Physiology Question

Jim,

Resting heart rate does slow due to the increase in plasma volume. The key here is that stroke volume increased due to decreased blood viscosity and greater venous return.

With a greater plasma volume, stroke volume will be greater at the same exercise intensity. Even though your hematocrit has decreased the O2 carrying capacity per heart beat of blood will be roughly the same.

So at the same exercise intensity, what's happening to HR? This is the part I find confusing: I understand the increased stroke volume, but it seems that to get the same O2 capacity, the stroke volume would have to increase by a larger percentage than the HR would decrease. e.g., if HR drops by 5% and there's a 5% increase in plasma volume, it seems that stroke volume would need to increase by more than 5% to keep O2 constant. Do you know what the relationship between these variables is? I can only assume that it's not a simple 1:1 linear function (i.e., a 1% increase in plasma volume does not produce a 1% decrease in HR and a 1% increase in stroke volume).

I've never read anything in great detail on this in any of the books I have nor have I ever taken a physiology course so please forgive my ignorance. I am trying to make sense of this in terms of the stuff I do know (engineering). Maybe looking at it like an engineering dynamics problem is not the best thing to do, but as they say "If you ask a carpenter to build you a bridge, don't be surprised when he makes it out of wood."

I'm not sure that your rbc count won't also rise. Certainly, a person's normal baseline hematocrit level appears to be heavily genetic. The body is nothing if not homeostatic. An increase in total blood volume (due to heat) might also spur the body to generate more rbcs to regain hematocritic equilibrium. I don't know this, but it's a thought. If you want to do an experiment of one, and you have a doctor friend, you might want to track your hemotacrit over the crucial month or so of the shift from cool to warm weather running.

When training in heat, your plasma volume and RBC count both rise, but RBC's don't rise in proportion to plasma volume; this leads to "runners' psuedoanemia" in which measured hemoglobin drops even though iron status remains normal.

I think the key to answering Jim's question about oxygen delivery lies in understanding that assuming normal iron and RBC status, the delivery of oxygen to the working muscles is not a limiting factor in performance - it's the utilization of that oxygen by end tissues that's limiting. If you take a bunch of time off and then go for a run your heart will ably perfuse your muscles with fully oxygenated RBC's - ventilation, and hence the oxygenation of RBC's in the lung capillaries, isn't limiting either - but the mitochondria in those muscles will be somewhat bewildered and unable to make good use of that oxygen until a period of training has been undertaken again.

Taking all of this into account, it is easier to see why the hemodynamics play out as they do even though a given volume of blood after plasma expansion does contain a lower density of oxygen-carrying elements.

Hope this makes sense. I also hope I'm right.

Sounds good anyway... could've fooled me. In fact, I may still be fooled. In the spirit of Letsrun, let's go with it.

This sounds believable, although I'm another engineer and don't have the knowledge to confirm this with certainty. Your explanation also supports / is supported by the observation that after a runner donates blood, his performance will return to a decent (though not equal to pre-donation maximal) level much more quickly than red blood cells are predicted to regenerate.

Pampiniform Plexus wrote:

I think the key to answering Jim's question about oxygen delivery lies in understanding that assuming normal iron and RBC status, the delivery of oxygen to the working muscles is not a limiting factor in performance - it's the utilization of that oxygen by end tissues that's limiting.

If I understand this right, just as an expired breath still contains a pretty high percentage of oxygen, the blood gushing around all of those muscle fibers contains more O2 than can be utilized, so it doesn't matter if the number of RBCs per unit of time actually drops (the larger stroke volume doesn't compensate for decreased hematocrit and decreased HR). That makes sense by itself, but if that's true then why do people take EPO to increase RBCs? If you already have too many to be used, what's the point of more? Further, if the capacity of the RBCs is underutilized, then why would your HR increase when your work rate goes up? You already have excess capacity, so why ask the heart to pump more? I can understand some increase due to the greater need for cooling and even glucose delivery over the long haul, but that doesn't seem sufficient.

I'm looking at this as if it were a simple engine, and it's not making sense to me. The only thing that seems to make sense so far is that increased plasma volume leads to increased stroke volume, but the function isn't 1:1, IOW, that the stroke volume increases faster than the plasma volume, and thus even with a decrease in HR, RBC delivery per unit time stays constant (e.g., a 5% increase in plasma volume leads to a 10% increase in stroke volume and a 5% drop in HR).

Ya know, when I have questions like this in my field, I just fire up a circuit simulator or go into the lab and build a test unit and take a bunch of measurements. This human stuff is much more cumbersome and time consuming!

Where's jtupper when you need him? ;-)

I think the better trained someone is, the more likely it is that that person's working muscles are able to operate near peak cellular "efficiency"; therefore, the amount of oxygen delivered does become limiting in such specimens. In other words, an undertrained schmoe might benefit to some (relatively minor) degree from EPO administration and the resulting increased hemoglobin in his circulatory system, but in percentile terms, such a runner won't benefit nearly as much as someone whose mitochondrial oxygen-acceptor mechanisms are extremely well-developed and therefore able to process inordinate oxygen loads.

Again, this is a mixture of basic knowledge and conjecture.

Opinion.com

There are two anemia conditions related to sports -- one real, the other false.

Strenuous exercise can produce "foot strike anemia,'' a true anemia that is an actual reduction in red blood cells. Exercise can also produce a false anemia, known as "pseudo'' anemia, which occurs when the red blood count wrongly appears to be depleted. This creates a situation for athletes that actually may turn out to be beneficial, although it doesn't seem so at first.

PSEUDO ANEMIA

Athletes who train tend to increase their plasma volume (plasma is the liquid part of the blood, which makes up about half its volume; cells make up the other half) so the percent of red blood cells often goes down as the plasma volume goes up.

This can be deceptive because the number of red blood cells has not actually dropped -- only its proportion to the plasma volume. So it may falsely appear in a hematocrit reading that the red count has gone down, raising concerns about anemia.

"There is the tendency to look at these values, and say `whoops, this looks like incipient anemia,' when it isn't,'' says Russell Pate, the associate dean for research at the school of public health at the University of South Carolina. "It does not mean in a clinical sense that a person is anemic. It means the blood cell volume hasn't increased as much as the plasma volume.''

In pseudo anemia, your oxygen-carrying capacity is unaffected, says Charles Peterson, M.D., program director of the blood diseases program at the National Heart, Lung and Blood Institute, part of the federal government's National Institutes of Health in Bethesda, Md.

"It's a concentration issue, like putting more water in a bucket and diluting what's in there,'' says Frank Pizza, an associate professor in the department of kinesiology at the University of Toledo in Ohio. Increasing the plasma volume through running is going to dilute the constituents of the blood, he adds, which is a good thing. "If you have more concentrated blood, it's more viscous -- and the more viscous it is, the harder it is for the heart to pump.''

If you were tested in a physician's office, it would look as though the hemoglobin was low, but you'd need to run much more specific tests, he says.

Who can argue with a Professor Pizza?

Jim: I am not the greatest typist so hate to do long things -- better to sit down and drw it out. A couple things to consider (1) Blood doping studies some years ago showed that the cells are capable of processing more if more can be delivered, but not as much more as the increase in O2carrying capacity would suggest. If the cells were the limiting factor then there wouldn't really be a benefit in blood doping, but it does result in higher VO2max. (2)I don't know of any study that shows what effect an increase in HCT has on cardiac output, but I imagine it has been studied. In other words if you have a 10% increase in HCT, I'm not sure how much that may slow down flow. (3) Keep in mind that venous blood (as it returns to the heart) is mixed venous blood and represents blood coming from all parts of the body, not just the exercising muscles, so you must look at venous blood as it exits the exercising muscle to see if that muscle is using all it receives. This has been done in animals and sometimes all the O2 has been used. Depends some on flow rate, just as in the lungs: when at high cardiac output there may not be maximal arterial saturation (some good runners have been shown to desaturate to under 90% at high work loads). Most conclusions are that cells can handle what is thrown at them, if well trained. One of the reasons VO2max drops at altitude is that max HR drops at altitude because not being able to go into oxygen debt the heart muscle must protect itself and the coronary system senses PO2 and at altitude it gets too low so the HR slows.

Jim: I know you enjoy calculations. A couple more to consider. Each g hemoglobin can carry 1.34ml O2, so if you have 15 g Hb (per 100 g or 100 ml blood), arterial blood could carry 1.34X15 = 20.1 ml O2. But it's only about 96 or 97 % saturated, .96X20.1= 19.3 vol% is the arterial content of O2. About the lowest you will see venous content is 4 vol%, so the different is what was deliverd and used, which = 19.3 - 4 = 15.3 ml O2 per 100ml blood, or 153ml per liter. If you have a 30liter max cardiac output (say 150ml stroke volume X 200 HR), this gives you a VO2max of 30X153 = 4590ml/min. If you weigh 60kg this is 4590/60 = 76.5 VO2max (or VDOT if you want to look up the performances). If you could increase stroke vol by 10% from 150 to 165 then cardiac output would go up to 200X165 = 33000ml or 33 liters/min. Just for calculations, say that Hb drops 10% from 15 to 13.6 because of the increased plasma (not necessarily so, but just to calculate), the arterial blood content is 13.6X1.34X.96 = 17.5ml/100ml or 175ml/liter. With the same venous content (which may not stay the same either) of 4.0 then O2a-v is 17.5-4 = 13.5 or a delivery of 135X33 = 4455ml and 4455/60 = 74.25 VO2max. In the vdot tables the difference between a max of 76.5 and 74.3 is just over 20 sec for 5K. So, you can see many factors coe into play -- there may be a change in cardiac output with subtle changes in plasma volume, there may be a change in arterial content (as I remember blood may get to going up to 20cm/sec through the pulmonary capillaries and increasing that velocity may change % saturation), there may be changes is off loading at the cells, so mixed venous content may change. Lots of possibilities

Thanks! Now that's something I can understand. The drop in VO2max is what I would've thought given those sorts of numbers. So it seems that what we have is a system that has several interacting variables that don't necesarily have nice 1:1 linear relationships. If I understand this correctly, if blood plasma goes up by 10%, that DOESN'T mean that stroke volume will increase by 10%, nor will the O2 utilization necesarily be the same in the working muscles, nor will HR drop by 10%, and so on. Consequently, in the real world, in response to heat stress might we see something like: plasma up 10%, RBC up 3%, stroke volume up 8%, HR down 2%, muscle uptake up 1%, and the individual winds up at pretty much the same performance level, but better adapted to heat (numbers just for arguments sake). I would also assume that it's possible (especially during the adaptation phase) to see decreased performance, yes?

This sounds like an interesting system to model. A few years back a colleague and I did some work using analog neural networks to model locomotion (a simple leg, where the output voltages represented variables such as force and velocity). The neural network design was his baby, my part was turning the idea into real circuitry. I'm thinking we could do the same thing here. The cool thing about the neural network design is that you can get them to "learn" what works. Ultimately, it's not that far from what seems to be happening in real-world organic neural systems. It would be interesting to design a system that responded the same way a human does, and then try to "tweak" it. (I guess that's how the gods of biomechanics have fun on the weekends, but with living creatures ;-)

Got it. As you see many variables are intertwined and who knows which does what. To further complicate things the "professional subjects" who are will to go through arterial punctures, blood volume measures, cardiac output stuff, and all the things that play a part, are not necessarily all that well trained and certainly not elite in most cases, so the results are scoffed at by the elite coaches and runners. What you have to look at, at the practical level, are VO2max, running economy and blood lactate profiles under the various conditions of concern, to prove that what you theoretically calculate actually happens in the real world. This is always what I am concerned with, and few are interested in funding research using healthy subjects.

jtupper wrote:

As you see many variables are intertwined and who knows which does what. ... and few are interested in funding research using healthy subjects.

Beautiful. I learned something today. In neural networks it is possible to create several different systems that all work (do the job at hand) but which don't operate in the same fashion. I would assume then that the response of any two individuals to this stress could produce considerable variation. Maybe one person would have a large variation in stroke volume while another might see more or less change HR, and so on. In a way it's sort of funny because in engineering we try to make systems respond identically. We do everything we can to make things perfectly deterministic and well defined. You take components that have variations in performance and you connect them in ways that are insensitive to those variations.

It's unfortunate that there are so few willing to fund research on healthy subjects. I guess that's a product of our system. You can't make money off of healthy people (at least not in the short term). I've always been one for research for the sake of just understanding though. Curiosity may have killed the cat, but it's what made the human being.