Chapter 6 Hematopoiesis Hematology Unit 2 Chapter 6 Hematopoiesis Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Hematopoiesis The production of blood cells and platelets Whole blood is composed of fluids and cells Plasma – fluid portion Cells – RBCs, WBCs, and thrombocytes (platelets) White blood cells Agranulocytes – no granules present Lymphocytes Monocytes Granulocytes – granules Neutrophils Eosinophils Basophils Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

White Blood Cells White blood cells Agranulocytes Granulocytes Normally no granules present Lymphocytes Monocytes If small granules present Mononuclear leukocytes Granulocytes Granules Neutrophils Eosinophils Basophils a.k.a. polymorphonuclear leukocytes (PMNs) Segmentation or lobulation of nucleus Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Blood Cells Constantly produced Finite life span so must be replaced Life span differs by cell type and species Begin in embryonic stages Changes in processes as aging occurs Hematopoietic activity Prenatal Liver, spleen, thymus, red bone marrow Adult Primarily red bone marrow If stressed, may revert to production in liver and spleen Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Terms Erythropoiesis Leukopoiesis Thrombopoiesis Production of erythrocytes Leukopoiesis Production of leukocytes Thrombopoiesis Production of thrombocytes All involve different pathways and chemical messengers Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Pluripotent Hematopoietic Stem Cell (HSC) All cells arise from this cell Development determined by chemical messengers or cytokine HSC Common Myeloid Progenitor Cells Common Lymphoid Progenitor Cells (CMP) (CLP) Lymphocytes Erythrocytes Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Erythropoiesis Erythropoietin (EPO) Cytokine responsible for production of RBCs Produced by cells in kidneys in response to decrease in oxygen tension in blood EPO circulates in the blood to the red bone marrow Binds to receptors on erythroid precursor cells, causing them to divide and mature Lesser amounts of APO = hepatocytes Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

RBC Development EPO Erythroid precursor cells Rubriblasts Pro-rubriblasts Smaller than rubriblasts, slightly more dense basophilic cytoplasm, no visible nucleus Rubricytes Basophilic cytoplasm and clumping nucleus but changes as it matures Metarubricytes Smallest cells, condensed nucleus, and deep red cytoplasm Cannot divide and hemoglobin formation completed Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

RBC Development (cont.) Reticulocytes Immature RBCs Lose ribosomal material Small pieces remaining – punctate reticulocytes Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Thrombopoiesis Thrombopoietin Progenitor cells Produced primarily in the liver Progenitor cells Megakaryoblast Single nuclei – dark blue cytoplasm Promegakaryocyte Large cell – 2-4 nuclei Megakaryocyte Numerous nuclear lobes and reddish granules in cytoplasm Cells are very large and shear apart in blood flow Creating proplatelets Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Granulopoiesis Leukopoietin and numerous other cytokines Cells are divided into a proliferation pool Representing cell capable of mitosis Includes Myeloblasts Large with round to oval nucleus, prominent nucleolus, pale gray–blue cytoplasm Promyelocytes Large, pale-staining, prominent reddish cytoplasmic granules with no obvious nuclei Myelocytes Smaller with a round nucleus – characteristics of mature cells appear Band cells Horseshoe-shaped nucleus with parallel sides Segmented granulocytes Nuclei with 2 or more lobes Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Monopoiesis Monoblasts Promonocytes Monocytes Similar to myeloblasts but with a irregular-shaped nucleus Promonocytes Similar to myelocytes and metamyelocytes Monocytes May develop into macrophages with the right cytokines Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Lymphopoiesis Production of lymphocytes Develop T-lymphocytes B-lymphocytes Natural killer cells (NK) Develop CLP to lymphoblast and prolymphocyte stages Differentiated by B-lymphocyte precursor T-lymphocyte or NK precursor Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Lymphopoiesis (cont.) T-lymphocytes Requires certain cytokines and antibodies Juvenile B-lymphocytes Mature primarily in the bone marrow or specialized ileal Peyer patches in dogs, pigs, and ruminants or in the bursa of Fabricius in birds T-lymphocytes Mature in the thymus NK cells Mature in bone marrow but also thymus and other lymphoid tissues Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Terms -penia -philia Left-shift Leukemia Leukemoid response Decreased number of cells Neutropenia = decreased neutrophils Pancytopenia = decrease of all blood cell types -philia Increased number of cells Left-shift Increased numbers of immature neutrophils Leukemia Neoplastic cells of blood or marrow Leukemoid response Mistaken for leukemia Marked leukocytosis, usually inflammatory disease Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Summary Hematopoiesis Erythropoiesis Thrombopoiesis Leukopoiesis Granulopoiesis Monopoiesis Lymphopoiesis Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.