 This video will cover the following objective from Physiology of Blood Hematology. Define and describe the process of hematopoiesis, Define anemia, polycythemia, and leukocytosis. Hematopoiesis is the formation of the blood cells from stem cells in the red bone marrow, which are known as hemopoietic stem cells. Hemopoietic stem cells are a type of multi-potent stem cell in that they can differentiate to produce a wide variety of different cells. The hematopoietic stem cells can differentiate into all of the formed elements of blood. Here we see the process of erythropoiesis, which is the formation of erythrocytes, where the hematopoietic stem cell differentiates into a more restricted lineage to produce the myeloid stem cell that then becomes an erythroblast, and then the erythroblast starts producing large amounts of the protein hemoglobin, filling the cytoplasm, and erythroblast will then eject their nucleus in order to make more space for hemoglobin. And when this occurs, the erythroblast differentiates into a reticulocyte. Then the reticulocytes migrate out of the bone marrow into blood, where they mature into erythrocytes. Then erythrocytes circulate in the blood transporting oxygen and carbon dioxide for approximately 120 days. After their life cycle when an erythrocyte becomes worn out, macrophages in the liver and spleen perform phagocytosis to engulf the worn out erythrocytes, and then the worn out erythrocytes are broken down inside of the lysosome. The amino acids from the globin polypeptides of hemoglobin can be recycled to build new proteins, and the heme groups are taken from hemoglobin and then need to be broken down and excreted from the body. The hematopoietic stem cell, which is also known as a hemocytoblast, is a multi-potent cell that can differentiate to form all of the formed elements of blood. In the first step of differentiation, the hematopoietic stem cell can form either a myeloid stem cell or a lymphoid stem cell. The myeloid stem cells are restricted in their fate. They cannot form the lymphocytes, but myeloid stem cells can form platelets, erythrocytes, basophils, neutrophils, eosinophils, and monocytes. In contrast, the lymphoid stem cell forms all of the lymphocytes, including the B lymphocytes, T lymphocytes, and another type of lymphocyte called a natural killer cell that's important for the innate immunity. So a myeloid stem cell will further differentiate into immature cells called megakaryoblasts that can further mature into megakaryocytes that form the platelets or thrombocytes as cytoplasmic fragments from the megakaryocytes that are found in the red bone marrow. The pro-erythroblast are the immature cells that differentiate into reticulocytes and then the reticulocytes further mature into erythrocytes. A myeloblast is a stem cell that can differentiate into any of the granulocytes of blood, basophils, neutrophils, or eosinophils. Whereas a monoblast is an immature cell that can mature into a monocyte and then monocytes can travel through the blood, helping to defend against infection. And when a monocyte leaves the blood and enters into another tissue, it can differentiate into a macrophage. The lymphoid stem cell differentiates into a lymphoblast, an immature lymphocyte, and then a lymphoblast can differentiate to form natural killer cells, T lymphocytes, and B lymphocytes. The process of hematopoiesis is regulated by hormones. For example, the hormone erythropoietin, commonly abbreviated EPO, is a glycoprotein hormone secreted by the kidneys in response to low oxygen levels. So low blood oxygen levels are also known as hypoxia. In response to hypoxia, the kidney releases EPO, erythropoietin, and then EPO stimulates the process of erythropoiesis in the red bone marrow. So this functions as a homeostatic control mechanism in order to maintain the blood oxygen concentration. However, erythropoietin is abused as a performance enhancing drug by some athletes in order to increase the oxygen delivery to tissues throughout the body. This is referred to as blood doping and the use of erythropoietin for blood doping to gain a competitive edge has been banned in most organized sports. However, erythropoietin is used therapeutically as a medication to treat certain forms of anemia. Another hormone regulating hematopoiesis is known as thrombopoietin. Thrombopoietin, or THPO, is produced by the liver and stimulates the production of thrombocytes in the red bone marrow. Cytokines is a group of other hormones and paracrine signaling proteins that have important functions in regulating the production of leukocytes and also regulating the functions of leukocytes. These cytokines are all glycoproteins that are secreted by a wide variety of cells throughout the body. Many of the cytokines are secreted by leukocytes, but cytokines are also produced by other cells. Your adipose tissue and the cells in your liver and skeletal muscles can all secrete cytokines as a way of regulating the functions of the leukocytes in the immune system. There are lots of specific cytokines, but all of those cytokines are glycoproteins and most of them are involved in regulating the immune system by binding to receptors on the surface of leukocytes. Here we see two specific examples of cytokines, interleukin-3 and interleukin-7 are cytokines that are involved in regulating the differentiation of multipotent hematopoietic stem cells to form the myeloid stem cells and lymphoid stem cells. The cytokine interleukin-3 stimulates the differentiation of the hematopoietic stem cells into myeloid stem cells, whereas the cytokine interleukin-7 stimulates the differentiation of hematopoietic stem cells to form lymphoid stem cells. Sickle cell anemia is a specific form of anemia resulting from a mutation in the gene for the hemoglobin protein. Anemia is a decreased number of erythrocytes in the blood leading to a low oxygen carrying capacity of the blood. There are many different causes of anemia, but one of them is a genetic cause. Sickle cell anemia is a genetic form of anemia where mutation in the hemoglobin gene leads to a change in the structure of hemoglobin, which causes the hemoglobin to clump and affect the shape of the erythrocyte, making the erythrocyte a sickle shape, which is a more fragile cell shape and also more prone to clumping together. These erythrocytes are weak and break down easily in circulation, which leads to a lower number of erythrocytes in the blood of patients with sickle cell anemia. Anemia can be diagnosed by measuring the number of erythrocytes relative to the total volume of blood. A normal hematocrit for men is between 42 and 52%, whereas the normal hematocrit for women is between 37 and 47%. A hematocrit reading below that normal range is diagnostic for anemia. In contrast, an elevated hematocrit indicates polycythemia. Polycythemia is an increased number of erythrocytes. A mild form of polycythemia could be caused by dehydration. Another form of polycythemia can result from exposure to high altitude, as the low partial pressure of oxygen stimulates the kidneys to produce more erythropoietin. This can stimulate increased erythropoiesis leading to polycythemia. Another cause of polycythemia is genetic. There's a rare form of bone marrow cancer called polycythemia vera, where mutations in the genes that are controlling the production of erythrocytes are leading to increased erythropoiesis, stimulating the production of excess erythrocytes and an uncontrolled cell division process leading to polycythemia. Leucocytosis is an elevated number of white blood cells or leukocytes in the blood. Leucocytosis is a fairly common sign of infection, so the image of blood in the center here shows us the leukocytosis associated with a bacterial infection, where a high number of neutrophils are seen in the blood. An elevated number of neutrophils is a common result from a bacterial infection. Leucocytosis can be seen in a wide variety of infections, and there's several different types of leukocytosis, depending on which specific lineage of leukocytes is elevated. The image on the left shows us an example of a type of leukemia where there's a large number of monocytes in the blood. And so leukemia is a cancer of the bone marrow, and in this specific type of leukemia, the myeloid stem cells that form the monoblasts and monocytes are cancerous and starting to divide uncontrolled and leading to excessive production of monocytes. And as a large number of monocytes are produced, there will be a smaller number of erythrocytes and other cells that can be produced in the bone marrow as the majority of the stem cells and the majority of the space in the bone marrow is being filled with the cancer producing monocytes.