I feel like I haven't spent nearly enough time lately talking about all the stupid and dangerous things you can do to your own body, so let's talk about doping.

You probably have heard of this thanks to Lance Armstrong, who secretly messed with his own blood so that he could illicitly win the Tour de France seven times in a row. You might be dimly familiar with the fact that doping isn't like shooting steroids, but it is still cheating, even though, like, why is it cheating, and how does it work, and is it even possible to make your blood better at being blood? In other words, how can some people treat or mistreat their own blood like it's some sort of drug?

Short answer: because your blood is incredibly powerful stuff. And its power rests largely in you erythrocytes, or red blood cells. They're the most abundant type of cell in your blood, accounting for nearly 45 percent of its volume. Every time you take a breath, they pick up oxygen in your lungs and distribute it through your body and then grab carbon dioxide and bring it back to the lungs where it can be exhaled. The main mission of erythrocytes is to keep your body fed with oxygen so your muscles can do their thing and you brain can continue to think and feel and boss around your various parts. 

But you don't want to mess around with your red blood cells because erythrocytes are weird characters. They go places that other cells won't; they purge themselves of their most precious inner belongings, preferring instead to live as hollow shells; because of the crushing demands of their job they don't live very long; and just like with your blood pressure, too much of these good things can turn bad quickly.

So the erythrocytes must be respected, it is not for doping, or for dopes.

(Intro)

Despite their prominent role in some international scandals, your red blood cells are fairly simple and unassuming little cells. They've got a distinct biconcave shape, which just means that they're concave on both sides, making them look kind of like a breath mint - a tiny, bloody breath mint. And while they do have a plasma membrane, they don't have a nucleus and don't have most of the parts that other cells do. So they're basically just glorified protein-filled phospholipid-bilayer sacks, but they're still another great example of that harmony between form and function. For one thing, that biconcave shape gives them a large surface area that's ideal for gas exchange. It also makes them flexible and able to change shape as they squeeze through tiny capillaries with diameters smaller than the cell itself.

Of course, all that squeezing and twisting is hard on a cell's membrane, and that, combined with their general lack of organelles to help repair the membrane, means these cells don't live very long, surviving, on average, only 120 days. But they sure work hard while they're alive, and their work is mostly in gathering and transporting oxygen. They're able to do this because, if you don't count their water content, red blood cells are 97 percent hemoglobin, a molecule that easily binds to and releases oxygen. It's like an oxygen sponge.

Every hemoglobin molecule is really made of eight different component molecules. Four are a red pigment called heme and the other four are a protein called, you guessed it, globin. Each globin is a globular polypeptide chain, hence its name, and proteins, you'll probably remember, like to bind to stuff. So each globin has its own personal ring-shaped heme molecule, and in the center of that heme is an iron atom, kind of like a cherry on top of a protein-and-pigment sundae.

It's that iron in the center of the heme that makes our blood red. Incidentally, not all animals have red blood, because not all of them use hemoglobin to move oxygen. For example, most mollusks, like squids and snails, have blue blood because they use hemocyanin, a copper-rich protein pigment that turns blue when exposed to oxygen. But iron's what we're stuck with, and, I have to say, it's great at its job because each iron can bind with one whole oxygen molecule, and that oxygen really adds up. Since you have four iron atoms in every molecule of hemoglobin and every red blood cell contains something like 250 million hemoglobin molecules, that means that each one of your tiny, floppy, red breath mints can grab about a billion molecules of oxygen.

Exactly how they transfer oxygen and carbon dioxide from your tissue cells is something that we'll get into more when we talk about the respiratory system, but if you're wondering why all this hemoglobin can't simply skip the red-blood-cell rigmarole and just run around naked in your blood, it's because free-range hemoglobin would actually thicken the blood, making it so viscous that it would impede blood flow. This also happens to play a part in blood doping, which - stick with me - I will explain in a bit. 

So what does the brief but glorious four-month life of an erythrocyte look like? Well, remember when I said that a red blood cell doesn't have a nucleus? And maybe you thought, "Hey, wait a second, how can it even be a cell without a nucleus or DNA?" First of all, nice catch, but actually, erythrocytes do start off with a nucleus and DNA; they just get rid of them because their entire purpose for exiting is to schlep around hemoglobin and oxygen and they want the extra room. The whole process of forming red blood cells, called hematopoiesis, happens in your red bone marrow, which is mostly made of of reticular connective tissue snuggled up to special capillaries called blood sinusoids. 

In short, the process begins with a hemocytoblast - or a specialized stem cell - which soon differentiates into an early erythroblast. Then it starts making a whole bunch of ribosomes, the organelles that manufacture proteins, and in this case, the ribosome start cooking up tons of hemoglobin as the cell transforms into a late-stage erythroblast. When it's got enough hemoglobin, it suddenly jettisons most of its organelles, which causes the cell walls to collapse a little, giving it its biconcave bloody-breath-mint shape. Now you're left with a reticulocyte, which is pretty much an early erythrocyte that still has a little group of ribosomes left, called a reticulum. 

So far, this whole journey has taken about fifteen days. When the reticulocyte is finally just about bursting with hemoglobin, then it leaves the marrow and enters the bloodstream, and a couple of days later, when the last of the ribosomes have degraded, you've officially got yourself a mature red blood cell, and that cell travels around your body doing its job for a few months before it gets old or damaged and needs to be replaced. 

Now, maintaining the balance between production and destruction of these cells is crucial: too many will make the blood too viscous and difficult to pump, and too few leads to oxygen deprivation, or hypoxia. The process of maintaining the right levels of red blood cells is regulated by a special hormone called erythropoietin, or EPO. It's produced mostly by the kidneys, but also in the liver, and is constantly circulating in the blood. If you're anemic or hiking in high altitude or hemorrhaging blood or experiencing anything that creates a drop in your blood oxygen levels, certain cells in your kidney will take notice and take action, and they can do that because they traffic in a signaling molecule called hypoxia-inducible factor, which monitors your blood's levels of oxygen. The way that this works is pretty cool: these special kidney cells need oxygen in order to break down that signaling molecule, so if oxygen levels in the blood are low, they can't turn the signal off. This means that the signal keeps going, which triggers the release of more and more EPO, which stimulates your red bone marrow to pump out more red blood cells to carry around more oxygen. As oxygen levels in your blood increase, the signal is degraded, and EPO production slows, and EPO is a key player in blood doping, too, but we're gonna have to wait a minute before we get there, because I first want to get back to the fate of your hard-working erythrocytes.

So if you're generating around two million new blood cells every second, you also have to dispose of about the same number of dead ones to maintain the balance, right? When these cells get old, they turn rigid and their hemoglobins start to fall apart. As they get stiffer, they can end up getting stuck in capillaries in your brain or heart, which would not be good. Luckily, you have certain channels to corral these dying cells, especially around the spleen, which some anatomists call "the red blood cell graveyard." So these tired old cells get trapped and then basically ambushed by big, macrophage white blood cells in the spleen, liver, and bone marrow, which break them down and recycle their various components. The globin proteins are broken down into their basic components, amino acids, which go back into the blood to be used by other cells for making more proteins. Iron from the heme group is separated and either bound to proteins and stored in the liver or put right into a new hemoglobin molecule, and the heme gets turned into bilirubin, a yellowish pigment that goes to the liver, where it's added to the bile that it secretes into the intestine and eventually leaves the body in your poop.

Now that you know how your erythrocytes function naturally, it's easier to see how they can be messed with, often with bad results. You can dope your blood in a few different ways, but the most common technique is to inject natural or synthetic EPO hormone to boost your red blood cell production. It's also possible to draw and store some of your own blood and then transfuse it back into your body after it's recovered from the blood loss, effectively raising your volume of red blood cells. The logic, if you can call it that, is that more red blood cells equals more oxygen being carried to your muscles, and therefore, better physical performance. Now the extra oxygen can't change your actual muscle strength, but the added aerobic capacity does reduce muscle fatigue and enhance endurance by allowing your muscles to work harder for longer, and it can provide enough of an extra edge to win a race, like, say, the Tour de France. Seven times. But not only is it banned in athletic competitions, blood doping is also dangerous, because remember, a red blood cell count that's too high thickens the blood and that actually makes it harder for the heart to pump blood around the body. In addition to defeating the purpose of enhancing the blood's effectiveness, this can lead to blood clots and strokes and heart failure, so, no, thank you, plus, cheating sucks.

But today, you learned about the structure and function of your erythrocytes, and of hemoglobin, which they use to carry oxygen. We also went through the formation and life cycle of a red blood cell, and studied how their levels are regulated by EPO and their signalling molecules. Finally, we learned how doping the blood is a recipe for disaster and for finding yourself on Oprah and apologizing to everyone you know and losing all of your yellow jerseys.

Thanks to all of our Patreon patrons who help make CrashCourse possible for themselves and for everyone for free with their monthly contributions. If you like Crash Course and want to help us keep making videos like this one, you can go to patreon.com/crashcourse. This episode was filmed at the Dr. Cheryl C. Kinney Crash Course Studio, it was written by Kathleen Yale, the script was edited by Blake de Pastino, and our consultant is Dr. Brandon Jackson. It was directed and edited by Nicole Sweeney, our sound designer is Michael Aranda, and the graphics team is Thought Café.