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LEFT OR RIGHT?
I recently tweeted asking whether the rightward shift of our O2 dissociation curve (ODC) (reduced O2 affinity, increased O2 offloading in tissues) when we climb a mountain is a good thing.
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I pointed out that animals that have evolved at high altitude (e.g., bar-headed goose, llama) actually shift their curve to the left (they have a special mutation in their Hb).
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Similarly, human fetuses, who are normally exposed to limiting amounts of O2 from mom's circulation, shift their ODC to the left (a characteristic feature of fetal Hb).
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To further address the question of whether a left or right shift is adaptive at high altitude, a 1974 paper in Science reported that rats chemically manipulated to shift their ODC to the left fared better when exposed to simulated high altitude.
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This was followed by a classic study by Bob Hebbel, a hematologist at the University of Minnesota. He reasoned that if a shift to the left is adaptive at high altitude, then humans with congenital high-affinity hemoglobin should do better under these conditions.
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Indeed, this is what he found. He took 2 subjects with Hb Andrew-Minneapolis and 2 of their normal siblings up to about 9,000 ft. for 10 days and showed that the ones with Hbopathy fared better.
Such a cool experiment that would NEVER be funded in this era!
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The bottom line then is that in situations where environmental oxygen is limiting (high altitude, in the womb), the benefit of increasing O2 uptake in lungs/fetus with a shift to the left outweighs the disadvantage of unloading less O2 to the tissues.
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