Hematopoiesis

Histology and Cell Biology Block II Notes

Instructor Information

• Dr. Dinipre B. McGregor, Assistant Professor of Histology, Cell Biology, and Genetics

Learning Objectives

• Describe the histological features of the bone marrow and correlate them with functional roles in hematopoiesis.

• Differentiate between myeloid and lymphoid lineages of hematopoietic cells based on morphology and developmental stages.

• Identify and interpret histological sections of bone marrow involved in hematopoiesis and immune cell maturation.

• Explain the microenvironment and cellular interactions in the bone marrow that regulate hematopoietic stem cell differentiation and proliferation.

Histology of Hemopoiesis

Definition of Hematopoiesis

• Formation of blood cells, which includes:

  • Erythropoiesis: Formation of red blood cells (RBCs).

  • Leukopoiesis: Formation of white blood cells (WBCs).

  • Thrombopoiesis: Formation of platelets.

• Hematopoiesis occurs primarily in the red bone marrow with peripheral function and destruction regulated by cytokines, stressors, and infections.

Phases of Hemopoiesis

Prenatal Hemopoiesis

1. Yolk Sac Phase:

   • Origin: Mesoderm of yolk sac.

   • Timeline: Begins at the 3rd week of gestation.

2. Hepatic Phase:

   • Location: Liver and spleen.

   • Timeline: From the 3rd to the 7th month of gestation.

3. Bone Marrow Phase:

   • Begins: 5th to 7th month of gestation.

   • Function: Bone marrow takes over as primary site post-birth, with the liver and spleen ceasing hemopoiesis.

Postnatal Hemopoiesis

• Red Bone Marrow Locations:

  • Axial skeleton: vertebrae, sternum, ribs.

  • Appendicular skeleton: epiphysis of long bones.

  • Site of hematopoiesis in adults.

Clinical Application Example

• A baby diagnosed with a mutation in the erythropoietin receptor gene leading to familial erythrocytosis (familial polycythemia), the primary effect on red blood cell production after birth occurs in:

  • e. Bone marrow.

Histology of Bone Marrow

Overview of Structure

• Areas include:

  • Diaphysis: Contains hemopoietic tissue, sinusoids, trabeculae.

• Cellular Components:

  • Hematopoietic islands (Erythropoietic and Haemopoletic), macrophages, reticular cells, osteoblasts, osteoclasts, pericytes, adipocytes, and endothelial cells.

Bone Marrow Components

• Sinusoids:

  • Venous vessels lined by endothelial cells that prevent the release of immature cells.

• Stromal Cells:

  • Macrophages: secrete hemopoietic growth factors.

  • Adventitial reticular cells (ARC): accumulate fat.

  • Fibroblasts: secrete hemopoietic growth factors.

Bone Marrow Histology

• Active hemopoiesis: characterized by

  • Erythroblastic islets engaged in erythrocyte formation and megakaryocytes discharging platelets into the sinusoids.

  • Endothelial cells resting on a basal lamina, absent where blood cells enter sinusoids.

  • Close proximity of hemopoietic centers to bone marrow sinusoids.

Types of Bone Marrow

Yellow Bone Marrow

• Location: Medullary cavities of the diaphysis of long bones in adults.

• Features:

  • Filled with adipocytes.

  • Contains fewer hemopoietic stem cells.

  • Hematopoietically inactive but can revert to red marrow during significant blood loss or hypoxia.

Red Bone Marrow

• Location: Epiphysis of long bones and flat/irregular cancellous bones.

• Features:

  • Hematopoietically active, site of blood cell differentiation and maturation.

  • Largest cells in bone marrow are megakaryocytes (generate platelets).

Stem Cells in Hematopoiesis

Classification of Stem Cells

• Types of Stem Cells:

  1. Totipotent Stem Cells:

  • Can differentiate into all tissue types.

  1. Pluripotent Stem Cells:

  • Differentiate into various cell types in the body.

  1. Multipotent Stem Cells:

  • Differentiate into a limited number of cell types.

  • Examples:

    • Type I: Common lymphoid stem cells (lymphoid lineage).

    • Type II: Common myeloid stem cells (myeloid lineage).

Hemopoietic Stem Cells (HSCs)

• Characteristics:

  • Able to divide by mitosis and differentiate into specialized cells.

  • Marker: CD34 – surface glycoprotein indicative of pluripotent hemopoietic stem and progenitor cells.

  • Expressed on HSCs in bone marrow, cord blood, and peripheral blood.

Progenitor Cells

• Unipotent committed cells to a single lineage forming colony-forming units (CFU).

• Differentiation into respective precursor cells.

Precursor Cell Types

• Cells in each lineage display distinct morphologic characteristics.

Hematopoietic Growth Factors

Major Hematopoietic Growth Factors

Erythropoiesis

Process of Erythropoiesis

• Begins with hemopoietic stem cells (HSCs) that undergo a series of differentiation and development stages, including proerythroblast, basophilic erythroblast, polychromatophilic erythroblast, and orthocromatic erythroblast leading to reticulocyte and finally mature erythrocytes.

• Key Features at Each Stage:

  • Proerythroblast: Large and round, contains nucleoli, begins mitosis.

  • Basophilic Erythroblast: Smaller, increases hemoglobin production.

  • Polychromatic Erythroblast: Capability of mitosis, hemoglobin fills cytoplasm.

  • Orthochromatic Erythroblast: Nucleus condenses, extruded during maturation.

Granulopoiesis

Formation of Granulocytes

• Begins from CFU-GEMM transitioning into granulocyte/monocyte progenitor cells (GMP) that lead to differentiated granulocyte types (neutrophils, eosinophils, and basophils).

• Key Cytokines/Chemokines:

  • G-CSF, GM-CSF (Granulocyte-Monocyte CSF), IL-3, and IL-5.

Monocyte and Platelet Formation

Monocyte Formation

• Begins from the CFU-M (monocyte progenitor), producing monoblasts and promonocytes, which develop into mature monocytes entering into circulation and eventually differentiating into macrophages and dendritic cells.

Platelet Formation (Thrombopoiesis)

• Initiated by CFU-Meg (megakaryocyte-committed progenitor cells) which transform into megakaryoblasts, maturing into megakaryocytes that shed platelets into the sinusoidal lumen.

• Endomitosis: Special type of cell cycle where a cell undergoes DNA replication without cytokinesis, leading to a polyploid state significant for megakaryocyte function.

Clinical Correlates

Anemia and Related Disorders

• Anemia Classification:

  • Normocytic Anemia: Normal MCV but low Hb and Hct.

  • Megaloblastic Anemia: Macrocytic lacking adequate DNA synthesis and characterized by hypersegmented neutrophils. - Microcytic Anemia: Low MCV due to defective hemoglobin synthesis.

Common Clinical Conditions

• Chronic kidney disease → decreased EPO production, leading to anemia.

• CML (Chronic Myeloid Leukemia): A myeloproliferative neoplasm associated with the BCR-ABL fusion gene.

• Thrombocytopenia: Low platelet count may lead to increased bleeding.

Key Cell Indicators

• Howell-Jolly Bodies: Indicate absent or impaired splenic function.

• Ringed Sideroblasts: Found in conditions like sideroblastic anemia indicating defects in hemoglobin synthesis.

Summary

• This study guide emphasizes the complex process of hematopoiesis, including the various stem cells, progenitor cells, and their differentiation pathways, alongside clinical correlations in understanding hematological disorders.

Thank You!

• These comprehensive notes can serve as a critical resource for understanding hematopoiesis and related histology.