HEMATOPOIESIS (1)

UNIT II - HEMATOPOIESIS

Overview of Hematopoiesis

  • Definition: The process of blood cell production, differentiation, and development.

  • Key Phases:

    • Formation

    • Development

    • Specialization

Key Points

  • Mature blood cells have a limited lifespan but are capable of self-renewal through Hematopoietic stem cells (HSC).

Types of Human Stem Cells

  • Totipotential Stem Cells: Can develop into any cell type including those that support embryonic development.

  • Pluripotential Stem Cells: Capable of developing into most cell types.

  • Multipotential Stem Cells: Can form several different cell types within a specific lineage.

Hematopoietic Development Stages

Types of Hematopoiesis

  • Embryonic Hematopoiesis: Occurs in specific sites during early development.

  • Adult Hematopoiesis: Primarily localized to the bone marrow (BM).

Early Development of Blood Cells

  • Primitive Hematopoiesis:

    • Originates from mesoderm cells in the yolk sac.

  • Definitive Hematopoiesis:

    • Originates from the aorta-gonad-mesonephros (AGM) region.

Phases of Hematopoietic Development

  • Mesoblastic Phase: 19th day of embryonic development; blood islands in the yolk sac produce primitive erythroblasts.

    Site of primitive hematopoiesis: (Large, megaloblastic and inravascular, Retain nuclei)

    Produce hemoglobin (gower 1, gower 2, and portland)

  • Hepatic Phase: Begins at 5-7 gestational weeks in the liver, where definitive hematopoiesis starts.

  • Medullary Phase: Begins in the 4-5th month of fetal development; the bone marrow becomes the main site of hematopoiesis postnatally.

Adult Hematopoietic Tissues

  • Key Organs:

    • Bone marrow

    • Lymph nodes

    • Spleen

    • Liver

    • Thymus

Bone Marrow Characteristics

  • Found within all bones, may be yellow (inactive) or red (active).

  • In infancy, red marrow is predominant; increases in adipose tissue by age 5-7 years.

  • Represents approximately 3.5% to 6% of total body weight, averaging 1,500 g in adults.

Extramedullary Hematopoiesis

  • Ocurrs under abnormal circumstances in the liver, spleen, and lymph nodes when bone marrow is dysfunctional (e.g., in aplastic anemia).

Hematopoietic Microenvironment

  • Composed of various cell types:

    • Endothelial cells

    • Adipocytes

    • Macrophages

    • Osteoblasts

    • Osteoclasts

    • Fibroblasts

Functions of Hematopoietic Microenvironment Cells

  • Endothelial Cells: Regulate the flow of particles in hematopoietic spaces.

  • Adipocytes: Help regulate marrow volume for active hematopoiesis.

  • Macrophages: Involved in phagocytosis and cytokine secretion that regulates hematopoiesis.

Types of Erythropoiesis and Related Processes

  • Lineage Specific Hematopoiesis:

    • Erythropoiesis: Takes place in distinct anatomical sites called erythropoietic islands.

    • Granulopoiesis: Maturing cells spend 3 to 6 days in the proliferating pool, circulating for 6 to 10 hours.

    • Megakaryopoiesis: Takes place adjacent to the sinus endothelium, developing platelets in about 5 days.

Interleukins and Hematopoietic Growth Factors

  • Cytokines: Such as IL-1, IL-3, IL-6, GM-CSF, and EPO encourage hematopoietic growth, function, and survival of mature blood cells.

  • Gene Regulation: EPO is encoded by a single gene on chromosome 7; other growth factors are located on different chromosomes.

Examination of Maturing Blood Cells

Cellular Characteristics

  • General Characteristics:

    1. Overall cell size decreases with maturity.

    2. Nuclear-cytoplasmic ratio typically decreases with maturity.

Nuclear Characteristics

  • Chromatin pattern transitions from loose to clumped.

  • Distinctive nuclear shapes characterize different cell types.

  • Presence of nucleoli typically decreases with maturation.

Cytoplasmic Characteristics

  • Staining color ranges from darker blue to lighter blue.

  • Granulation evolves from none to specific granules.

  • Quantity of cytoplasm increases with age; vacuolization may occur with age.

Blood Cell Development Nomenclature

  • Normal Cell Lines:

    • Erythrocyte: Immature forms include Rubriblast, Promormoblast, etc.

    • Megakaryocyte: Involves stages from megakaryoblast to mature platelets.

    • Granulocyte and Monocyte: Includes Myeloblast, Promyelocyte, Metamyelocyte, etc.

Specific Blood Cells Functionality

  • Neutrophils: Phagocytosis, antibacterial activity, and chemotaxis; life span of 6-10 hours.

  • Eosinophils: Play a role in allergic responses and defense against parasites.

  • Basophils: Involved in hypersensitivity reactions and inflammation.

  • Monocytes: Become macrophages; involved in phagocytosis, antigen processing, and immune responses.

  • Lymphocytes: T cells, B cells, and natural killer cells involved in immune responses.