The physiology thread

[FrankDay]

The problem is that you keep referring to "anaerobic metabolism" as if it means that this only occurs when there isn't enough oxygen around. Without bothering to go to the literature and read about the mechanisms that underlie the lactate threshold, you decided to make up your own little story about it.

So you invented this little "explanation" about the end capillary pO2 dropping to zero and hence those muscle fibres being perfused by the end capillary start going "anaerobic".…

Thanks for your reply. In researching my response I have actually learned some stuff (probably not the stuff you want me to learn but that is another story). However, it seems you are under a great misconception. Anaerobic metabolism does not mean metabolism in the absence of oxygen, i.e., end capillary pO2 dropping to zero. Rather it means invoking a metabolic pathway that doesn't require oxygen, an anaerobic metabolic pathway. Anaerobic metabolism occurs in the presence of oxygen. It is just inadequate oxygen to support the aerobic metabolic pathways. I think if you look hard you will find that concept in your basic physiology text. If it isn't there, it should be.

Anyhow, after I have thought about some of the other issues here I will be back.

 

[FrankDay]

Frank,

You've alluded to your "Engineering background" a number of times in the past. Do you hold a degree in engineering and if so what branch and from what institution? Just trying to understand where you're coming from a bit better.

Hugh

I graduated US Naval Academy and spent 5 years as a nuclear engineer in the Navy's Nuclear Submarine Program. Of course, this was back in the days shortly after transition from wood, sails, and iron cladding so perhaps in the intervening time engineering principles may have changed similar to, it seems, physiology principles have, or so I seem to be being told

Edit: I might add that back in those days the boat school was not like it is now, where people can major in the biological sciences and go right to medical school (a policy I disagree with). When I was there the closest course related to the biological sciences was organic chemistry, a course I didn't take there. Although they tried to make us well rounded by requiring history, literature, and foreign languages, it really was primarily a practical engineering oriented school.

 

[FrankDay]

Many thanks, that is some excellent advice.

Fergie, you ought to make sure that this excellent advice makes it over to the power meter thread. It is my experience that such thoughts are generally pretty good fodder for a lively discussion. I will leave this up to you though as you asked the question. LOL.

 

[FrankDay]

The problem is that you keep referring to "anaerobic metabolism" as if it means that this only occurs when there isn't enough oxygen around. Without bothering to go to the literature and read about the mechanisms that underlie the lactate threshold, you decided to make up your own little story about it.

So you invented this little "explanation" about the end capillary pO2 dropping to zero and hence those muscle fibres being perfused by the end capillary start going "anaerobic".

But there is no evidence for this little imaginary story you invented in the scientific literature. It is very easy to disprove though by asking the question "is venous pO2 zero above the lactate threshold?". The answer to that question is a definitive NO. We could also ask is venous HbO2 saturation zero? The answer to that question is also a definitive NO.

The reality is that the term "anaerobic metabolism" does not even refer to a scenario in which the pO2 in the end capillary or the muscle fibre is zero. It does not mean there is NO OXYGEN present. What this term actually means is that oxygen is NOT REQUIRED to produce the ATP. A biochemist would refer to this as "substrate level phosphorylation" whereas they would call aerobic ATP synthesis "oxidative phosphorylation".

The question you are really asking is the following:

What causes the rate of substrate level oxidation to rapidly increase while in the presence of oxygen?

2 events occur here 1) PCr breakdown supplies enough ATP for a few seconds of "anaerobic ATP synthesis" and 2) increased glycolytic flux... which results in elevated lactate production

So the question thus becomes... what increases the glycolytic flux and therefore lactate production?

The answer is NOT a lack of oxygen. The correct answer is increasing sympathetic activation. This is a feedforward mechanism. The conscious effort required to exercise at higher intensity increases sympathetic activation, this in turn increases glycolytic flux and lactate production. If we recruit fast twitch fibres which have very high level of glycolytic enzymes but low mitochondrial density, then there is going to a lot of pyruvate being formed and not enough mitochondria around to oxidise it. This mismatch doesn't occur because oxygen supply to the mitochondria starts to decrease as a result of your fairy world end capillary zero pO2 hypothesis, it occurs because the rate of glycolysis is simply too high and the mitochondrial density is too low.

I have had some time to consider what you have written. Rather than try to get into nitpicking of every point I will try to keep my response more general but to your point.

The first very big defect in the argument seems to be the deliberate denial that anaerobic metabolic pathways for the production of lactate can be active in the presence of any oxygen. Hence your misinterpretation of my contention that anaerobic metabolism occurs as extraction increases and the ability to deliver adequate oxygen to all of the cells decreases due to diffusion limitations. You interpreted that as my saying the end capillary pO2 had to be zero for such a condition to occur. There is simply zero science to support that view. What is more amazing to me is that other exercise physiologists (such as Dr. Coggan) and physicians are here and not one jump in to correct your mistaken understanding. This misconception must be either very widespread or people just don't like confrontation. All it takes to activate the anaerobic metabolic pathways in the cell is an oxygen pressure less than is necessary to support the aerobic pathways combined with the cells need for more energy.

Next, you hypothesize that lactate accumulation at VO2max has nothing to do with anaerobic metabolism but rather is a result of glycolysis. I guess one could think that might be possible since a lactate is made during glycolysis but if it were true one should expect blood lactate concentration to follow glycolysis, which generally follows cell work load. That doesn't happen.
Here is a chart detailing typical blood lactate during an incremental exercise test.

This was taken from this article from the NIH. Lactate levels remain flat despite ever increasing glycolysis demands until they start to rise exponentially. While glycolysis might have a role in explaining some of the background lactate blood levels seen your overall explanation fails right here to explain all that is going on and especially fails to describe the exponential increase in blood lactate seen as one approaches VO2max. Your explanation is not the only one that might explain a background lactate level nor is there much evidence, IMHO, to support it as even having a major role although I will admit, it might.

I think it is clear that the cell tries to maintain a milieu that is conducive to rapid energy demands but also energy efficient. Clearly a ready supply of pyruvate is necessary for this task. The equilibrium that exists between pyruvate and lactate in the cell allows for a rapid replenishment of pyruvate concentrations so oxidative metabolism levels can be high and not restricted by fuel supply, at least in the short term. Glycolysis, being a little slower, simply replenishes both the pyruvate and lactate that are used up immediately. The cell (except for, perhaps, the RBC because it doesn't have any mitochondria) wants to keep all of these molecules for its own use. I guess some might leak out and into the blood, again in equilibrium, but it also might be the case that some leaks in, as everything is in equilibrium. Only when the equilibrium is upset will molecules "move".

Here is an anesthesia web site that I think had a pretty good discussion of most of these dynamics (although I think they missed one thing). Enjoy.

 

[acoggan]

What is more amazing to me is that other exercise physiologists (such as Dr. Coggan) and physicians are here and not one jump in to correct your mistaken understanding.

You're the one laboring under misconceptions, Frank. However, you've repeatedly proven yourself uneducatable, so there's no point in myself or anyone else attempting to correct them.

 

[FrankDay]

You're the one laboring under misconceptions, Frank. However, you've repeatedly proven yourself uneducatable, so there's no point in myself or anyone else attempting to correct them.

So, let me get this straight. You, Dr. Andrew Coggan, agree with Krebs that there can be no "anaerobic metabolism" (useful energy produced without the need for oxygen) in the cell unless the partial pressure of oxygen is zero, or in other words, anaerobic conditions exist?

 

[acoggan]

So, let me get this straight. You, Dr. Andrew Coggan, agree with Krebs that there can be no "anaerobic metabolism" (useful energy produced without the need for oxygen) in the cell unless the partial pressure of oxygen is zero, or in other words, anaerobic conditions exist?

That's not his position (nor mine).

 

[FrankDay]

That's not his position (nor mine).

Really? then why would he write:

So you invented this little "explanation" about the end capillary pO2 dropping to zero and hence those muscle fibres being perfused by the end capillary start going "anaerobic"

Someone on your side needs to clarify what is meant by that statement when I have never said that end capillary pO2 drops to zero. You, at least, agree that some muscle fibers are going into anaerobic metabolism well before VO2max. Correct? And, many more are in anaerobic metabolism at VO2max. Correct?

 

[CoachFergie]

Fergie, you ought to make sure that this excellent advice makes it over to the power meter thread. It is my experience that such thoughts are generally pretty good fodder for a lively discussion. I will leave this up to you though as you asked the question. LOL.

Can we only discuss revisionist physiology here?

 

[FrankDay]

Just so everyone doesn't think I am just pulling this stuff out of my you know what I did go look for a little support for my position. Here is one

For O2, maximal diffusion-distance conventionally is referred to as Krogh's radius, R.

Then there is this one. I actually learned something reading this but here are a few things of interest.

The diffusion distance from the capillary blood through the tissues to the mitochondria is long in many organs. Here, the conditions are less favourable and diffusion-limitation is sometimes present in cells at the far end of the capillaries, although their mitochondria can maintain oxidative metabolism even at 1 mmHg (0.133 kPa).

The force driving oxygen to the most distant mitochondria is often small. Fortunately, mitochondria have the capacity to maintain oxidative metabolism at a tissue tension as low as 133 Pa or one mmHg. Even such a low PO2 increases the rate of the respiratory chain events.

The only way in which the diffusion distance can be reduced is by recruitment of more capillaries at increasing demand. This is particularly important in skeletal muscles during exercise, where the capillary density increases threefold. Such a rise increases the systemic, capillary surface area, simultaneously with the decrease in diffusion distance.

And, here is what I learned, the stabilizing effect of having a hemoglobin like molecule in the muscle, the myoglobin.

In the muscle capillaries bloodflow is interrupted during the contraction phase, and the tissue-PO2 falls toward zero. At low PO2, the gradient of the dissociation curve of myoglobin is at its steepest. Hence, myoglobin releases its O2 readily. During muscular relaxation, bloodflow is restored and myoglobin is rapidly reloaded with oxygen. The myoglobin dissociation curve has a P50 some five-fold lower than that of haemoglobin.

And, lastly, this:

Intensively working skeletal muscles - just like the myocardium at rest - utilise 140- 170 ml O2 per l of blood. The main part of the cardiac output is directed for exercising muscles during severe work. The arterio-venous O2 content difference for the total muscle mass will become almost equal to that of the entire body.

The typical capillary passage period for blood is 0.75-1 second (s). Oxygen is rapidly released from haemoglobin. At the venous end of the capillary the most distant mitochondrion has the poorest oxygen supply.

 

[JayKosta]

This article from 1996 includes discussion of the relationship among: blood pH, lactate, glycolysis, VO2max, etc.
Although not the main topic of the article, I found the information very relevant to what is being discussed here.

http://www.billat.net/attachments/020_13.1996-Billat-use_of_blood_lactate_Mesasurements-SportMed.pdf

Sports Med. 1996 Sep;22(3):157-75. Review. Billat V.

The section of the article that I'm referring to is '1. Definition of the Blood Lactate Level'.

Is the info in section 1 of the article currently accepted as the 'current knowledge' ?

Jay Kosta
Endwell NY USA

 

[FrankDay]

This article from 1996 includes discussion of the relationship among: blood pH, lactate, glycolysis, VO2max, etc.
Although not the main topic of the article, I found the information very relevant to what is being discussed here.

http://www.billat.net/attachments/020_13.1996-Billat-use_of_blood_lactate_Mesasurements-SportMed.pdf

Sports Med. 1996 Sep;22(3):157-75. Review. Billat V.

The section of the article that I'm referring to is '1. Definition of the Blood Lactate Level'.

Is the info in section 1 of the article currently accepted as the 'current knowledge' ?

Jay Kosta
Endwell NY USA

Well, it probably isn't accepted as current knowledge by Coggan and Krebs, since it pretty much agrees with me, at least as regards what is going on at VO2max. The one area I would have to question is their explanation of the transition stage that they attribute to lactate production due to increased glycolosis. They point out that this stage is marked by a non-linear increase in lactate but I simply don't understand how lactate production due to glycolosis can be associated with an non-linear increase. To me this has to be the start of anaerobic metabolism at the far reaches of the diffusion distance from the end capillary. Such a mechanism would explain the non-linear aspect to this change.