How Your Body Makes New Blood

Say you’re feeling particularly kind one day, so you decide to make a donation to the local blood bank. You come in, you fill out your paperwork, and sit down for ten minutes while they take about a pint of blood out of your body. It’s all good though, the blood is going to someone who really needs it. Plus, they usually have free cookies at these things. And while you’re naming on that little packet of treats, you can’t help but notice that there’s a lot of blood around you. Not in a creepy way, but in a way that makes you wonder “If that just came out of me, how is my body replenishing my own blood supply?” The fact that we can donate blood is a really cool feature of our physiology, in part because of how blood cells are made.

Red blood cells, or erythrocytes, don’t have a nucleus. And without the genetic information inside of a nucleus, they have to come up with a different way of making copies of themselves. And then we have the task of cleaning and excreting all the old ones. The creation, maintenance, and filtration of blood is a unique process that’s different from other cells. Luckily, we’ve got some organs and physiology up for the task. When our bodies want to create new skin or stomach cells, old cells will duplicate their inner contents, including their genetic information, and split into two new identical daughter cells. This is good old-fashioned mitosis. 

But because red blood cells ditch their nuclei as mature cells, they can’t make direct copies of themselves. This means the body has to constantly manufacture and eject blood in order to keep the right number of cells in circulation and function as a human. It gets complicated, but too many red blood cells can increase the thickness of blood to a dangerous amount, and too few red blood cells and your tissues can’t get the oxygen they need. To keep that balance, we eliminate and restock our blood with literally millions of new blood cells every second of our lives. So yeah, the process is kind of important. Our journey starts in the bone marrow, the soft tissue inside of certain bones, although similar processes are happening in the lymph nodes, spleen, and thymus as well.

That’s where we’ll find hematopoietic stem cells, or HSCs. These things are a cool type of cell that can become any of our blood cells — red blood cell, leukocyte, or platelet-producing cell, it doesn’t matter, they all start as an HSC. It can also make copies of itself, which is awesome because you never want to run out of a cell that can become anything. It’s just like getting a magic genie. The first thing you do is wish for more wishes. It’s the exact same thing with stem cells, you make more stem cells. From there, the HSCs start differentiating into more specialized types of cells. At this point, the cell has a few different options: it can either become a common myeloid progenitor, and have the option of turning into a platelet-producing cell, a red blood cell, or certain types of white blood cell. Or it can become a common lymphoid progenitor where it can become a Natural Killer cell or lymphocyte like a B or T cell.

These progenitor cells are kind of an in between step in cell differentiation. They’re not full-blown stem cells where they can become anything, but they still have options. That’s what it’s like to be a progenitor cell. The future identity of the cell is starting to take shape. And depending on what kind of chemical environment the cell is exposed to will determine what type of cell these multipotent cells become. Take the red blood cell for example. A common myeloid progenitor has a few options in front of it. Not infinite options, but it still has options. It can become a myeloblast and turn into a number of white blood cells, or turn into megakaryoblast and produce platelets. Also megakaryoblast is the coolest cell name of all time.

Now, the progenitor could turn into a proerythroblast. The Erthryo- part tells us that it’s a red blood cell, and -blast tells us it's a cell that creates a certain cell type. You can see more examples of that in the hematopoietic family tree. A lymphoblast turns into a lymphocyte and a monoblast turns into a monocyte. At this point, the erythrocyte-in-the-making still has a nucleus, albeit, one that’s condensing over time. From there, it keeps condensing down and loses its nucleus to become a reticulocyte, and after ditching even more of its contents and slipping into the bloodstream it becomes a mature red blood cell. 

This process of going from proerythroblast to mature erythrocyte takes up to 5 days although your body can speed it up if it needs more of them. A few different factors can bump up the production rate, like a lack of oxygen for example. And if your tissues detect that your blood is running low on oxygen, your kidneys will crank out a hormone called erythropoietin, or EPO, which tells the bone marrow to get busy making red blood cells. Then as the kidneys detect that oxygen levels are back to normal; they’ll back off the EPO production which brings our bodies back to homeostasis. If you’ve ever traveled somewhere at a high altitude, your body needs to get used to the new oxygen situation and can adjust EPO accordingly. Likewise, other events like infection will trigger your body to make more white blood cells, and bleeding will trigger the creation of more platelets to plug up that new cut. So, at this point, you’ve got a certain amount of red blood cells floating through circulation.

They’ll live their lives for about a hundred and twenty days before being cleaned out and replaced. Now, this process is different from when you’re making your very first blood cells when you’re still in the womb. After all, you have to make your very first stem cells before they can start differentiating. Unfortunately, we know much less about the embryonic version than we know about the adult version. And as an adult, since you’re constantly making new blood cells, you’ve also got to get rid of old cells to maintain a consistent blood volume and thickness. That’s where a few important organs come in, namely the liver and the spleen.

For such a useful, and you know what, I’ll say it, underrated organ, the spleen itself is pretty tiny. It’s about the size of an old Gameboy Color and only weighs on average up to 200 grams. Although scientists would never shame a spleen for its small stature. In fact, an enlarged spleen, a condition called splenomegaly, is a sign that something bad is happening. It can happen when someone has liver disease, or other chronic illnesses, like the classic virus mononucleosis, or mono. But when it’s healthy, the spleen works as a lymphatic and immune center while also picking off old red blood cells and preparing them for excretion. And if you were to slice it open, you’d find two main units, red pulp and white pulp. The same colors as our blood cells. And lucky for you, the colors roughly match up with the cell type.

The white pulp is built around a central blood vessel and stacks a bunch of B cells and T cells so it can be ready to pump those cells into the bloodstream during an immune response. All in all, about a quarter of all the body’s lymphocytes live in the spleen and at most, about a cup of blood. And that blood is found in the other segments of the spleen known as red pulp, which is where the heavy-duty blood filtration happens. When blood first comes into the spleen, it fills into empty space that surrounds the white pulp, eventually collecting into little empty pockets within the red pulp. In particular, all red blood cells have to pass through the narrow splenic cords, also known as the Cords of Billroth. Sounds like a DnD character. And remember how red blood cells are ridiculously tiny? Only six thousandths of a millimeter across? 

In order to pass through those splenic cords and stay in circulation, they have to contort themselves into an even smaller shape. When they’re young and flexible, red blood cells slip through without any trouble. But as they get older, they also get bigger and stiffer, so they get trapped at this step, which is when they start the process of getting recycled. The hemoglobin in those old red blood cells is still a valuable resource for future cell material. So immune cells in the red pulp recycle the hemoglobin’s iron molecules and either store them in the liver or spleen, or send them back to the bone marrow to make more hemoglobin for new red blood cells. And all those globin proteins get broken down into smaller amino acids and recycled for new red blood cells as well. Meanwhile, all the non-useful material from those dead cells gets transformed into bile and then ends up in your poop. Now clearly, there’s more in your blood that your body might want to clean out than just blood cells. When people are looking to “detox”, they’re probably thinking about this part. That’s what we have a liver and kidney for. Well, hopefully two kidneys. But you don’t need to buy a charcoal drink or a special juice or eat anything special, your body’s built to clean its own blood.