Anatomy and Physiology Chapter 17 Part A Lecture: Blood

All right guys, so this is going to be the chapter on blood, chapter 17. This chapter, it's not very long, but there's a lot of information in it. So I'm probably going to be breaking this down into two parts. So be sure to look out for the second part. It should be up, uh, hopefully within a couple of days after this one, uh, if not at the same time.

Um, also, be sure to let your instructors know, let your classmates know, let your friends know, anybody that you think may, that may find this lecture helpful.

All right, so let's get started. So blood is the life-sustaining transport vehicle of the cardiovascular system. And what they mean by this is that when you look inside of our body, we have multiple organs, okay? We have heart, we have liver, we have our stomach, our intestines, uh, our skin, all these things, and everything else. It needs chemicals, it needs nutrients, it needs oxygen that needs to be delivered to it. And that things also, other substances that need to be removed away from those, uh, tissues. So how does that happen? Well, it happens by actually a series of things, and it's all part of this cardiovascular system. And blood is one of the components for this cardiovascular system.

So when you look at this term cardiovascular, what we see is heart and vessels. So the vascular or the vessels are our, our arteries, our veins, and capillaries. And then cardio is the heart. So this is the, the energy or the pump that's transporting or that, or that's pushing all the blood around. So think of blood as being kind of like, uh, the carriers or baskets that are, you know, shipping things or boxes. Think of it like that. These are the substance, blood is the substance that is, uh, transporting all those things, uh, throughout our body. And think about the vessels as the roads to it, the roads, the bridges. And think of the, the cardio or the heart as the energy, as the main pump behind, um, this entire cardiovascular system.

So, uh, blood, it's a key component of this cardiovascular system. You can have blood vessels and you can have a pump, but if you don't have anything that's with, with inside this system that's going to be moving things around, then it's a complete waste. It's not useful. So again, this is why it's very important when you do have blood loss, when you have a lot of blood loss, that is essential to replenish that loss with fluids. Uh, otherwise, you're going to go into, you know, your system is going to go into failure. Your blood pressure is going to drop. Your, uh, organs, they're not going to be receiving enough or adequate, uh, the primary thing is going to be oxygen and, uh, nutrients, oxygen and, and glucose. So if your brain goes without, uh, you know, sufficient oxygen and, uh, nutrients for more than a few minutes, for more than four or five minutes maximum, there's going to be irreversible damage, uh, that's going to be done to your brain. And the same goes to the heart. If the heart's not receiving an adequate amount of, uh, oxygenated blood, uh, along with the nutrients, along with energy, glucose, then that heart is going to start to die. It will infarct.

So again, blood, it's, it's very important. And, uh, as we move forward, you're going to be getting a better understanding of, of what exactly is blood made up of, what's the magic in it. Now that we have a general grasp of what the cardiovascular system is and what blood's role is in this, let's take a look at some of its specific functions that blood has. So three things that we're going to be looking at are transport, regulating, or its regulation, and also the protective properties of blood.

So the main function for blood is its ability to transport substances throughout the body. So the first thing that we look at is that, probably the most important thing, is that blood is able to deliver oxygen to all of our cells of our body. And we're going to be taking a closer look at this in the next few slides. In addition to that, it also delivers nutrients throughout our body.

Now, the other part of, uh, delivering goods is that we always, always have waste products. So if you think about it, you know, you guys just went through a holiday, a birthday, and you receive gifts. Well, in order for you to get to the gift, you had to remove all the packaging and the, maybe it was in a wrapper. Um, so that's all the waste products. It's the same thing. Well, not that same, but, but in our body, once we get the goods, there's always going to be waste at the end. So the waste needs to be removed from the body also. So blood is what's delivering the goods as well as removing the waste products.

So the, the second key point, uh, over here, blood is what transports metabolic waste to the lungs. We're talking about carbon dioxide, in addition to other, um, waste products, to the kidney for elimination. In addition to that, blood is also transporting hormones from the endocrine system to all the other organs of our body. So if you think about all the organs that we have in our body, they're linked together to one another by way of blood. So these all the endocrine glands that we have and the products they produce, the hormones that they produce, they need to work with all the other organs in our body. And the way that they're connected to by is through blood. It's through the cardiovascular system.

The next thing that blood does is regulate. So one of the things that it regulates is our body temperature. So when you think about what happens inside all the chemical reactions that are taking place in our body, it's producing heat. And if that heat that it produces gets absorbed by blood. So if you're wondering why blood is warm, is because it's removing the heat. It's, it's maintaining the temperature. It's trying to keep things stable. And remember, our body, just like everything else in our, our blood, I'm sorry, just like everything else in our body, needs to have some type of a stability. So there's a very fine, um, range that our body temperature needs to operate. And think about it, what happens if you have, you know, when your body temperature reaches 100, we say we have a fever. And think about how we feel, or generally overall, we feel lethargic. We do not, we don't feel good. You don't want to go outside and running when you have a fever of 100 degrees. Same thing. Think about what happens when you're shivering when you're really, really, really cold. If one of you were to go out, uh, in the winter time and jump into a lake, uh, that's, uh, again, probably fro, well, not frozen, but almost frozen, uh, what's going to happen? Your body temperature will drop. You're not going to be feeling good. Again. So again, you could very well, in both cases, in both extremes, you can very well die. So your body needs to be at, um, again, it needs to maintain homeostasis for body temperature. And blood has the ability to do this. So it's removing the waste, or not only is it removing the waste, but at the same time, along with that, it's also regulating the body temperatures, removing the heat as well.

So when the temperature gets high inside of our body, think about what happens during exercise. Our blood vessels, they dilate, our pores open up, and, uh, this is how your body cools the temperature by sweating, by the, this, uh, the pores opening up and the blood vessels enlarging. So more as more blood comes closer to the skin, uh, and the air is, uh, passing by over it, the heat is being dissipated.

In addition to that, blood also maintains our, the pH of our body by using the buffer systems. And we spoke a little bit about this in the chapter on chemistry, all the way in the beginning, in chapter 2. So remember, the acidity and alkaline balance is maintained by blood as well.

And lastly, blood has the ability to help maintain adequate fluid volumes within the circulatory system. So, and it does this by means of the salts, like sodium chloride, and also some of the blood protein that we have, uh, within blood, uh, to help maintain excessive fluid loss from the bloodstream. And we're going to be talking about this in this, uh, in the next few handful of slides that we, as we move forward in this chapter. Um, so again, this is a very important function, uh, that blood has. Because of these proteins and the salts, our body is able to, or the circulatory system, it's able to maintain adequate levels, uh, of fluid at all times throughout the body. And if this were not the case, then we would undergo circulatory collapse. And if that happens, then blood is not circulating, and you know, we would not be able to live for more than a few minutes. Again, remember, uh, your heart and brain, if they're not getting adequate amounts of blood, oxygenated blood, along with nutrients for more than 5 minutes, irreversible damage starts to result.

Finally, we said that blood has the ability to protect. This includes preventing blood loss and also, uh, fighting infections or preventing infections. So when we have injury to our body, what's going to happen? Or one of the things that could happen is a blood vessel could become injured, a blood vessel could become damaged or severed. And when that happens, blood leaves the cardiovascular system. Now, because we have these formed elements like platelets, and also we have plasma proteins, specific plasma proteins, our body is able to initiate a clot formation. And this clot that forms is what prevents excessive fluid loss. In other words, um, you're going to bleed, but again, within minutes, as all the, the, the proteins, the platelets, they come to the site of injury, and this clot forms, this is when the blood loss stops. And again, this doesn't happen all the time. Again, depends on how large the wound is, but for the most part, in smaller wounds, uh, this happens relatively quickly. It happens within minutes. And, uh, we, in other words, you have a clot that forms within minutes, and this prevents excessive fluid loss.

The other thing that blood does is it protects you against, uh, infections. Now, we have bacteria, we have germs all around us, okay? We are essentially competing with all this, uh, flora of bacterial, these microbial life that's all around us. And one of the reasons that we're not always becoming, becoming sick is because blood has the ability to combat, uh, all these other microbes. So, uh, we have, uh, antibodies, these complement proteins, and white blood cells that are able to neutralize any invading microorganisms that may enter our body.

When you look at the composition of blood, blood is a connective tissue. It's a tissue. It's liquid connective tissue. Now, let me rephrase this. Let me be a little bit more clear. When, as long as blood is within the blood vessels, it's a liquid connective tissue. When blood leaves the, the blood vessels, it no longer is a liquid. It will clot. And it's at that point that it becomes a solid. And, uh, if you've any of you have given blood at, uh, for a blood test, and depending on which type of a test tube they use to remove the blood, if you look back after a few minutes at that test tube, you'll notice that that blood has turned into, uh, a solid, uh, blob, almost, you can say it. Uh, and, uh, this is what happens to blood when it leaves the body. It clots. And, uh, as long as the blood is within the blood vessels, it will not clot. But when it leaves, it will clot. So again, it's a type of a connective tissue.

So the matrix for the connective tissue is called plasma, and this is a non-living fluid. Now, the living part of connective tissue are referred to as the formed elements. And these are the living blood cells. And these formed elements, they're suspended within the plasma. In other words, they're floating about within the plasma. And they include erythrocytes, which are the red blood cells, leukocytes, which are the white blood cells, and platelets. And these are these fragmented cells which help form the clot when there is a damage to the blood vessel.

So when you look at this term over here, erythro, erythro means red. So essentially translates into red cell. When you look at leuko over here, in this room, leuko means white. So we have white cells. So again, this is an easy way to remember these, these, uh, these terms if you know the roots of these, uh, these medical, these terms. So you write there again, site means cell. Uh, this is going to help you throughout, not even this course, but you know, all the other, uh, some of you that are going into professional programs, such as nursing school or PA school, physical therapy, this is going to be a great help to you to, uh, recognize these terms.

The composition of blood can be viewed very easily. So if we go to the doctor and they remove blood from our arm into a test tube, and you look at that test tube, it's going to be red in color, okay? Now, when the test tube is placed into this machine that's called the centrifuge, what the centrifuge does is that it spins very fast at a very high speed for about 5, 6, 7 minutes, for example. When you remove that test tube and you look at it, now it's not going to be nice and red anymore. You, instead, you're going to find several different layers. The layer that you find all the way on the bottom is where we have all the red blood cells. This makes up about 45% of whole blood. Then, when we look all the way on top, we find a layer that's slightly like a straw color to a yellow color. This is blood plasma, and this makes up about 55%. Now, in between the bottom and top layer, in other words, in between where the red blood cells and the plasma are, in the middle, we have what's called a buffy coat. This makes up less than 1%, and it's over here that we have our platelets and white blood cells.

This term that you see over here, hematocrit, this is just the percentage of, uh, red blood cells that we have in our blood volume. This value varies from males to females. Uh, so in males, we, it's roughly 47% plus or minus 5. And in females, it's about 42% plus or minus 5. Now, this will vary from person to person. Remember, there's a plus or minus five. So, for example, if you take a male, uh, who does not exercise a lot, who doesn't eat well, who just sits at home, does nothing all day, then, you know, that person's hematocrit value may be about 43, for example. Then you find a female, and when you look at her lifestyle, for example, this, uh, female exercises, uh, daily, she runs, you know, 5 miles a day, she lifts weights, she may, she also, she works, she's not a couch potato like, you know, the first person that we spoke about. In other words, this is a very active individual. When you look at her, uh, her hematocrit, it could be roughly 47%. So again, you can see that again, your lifestyle, in addition to, uh, the foods you eat, as well, okay? And then also just your overall size, it's, these are all part of what determines, uh, this number, this hematocrit value.

So this slide over here kind of goes over what we just spoke about in the previous slide. So again, you have an arm over here, you draw some blood from this arm, you place the blood into a test tube, take this test tube, place it into the centrifuge. Centrifuge spins very fast for maybe 5 minutes, 7 minutes. And then after that, end of that time, when you remove that, uh, test tube, this is what you see. As you can see, it's no longer uniformly red. Now we have a layer on top. This is where the plasma is, and notice this is about 55%. Then you have this very red layer on the bottom, which is where all the red blood cells are. This is 45% of whole blood. Then this is that buffy coat. This is the layer that's right in between, and it's over here where we have the, uh, platelets and white blood cells, or the leukocytes, that are found. So it's the combination of the red blood cells, the platelets, and leukocytes that are collectively known as the formed elements.

So let's look at some of the physical characteristics and volume of blood. So blood, it's sticky. If you ever cut yourself and again, you, you touch blood, you'll notice that it's sticky. And again, the reason it becomes sticky is because you got the, the clotting formation that's starting to happen. But aside from that, when you look at blood, it's also, you'll notice that it's not transparent, it's opaque. And again, if you ever stuck your, your finger when you cut it into your mouth, you'll notice that it has this metallic and salty taste to it. Um, again, the color of blood, it will vary in accordance with this oxygen content. If you were to draw blood from a vein, you will, you'll find the color to be dark red. And the reason for this is because it's low in oxygen. If you draw blood from an artery, you'll find that the color is going to be bright, it's like a scarlet red, okay? This re, the reason for that is because it's high in oxygen.

Now, the pH for blood, it ranges from 7.35 to 7.45. And again, the average is about 7.4. So it's a plus or minus 0.05, uh, value. Now, this is very important. It has to be maintained within these boundaries. When this is not the case, then you can have serious, life-threatening problems. Blood makes up roughly 8% of your body's weight as well. And an average person. Now, again, remember, this is going to vary from person to person, individual to individual, from, again, from ethnicities, uh, from one ethnicity to another, depending on where, which part of the world you're living in. Because remember, when you go to the, for example, when you go to the, to Europe, European North Americans, much larger individuals. When you go to other parts of the world, for example, uh, to the east, to the Far East, much smaller people, their body weight is, uh, much, uh, less than of that of the Europeans. Uh, in addition to that, they're not as tall. So again, uh, the blood volume, it's going to be a little bit different as well.

So, um, in generally speaking, in men, men typically typically have anywhere from 5 to 6 liters of blood. And in females, you're going to find anywhere from 4 to 5 liters of blood. Now, again, why do men have more blood than women? Main reason being, again, men tend to be a little bit larger, they have a lot more muscle, and also because, uh, traditionally men, uh, will do a lot more, uh, physical labor than women do. So again, there you need a lot more blood. Now, remember, as I mentioned earlier, if you have women that are exercising a lot, that are very active, their body's going to have a lot more muscle. Because they have a lot more muscle, now your body is going to naturally produce more blood as well to keep it to, to meet them, the needs, the demands of your body. And then likely the case is going to be at the reverse in a male that's a couch potato, that's not doing much, blood volume is going to be lower, the amount of red blood cell is going to be lower as well, the hematocrit is going to be less. So again, what the way you live your life, okay? And what you put inside your body as well, we're talking about nutrients, it's going to dictate all these things.

When you look at blood plasma, it has this straw-like, uh, appearance in color. So as I mentioned earlier, it's almost like a, a shade of yellow. And if you were to touch it, you're going to find it to be sticky. Um, now, it's made up of a fluid, and that fluid, 90%, it's water. Now, the other 10% are the dissolved solutes that we find within plasma. And they consist of nutrients, gases, hormones, waste products, and other inorganic ions.

Now, by far the most abundant, and this accounts for about 8% by weight of the plasma volume, are the plasma proteins. These plasma proteins, they stay in blood. In other words, they're not taken up by cells, they're not used to build other proteins or other molecules. They're produced mostly by the liver. And the most abundant of these plasma proteins is albumin. Albumin makes up about 60% of all the plasma proteins. And its main job, its key job, is that it contributes to the, uh, to the blood, uh, blood's osmotic pressure. So this is one of the reasons why blood is not, does not, uh, escape. In other words, this is what helps blood stay within within the blood vessels. In other words, um, when we talked about, uh, the regulatory functions of blood earlier on, we mentioned there's proteins that help blood stay within the blood vessels. This is it. This is the key protein that does that job. Albumin. In addition to that, albumin, it also functions as a carrier of other molecules, in addition to to being a buffer for blood.

And the most abundant of these plasma proteins is albumin. Albumin makes up about 60% of plasma proteins. Its main job is to keep the watery part of blood, in other words, to keep the plasma within the blood vessels. So when we talked about the regulation of blood and we said that, uh, we have plasma proteins that help keep the blood inside, that regulates blood loss, this is that protein, albumin. So aside from albumin, uh, salt, okay, which is also found in plasma, is what also helps keep, uh, the plasma within the blood vessels. In addition to that. So aside from, uh, the, the function to regulate osmotic pressure, albumin also functions to carry other molecules, as well as it does to buffer blood.

And albumin is the most numerous of the plasma proteins. It makes up 60% of the plasma proteins. Its key function is that it contributes to the plasma's osmotic pressure. In other words, this is a plasma protein that helps keep water within the bloodstream. The other thing that does, uh, contributes to, uh, the blood's osmotic pressure are sodium ions. So both albumin and sodium ions help keep the water within the bloodstream. Aside from that, albumin also functions as a carrier of other molecules and it also acts as a blood buffer.

And here's a good study table that goes over the composition of plasma. So as you can see here, plasma, it's made up of water and solutes. Water accounts for about 90% of the plasma's volume, and it acts as a dissolving and a suspending medium for the solutes of blood. In addition to absorbing heat. As for the solutes, we find electrolytes and plasma proteins. Now, by far the most abundant solutes by number are the electrolytes. We have cations and anions. The cations for these electrolytes include magnesium, calcium, sodium, and potassium. The anions include phosphate, sulfate, chloride, and bicarbonate. And they help maintain the, uh, plasma's osmotic pressure, in addition to helping maintain the proper blood pH. So again, this is a very good test question. What is the blood's pH? What is the range? What's the average? Guaranteed, you'll probably see something like this on the exam. So remember, the range is 7.35 to 7.45, and the average is 7.4. So keep this in mind. Do not forget this number. Very important moving forward.

With the plasma proteins, they account for about, again, 8% by weight of plasma, and they contribute to the osmotic pressure. Uh, in addition to that, they have functions such as transport and enzymatic activities. So the most numerous of the plasma proteins, as we mentioned earlier, was albumin. So 60% of the plasma proteins is, are albumin, and they're produced by the liver. And as we mentioned earlier, they contribute to the osmotic pressure along with the, uh, sodium ions. So again, along with these electrolytes.

Moving down, 36% of plasma proteins are globulins. These are, um, we have three kinds of globulins. So we have the alpha and beta, and we have gamma. The alpha and beta globulins are produced by the liver, and most of these are transport proteins that bind to lipids, metal ions, and fat-soluble vitamins. Gamma globulins, this is another term for antibodies, and they're released by plasma cells during an immune response.

Fibrinogen, for 4% of the plasma proteins, and it's produced by the liver as well. So all these plasma proteins, we have, they're all produced by the liver with the exception of gamma. Now, going back down to fibrinogen, fibrinogen forms these fibrin threads that the platelets end up sticking themselves on to to form a clot when you have injury to the blood vessels.

Other solutes we find include nonprotein nitrogenous substances, and these are byproducts of cellular metabolism. So things like creatinine, uric acid, urea, and ammonium salts. We also have organic substances. We find these are nutrients. So they're absorbed from the digestive tract and they get transferred throughout the body. They include glucose and other simple carbs, uh, we have amino acids, fatty acids, glycerol, cholesterol, vitamins, triglycerides. Also respiratory gases, we can find over here. So what do we find? Oxygen and carbon dioxide. In addition to that, we also find hormones. So, uh, steroid and thyroid hormones, these are also found, carried by these plasma proteins.

Moving on to the formed elements, we find red blood cells, white blood cells, and platelets. And it's only the white blood cells that are considered to be complete cells because they have a nucleus and they have functional organelles. Red blood cells, they don't have a nucleus or organelles. And platelets, they're just fragments of a cell. Most of these formed elements, they survive in the bloodstream only a few days. And we're talking about white blood cells and platelets. Uh, the red blood cells, they can live up to about 120 days. So they have a lifespan of up to 4 months. Most of these blood cells, they originate in red bone marrow, and they don't divide. Instead, what ends up happening is they get replenished within the red bone marrow.

And in this slide here, we have a couple of images. This one up over here is from, from a scanning electron microscope, and it's, uh, at 1,800 magnification, and it's also been artificially colored. So we're looking at blood over, over here. These are white blood cells. These are the red blood cells. And these down over here, these are all platelets. So you can see the most numerous are the red blood cells, followed by the platelets, and then lastly, we have the white blood cells over here. Again, it's the same thing. These are all the red blood cells over here. And notice, so this part over here, here, this is where it kind of, uh, when we talk about the shape of red blood cells, we say that they're, you can see over here, they're concave. And this is, uh, what's how it looks like under the microscope. So this is actually a photomicrograph, and they stained this, and you can see the, the white blood cells, they end up getting, uh, stained purple. So we have over here, this is a neutrophil. This right over here, this is an eosinophil. And then over here, these are lymphocytes. Here's a monocyte over here. And we're going to be talking about all these individually, so don't worry about it right now. But again, notice that the most numerous of, uh, what we have are the red blood cells, then we have all these guys over here, these are the platelets that you can see floating around. And then finally, we have the white blood cells.

So moving along again, what we have here, this is the same picture of the scanning electron microscope. So notice again, you can see better over here that the, this red blood cell, it's, it's concave over here, as you can see, see this divot over here? We're going to be talking about why this is there, um, as we move forward. And then we have these white blood cells. And these over here, these are just fragments of itself, cell. These are the platelets. And again, they're very important, uh, in the clotting process. And here's another image of the other, the, the photomicrograph. And we can see over here, we have these, uh, red blood cells, okay? Then these little fractured cells, these little fragments of the cell, these are the platelets, okay? Find them over here, all around. So again, the most numerous are the red blood cells, then next are these platelets, finally followed by the white blood cells. So here's this monocyte, we have a neutrophil over here, a lymphocyte, and another white blood cell here, an eosinophil. And we're going to be talking about these individually as we move forward.

When we look at the structural characteristics of these red blood cells, which are also known as erythrocytes, their diameter is quite small at only 7.5 micrometers. And remember, their main job is to transport gases. So they're transporting oxygen and carbon dioxide. When you look at their shape, they're said to have this biconcave disc shape. And this happens because their nucleus is ejected. This is one of the reasons why they end up having this shape. So at one point in a red blood cell's life cycle, a young red blood cell does have a nucleus, but when it matures, the nucleus is ejected, and then it enters circulation to function as a red blood cell. So again, what we end up having happening is what we end up finding is that they lack a nucleus in addition to organelles. So they have no mitochondria either. So keep that in mind. And because they don't have mitochondria is why they end up being these very efficient gas transporters for oxygen. They don't end up using the oxygen that they're transporting.

Now, uh, they're also packed with hemoglobin, okay? And hemoglobin, this is a protein that's actually binding to the oxygen molecules. So we're going to be talking about hemoglobin, uh, in a few slides later. Very important. It's a fascinating protein structure that, uh, we're going to be discussing.

The red blood cells diameters, they're quite large, and sometimes they end up being, uh, larger than some of the capillaries that they're passing through. Now, remember, what would we say? We said they're the diameter is quite small, right? 7.5 nanometers. But comparatively, compared to some of the capillaries, they end up being quite large. But because they have this protein, this protein called spectrin, it gives this red blood cells some flexibility and it allows it to change shape, so it can pass through these very small capillaries.

The red blood cell is an excellent example that shows the complementarity of structure and function. And there's three structural components that contribute to the red blood cells efficient gas transportation function. The first thing is that the biconcave shape provides a huge surface area relative to the volume. Additionally, the dish shape is ideally suited for gas exchange because no point within the cytoplasm is far from the surface. The next point is that red blood cells are packed with hemoglobin. Hemoglobin makes up 97% of the volume of that cell. And what's so important about hemoglobin? This is the molecule that's actually binding onto these respiratory gases. And the final point is that red blood cells lack a mitochondria. Now, why is this helpful? Well, because they don't have a mitochondria, they're producing energy anaerobically. So what this means is that they don't end up using that oxygen that they're transporting, that they're carrying. So again, this is a very, very important characteristic of red blood cells.

In this slide here, we have a picture of a, and in this slide here, we have a picture of a red blood cell. So you can see its diameter, 7.5 micrometers. In this slide here, you can see the red blood cell, and over here, you can see the diameter of the red blood cell is 7.5 micrometers, and it's only about 2.5 micrometers thick. So again, these are quite small cells.

Moving on to the functions of red blood cells. As we discussed earlier, the red blood cells main job is to transport their respiratory gases. The main molecule that we find within the red blood cells that has the ability to reversibly bind with oxygen is hemoglobin. Now, in males, the normal range for hemoglobin is anywhere from 13 to 18 grams per 100 ml of blood. And in females, we have the range between 12 to 16 grams of hemoglobin per 100 milliliters of blood.

When we look at this term hemoglobin, it's made up of two parts. You have this one part here, globin, and you have this other part, heme. So hemoglobin, so there's two things that make up hemoglobin. The first thing, when we're going to be looking at both of these things in the next few slides, is this, the red pigment bound, which is the heme, to the protein globin. Right? So you have heme. This is the pigmented part of hemoglobin, and it's bound to this protein called globin. When you look at globin, globin is made up of four polypeptide chains, and they're found diagonal to another. So you have two alpha and two beta chains that are diagonal to one another. And you'll see that, uh, when we move on to the next, uh, the next few slides.

Now, the heme pigment is bound to each globin chain. In other words, you have one heme pigment to one globin chain. In other words, in one molecule of hemoglobin, you have four heme molecules. Okay? So you have four hemes to each, uh, four hemes in a hemoglobin. Each heme's central iron is where the oxygen is going to be binding to. So remember, this is an oxygen molecule that binds, not an oxygen atom, but an oxygen molecule.

So here we go. In this slide, you can see this hemoglobin molecule here. So notice what do we have? It's made up of alpha and beta chains. And, um, these, they should be, uh, across from one another. In other words, you should have one alpha here, another alpha over here, and one beta here, another beta over here. So they should be diagonal to another. I believe this is an error in this, uh, drawing that they have given over here. But, uh, you don't have to worry about that. This is not a biochemistry class or anything. But notice that each one of these chains of the, the hemoglobin, each one of these alpha chain and each one of these beta chains, they contain a single heme molecule. So here's this heme molecule here, another one over there, another one over here, another one over here. So it's this part over here, this triangle part, that, uh, this heme molecule is situated in. So, and right over here, this is that heme molecule. And, uh, this is going to be an ionized form of iron over here. So this should say Fe2+.

Moving forward, again, this is another image of this hemoglobin molecule that we looked at in the previous slide. So remember, we have two alpha chains and two beta chains. That's a big picture to understand. Two alpha, two beta chains. And we have a heme group that we find within a heme molecule. So here is this heme molecule again. And notice, you know, it's a, this is actually quite a, it's a very strong, uh, molecule over here. Uh, we have lots and lots of these rings over here. We have nitrogen atoms here as well. Um, so, and then over here, centrally located, you have this iron atom here. So remember, this is an ionized form of iron. Should, this should say Fe2+. And it's because it's ionized that it gives the ability, uh, for oxygen molecules to bind.

Now, keep in mind, it's an oxygen molecule that's binding, not an oxygen atom, but an oxygen molecule. So we know that a hemoglobin molecule is made up of two alpha and two beta chains. And it's within these alpha and beta chains is where we find this heme molecule. We know that one heme molecule will attach one oxygen molecule. So what does that mean? A hemoglobin molecule has the ability to transport up to four oxygen molecules. Okay? Four oxygen molecules, not atoms, but molecules.

So what's quite fascinating is that each red blood cell is packed with 250 million hemoglobin molecules. That's a huge number. So if you think about it, if you do the math, you take 250 million hemoglobin molecules, and you know that each molecule has the ability, each hemoglobin molecule has the ability to transport up to four oxygen molecules. That means 250 times 4, that's 1 billion oxygen molecules that's being transferred by a single red blood cell. 1 billion oxygen molecules. In other words, we're looking at two billion oxygen atoms in a single tiny red blood cell that you can't even see with the naked eye. That's quite fascinating.

So when the oxygen is bound to hemoglobin, it's referred to as oxyhemoglobin. When you look at it in appearance, it's going to have this bright red, ruby red, uh, color to it. When the oxygen is unloaded to the tissues, so the oxygen leaves, now we refer to this as deoxyhemoglobin. Okay? So it's called deoxyhemoglobin when the oxygen is unloaded from the hemoglobin. And what happens is the appearance changes again. Now it has this dark red color, this, uh, dull red. So in other words, you're looking at deoxygenated blood, blood that you're going to find within your veins. And then when you look at the blood that's found within your arteries, or oxygenated blood, you're looking at this bright red color, oxyhemoglobin.

When the carbon dioxide leaves the tissue and enters the bloodstream, 20% of the carbon dioxide in the blood is going to bind to hemoglobin. However, it's not going to be binding to the iron. Instead, it binds to the amino acids of the protein. So when that happens, it's called carbaminohemoglobin. In other words, when you look at this word, we have carba, amino, hemoglobin. Carba, this refers to the carbon dioxide. Amino, because it's attached to the amino acid of this protein. Okay? Carbaminohemoglobin.

So real quickly, when oxygen attaches to hemoglobin, the structure changes of the protein. In addition to that, the color changes as well to this bright red, and it's called oxyhemoglobin. When the oxygen leaves the hemoglobin, the structure changes again, and the color changes too, and it's called deoxyhemoglobin. So as far as we can tell, we can see visually, oxygenated blood is going to be bright red. Deoxygenated is going to be dark red. Then you go down to carbon dioxide. When it leaves the tissue and it enters the bloodstream, when it attaches to the amino acids of hemoglobin, it's referred to as carbaminohemoglobin.

Moving on to the production of red blood cells, or production of erythrocytes. The term for blood production is hematopoiesis. Not just red blood cells, but for all of the formed elements is hematopoiesis. So when you look at this term here, hemato means blood, poiesis means formation or creating. So creating blood. This occurs in the red bone marrow. And it's within the red bone marrow that we find reticular connective tissue that's lined with this wide blood sinusoids. And these are capillaries, essentially. Where do we find or which which bones do we have this in? Which bones do we find it in? Well, you're going to find it in the bones of your axial skeleton, the girdles, in addition to that, the proximal epiphysis of the humerus and femur.

The process of hematopoiesis is going to start with a stem cell, and that's known as a hemocytoblast, or more traditionally known as the hematopoietic stem cells. Now, these hematopoietic stem cells, they will give rise to all of the formed elements. We're talking about your red blood cells, your white blood cells, and the platelets. What happens is that once this cell starts to differentiate, and when you look at it, you're going to be able to tell out of a certain point that there's a change that's taking place. In other words, when you look at it, you're going to start seeing these receptors that start to appear on the membrane surface. When that happens, that tells us that this cell is committed. And in other words, it's committed to becoming a specific cell. It's either committed to becoming a red blood cell, a white blood cell, or a platelet. Now, once that happens, that cell is not able to change anymore. It can't. So once the cell is committed to being a red blood cell, that's all it's going to be, a red blood cell. It can't change its mind. Nothing else can happen for it to become another type of a cell, a white blood cell.

So what happens is that these receptors that start to appear on the surface of that membrane, they're going to be sensitive to hormones and growth factors. And these hormones and growth factors, they end up driving or steering that cell to the specific pathway for development.

In the previous slide, we looked at the term hematopoiesis, and now we're looking at erythropoiesis. So, erythropoiesis, this is going to be the formation of red blood cells or RBCs. This takes usually about 15 days. So the steps for erythropoiesis, they also start off with this hematopoietic stem cell. And this hematopoietic stem cell will transform into a myeloid stem cell. What happens is that the myeloid stem cell will differentiate into a proerythroblast. This proerythroblast then goes and divides several times, and it transforms into this basophilic erythroblast. The basophilic erythroblast has two stages: an early stage and a later stage. In the early stage, essentially what's happening is it's synthesizing lots and lots and lots of ribosomes. And when you stain it, it turns blue. So remember, this is the early stage, the basophilic erythroblast.

When you get to the second stage, the polychromatic erythroblast, what happens over here is that when you look at the term again, polychromatic, you're talking about color and many, so many colors. So now when you stain it, you see many different colors. Essentially, what's happening is this, the cell at this point is producing a lot of hemoglobin, okay? A lot of hemoglobin is being synthesized. In addition to that, the iron is accumulating within that cell. So this gives it a different appearance. So in other words, you have the, the ribosomes which are staining blue, and then also you're having the hemoglobin that's, uh, giving it a different color, the hemoglobin and the oxygen that's coming through. So now you have the cell that looks both pink and blue in areas.

The next part, the next step that's going to happen is that this polychromatic erythroblast will differentiate into an orthochromatic erythroblast, or normochromatic erythroblast. Now, this is going to contain mostly hemoglobin. So when you look at the appearance, it's going to be pink. Now, the reason that it's going to be mostly pink is that the organelles that are inside of it, they're starting to to be dismantled. They're breaking down, they're disintegrating. In addition to the nucleus, which is also starting to be degraded. Eventually, what ends up happening is the nucleus gets ejected. Once that nucleus gets ejected, it's going to give that red, this erythroblast, this biconcave shape. So, uh, when that happens, now we call this a reticulocyte, or in other words, an immature red blood cell. And this immature red blood cell, it still has some ribosomes that are a part of it that are inside. However, it's going to be, it's mostly hemoglobin. So this reticulocyte will enter the blood vessels. In other words, it's entering circulation now.

So steps 1 through 6 all occurred within the red bone marrow. Now, step 7, this reticulocyte, it's going to the blood, the blood vessels. In other words, it's entering circulation. Now, at this point, it's going to start circulating within the blood vessels, and it's going to be transporting oxygen. But what ends up happening is usually within two days, whatever ribosomes that are left ends up getting further degraded and broken down, and it's completely anucleated. So now, within 2 days, that red, this reticulocyte will eventually become a mature red blood cell. In other words, the reticulocyte, this immature red blood cell, it matures in 2 days. And when you look at the reticulocyte count, it gives us a rough index of the rate of red blood cells that are being formed. So in healthy individuals, the reticulocyte count is going to be about 1 to 2%. Now, when you have values above 2% or below 2%, this indicates an abnormal rate of red blood cell formation.

This slide here graphically represents what we learned in the past couple of slides. So we have this hematopoietic stem cell or hemocytoblast, and remember, it's just a stem cell that ends up getting committed. Okay? It transforms into a proerythroblast. So when it turns into proerythroblast, it's committed because at this point, it cannot become anything else. Okay? Once this hematopoietic stem cell turns into a proerythroblast, this is the route to becoming a red blood cell. That's it. It can't change any more directions. Now, this proerythroblast will then differentiate into a basophilic erythroblast or an early erythroblast. And over here, remember what's happening? Lots of ribosomes are being produced. Next, what is up happening is that it will turn into a polychromatic erythroblast. And over here, we're starting to get an accumulation of a lot of iron. In addition to that.

Lots of hemoglobin is being produced now. Next thing happens is that this laterior blast will turn into a orthochromatic eriol blast. So what's happening over here is that the cells starting to break down all the ribosomes. In other words, machinery starting to get broken down. And as you can see here, the nucleus start to get degraded, and the nucleus gets ejected from this cell.

Once that happens, we have a little bit of ribosomes that are still left within the cell, but we now have this immature red blood cell, and this is called a reticulocyte. This reticulocyte will enter circulation. In other words, it enters the bloodstream, and it'll swim around for a couple of days. It'll still be carrying, transporting oxygen and carbon dioxide. And within two days, all this machinery that's left over, ribosomes that's there, it'll be broken away and degraded, and it will then become this erythrocyte, or in other words, a mature red blood cell.

Looking at the regulation and requirements for erythropoiesis. If our body is not producing enough red blood cells, it leads to a condition called hypoxia. And in hypoxia, the tissues in our body are not receiving enough oxygen. On the other hand, if our body is making too many red blood cells, then what's going to happen is our blood gets too thick, so the viscosity increases. So why is this bad? Well, think of it this way, it's harder for the blood to flow through your body when you have too many red blood cells. So if you want a comparison, think about what happens during rush hour traffic. Uh, in the evening, everybody wants to go home, and there's a lot of cars on the on the roads, uh, and what happens? Traffic just slows down. It's very hard for all those cars to move. Same thing in your body when you have too many red blood cells. Think of the red blood cells as cars, and think of the blood vessels as roads. When your body is, when the blood is flowing through your body, and you have so many of these red blood cells, it's going to be hard for it to, for all these things to move through because there's just too many of these red blood cells.

Now, our body is producing about 2 million red blood cells per second. Okay, this is not an error, it's 2 million per second. It's a huge number. So how do your body balance the amount of red blood cells that is being produced and that's being destroyed? Well, that depends on a couple of different things. First is hormonal control, and we're going to be looking at this in the next few slides. The other are is the dietary requirements. So if you're getting enough iron in your diet, enough protein, and enough, um, um, vitamins, specifically looking at B vitamins, then you should have everything that you need to produce enough red blood cells. But if you don't have a proper diet, a healthy diet, then your body is not going to have enough of what it needs to produce this, uh, red blood cells.

The stimulus that's responsible for erythropoiesis, it's a hormone called erythropoietin, or the acronym EPO. This is what stimulates the formation of red blood cells. And we have a small amount of EPO that's in our bloodstream at all times, and this is what maintains this basal rate, this constant rate of red blood cell production. While the liver produces some EPO, the kidneys are the main organ of production for erythropoietin. So what happens is when specific cells within the kidney become hypoxic, oxygen-sensitive enzymes aren't able to degrade an intracellular signaling molecule called hypoxia-inducible factor. Its acronym is HIF. And as HIF accumulates, it speeds up the production and release of EPO.

All right, so let's look at some of the causes of hypoxia. So the first thing that's listed here is a decreased number of red blood cells, and this could be because of a hemorrhage. In other words, you're bleeding. Or the other problem could be your body is just breaking down too many RBCs. Next, we have listed is an insufficient hemoglobin per red blood cell. So what this means is, first of all, let's look at this. Hemoglobin is made up of two things. We have heme, and we have globin. So this is a protein part, and this is the heme part. And the heme is where the iron is found. And remember, iron has that two-plus charge to it. So the iron is what's binding to that oxygen molecule. So if you don't have enough iron, how are you going to have enough hemoglobin? Proper functioning hemoglobin, we won't. And this is going to be a cause for hypoxia. Last, they say a reduction in the availability of oxygen. When could that happen? Well, if you go up to areas that are very high, so you're looking at mountains, for example, high altitudes, that's going to be a cause for hypoxia. Okay, when you go up there, what happens? Air becomes thin, uh, so not enough oxygen up there. The other problem is you could have some issues with lungs, maybe lung problems like pneumonia. Again, when you have pneumonia, what happens? Um, again, you end up getting fluid, you have an infection going on, and now you know you're not able to get enough oxygen inside, uh, your lungs, and you're not getting enough oxygen, enough air inside your lungs, then your blood is not going to be able to pick up that oxygen.

The other thing that could happen is you have too many red blood cells or too many erythrocytes, or high oxygen levels in the blood. When this happens, the production of EPO is inhibited. In other words, your body is not going to produce enough EPO. So when you don't have enough oxygen, your body produces EPO. When you have a lot, too much oxygen, then your body is not going to produce it. It's going to cut it off. Why do you want to produce more, uh, red blood cells when there you have too much oxygen? Your body doesn't need it. Remember, guys, your body does not like to waste. Okay, when you're not using it, you lose it. You either use it or lose it. This is the key thing for the body. You use it or lose it. So I mean, think about it this way. If you guys go out, you're exercising, so the gym just started, you head out to the gym, first few weeks, you know, you're hard at it, you're lifting weights or you're running, what's going to happen is this, your muscles going to grow, your body's going to start producing more red blood cells too. But then, you know, you lose your motivation after the fifth week and you stop. What happens to all that muscle? It's gone. Okay, you use it or you lose it. Same thing to the red blood cells. You lose it. Your body, the, the, when you start exercising, when you start running, your body produces lots of blood cells, in other words, uh, because of that, due to that hypoxia, uh, when you first start to run, your body's like, whoa, this guy is starting to do a lot more work. We need to produce more red blood cells for him because this person is starting to, uh, run regularly. So your body is going to start producing more red blood cells. But you know, when you stop running, when you start, stop exercising, then your body does not have a need for all those extra red blood cells. So your body will not be producing more of it.

So again, remember, EPO, it also causes erythrocytes to mature much faster. Testosterone, it enhances the EPO production. So again, when you're working out, when you're doing a lot of lifting, a lot of weights, one of the things that happens is your body starts producing more testosterone too. And testosterone, it just goes and reinforces this EPO production. So this will lead to a higher red blood cell count in men.

So remember, this works on a negative feedback. So remember, the stimulus is hypoxia. Your body doesn't have enough oxygen, specifically looking at some of the cells in the kidney that's not receiving enough oxygen. When that happens, eventually the kidney will start to release erythropoietin, or the EPO. EPO is going to stimulate the production of red blood cells. And as the red blood cell count increases, it's going to start carrying more oxygen. As more oxygen is carried, then that's going to cut off this production of EPO. In other words, you end up getting homeostasis back. So remember, we're looking at a negative feedback. Low oxygen, kidney will start producing EPO. EPO is going to stimulate RBC production. RBCs will start, once they're produced, will start carrying more oxygen. Once that happens, we have normal, we have a balance again, so we have homeostasis again, and that's normal blood oxygen levels.

This is a very good example of what we just learned in the past few slides to real-life application. So some people, some athletes, they abuse their bodies. What they do is they artificially increase their red blood cell production. In other words, what they do is they dope themselves up with artificial EPO. And what this does is this again, it's going to increase the production of red blood cells. Hematocrit goes up. What, how does this affect the athlete? Well, they have a lot more energy now, increased stamina, they perform much better. But it comes at a very, very high cost. It could kill you. All right, so it's not worth it. But let's just look into it, uh, into detail. So what are they actually doing? Remember, when they're injecting themselves, when they're taking this EPO, this artificial EPO, their body starts producing a lot more red blood cells. Now, keep in mind, any athlete, it doesn't make a difference what your sport is. You could be a runner, a basketball player, a bicyclist, a swimmer, uh, baseball player, basketball player, whatever. What happens is this, you're exerting yourself, you're overexerting yourself, you're an athlete. So you're going to be running far, whatever your sport is. The first thing that happens is you're breathing, right? You start breathing much, much faster. Why? Because you need a lot more oxygen. You're using your muscles, uh, again, you're doing very high endurance exercise, or you know, your body movements, and now your body needs more oxygen. So your oxygen demand just went up with exercise. And what's your body, again, when you're a trained athlete, your body is naturally going to be producing more red blood cells because why? Remember, EPO is going to be going up when you're keeping, when you're exercising. So you're going to have a lot more red blood cells than an average person will have. However, what these guys are doing is they're giving themselves way too much of it, too much EPO. So what could happen is again, the hematocrit, they can go up from 40 up to 65%. This is very, very dangerous because what's happening is now, think with this one, your body has all this extra red blood cells inside of it. All right? Now, keep in mind, what happens? What's the other thing that's happening when you're exercising, when you're playing sports? You sweat a lot, right? Because again, heat is being produced. As you sweat, you're losing water. And what happens is this, when you start losing water, blood starts become much, much more thick. And what could happen is eventually you could have a clot, you can have a stroke, you can have heart failure, you can have a heart attack, you can die. So again, it's not worth it. Um, don't dope yourself up. Again, if you're a health professional, you end up, you have an athlete, a patient that comes up to you, and you know, if they confide that they are doing this, you need to let them know the consequences of what's actually going on, uh, what the consequences are, what they could die from, and also let them know what's going on in your body, why is it so dangerous? Paint a picture of what's going on inside their blood cells, uh, what their blood is doing.

Dietary requirements for erythropoiesis include amino acids, lipids, and carbs. In addition to that, we need iron. And iron is available from our diet. Some of these other things, your body can break other things down and obtain it. But iron has to be obtained from our diet. 65% of the iron is found in hemoglobin. The rest we're going to find in the liver, spleen, and bone marrow. We're not going to find free iron floating around our body because it's toxic. So on a happening is that the free iron ions end up getting stored in these protein iron complexes such as ferritin and hemosiderin inside the cells. The other thing that could happen is that the free iron could be transported to the bone marrow by a protein, by transport protein called transferrin. So let's just say a red blood cell is being broken down. As it gets broken down, the iron gets liberated. Transferrin will come pick up that free iron and then transport it to the bone marrow, the red bone marrow. And at the red bone where new red blood cells are being produced, again, you, it's going to be taken in by the hemoglobin and it gets added to the hemoglobin. The hemoglobin will get packed into the red blood cell, and now you end up recycling that iron, that free iron. This way.

The other thing that's required are B vitamins. And we have two specific B vitamins, B12 and folic acid. These are both necessary for DNA synthesis for rapidly dividing cells, such as this developing red blood cell.

As to the life cycle of a red blood cell, they usually live anywhere from 100 to 120 days. So we're looking at about four months. Red blood cells, as we know already, they lack a nucleus, so they're not able to synthesize, they can't make any new proteins or grow or divide. What ends up happening is the red blood cells, as they become old, as they age, they become fragile. The hemoglobin, it also starts to degenerate. Why is this? Think about it. Now, your body has roughly 60,000 miles of blood vessels. So these red blood cells, they're traveling every day, day in and day out, through all these blood vessels, 60,000 miles. Now, that's a huge, huge, huge distance. Just to give you kind of give you an example of comparison, the circumference of the Earth at the equator is 25,000 miles. So when we're talking about 60,000 miles, our blood vessels, they can theoretically, if we stretch them out from end to end, they can go around the Earth more than two times. All right? So now think about it, these bloods, these RBCs, these red blood cells, they're swimming around for about, you know, four months. What's going to happen? They're going to end up getting worn away. Just like a car, if you take a car, what ends up happening if you drive it more than 50, 70, 80,000 miles? What's going to happen to that car? It's going to start breaking down. It's going to get old. The tires going to start to wear away, the brakes are going to be worn away, uh, the, the engine, the cylinders, the pistons, all these components are going to start, you, you end up having normal wear and tear. Same thing happens to the red blood cells, normal wear and tear. And as that happens, it starts to become less and less efficient. And again, it, once right around 100 to 120 days, it's going to end up, uh, being recycled. It's going to, going to end up getting broken down.

Now, another thing that I wanted to mention, an interesting fact is that, um, now this number that I threw at you, 60,000 miles, this isn't an average human body. An average normal healthy person, for every pound of extra fat that you have, your body is going to produce an extra seven miles of blood vessels. Okay? So for every extra pound of fat, seven extra miles of blood vessels. So if you want to think about another reason why it's so unhealthy to be overweight is because your heart has to work so much harder to pump blood through all these extra miles of blood vessels, right? So try to understand that, you know, somebody that's, you know, 200, 300, 400 pounds, think about how many miles that translates into and how much harder that heart has to work. Uh, so again, this is, obesity, it's a very, very dangerous, uh, medical condition.

Now, moving along, the area in the body where the most wear and tear is taking place for these red blood cells are going to be at the capillaries. Now, what ends up happening is that in some capillaries, some capillaries are so small that the red blood cells are actually larger than the capillaries are. So that red blood cell needs to twist and contort in order to be able to pass through that capillary. And the spleen, the liver, and bone marrow, the red bone marrow are three places where the capillaries are the smallest. And a lot of times, again, as you approach this 100 to 120 day mark, these red blood cells, they'll get trapped over there, they die, and then they end up getting recycled at these locations. So again, this is one of the other reasons why the spleen is referred to as the graveyard for red blood cells.

Macrophages in the spleen, they'll come in, they'll break down, they'll swallow these dying red blood cells. So when the red blood cell gets broken down, it'll get broken down into the globin and the heme. So the hemoglobin gets broken down. The globin ends up getting recycled. And the heme part, it gets separated into the heme and the iron portion. Now, the iron will get picked up by, for example, maybe the transferrin. Transferrin will pick it up, take it to the red bone marrow, and then it gets recycled over there. Or it could be incorporated into ferritin or hemosiderin where it could be stored for later use.

Now, the other thing that's going to happen is that the heme, it's going to get broken down into something called biliverdin. Now, your book doesn't have it listed here, but it should. Uh, so it gets converted into biliverdin. Biliverdin then will get converted into bilirubin. And bilirubin has this yellow color to it. It has this yellow pigment to it. Now, yellow, the bilirubin, when it gets, uh, into the bloodstream, it gets picked up by albumin. Albumin, it's a plasma protein. It picks up the bilirubin and it takes it to the liver. From the liver, the bilirubin will get secreted into the small intestines. And from the small intestines, it's going to move down into the large intestines where it gets converted into urobilinogen. Now, most of this urobilinogen will get converted into another pigment called stercobilin. This is what gives feces the brown color. Now, some of this urobilinogen ends up getting reabsorbed into the system, into your bloodstream, where it gets oxidized into something called urobilin. Urobilin is then excreted into the urine. And urobilin is what gives urine the yellow color. And as I mentioned earlier, the globin, the protein part of hemoglobin, ends up getting broken down and reused. The amino acids will be recycled as well.

So let's go over this illustration over here, uh, so what do we have over here going on? Number one, it says low oxygen levels in the blood stimulates kidneys. All right, so when oxygen levels, in other words, when you have hypoxia, what's going to happen is, um, the HIF starts to accumulate. When it starts to accumulate, it's going to stimulate the production of erythropoietin. Okay? So as the levels of erythropoietin rise, it's going to cause the production of red blood cells. All right, so that's step number three over here. And once the blood cells enter circulation at roughly about 120 days or so, they start to die. And when they do die, what ends up happening is it gets broken, the hemoglobin ends up getting broken down. So you have heme and you have globin. The globin, that's a protein part, it ends up getting broken down into the amino acids. It enters circulation, ends up getting recycled. Now, the heme part, the heme, it, remember, two things will happen. First of all, the iron will get separated. The iron can either get stored as ferritin or hemosiderin. And the other thing that could happen is that the iron, it could get picked up by transferrin, get into the bloodstream, and then and shipped to the red bone marrow where it ends up getting recycled as well. Now, that takes care of that for the iron. Now, the other part of the heme, in other words, heme minus iron, what's going to happen is that first, it's going to get converted into biliverdin. Biliverdin then gets converted to bilirubin. And then that bilirubin, when it enters, when it's inside the blood vessels and the, it's going to end up getting picked up by albumin. Albumin will then transport it to the liver. The liver secretes that bilirubin to the small intestines. From the small intestines, the bilirubin will move down into the large intestines where it gets converted into urobilinogen. Now, most of that urobilinogen ends up getting converted into stercobilin. This is the pigment that gives feces the brown color. Now, some of that urobilinogen ends up getting absorbed back into the bloodstream or ends up getting oxidized into urobilin. Now, the urobilin then goes to the kidneys and gets excreted. And this is what gives urine the yellow pigment to it. It's the urobilin. And again, over here, it says, uh, food nutrients, amino acids, iron, your B vitamin, vitamin B12, and folic acid, they end up getting absorbed in the intestines, they end up getting into circulation, and again, they're going to go to where it's needed for the production of red blood cells.

Now, let's take a look at some of the red blood cell disorders. Most erythrocyte disorders, they're classified being either as some type of an anemia or a polycythemia. In anemia, blood has an abnormally low oxygen-carrying capacity. It's so low that it's not able to support normal metabolism. And this is a sign of the problem, it's not the disease itself. In other words, there's an underlying cause that contributes to this issue. Now, symptoms include fatigue, pallor, dyspnea, and chills. So if you're not familiar with some of these terms, pallor, again, you know, you're pale. Dyspnea, you have a hard time breathing. And again, chills, you should know these two already. Fatigue and chills, you get tired very easily, and again, you get cold, you know, your body shaking. So three groups are based on on the cause for anemia. This could be due to blood loss. It could also be because there's not enough red blood cells being produced, or it could be that too many red blood cells are being destroyed. So again, we have these three main causes. So let's try to take a look at some of these diseases as we move forward.

Now, let's take a look at the first group of causes for anemia, which is blood loss. And the first example that's given is hemorrhagic anemia. What's happening over here is that you're having a lot of blood that's being lost over a short period of time, so rapid blood loss. How does this happen? Usually due to some type of a trauma. This could be due to a stab wound, a gunshot wound, or you know, it could be just a simple laceration. So somebody's at home, they're chopping some onions or a carrot, and they end up cutting themselves. Or again, you know, you're cleaning the window, you push too hard on the window, for whatever reason, your hand goes through the glass, and you end up cutting your arm. So again, what's happening is a lot of blood is being lost. So how do you treat this? Well, of course, you have to treat the wound. But, uh, remember, this is anemia, we're looking at. So we have to treat, we have to replace the blood that's lost.

Now, the other type of blood loss could be long-term blood loss, and this is chronic. So chronic is long-term. So chronic hemorrhagic anemia, blood loss that's happening over a long period of time. So this is a slight but a persistent blood loss. In other words, you're bleeding very, very slowly over a long period of time. And this could be hemorrhoids, or it could be ulcers. So how you treat this? Well, all you have to do is treat the underlying cause. So if it's an ulcer, you need to treat the ulcer. If it's a hemorrhoid, you have to treat the hemorrhoid. And once you treat this, then the bleeding stops, the anemia goes away.

The second group of causes for anemia is not enough red blood cells being produced. The first example that they give is iron deficiency anemia. So why is this happening? Well, this could be a cause of hemorrhagic anemia, but usually this is because you're not getting enough iron in your diet, or your body is not absorbing that iron. So what ends up happening is when you look at the red blood cells, they're very small and pale in color. So they're called microcytes. They're referred to as microcytes. And what's happening is the reason that they're turning into microcytes is because your body is not able to produce hemoglobin. Why? Because there's no iron there. Remember, heme, globin, right? This is the protein part, and this part over here is where, and the heme is where you need to have the iron ion over there. So if you don't have that iron ion, then you cannot produce heme, and then therefore you cannot produce hemoglobin. So what do you have? You got cells that are not pink in color and, uh, that are not functional. So this is why they're referred to as microcytes. Now, how do you correct this condition? Usually, if you give the individual iron supplements, they're able to reverse this condition, and you know, they can have normal levels of hemoglobin again. You can reverse the anemia.

Another cause for there not being enough red blood cells being produced could be a lack of vitamin B12 that's available. Now, this is referred to as pernicious anemia. What causes pernicious anemia? There's a couple of different things, but usually for the most part, it's an autoimmune disease. What does that mean? Autoimmune disease is when the body is attacking itself. And in this condition, in this case, the body is attacking the stomach mucosa that produces intrinsic factor. Intrinsic factor is one of the substances that's needed to absorb vitamin B12. And if you remember a few slides ago, vitamin B12 is one of the things that's needed to produce healthy red blood cells. So because there's a lack of vitamin B12, red blood cells are not able to divide. So they just keep getting bigger and bigger, and they're termed macrocytes. They turn into these large cells. How do you treat this? Usually, if you give injections of vitamin B12's or these nasal gels that have vitamin B12, about once a week, it ends up controlling this condition.

Now, the other cause could be dietary. So if you're not getting enough dietary intake of vitamin B12, usually for most Americans, this is not a problem because foods like meats, poultry, and fish are rich, are abundant in vitamin B12. Most Americans, we eat enough of meats and fishes and, uh, poultry. So the problem that you see this, the group of people that we tend to see this are strict vegetarians and vegans. And these individuals, they may need to take a supplement. Now, they have vitamin B12's available in a pill form, uh, that can get, um, that you can take to prevent this type of anemia from developing.

Another cause for there not being enough red blood cells being produced could be due to renal anemia. And this is caused by a lack of erythropoietin that's being produced. Now, when you look at this term, renal, renal means kidney. So this is usually accompanied by some type of kidney disease where the kidneys are not able to produce enough erythropoietin. So how is this treated? The patient usually gets synthetic erythropoietin administered.

The last condition that they have listed for not enough red blood cells being produced is aplastic anemia. In aplastic anemia, the red bone marrow is either being destroyed or inhibited by drugs, chemicals, radiation, or viruses. But usually, the cause is unknown. Now, not only are the red blood cells being affected, but all the formed elements are, because in the red bone marrow, not only are red blood cells produced, but white blood cells and platelets. So not only do we see anemia, but we also see clotting and immunity defects as well. So how is this treated? Short term is with transfusions. Long term requires transplantation of stem cells.

The final group of causes for anemia are where there's too many red blood cells being destroyed. So the first thing we have listed are premature lysis of red blood cells, and this is referred to as hemolytic anemias. And hemolytic anemias can be caused by incompatible transfusions or infections.

Moving along, production of abnormal hemoglobin usually has a genetic basis to it. So we have conditions such as thalassemia and sickle cell anemia. Thalassemia are typically found in people of Mediterranean ancestry, such as Greeks and Italians. So if you remember, globin has four chains, two alpha and beta chains. In thalassemia, one of the globin chains is either faulty or absent. So the red blood cells are thin, delicate, and deficient in hemoglobin. Now, there's many subtypes of it that range in severity from mild to being extremely severe. And in very severe cases, the treatment may require monthly blood transfusions.

In sickle cell anemia, we have a mutation of the hemoglobin, which is called hemoglobin S. The globin in hemoglobin is made up of 146 amino acids, and one of the amino acids in the chain is incorrect. It's a sixth amino acid that's incorrect, and this is what leads to this mutation that we see in hemoglobin S. So what ends up happening is when oxygen levels are low, the amino acids, they start to link up with one another, and this ends up changing the entire shape of the cell, of the red blood cell, and now it becomes, it takes on this crescent shape. And we tend to see this again when oxygen levels are low, so when you're under a lot of stress, for example, during exercise. So as these blood cells are passing through the blood vessels, and when they approach the smaller vessels and capillaries, they end up starting to get backed up and buckling up. And because of that, they start to rupture easily. And also the tissue is being deprived of oxygen. So this ends up leading to a lot of pain, excruciating pain. The patients will also be gasping for air. Um, we tend to see other problems, pains in bone, chest pain. Uh, also this can lead to infections and stroke. So as these sickle-shaped cells are passing through the smaller blood vessels and capillaries, they have a very hard time passing through because of their shape. So now what you end up having is a backup of all these cells, so they start to back up on top of one another, and this leads to these cells rupturing easily. In addition to that, the tissue is not receiving adequate oxygen delivery. So now you end up having a lot of pain, uh, we see bone pain, chest pain, the patients, they, they're gasping for air, uh, in addition to that, we end up seeing strokes and infections that are quite common as well.

Sickle cell is prevalent among the African population, specifically people coming from the African malaria belt, including their descendants. So these countries include, starting on on the west coast of Africa to the north at Senegal, going all the way down south to Angola, and then stretching all the way to the east coast of the continent to Tanzania, then heading back all the way north to Somalia. So this is a very large area of land that's being affected by this condition. One of the possible benefits for people that have sickle cell is that they do not contract malaria. Globally, 300 to 500 million people are affected by malaria each year, and out of that number, 1 million people die from it. People with two copies of this sickle cell gene develop sickle cell anemia, while people with only one copy of the gene have a much milder form of the disease. Their cells sickle only under abnormal conditions, such as when they have malaria. And this enhances the macrophages, which are the white blood cells' ability to go and destroy the infected red blood cells and the parasites they contain.

As for treatment, during an acute crisis, a blood transfusion may be administered. Nitric oxide, when administered, also dilates blood vessels. There are also several treatment options available that focus on preventing the red blood from sickling. Fetal hemoglobin doesn't sickle, even in those people that are destined to have sickle cell anemia. So a drug called hydroxyurea, which is used to treat chronic leukemia, switches this fetal hemoglobin gene back on. Other treatment options include stem cell transplants and gene therapy to deliver genes for synthesizing normal beta chains. Another option being investigated is administering oral arginine to stimulate nitric oxide production for vasodilation.

So in this slide over here, here's a picture of a normal red blood cell, and this is a picture of a sickled red blood cell. So again, remember what's being affected is the globin chain. And when you look over here, remember we said there's 120 amino acid chain, and at this sixth amino acid over here, notice what it is. This is glutamine. So when you look over here, now it's valine. So this is what causes this entire problem. Just one amino acid ends up changing the entire shape of this red blood cell. So that's it for the anemias.

Now we move on to polycythemia. And as was mentioned earlier, this is an abnormal excess of red blood cells. And what, what this does is that it increases the blood's thickness, or its viscosity. Now, why is this a problem? Here's an example. If you have a glass of water in one hand and you have an empty glass in the other, and you want to pour it, that water is going to flow from one glass to the other quite freely, quite easily. You're not going to have to put much effort to it. Now, on the other hand, if you have a jar of honey in one hand and an empty jar on the other, and you wanted to transfer some of that honey to that empty jar, think about what's going to happen when you tilt that jar. The honey is going to come out very slowly. So a lot of effort is going to be required. You're going to have to be waiting, you may need even need to take a spoon to move that honey from one jar to the other. So similarly, in the body, while we don't have spoons to help move the blood flow through, what's going to happen is the blood becomes very sluggish as it's traveling through the blood vessels.

Polycythemia vera is a bone marrow cancer, and this causes an excess production of red blood cells. People that have this disease, their red blood cell count will be 8 to 10 million per microliter, and their hematocrit could go up to as high as 80%. And blood volumes can double in individuals that have this disease. So what needs to be done is to remove that extra blood. How is that done? Through therapeutic phlebotomy. In other words, they're just drawing blood out.

Secondary polycythemia is caused when less oxygen is available or EPO production is increased. And we see this in individuals that are living at higher altitudes. So when the body is not receiving enough oxygen because the oxygen concentration is much lower at higher altitudes. So when you're looking at the mountain areas, the body is going to, going to naturally increase the production of EPO to produce more red blood cells. So in these individuals, it's very common to see RBC counts of about 6 to 8 million per microliter of blood. And I'm not sure if the book gives you a normal range for a healthy red blood cell count, but it could be anywhere from 4 to 6 million red blood cells per microliter of blood.

Blood doping is practiced by athletes, usually that are involved in aerobic events. And what they do is they remove blood from themselves and then they store it for a few days, and then on the day of the event that they have, they end up injecting that blood back in. So what's happening is this, from the time that they remove the blood, the body is going to start producing that blood that's been taken out. So again, in two or three days' time, the body replenishes that blood that's been removed. Now, on the day of the event, remember, the athlete ends up injecting that blood that they took out back into themselves. So now what ends up happening is they have a higher amount of red blood cells that are present. So they end up having this extra boost, or they end up having this extra edge, uh, to help them get through this competition. Why? Because they have a lot more blood cells that are, you know, carrying oxygen, delivering oxygen to the tissue in their body. Now, this practice is banned in the Olympics and a lot of other, uh, professional sporting, uh, events. So, uh, this is unethical. But aside from that, remember, it comes with, uh, health risks that we discussed earlier in the lecture. You have an increased chance of a stroke or a heart attack. So this practice should not be done. The risks do not outweigh the rewards, and it is unethical.

And that's all for red blood cells. So I'm going to stop it over here, and then we're going to continue with the rest of the chapter in Part B. So if you like this video, please be sure to give it a thumbs up. Also, let your friends know, your classmates, your instructors, anybody who you think that may find this lecture helpful. If you haven't subscribed, please be sure to subscribe. Hit that like button, uh, or that subscribe button down now. And also, if you have questions, please email me directly, or you can leave it in the comments below. Thank you so much for watching, guys.