transport. I am not a doctor but my understanding is that under normal circumstances the CO bond isn't broken and can only be broken under high o2 hyperbaric situations hence the use of chambers for smoke inhalation victims.

 

[DivingDoc]

Originally posted by Dr Paul Thomas
Hi Piscean,

The effect you ask about is known as the Bohr effect. Carbon dioxide competes with oxygen for sites on the haemoglobin molecule. The effect is shown on the following neat program

http://www.manbit.com/hbdiss.htm

In a nutshell it makes a great deal of sense for carbon dioxide to displace oxygen in the blood. Where there is a lot of carbon dioxide - in the tissues where oxygen is being used and therefore needed - the haemoglobin molecule looses its affinity for oxygen and releases it as molecular oxygen for use in those tissues.

Acidity has the same effect.

Great program. But it seems to me that the predominant item affecting the shifting of the Hb dissociation curve is the pH. If you download the program and play with the settings, you will notice that decreasing pH has the effect of shifting the Hb dissociation curve rightward and lower. Changing the pCO2 by itself has less effect. Of course, in humans, rising pCO2 is normally associated with lower pH.

In diving, as the diver descends, the pCO2 rises because of the greater density of air and the increased work of breathing due to that greater density. Also, the stimulus to breathe is somewhat decreased because of the higher than normal pO2.

I don't see how the displacement of O2 by CO2 attached to the heamoglobin molecule could account for ox-tox as this is not really depriving tissues of O2. The pO2 is still high as is the amount of oxyhemoglobin.

Although a common explanation for the effects of Oxygen toxicity on the nervous system relates to the toxic effects of superoxide radicals, no one really knows the real reason.

See an article on the DAN website:
http://www.diversalertnetwork.org/medical/articles/article.asp?articleid=35

 

[The Iceni]

Hi Diving Doc,

You said
In diving, as the diver descends, the pCO2 rises because of the greater density of air and the increased work of breathing due to that greater density. Also, the stimulus to breathe is somewhat decreased because of the higher than normal pO2.

I am not so sure this is strictly correct as it reads. It sounds like pp CO2 linearly increases with depth. It is well known that the resistance to breathing will effectively increase the dead space and the work involved in breathing and so elevate the pp CO2 at extreme depth. But with modern equipment and relaxed diving CO2 retention is not the problem it once was, at least for recreational divers. However I cannot see that CO2 alone will be sufficient to alter the local pH in parts the brain enough to produce the variability of CNS Oxtox snisitivity at the pressures to which recreational divers are exposed.

There must be something else at work.

You also said
Great program. But it seems to me that the predominant item affecting the shifting of the Hb dissociation curve is the pH. If you download the program and play with the settings, you will notice that decreasing pH has the effect of shifting the Hb dissociation curve rightward and lower. Changing the pCO2 by itself has less effect. Of course, in humans, rising pCO2 is normally associated with lower pH.

Absolutely! Unfortunatly the program is designed to demonstrate the Bohr effect at normal pp O2. As I have said eslewhere I am convinced that the hydrogen ion is greatly implicated in CNS Oxtox and it is well know that high levels of CO2 predispose to CNS Oxtox.

Are the two related? I very much think so!

As you know at inspired pp O2 of greater than 3 bar the venous haemoglobin remains effectively fully saturated with oxygen and is unable to carry any CO2 whatsover in an inactive form, obliterating the Haldane Effect.

As with oxygen, if the CO2 is not bound to Hb it must remain in its molecular form; free to form carbonic acid. Thus changing the local pH at tissue level!

In excess free CO2 the following reaction is pushed to the right

H2O + CO2 <=> H2Co3 <=> H+ + CO3 -

This is only theory, but not wildly out of the blue and based on established biochemical phenomena. There is indeed speculation about free radicals but why look elswhere when the hydrogen ion is so powerful and is produced a-plenty by anaerobic respiration.

I would love to have the opportunity to do some research on this. I was a neurophysiologist at one time! (I think it very ulikely I will be given the opportunity though!)

Take a look at my contribution on http://www.scubaboard.com/showthread.php?threadid=4425

I have refined the above post as an article for discussion and will send it to you from my office tommorrow. If I can get an email to you!

Kind Regards,

 

[Dr Deco]

Dear Doc and Doc:

I believe that the question here concerning carbon dioxide and oxygen toxicity lies with the effect of CO2 on the auto regulation of cerebral blood flow. When carbon dioxide is present in elevated partial pressures, the cerebral blood flow is increased. This will bring increased amounts of oxygen into the brain. This will be in amounts greater than can be metabolized, the generation of reactive oxygen intermediates occurs and seizures follow.

When carbon dioxide partial pressure is low, blood flow is decreased and consequently so in oxygen. This is commonly observed when on hyperventilates, blowing off CO2, and light-headedness results. Many know that if you want to hyperventilate without becoming dizzy, it is necessary to breathe into a bag to rebreathe your expired air.

When individuals are seated in a hyperbaric chamber, it is common to have them breathe oxygen at a partial pressure of 2.8 ata. They are seated and resting and the CO2 production is low.:nurse:

This is much different than a diver who is actively swimming. Here carbon dioxide is elevated in the arterial circulation.

Dr Deco:doctor:

 

[DivingDoc]

Originally posted by Dr Deco
Dear Doc and Doc:

I believe that the question here concerning carbon dioxide and oxygen toxicity lies with the effect of CO2 on the auto regulation of cerebral blood flow. When carbon dioxide is present in elevated partial pressures, the cerebral blood flow is increased. This will bring increased amounts of oxygen into the brain. This will be in amounts greater than can be metabolized, the generation of reactive oxygen intermediates occurs and seizures follow.

Good point.

When individuals are seated in a hyperbaric chamber, it is common to have them breathe oxygen at a partial pressure of 2.8 ata. They are seated and resting and the CO2 production is low.:nurse: [/B]

This is probably a stupid question (I am a comparative newbie diver), but as a clinician, I am used to expressing the pO2 in arterial (or venous for that matter) blood in mm Hg. Normal is in the range of 95 or so. So how does this relate to the "pO2" people talk about in nitrox diving or that they set as an alarm level on their computers at 1.4? What does ata refer to?

 

[Piscean]

DivingDoc,

This time no dissertation:

1 ata = 1 atmosphere absolute
760 mm Hg = 1 ata
1 mm Hg = 1 Torr
1 ata = 14.72 psi
1 ata = 1.01325 bar
1 bar = 100000 Pa (Pa = pascal)
1 Pascal = 1 Newton/m2 = 10 dyne/cm2

The 1.4 ata that people set there alarms to refers to the inspired partial pressure of oxygen, that is the partial pressure of oxygen in the gas supplied by the regulator. How this relates to the partial pressure of oxygen in the blood can be extracted from other posts prior to this one or probably from more reliable sources which are unknown to me.

Piscean.

 

[The Iceni]

By Dr Deco
I believe that the question here concerning carbon dioxide and oxygen toxicity lies with the effect of CO2 on the auto regulation of cerebral blood flow. . . When carbon dioxide partial pressure is low, blood flow is decreased and consequently so is oxygen.

I agree the phenomenon of cerebral autoregulation has been proven many times but I suspect seldom, if ever, in the hyperbaric environment. As I understand it, this allows blood to be diverted from areas of adequate or excessive oxygenation (by localised vasoconstriction) to areas of low oxygenation (and high carbon dioxide tension) by localised vasodilatation, while total cerebral blood flow remains relatively constant and fairly high.

The thing that puzzles me about relying on this to explain the cause of oxtox - is that both carbon dioxide and more so oxygen are present in excess of their normal physiological ranges when diving and extrapolation of this phenomenon to the hyperbaric situation may not necessarily follow. In addition autoregulation may increase the local pp O2 but not in an explosive manner. I am sure there exists some work on this in the archives.

By Dr Deco
When individuals are seated in a hyperbaric chamber, it is common to have them breathe oxygen at a partial pressure of 2.8 ata. They are seated and resting and the CO2 production is low.

This is much different than a diver who is actively swimming. Here carbon dioxide is elevated in the arterial circulation.

I couldn't agree more, Dr Deco. Not only do you have the effects of exercise, which alone can raise the venous (alveolar) pp CO2 to more than 70 mmHg on the surface, you also have to deal with increased dead space and a stressful environment when diving.

By all accounts elevation of the partial pressure of carbon dioxide at tissue level causes a Bohr shift to the right in both the haemoglobin and myoglobin dissociation curves (and a reduction in acidity by the formation of carboxyhaemoglobin) but oxygen and CO2 compete for the Hb sites. However, what seems certain to me is that the formation of carbaminohaemoglobin is inhibited in the presence of relatively high partial pressures of oxygen. (The Haldane effect) This leads to a preponderance of free and active CO2 molecules in the tissues which further increases the acidity already present because of the increases in aerobic and particularly anaerobic metabolites due the increased levels of exercise AND the inhibition of the enzymes of oxidative phosphorylation. Thus localised acidity is increased even further.

I think it is generally accepted that high levels of CO2 (in respiratory failure, say) causes an acidosis and the effects of surface hyperventilation, including tetany, is caused by a respiratory alkalosis. I fail to see why these same effects are not reproduced in the tissues in the hyperbaric environment.

I do believe free radicals play a part but . .

DivingDoc said
I don't see how the displacement of O2 by CO2 attached to the heamoglobin molecule could account for ox-tox as this is not really depriving tissues of O2. The pO2 is still high as is the amount of oxyhemoglobin.

Can I ask you to look at how cyanide works, Diving Doc? It irreversibly blocks the cytochrome of adenoside triphosphatase bringing cellular respiration to a halt. Death from tissue asphyxia follows - in the presence of adequate molecular oxygen! Excessive oxygen itself is known to denature these same enzymes bringing cellular respiration to a halt in the presence of excess molecular oxygen. I do not think true tissue hypoxia is implicated in the genesis of CNS oxtox in any way.

I believe this could be the trigger for a chain reaction in the brain which is the set of circumstances needed to initiate a grand mal convulsion;-

1) In an high pp O2 environment cellular respiration is inhibited. A reduction of respiration means less oxygen is metabolised so its intramtiochondrial level is not reduced as rapidly as normal and will rise as more oxygen is delivered to the tissues by the circulation. An even higher pp O2 environment means cellular respiration is inhibited even more and even less oxygen is metabolised so its level will continue to rise as more oxygen is delivered to the tissues by the circulation. . . .

2a) An increasing pp O2 causes carbon dioxide to dissociate from haemoglobin and myoglobin - increasing localised acidity.

2b) Inhibition of cellular respiration means muscle, in particular, will rely on anaerobic metabolism with the production of lactic acid.

3) Acidity shifts the Hb dissociation curve to the right, releasing even more molecular oxygen locally, and so back to step 1!

I think this fits the bill pretty well and would like to see it tested, or disproved.
__________

PS. Diving Doc.

I cannot send my article to you. I cannot get "private messages" to work for me so if you really want to be confused send an email to paul@gippingvalleypractice.co.uk and I'll return the compliment.