Hematopoiesis Hematopoiesis is the formation of blood cells. The liver is the major hematopoietic organ of the fetus, but then the stem cells migrate to the bone marrow. The hematopoietic stem cells form a population of relatively undifferentiated, multi-potent stem cells that give rise to all of the specialized blood cells. The hematopoietic stem cells are self-renewing, duplicating themselves by mitosis. Erythropoiesis refers to the formation of erythrocytes, and leukopoiesis to the formation of leukocytes. The bone marrow produces all of the different types of blood cells; the lymphoid tissue produces lymphocytes derived from cells that originated in the bone marrow. 1

The earliest cells that can be distinguished under a microscope are the erythroblasts (which become erythrocytes), myeloblasts (which become granular leukocytes), lymphoblasts (which form lymphocytes), and monoblasts (which form monocytes). Agranular leukocytes remain functional for 100 to 300 days under normal conditions. Granular leukocytes, by contrast, have an extremely short life span of 12 hours to 3 days. The production of different subtypes of leukocytes is stimulated by cytokines, which are secreted by various cells of the immune system. The production of red blood cells is stimulated by the hormone erythropoietin, which is secreted by the kidneys. Thrombopoietin stimulates proliferation of megakaryocytes and their maturation into platelets. 2

3 Regulation of Leukopoiesis The cytokines known as multipotent growth factor-1, IL-1, and IL-3 have general effects, stimulating the development of different types of white blood cells. Granulocyte colony-stimulating factor (G-CSF) specifically stimulate the development of neutrophils. Granulocyte-monocyte colony-stimulating factor (GM-CSF) stimulates the development of monocytes and eosinophils. Regulation of Erythropoiesis The primary regulator of erythropoiesis is erythropoietin, secreted by the kidneys whenever blood oxygen levels are decreased.

4 An increased secretion of erythropoietin and production of new RBCs occurs when a person is at a high altitude or has lung disease, which are conditions that reduce the oxygen content of the blood. The stages of erythropoiesis. The proliferation and differentiation of cells that will become mature erythrocytes (red blood cells) occurs in the bone marrow and is stimulated by the hormone erythropoietin, secreted by the kidneys.

5 Reticulocyte normally stays in the bone marrow for 2 days and then circulates in the blood on the third day. The production of RBCs and synthesis of hemoglobin depends on the supply of iron, along with that of vitamin B 12 and folic acid. There are no normal mechanisms for the elimination of iron, other than by menstruation. ABO System Red blood cell antigens are of extreme clinical importance because their types must be matched between donors and recipients for blood transfusions. There are several groups of red blood cell antigens, but the major group is known as the ABO system.

6 A person may be type A (with only A antigens), type B (with only B antigens), type AB (with both A and B antigens), or type O (with neither A nor B antigens). Each person inherits two genes (one from each parent) that control the production of the ABO antigens. The genes for A or B antigens are dominant to the gene for O. A person who is type B may have the genotype BB or BO. A person who is type O may have the genotype OO. A person who is type AB may have the genotype AB. A person who is type A may have the genotype AA or AO.

7 People who are type A, for example do make antibodies against the B antigen and, conversely, people with blood type B make antibodies against the A antigen. This is believed to result from that antibodies made in response to some common bacteria cross-react with the A or B antigens. People who are type AB do not produce either anti-A or anti-B antibodies. Those who are type O have both anti-A and anti-B antibodies in their plasma. The ABO System of Red Blood Cell Antigens.

8 Transfusion Reactions Before transfusions are performed, a major cross-match is made by mixing serum from the recipient with blood cells from the donor. If the types do not match—if the donor is type A, for example, and the recipient is type B—the recipient’s antibodies form bridges that cause donor cells to clump together, or agglutinate. Transfusion errors can lead to blockage of small blood vessels and cause hemolysis, which may damage the kidneys and other organs. In emergencies, type O blood has been given to people who are type A, B, AB, or O, because type O red blood cells lack A and B antigens. Type O is a universal donor and type AB people are universal recipients. The use of the universal donor and recipient concept is strongly discouraged in practice.

9 Rh Factor Rh factor is another group of antigens found on the red blood cells of most people. It is often termed D antigen. If Rh antigen is present on a person’s RBCs, the person is Rh positive; if it is absent, the person is Rh negative. The Rh factor is of particular significance when Rh- negative mothers give birth to Rh-positive babies. At the time of birth blood mixing may occur, and the mother’s immune system may become sensitized and produce antibodies against the Rh antigen of the fetus. If the woman does produce antibodies against the Rh factor, these antibodies could cross the placenta in subsequent pregnancies and cause hemolysis of the Rh-positive RBCs of the fetus.