Hematopoiesis L02 PDF

6/28/2024 Chapter 4 Hematopoiesis Preamble PowerPoints are a general overview and are provided to help students take notes over the video lecture ONLY. PowerPoints DO NOT cover the detail...

6/28/2024 Chapter 4 Hematopoiesis Preamble PowerPoints are a general overview and are provided to help students take notes over the video lecture ONLY. PowerPoints DO NOT cover the details needed for the Unit exam Each student is responsible for READING the TEXTBOOK for details to answer the UNIT OBJECTIVES Unit Objectives are your study guide (not this PowerPoint) Test questions cover the details of UNIT OBJECTIVES found only in your Textbook! 1  6/28/2024 Introduction Hematopoiesis is the process of blood cell production, differentiation, and development. The hematopoietic system consists of the bone marrow, liver, spleen, lymph nodes, and thymus in a developing adult. Fetal hematopoiesis also takes place in the yolk sac, aorta-gonad-mesonephros (AGM) region, fetal liver, and bone marrow. Phases of Hematopoiesis #1 The Embryonic Phase Primitive hematopoiesis takes place in the yolk sac in blood islands. Begins approximately on day 19 postconception and continues until week 8 of gestation. Cells produced: erythrocytes, macrophages, and platelets. Erythrocytes contain Gower and Portland hemoglobin. 2  6/28/2024 Phases of Hematopoiesis #2 The Fetal Hepatic Phase Begins at 5 to 7 weeks postconception and continue until approximately 24 weeks of gestation (6th month). Peak hematopoiesis is approximately 3 months of gestation. Clusters of erythroblasts, granulocytes, and monocytes colonize the fetal liver to eventually mobilize to the bone marrow. Microenvironment conducive to hematopoiesis is created by different cell populations that produce cytokines and chemoattractants to the liver. Spleen, thymus, and lymph nodes contribute to hematopoiesis during this phase. Phases of Hematopoiesis #3 The Medullary (or Myeloid) Phase Bones are large enough to have marrow cavities. Fifth month the bone marrow takes on its role and the chief organ of hematopoiesis in the adult with the liver and spleen acting as supplementary organs of hematopoiesis when the need arises (extramedullary hematopoiesis). Erythropoietin (EPO), granulocyte colony–stimulating factor (G-CSF), and granulocyte-monocyte colony– stimulating factor (GM-CSF) are present. M:E ratio is 3:1 at this stage. 3  6/28/2024 Hematopoietic Organs and Tissues Hematopoietic system includes bone marrow thymus liver spleen lymph nodes Origin of Blood Cells Stem cell – first in sequence of steps in hematopoietic cell generation and maturation. Progenitor of all blood cells is multipotential hematopoietic stem cell Three types of stem cells exist: Totipotential stem cells: These cells are present in the first few hours after an ovum is fertilized. Totipotential stem cells, the most versatile type of stem cell, can develop into any human cell type, including development from embryo into fetus. Pluripotential stem cells: These cells are present several days after fertilization. Pluripotent stem cells can develop into any cell type, except they cannot develop into a fetus. Multipotential stem cells: These cells are derived from pluripotent stem cells. They can be found in adults, but they are limited to specific types of cells to form tissues. For example, bone marrow stem cells can produce all type of blood cells, bone cartilage, and adipose (fat) cells. 4  6/28/2024 Cellular Elements of Bone Marrow #1 Cellular Elements of Bone Marrow #2 Hematopoietic cells can be divided into four phases according to cell maturity: Primitive, multipotential cells. The most immature group capable of self-renewal and differentiation into all blood cell lines. Intermediate cells (committed progenitors). This group consists of committed progenitor cells destined to develop into distinct cell lines. Precursors: Give rise to mature cells; morphologically distinguishable in bone marrow and peripheral circulation. Mature cells. The most developed group with specific physiologic functions. 5  6/28/2024 Hematopoietic Progenitor Cells (HPCs) #1 Hematopoietic Progenitor Cells (HPCs) #2 Erythropoiesis Erythropoiesis occurs in distinct anatomical sites called erythropoietic islands, specialized niches in which erythroid precursors proliferate, differentiate, and enucleate. Each island consists of an iron-laden macrophage surrounded by a cluster of erythroblasts. Within each island, cell-cell and cell-extracellular matrix adhesion, positive and negative regulatory feedback, and central macrophage function occur. 6  6/28/2024 Hematopoietic Progenitor Cells (HPCs) #3 Granulopoiesis Myeloid cells account for 23% to 85% of the nucleated cells in normal bone marrow. Early cells are located in the cords and around bone trabeculae. Neutrophils in the BM reside in the proliferating pool and the maturation storage pool. Need 3 to 6 days in the proliferating pool to mature. If needed, the cells from the storage pool can enter peripheral circulation and have a life span of 6 to 10 hours. Hematopoietic Progenitor Cells (HPCs) #4 Lymphopoiesis Unlike other cell lines, lymphocytes and plasma cells are produced in lymphoid follicles. Plasma cells are located along the vascular wall. Lymphoid cells typically account for 1% to 5% of the nucleated cells in the normal BM. 7  6/28/2024 Hematopoietic Progenitor Cells (HPCs) #5 Megakaryopoiesis Megakaryopoiesis takes place adjacent to the sinus endothelium. Megakaryocytes protrude through the vascular wall as small cytoplasmic processes to deliver platelets into blood. Take approximately 5 days to develop. Hematopoietic Progenitor Cells (HPCs) #6 Other cells found in bone marrow Marrow stromal cells The meshwork of stromal cells is composed of reticulum cells, histiocytes, adipose cells, and endothelial cells. Mast cells Tissue mast cells, a connective tissue cell of mesenchymal origin, are normally observed in bone marrow. 8  6/28/2024 Hematopoietic Progenitor Cells (HPCs) #7 Macrophages Macrophages, also called reticulum cells or histiocytes, appear as large cells in the bone marrow. Bone cells Osteoblasts are bone matrix–synthesizing cells that resemble plasma cells and are usually observed in groups. Interleukins #1 Protein molecules that work in conjunction with hematopoietic growth factors to stimulate proliferation and differentiation of specific cell lines are the interleukins. Interleukins are cytokines that act independently or in conjunction with other interleukins to encourage hematopoietic growth. Interleukins are cell signaling molecules and a part of the cytokine super family of signaling molecules. 9  6/28/2024 Cytokines Proteins produced by many different types of cells. Cytokines include: Interleukins Colony-stimulating factors Interferons Cytokines: Bind to their receptors on the surface of a target cell Induce intracellular signaling to the target cell for survival, proliferation, or differentiation responses to initiate a signaling pathway Interleukins #2 Protein molecules with complex functions including blood cell proliferation, maturation, migration, and adhesion. Method of immune cross talk and communication. Primary messengers and directors of the immune system. There are currently 35 well-known interleukins; however, there are many more to be found and characterized. 10  6/28/2024 Hematopoietic Growth Factors #1 Each hematopoietic growth factor is encoded by a single gene. Chromosome 7: EPO Chromosome 17: G-CSF Regulate the proliferation and differentiation of HPCs as well as regulating the survival and function of mature blood cells. Synthesized in the lab and being used in clinical trials to patients with depleting cell counts associated with chemotherapy. Hematopoietic Growth Factors #2 Examples of various factors and the target cells include the following: G-CSF and GM-CSF predominantly affect myeloid cells IL-7 stimulates T and B lymphocytes IL-12 targets natural killer cells Capable of mobilizing HPCs to peripheral circulation 11  6/28/2024 Video Summary of Hematopoiesis 23 Examination of Maturing Blood Cells A comprehensive examination of bone marrow involves examination of both bone marrow smears and histological tissue sections. It is also important to evaluate morphology in both bone marrow and peripheral blood. 12  6/28/2024 General Cellular Characteristics The identification and stage of maturation of stained blood cells can be guided by a variety of systematic features. Two important characteristics to observe initially in cell identification are as follows: Overall cell size Nuclear-cytoplasmic ratio (N:C Ration) Nuclear Characteristics #1 Nuclear characteristics play an important role in cell identification. Important features of the nucleus include the following: 1. Chromatin pattern 2. Nuclear shape 3. The presence of nucleoli 13  6/28/2024 Nuclear Characteristics #2 Chromatin patterns Lymphocytes exhibit a smooth or homogeneous pattern of chromatin throughout development until the mature stage, when clumped heterochromatin is more obvious. Granulocytes progress from having a fine to a highly clumped pattern. Monocytes have a lacy pattern, which becomes finer as the cell matures. Erythrocytes continue to develop a more clumped pattern as maturation progresses, until the extremely dense (pyknotic) nucleus is lost (extruded) from the mature cell. Nuclear Characteristics #3 Nuclear shape Lymphocytes usually continue to have a round or oval nucleus. Some cells may have a small cleft in the nucleus. Monocytes have a kidney bean–shaped nucleus, but folded or horseshoe shapes are common. Mature neutrophils, eosinophils, and basophils have segmented nuclei attached to one another by fine filaments. The number of distinctive lobes ranges from two to five depending on the cell type. 14  6/28/2024 Nuclear Characteristics #4 Presence of nucleoli The presence or absence of nucleoli is important in the identification of cells. The three cell lines of erythrocytes, leukocytes, and megakaryocytes all have nucleoli in the earliest cell stages. As cells mature, nucleoli are usually not visible. These changes in the appearance of the nucleoli are related to the rate of synthesis of ribosomal RNA. Nuclear Characteristics #5 Lymphoblasts have one or two nucleoli. Myeloblasts have one to five nucleoli. Monoblasts usually have one or two nucleoli but occasionally may have three or four. Erythroblasts may not have any nucleoli or may have up to two nucleoli that may stain darker than in other types of blast cells. Megakaryoblasts typically have one to five nucleoli. 15  6/28/2024 Cytoplasmic Characteristics #1 Staining color and intensity Variation among stages of maturation: younger cells tend to be more blue, whereas more mature cells are more pink to neutral colored. Granulation Identify both the presence and granule to identify the cell. Shape Blasts, monocytes, and megakaryocytes are most distinctive. Cytoplasmic Characteristics #2 Quantity of cytoplasm In some cell types, such as megakaryocytes, the quantity of cytoplasm increases with age. Vacuolization Vacuoles can be seen in monocytes as a normal finding. In other cell types, however, they are a sign of increasing age or abnormal conditions. Inclusion bodies Examples include Auer rods, which can aid in the identification of the cell that contains it. 16  6/28/2024 What Happens as the RBC Matures? Mature Blood Cells in Peripheral Blood 17  6/28/2024 Postamble READ the TEXTBOOK for the details to answer the UNIT OBJECTIVES. USE THE UNIT OBJECTIVES AS A STUDY GUIDE All test questions come from detailed material found in the TEXTBOOK (Not this PowerPoint) and relate back to the Unit Objectives 18