Read on Twitter
1/n More High Altitude Hematology! So today lets talk about the Oxygen Disassociation Curve! If I ever get tattoos, one arm will be the ODC and the other the Bob Dylan Eye
2/n What so special about the ODC? It remind us that hemoglobin is a very active molecule that can respond rapidly to environmental conditions by varying its ability to bind oxygen.
3/n Also its sigmoid shaped because when hemoglobin binds its first oxygen this increases the affinity for bind more (and vice-versa for “unloading”). P50 is the oxygen level were hgb is 50% saturated. So the higher the P50 the less hemoglobin can bind oxygen.
4/n As this graphic from Wikipedia reminds use: Right shifted-> less O2 affinity->higher P50. Seen with higher PC02, higher temp and lower pH. Left shifted -> more O2 affinity-> lower P50. Seen with lower PC02, Low temp and higher pH.
5/n One of my favorite all times articles discusses the “Respiratory Function of Hemoglobin” and emphasizes the role of oxygen loading and unloading – which we will demonstrate by climbing a few mountains (PMID: 9435331)
6/n OK so what happens at altitude? Lets climb Oregon's Mt Hood! 11,250 ft were the inspired O2 is 65% of sea-level
7/n and the curve shifts left! We are still on the “flat” part of the loading curve but need to deliver oxygen more efficiently to tissues.
8/n OK – lets go to Alaska and climb Denali! 20,325 ft with inspired 02 42% of sea level
9/n And the curve shifts back to baseline as now we need higher affinity hemoglobin to be able to load oxygen from the thin air
10/n Now to the top of Everest! 29,000ft 27% sea-level O2! (picture from Wikipedia as I can’t get enough time off to travel there)
11/n And now we shift left because hemoglobin needs to grab every molecule of oxygen it can!
12/n While standing on the Everest summit we look up and see a flock of bar-headed geese fly over...
13/n These amazing birds migrate from India to Mongolia and back flying over the Himalayas! (PMID: 23118436)
14/n One of the many metabolic tricks these birds use is to have a lower P50 compared to lower altitude birds! (PMID: 20116442)
15/n And indeed many high altitude animals have hemoglobins with lower P50 - which make total sense since computer modeling shows in severe hypoxia this augment tissue oxygen delivery (PMID: 7085405)
16/n So what about us? Lets go back to Mt Everest. A 2009 study showed these amazing blood gases at 8400m. Subject 2 had an O2 sat of 34.4% but a had just summited Everest! And note the mean pH of 7.53 (PMID: 19129527)
17/n During a research expedition to Everest in 1981 detailed RBC studies were done and confirmed very low P50 at extreme altitude – despite higher DPG levels (remember DPG raises P50) – due to the extreme respiratory alkalosis. (PMID: 6693310)
18/n More evidence of benefit of a lower P50 at altitude is this study showing native lowlanders who lived > 3500m for 10 years and Tibetans have lower P50 (PMID: 29130390)
19/n And what about people born with high affinity hemoglobin? In the legendary “Human Llamas” study a family with high affinity hemoglobin had preserved tolerance and exercise ability at 3100m. (PMID: 29054)
19/N This year in a very elegant study Dominelli showed people with high affinity hemoglobins had a lower drop off in exercise ability in hypoxic conditions. (PMID: 32324473)
20/n And another bird with low P50? Emperor Penguins! Future astronaut @astro_jessica found the P50 of these penguins were similar to bar headed geese! – presumably to help maintain oxygenation while diving (PMID: 19801437)
21/21 Given this maybe this summer when my students are (hopefully) doing research on Denali we should bring a few penguins with us! To summarize - the ODC is really cool and allows hemoglobin to rapidly adjust to all sorts of environment conditions!
