0:00:00.000,0:00:03.660
Picture this: You’re getting ready to give[br]a big presentation in front of, like, a lot

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of important people. You’re practicing in[br]front of your mirror, and then just for a

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second you forget how to speak.

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Suddenly, you feel that familiar sting of anxiety,[br]like an icy hand on the back of your neck.

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You look at yourself in that mirror and you[br]start imagining some of the worst, worst-case

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scenarios. Like, what if you totally lose[br]your train of thought up there? What if you

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barf? What if everybody gets up and leaves?[br]Now you’re really nervous. I’m getting

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freaked out just talking about it.

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So ou start taking quick, shallow breaths,[br]and you’re feeling light-headed, and seeing

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stars, and now you, my friend, are hyperventilating.

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When we talk about respiration, we tend to[br]focus on oxygen -- and who could blame us?

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It’s easy to forget the equally important[br]role that carbon dioxide plays in maintaining

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homeostasis. Your internal balance between[br]oxygen and carbon dioxide factors heavily

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into all sorts of stuff -- especially in your[br]blood, where it can affect your blood’s

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pressure, its pH level, even its temperature.

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And now -- at, like, T-minus 5 minutes to[br]your presentation -- all of those things are

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out of whack, because you’re exhaling more[br]CO2 than you should.

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You’re just about to faint, when a friend[br]suddenly hands you a paper bag to breathe

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into. And you’ve never been so grateful[br]for a lunch bag in your life, because, somehow,

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it does the trick.

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Within seconds, you’re back to normal.

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The drop in CO2 that occurs in your blood[br]when you hyperventilate is called hypocapnia,

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and it signals a breakdown in one of the most[br]complex and important functions that your

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respiratory system performs.

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That is: the exchange of gases inside your[br]blood cells, where the stuff your body doesn’t

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want is swapped out for what it desperately[br]needs.

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This exchange -- between carbon dioxide and[br]oxygen -- is regulated by a whole series of

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biological signals that your blood cells use[br]to communicate with your tissues, about what

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they have, what they want, and what they need[br]to get rid of.

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It’s almost like a code, one that’s written[br]into your blood’s chemistry, in the folding

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of its proteins -- even in its temperature[br]and acidity.

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It’s what allows you to perform strenuous[br]physical tasks, like climbing a mountain.

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It’s also what lets you reboot your whole respiratory[br]system, with nothing more than a paper bag.

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I’ll admit it: when we’ve talked about the [br]chemistry of your blood so far, we’ve

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tended to keep things pretty simple.

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Like, hemoglobin contains four protein chains,[br]each of which contains an iron atom; since

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iron binds readily with oxygen, that’s how[br]hemoglobin transports oxygen around your body.

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Ba-da-bing.

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But the fact is, hemoglobin’s affinity for[br]oxygen isn’t always the same.

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In some places, we want our hemoglobin to[br]have a high affinity for oxygen, so it can

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easily grab it out of the air.[br]And in others, we want it to have

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a low affinity for oxygen oxygen, so it can[br]dump those molecules to feed our cells.

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So how does your hemoglobin know when to collect[br]its precious cargo and when to let it go?

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Well, a lot of it has to do with a principle[br]of chemistry known as partial pressure.

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One of the things that fluids always do is[br]move from areas of high pressure to low pressure.

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And molecules also diffuse from areas of high[br]concentration to areas of low concentration.

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But when we talk about gases in a mixture, we need[br]to combine the ideas of pressure and concentration.

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See, air is a mixture of molecules. And when[br]you’re studying the respiratory system,

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you often need to focus on the oxygen, which[br]makes up about 21% of it.

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But that doesn’t tell us how many oxygen[br]molecules there are. For that, we need to

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know the overall air pressure, since more[br]molecules in a certain volume means more pressure.

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So, partial pressure gives us a way of[br]understanding how much oxygen there is,

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based on the pressure that it’s creating.

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Example: The pressure of air at sea level[br]is about 760 millimeters of mercury. But since

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only about 21 percent of that air is oxygen,[br]oxygen’s part of that pressure -- or partial

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pressure of oxygen -- is 21% of 760, or about[br]160 millimeters of mercury.

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Now, that’s just outside, at sea level.

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When that air mixes with the air deep in your[br]lungs -- including a lot of air that you haven’t

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exhaled yet -- the partial pressure of oxygen[br]drops to about 104 millimeters of mercury.

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And in the blood that’s entering your lungs[br]-- after most of its oxygen has been stripped

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away by your hungry muscles and neurons -- the[br]oxygen partial pressure is only about 40 millimeters.

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This big differences in pressure make it easy for[br]oxygen molecules to travel from the outside air into

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your blood plasma, because, as a rule dissolved gases[br]always diffuse down their partial pressure gradients.

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This is why it’s so much harder to breathe[br]at higher altitudes. When you climb a mountain,

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the concentration of oxygen stays at about 21%.[br]But the pressure gets lower, which means the

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partial pressure of oxygen also decreases to about[br]45 millimeters of mercury at the top of Mt. Everest.

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So the partial pressure of oxygen at the top[br]of the highest peak in the world, is almost

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the same as the de-oxygenated blood that’s[br]entering your lungs.

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So basically there is no partial pressure[br]gradient, which makes it really hard to get

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oxygen into your blood. But, let’s get back[br]to the red blood cells.

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Remember that the globin in your hemoglobin[br]is a protein -- and when proteins bind to

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stuff, they tend to change shape. And that[br]shape-change can make the protein more or

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less likely to bind to other stuff.

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When an empty hemoglobin runs into an oxygen[br]molecule, things are a little awkward.

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It’s like a first date -- bonding isn’t[br]so easy.

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But once they finally bind, hemoglobin suddenly[br]changes shape, which makes it easier for other

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oxygen molecules to attach, like friends gathering[br]around the lunch table.

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That affinity for joining in -- or cooperativity,[br]as it’s known -- continues until all four

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binding sites are taken, and the molecule[br]is fully saturated.

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Now your hemoglobin is known as oxyhemoglobin,[br]or HbO2. It is not...not why the cable network

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is called that. That’s the “Home Box Office.”[br]Anyway.

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By the time the blood leaves the lungs, each[br]hemoglobin is fully saturated, the oxygen

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partial pressure in your plasma is about 100[br]millimeters, and now it is ready to be delivered

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to where it is needed most.

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Active tissues, like the brain, heart, and[br]muscles, are always hungry for oxygen. They

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burn through it quickly, lowering the oxygen[br]partial pressure around them to about 40 millimeters.

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So when the blood arrives on the scene, oxygen[br]moves down the gradient from the plasma to

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the tissues, to feed those hungry cells.

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That makes the oxygen partial pressure in[br]your plasma drop, so your hemoglobin starts

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to give up more of its oxygen to the plasma.

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BUT! Partial pressures are only part of what’s[br]prodding your hemoglobin to give up the goods.

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All of that metabolic activity going on in[br]your tissues is also producing other triggers,

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in the form of waste products -- specifically[br]heat and CO2.

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Both of those things activate the release of more[br]oxygen, by lowering hemoglobin’s affinity for it.

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Say you’re climbing that mountain again,[br]and your thighs are feeling the burn. Red

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blood cells saturated with oxygen are going[br]to the muscle tissue in your quads, where

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the hemoglobin can dump a bunch of O2, because of[br]the lower partial pressures of oxygen in your muscles.

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But a hard-working quad will also heat up[br]the surrounding tissues, and that rise in

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temperature changes the shape of hemoglobin -- and[br]it does it in such a way that lowers its affinity for O2.

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So when those red blood cells hit that warm[br]active tissue, they release even more oxygen

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-- like 20 percent more -- beyond what partial[br]pressures would trigger.

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But wait! There’s more!

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Carbon dioxide triggers the release of oxygen,[br]too, because it also binds to the hemoglobin,

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changing its shape again, lowering its affinity[br]for oxygen still more. And as oxygen jumps

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ship, the hemoglobin can pick up more CO2.

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Finally, JUST IN CASE the hemoglobin isn’t[br]getting the message at this point, there’s

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one more trigger that your respiratory system[br]has up its sleeve. The spike in CO2 that’s

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released by your active muscle tissues[br]actually makes your blood more acidic.

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Since your blood is mostly water, when CO2[br]dissolves in it, it forms carbonic acid, which

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breaks down into bicarbonate and hydrogen[br]ions. Those ions bind to the hemoglobin, changing

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its shape yet again, further lowering its[br]affinity for oxygen.

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So now, at last, your tissues have the oxygen[br]they need, and your red blood cells are stuck

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with all this CO2 that they need to get rid of.

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Your red blood cells ride the vein-train[br]back to the lungs,

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where they encounter a new wave[br]of freshly inhaled oxygen.

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And when that O2 binds to the hemoglobin -- which,[br]again, is hard at first -- it eventually changes

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its shape back to the way it was when we started,[br]which decreases its affinity for CO2.

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So the hemoglobin drops its carbon dioxide,[br]which moves down its partial pressure gradient

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into the air of your lungs, so you can exhale it,[br]and the whole thing can start all over again.

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Now if that isn’t enough to make you hyperventilate,[br]I’m not sure what is.

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But this brings us back to that unfortunate[br]episode you had before your big presentation.

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This whole complex code of chemical signals[br]that I just described? Well, it assumes that

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what your cells and tissues are telling each[br]other is actually true.

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But as we all know, sometimes our bodies don’t[br]mean what they say. Thanks, body.

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Like, when you’re freaking out about your[br]presentation, your sympathetic nervous system

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makes your heart race and your breathing increase,[br]to prepare you to fight or flee.

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The problem is: there’s nothing to actually[br]fight or flee from, so your muscles aren’t

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actually doing anything, so they’re not using[br]all the extra oxygen you’re breathing in.

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And they also aren't producing the extra CO2 that[br]you're suddenly exhaling all over the place.

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So when you start to exhale CO2 faster than[br]your cells release it, its concentration in

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your blood drops. And with less carbonic acid[br]around, your blood’s pH starts to rise.

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And you know what else? While low blood pH[br]does things like change the shape of your

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hemoglobin to deliver oxygen, high pH causes[br]vasoconstriction.

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Normally, this is supposed to divert blood[br]from the parts you’re not using during times

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of stress, like your digestive organs, to[br]the parts that you are using.

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But when you hyperventilate, this constriction[br]happens everywhere, which means less blood

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is delivered to your brain, which makes you[br]light-headed.

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Luckily, that trick with the breathing into[br]the paper bag -- it really does work.

0:09:07.820,0:09:12.180
It works because it lets you breathe back[br]in all of the CO2 you just breathed out. So

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the partial pressure of carbon dioxide in[br]the bag is higher, which forces that CO2 into

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your blood, which lowers its pH, and you get[br]back to homeostasis.

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And of course, homeostasis is the key to life...and[br]you know, also to a successful presentation.

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If you were able to remain calm today, you[br]learned how your blood cells exchange oxygen

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and CO2 to maintain homeostasis. We talked[br]about partial pressure gradients, and how

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they, along with changes in blood temperature,[br]acidity, and CO2 concentrations, change how

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hemoglobin binds to gases in your blood. And[br]you learned how the thing with the bag works.

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Of course, we must say thank you to our patrons on[br]Patreon who help make Crash Course possible through

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their monthly contributions, not just for themselves,[br]but for everyone. If you like Crash Course and want to

0:09:53.460,0:09:57.360
help us keep making videos like this one,[br]you can go to patreon.com/crashcourse.

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This episode was filmed in the Doctor Cheryl[br]C. Kinney Crash Course Studio, it was written

0:10:01.180,0:10:05.660
by Kathleen Yale, the script was edited by[br]Blake de Pastino, and our consultant is Dr.

0:10:05.660,0:10:10.270
Brandon Jackson. It was directed and edited[br]by Nicole Sweeney; our sound designer is Michael

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Aranda, and the graphics team is Thought Cafe.