18.2

18.2 Production of the Formed Elements

Learning Objectives

  • By the end of this section, you will be able to:

    • Trace the generation of the formed elements of blood from bone marrow stem cells.

    • Discuss the role of hemopoietic growth factors in promoting the production of the formed elements.

Lifespan of Formed Elements

  • Most erythrocytes (red blood cells), leukocytes (white blood cells), and platelets live only a few hours to a few weeks.

  • One type of leukocyte called memory cells can survive for years.

  • The body must continuously form new blood cells and platelets due to their brief lifespan.

  • When donating blood (approximately 475 mL or about 1 pint), the body replaces the donated plasma within 24 hours, but it takes approximately 4 to 6 weeks to replace blood cells.

  • This limits how frequently donors can contribute blood.

Hemopoiesis

  • The process of replacing blood cells is known as hemopoiesis (or hematopoiesis).

  • The term originates from the Greek roots: "haima" (blood) and "poiesis" (production).

Sites of Hemopoiesis

  • Prior to Birth: Hemopoiesis occurs in various tissues, starting with:

    • Yolk sac of the developing embryo.

    • Fetal liver.

    • Spleen.

    • Lymphatic tissue.

  • Following Birth: Most hemopoiesis occurs in the red bone marrow, a connective tissue within the spaces of spongy (cancellous) bone.

    • In children, hemopoiesis can also occur in the medullary cavity of long bones.

    • In adults, it is primarily restricted to:

    • Cranial bones

    • Pelvic bones

    • Vertebrae

    • Sternum

    • Proximal epiphyses of the femur and humerus.

  • Extramedullary Hemopoiesis:

    • This refers to hemopoiesis occurring outside the medullary cavity of adult bones, usually when bone marrow is damaged (e.g., from bone cancer).

Differentiation of Formed Elements from Stem Cells

  • All formed elements originate from stem cells in the red bone marrow.

  • Stem cells undergo mitosis plus cytokinesis to create new daughter cells:

    • One daughter cell remains a stem cell, the other differentiates into diverse cell types.

  • Stem cells exist in a hierarchical system:

    • Totipotent Stem Cells:

    • Example: Zygote (fertilized egg).

    • These cells can develop into all cell types in the human body.

    • Pluripotent Stem Cells:

    • Can give rise to multiple types of body cells and some supporting fetal membranes.

    • Mesenchymal Stem Cells:

    • Develop into connective tissue types but not epithelial, muscle, or nervous tissue.

    • Hemopoietic Stem Cells (Hemocytoblasts):

    • All formed elements of blood originate from this type of cell.

    • Differentiation Process:

    • Initiated by exposure to hemopoietic growth factors, which provoke stem cells to divide and differentiate.

    • One daughter cell remains a hemopoietic stem cell.

    • The other can become:

      • Lymphoid Stem Cells:

      • Differentiate into lymphocytes (T cells, B cells, NK cells) involved in immunity.

      • Lymphocytes migrate from bone marrow to lymphatic tissues (lymph nodes, spleen, thymus).

      • B cells mature in the bone marrow; T cells mature in the thymus.

      • Myeloid Stem Cells:

      • Differentiate into other formed elements, including:

        • Erythrocytes

        • Megakaryocytes (produce platelets)

        • Myeloblast lineage (monocytes and granular leukocytes: neutrophils, eosinophils, basophils).

Hemopoietic Growth Factors

  • The development process from stem cells to mature cells is mediated by hemopoietic growth factors:

    • Erythropoietin (EPO):

    • Glycoprotein hormone secreted by interstitial fibroblasts of the kidneys in response to low oxygen.

    • Stimulates production of erythrocytes.

    • Used in blood doping to increase RBC counts for enhanced athletic performance, banned in most sports.

    • Utilized medically to treat certain anemias and other disorders requiring increased erythrocyte counts.

    • Thrombopoietin:

    • Glycoprotein hormone produced by the liver and kidneys.

    • Triggers the development of megakaryocytes into platelets.

    • Cytokines:

    • Glycoproteins secreted by various cells (red bone marrow, leukocytes, macrophages).

    • Act as autocrine or paracrine factors, stimulate progenitor cell proliferation, and enhance immune response.

  • Subtypes of Cytokines:

    • Colony-Stimulating Factors (CSFs):

    • Act as local autocrine or paracrine factors.

    • Stimulate the differentiation of myeloblasts into granular leukocytes.

    • Different CSFs target different cell types (e.g., granulocyte CSFs for neutrophils, eosinophils, basophils).

    • Synthetic forms administered to chemotherapy patients to restore WBC counts.

    • Interleukins:

    • Another class of cytokine signaling molecules initially thought to be secreted only by leukocytes.

    • Now recognized to be produced by various cell types, including bone marrow and endothelium.

    • Important in cell differentiation, maturation, immunity, and inflammation.

    • Numerous interleukins identified, numbered IL-1, IL-2, IL-3, etc.

Blood Doping

  • Definition: Originally referred to enhancing athletic performance by injecting supplemental RBCs into individuals, increasing oxygen delivery to tissues.

  • Types of Blood Doping:

    • Autologous Transfusion: Source of cells is the individual.

    • Homologous Transfusion: Source from a compatible donor.

  • Risks:

    • Considered illegal in almost all sports.

    • Risks of infection and increased blood viscosity, which raises the chance of blood-borne pathogen transmission.

  • Synthetic EPO Use:

    • Developed in the 1980s to treat patients with anemia or renal failure.

    • Can artificially stimulate RBC production in the bone marrow, increasing hematocrit.

    • Large increases in hematocrit can lead to polycythemia and raise risks for heart issues.

    • High hematocrit levels can reach over 70, increasing blood viscosity and cardiovascular risks, including potential death.

  • Notable Case:

    • Lance Armstrong, stripped of titles due to admitted blood doping practices.

Bone Marrow Sampling and Transplants

  • **Procedures:

    • Bone Marrow Biopsy:** A diagnostic test where a sample of red bone marrow is taken for analysis.

    • Bone Marrow Transplant: A treatment where healthy bone marrow (including stem cells) replaces a patient's faulty bone marrow.

    • Commonly used for severe forms of anemia (e.g., thalassemia major, sickle cell anemia) and some cancers like leukemia.

  • Procedure for Bone Marrow Sampling:

    • Traditionally involved inserting a large-bore needle into the iliac crest of the pelvic bones, which is painful.

    • Modern methods allow for stem cell isolation from blood samples, reducing the need for invasive procedures.

  • Matching Donor Requirements:

    • Essential to prevent tissue rejection.

  • Patient Preparation for Transplants:

    • Patient's own diseased marrow must be destroyed via radiation and/or chemotherapy.

    • Healthy donor stem cells are intravenously infused, establishing themselves in the recipient's bone marrow.