Altitude Sickness, Part 4

How do you prepare for the rigorous physical requirements of high elevation adventure? Strength and endurance are key, but are only part of a more complex equation. How do you prepare for changes in altitude, exposure, diet, etc.? How do you mentally prepare? Learn from others and share what you know about training in advance for outdoor adventures.
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gregw822
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Altitude Sickness, Part 4

Post by gregw822 »

Altitude Sickness 4
Acclimatization

The onset of hypoxia triggers several physiologic responses. According to Wilkerson in Medicine for Mountaineering, these include increases in red blood cell count, pulmonary artery pressure, respiratory volume, and cardiac output, among others. However, the only one I will address here has to do with the transport of oxygen molecules.

Hypoxia stimulates the kidneys to release the hormone erythropoietin, EPO. This small signaling protein travels through the blood stream to find its protein partner. The encounter results in binding EPO to a receptor site on the partner. The binding event sets off a cascade of biochemical reactions that convert stem cells in the bone marrow into new red blood cells. One branch of the cascade produces hemoglobin, the protein in red blood cells that moves oxygen through the bloodstream from the lungs to muscle tissue.

Before examining hemoglobin, I will first introduce a few points about proteins using the simpler EPO as an example. The first illustration shows EPO in two forms. The left part is a so-called ribbon structure, which is essentially a cartoon depiction. A protein is a polymer made from 20 different natural amino acids, assembled as if they were beads on a string. The EPO protein has 166 amino acids in a specific sequence, forming a single chain 500 atoms long. That may seem like a long string of atoms, but EPO is actually a very short protein. The ribbon structure of EPO has four segments that are twisted into helices. The helix is a dominant substructure in protein chemistry, and the bundle of four parallel segments of helix is a particularly common motif. The ribbon of EPO is folded into a particular shape that shows little order or regularity other than the helices.
EPO Figure.jpg
Every third atom along the length of the protein bears a small side chain of atoms. Each of the 20 essential amino acids is characterized by its side chain. The right side of the illustration shows EPO with all of its side chain atoms.

We turn now to hemoglobin, one of the most thoroughly studied of all proteins. Literally thousands of research articles on hemoglobin have been published in the literature of chemistry, biology, physics, and everything in between.

In the second illustration, we see that hemoglobin is a much more complex protein than erythropoietin. Unlike EPO, hemoglobin (Hb) is not a single molecule. Instead, Hb has four distinct protein chains grouped together into a single structure. The four subunits are divided into two sets of two. The yellow and green subunits are identical, with 146 amino acids each. The blue and purple subunits are also identical, each with 141 amino acids. The two sets have only minor structural differences. Each Hb subunit includes an appended molecule called heme. Heme is the portion of hemoglobin that carries oxygen molecules from the lungs to muscle tissue. The color codes for the heme atoms are: carbon = black, hydrogen = white, oxygen = red, nitrogen = blue, and iron = orange.
HB.jpg
Each subunit has a cleft in its surface that holds the heme. The clefts are in clear view in the yellow and blue subunits. This illustration of Hb shows none of the protein atoms, but if it did, you would see the iron atom of heme tethered in its cleft to a protein side chain. The tether would be in plain site in the yellow subunit, but it would be hidden behind the heme in the blue subunit. In this model, heme is shown in space-filling format.

A ball-and-stick model of heme is shown in the third illustration. Heme has a flat structure, with an iron atom bonded to four nitrogen atoms arranged in a square plane.
Heme Sm.jpg
It is the iron atom of heme that carries O2. The oxygen molecule binds to iron on the side of heme across from the tether. The oxygen molecule can be seen clearly in the blue subunit. The O2 molecule is shown just a touch larger and brighter red than the oxygen atoms of heme. The O2 molecule in the yellow subunit cannot be seen. It's there, however, blocked from view, on the far side of the heme.

Heme can carry one oxygen molecule at a time, so the Hb protein carries up to four O2 molecules, one in each of its subunits. Countless Hb molecules travel inside red blood cells from the oxygen-rich lungs to the oxygen-poor muscle tissue. Hemoglobin releases its cargo of oxygen molecules into the muscle tissue, where it is stored in yet another protein, this one called myoglobin.

Myoglobin is not shown here, but it resembles very closely the structures of the Hb subunits. Myoglobin contains a heme group, bonded to a side chain in a cleft, again, very similar to a Hb subunit. Similar is not the same however. Myoglobin holds on to oxygen more tightly than Hb, as we might expect. Myoglobin, the storage protein, holds oxygen more tightly than hemoglobin, the transport protein.

One last thing about hemoglobin, something very cool. Why build four proteins into one complex, when four single proteins like myoglobin would serve just as well? Four oxygens is four oxygens, after all. The reason is, the subunits cooperate. Bonding the first O2 to one of the subunits, makes it easier to add the second. The second O2 makes it easier still to add the third, and the same goes for the fourth O2. Each addition of oxygen causes small changes in the orientations of the Hb subunits in a way that opens up the protein to more incoming oxygen. Cooperative bonding is a great facilitator for getting O2 out to the muscle tissue.

The synthesis of hemoglobin for all those new red blood cells is one of the key features of acclimatization.
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Re: Altitude Sickness, Part 4

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So -- any practical advice on how to apply this knowledge for acclimitization?

I've been using a variant of the "Russian Rest", which works well for my lifestyle - living in the Bay Area, at sea level, and climbing in the Sierras on weekends. The first climb of the season is always a bear, but after that I try to schedule a climb every other weekend, and have no problems with altitude for the rest of the season. But I haven't seen anyone discuss the physiology.

From "Training for the New Alpinism", p. 338: "The climbers of the Soviet tradition clearly remain among the strongest high-altitude alpinists in the world. The Soviets conceived the idea that after spending one night at the highest camp... they would go very low... for three nights of total rest."

For me, almost two weeks rather than 3 days of rest, but still seems to work well.
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Re: Altitude Sickness, Part 4

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Lots of us know how to slowly adapt by ascending only a limited amount each day. The question comes up: once I descend, how quickly will the adaptation be lost? The rule of thumb is that it will take about as many days for it to be lost on the way down as it took you to develop it on the way up.

There are actually two types of this adaptation, short-term and long-term. For short-term, it takes you only a day or three. Mostly your body learns to breathe slightly quicker, and your heart rate increases somewhat. For long-term, it takes two or three weeks. Your body creates more red blood cells (to carry oxygen better) and a few other subtle things.
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Re: Altitude Sickness, Part 4

Post by LincolnB »

Yes, that's what I heard for decades - no more than 1,000' gain per day etc. That's what startled me about the Soviet approach - you make a big ascent, provide significant altitude stress to your body, then return to low elevation for an extended period as your body adapts to that stress event. House and Johnston wrote that this produced "among the strongest high-altitude alpinists in the world" - and yet I've seen virtually no discussion of the "Russian Rest" method in western alpine literature, and nothing on physiology. So I'm wondering if anyone here has insights -
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Re: Altitude Sickness, Part 4

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The Soviet technique might be a pathway to an early grave.
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Re: Altitude Sickness, Part 4

Post by Wandering Daisy »

I used to do a lot of weekend climbing and yes, the first of the season I was more breathless, but soon adapted. Typically I would drive after work (from nearly sea level) and camp partway, at about 7,000 - 8000 feet. Next day go into a basecamp at about 10-11,000. Climb to about 13,000 and walk out, drive home. I think this works for some of us who are not prone to altitude sickness anyway. I feel that my body "remembers" how to quickly acclimate after several weeks of this. Not scientific in the least, but it works. And I am old and still alive.

Perhaps the Soviet method works because they have already weeded out those who tend to get altitude sick.
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Re: Altitude Sickness, Part 4

Post by gregw822 »

I don't have much to add here. As I've said, the "macro" part of it is outside my knowledge base. In general, climb high/sleep low coupled with a about 1000'/day of elevation gain is what I've read most often. I know I've read in a couple places that you lose acclimatization at about the same rate as you acquired. Mind you, I don't generally follow that advice, and I've never had trouble adjusting. Still, the risk is there, and I pay close attention.

I intend to ask my MD for a prophylactic prescription for low-dose Diamox for the first three days of my trip this summer. I've read it does help with apatite and sleeping the first few days. I will give her the literature information and expect she'll ok the prescription. I've also read that altitude headaches respond fairly well to ibuprofen.
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Re: Altitude Sickness, Part 4

Post by Wandering Daisy »

I recall that most of the high altitude studies are at very high altitudes. I am not sure they are totally applicable to transition altitudes of the Sierra. I do know that altitude vs oxygen is not the same worldwide- the atmosphere is thinner near the poles vs at the equator. Climbing Denali is supposedly similar to climbing Everest with respect to oxygen. And there must be some physiologic factor that makes loss of oxygen more severe the higher the altitude - it is not a linear impact. And populations that have historically lived at higher altitudes have distinct physiologic adaptations. And the way you breath while at higher altitudes matters too. Slow and steady breathing, matching pace with your breathing, slow but few dead stops, works better than stop and go. So many variables. Although interesting, I doubt the chemistry of it will give practical answers without more well designed studies with a more inclusive group of subjects, rather than just mountaineers.
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Re: Altitude Sickness, Part 4

Post by Jim F »

Gregw822,

Thanks for presenting this important material.

LincolnB,

I find your comments/personal observations on April 22 (The Russian Way) interesting. This is my understanding/personal observation:

As soon as the USSR was founded in 1922, tremendous effort was devoted to developing sports programs, ranging from the community to the national level. Just like track and field, gymnastics, soccer, boxing,...mountaineering was an official government sponsored/subsidized sport. The organization ranged from local clubs to establishing international expeditions.

In parallel, great effort was devoted to scientific research devoted to sport (again, mountaineering included). Early on Soviet researchers and trainers developed Intermittent Hypoxic Training. Findings were published in Russian and were not on the radar screen outside the Soviet Union. Intermittent Hypoxic Training has applications for people with diverse interests, ranging from runners to fighter pilots (and again, mountaineers).

Decades later (in the 21st century), scientists outside Russia have studied Intermittent Hypoxic Training and have uncovered many metabolic/physiologic pathways that might contribute to understanding its apparent beneficial results. Here in the United States I am hearing more about Live Low, Train High.

Personal experience/possible application - After a long winter at sea level, I often go up tp 14,000+ elevation on the first outing of the summer season. To acclimatize I might drive up to about 8,000' and run 6-10 miles, and then return home to sea level for a week.I repeat this a couple of more times. Then I am ready to go to 14,000'.

Jim
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Re: Altitude Sickness, Part 4

Post by Wandering Daisy »

Well, there are not many 14,000 ft+ locations! The least complicated 14,000'er is White Mountain - just a walk up a road. Other 14'er trips require permits from quota trailheads, are multi-day trips and some with technical climbing. I used White Mountain years ago to "acclimate". The parking area is pretty high altitude also if you just wanted to go up and hang out.
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