Hematopoiesis and Blood Cell Production

Hematopoiesis

• Hematopoiesis is the process of blood cell production from precursor cells
• It begins with hematopoietic stem cells
• The process is crucial for maintaining metabolism and the immune system

Learning Outcomes

• Explain prenatal and postnatal hematopoiesis
• Classify the stages of hematopoiesis (erythropoiesis, granulocytopoiesis, monocytopoiesis, platelet formation, lymphopoiesis) and explain relevant clinical correlations

Cell Types

• Progenitor cells are the precursors to various blood cell lines, each with a specific suffix ("-blast")
• Granulocytes (neutrophils, eosinophils, basophils), monocytes, lymphocytes, erythrocytes, and megakaryocytes are the primary blood cell types produced in the bone marrow.
• Mesenchymal stem cells in the bone marrow give rise to non-hematopoietic cells (bone, cartilage, muscle, and fat cells)

Haematopoiesis

• The process during the first trimester of fetal development occurs in specialized areas of the yolk sac called hematopoietic islands.
• This stage is known as the yolk-sac stage
• It is the first site in early development where blood cells are produced
• The liver becomes the main site of blood cell production(hemopoietic centers) during the second trimester (Hepatic Stage).
• A small amount of blood cell production also takes place in the spleen
• During the 7th month of pregnancy, the bone marrow becomes the primary organ for hematopoiesis (blood cell production) that continues throughout adulthood (Bone Marrow Stage).

Bone Marrow

• Under normal conditions, blood cells are produced by the bone marrow in the medullary cavities of long bones and the small spaces of flat bones.
• Red bone marrow is rich in blood cells and hematopoietic cells, which gives it its red color.
• Yellow bone marrow is filled with adipocytes (fat cells) and has fewer hematopoietic cells.
• In newborns, all bone marrow is red and actively participates in blood cell production
• As a person grows, most of the bone marrow turns into yellow bone marrow.
• In certain situations (severe bleeding or hypoxia), yellow marrow can reverts back to red bone marrow to increase blood cell production
• Bone marrow consists of two main parts.
• Stromal section: Consists of fat cells, fibroblasts, stromal cells, endothelial cells of blood vessels, macrophages.
• Hematopoietic section: Includes nutrient arteries, a capillary network, and specialized sinusoids that allow blood cells to pass

Bone Marrow Stroma

• Stromal cells (also called reticular or adventitial cells) are specialized fibroblastic cells in the bone marrow
• Reticular fibers form the supportive framework that supports the hematopoietic cells and macrophages
• Macrophages phagocytose old or damaged cells which remove defective or worn-out cells

Hematopoietic Cell Section

• This section is well-vascularized, essential for supporting blood cell production
• Key components include:
• Nutrient arteries supply necessary nutrients
• Capillary network facilitates nutrient and gas exchange
• Specialized sinusoids allow blood cells to pass easily
• Hematopoietic cells are blood-forming cells, including stem cells, progenitor cells, and developing blood cells

Cell Migration

• Mature blood cells (RBCs, some WBCs, and PLTs) migrate through the endothelial layer into sinusoids via transendothelial migration.
• Immature blood cells (stem cells and progenitor cells) cannot migrate through the endothelial barrier because they lack the necessary migration capabilities.

Regulation of Hematopoiesis

• Hematopoiesis is highly regulated, involving multiple redundancies, feedback mechanisms, and pathways overlapping other physiological and pathological processes.
• The hematopoietic system is under both local and systemic control, responding rapidly to stimuli
• Blood cell production and turnover are balanced to maintain normal cell numbers(steady-state kinetics)
• Cytokines play a key role in regulating hematopoiesis, affecting cells of different lineages and various stages of differentiation

Lifespan of Mature Cells

• Varying lifespans for different blood cells (neutrophils - hours, platelets - days, erythrocytes - months, lymphocytes - years).

Bone Marrow Responses to Injury

• Bone marrow can respond to injury with changes affecting hematopoietic function including:
• Hyperplasia (increased cell number)
• Hypertrophy (increased cell size)
• Myelophthisis (replacement of hematopoietic tissue by abnormal cells)
• Hypoplasia/aplasia (decreased or absent hematopoietic tissue)
• Myelofibrosis (bone marrow fibrosis)
• Bone Marrow Inflammation
• Myeloid metaplasia (blood cell production outside the marrow)

Histological Characteristics of Bone Marrow Cells

• Hematopoietic Stem Cells: small, round cells with a high nuclear-to-cytoplasm ratio
• Progenitor Cells: larger than stem cells, less nucleocytoplasmic ratio
• Erythroblasts: Round cells with a large, dark nucleus; cytoplasm with ribosomal RNA
• Myeloblasts: Large, round cells with a large nucleus; cytoplasm with no granules
• Megakaryocytes: Very large cells with multilobed nuclei
• Macrophages: Large, irregular cells with abundant pale cytoplasm and vacuoles.

Myeloid Cells (CMP)

• Erythrocytes are red blood cells that carry oxygen.
• Megakaryocytes produce platelets to involve in blood clotting.
• Basophils are white blood cells involved in allergic reactions and inflammation.
• Eosinophils play a role in fighting parasitic infections and allergic responses.

Granulocytic (Leukocytic) Series (Granulopoiesis)

• Process that differentiates cells from granulocytes and agranulocytes series which involved cytoplasmic changes dominated by protein synthesis or azurophilic granules and specific granules.
• Granulocytes-macrophage CFU is the precursor for neutrophils and macrophages.

Lymphocytes/Lymphopoiesis

• Lymphocyte precursor cells originate from the bone marrow.
• Some lymphocytes migrate to the thymus to acquire the characteristics of T lymphocytes, then migrate to lymphoid tissues to become effector cells.
• B lymphocytes mature in the bone marrow.
• Lymphoblasts are the earliest identifiable lymphoid precursors cells dividing 2-3 times to form mature lymphocytes.

Platelets (Thrombocytes)

• Thrombopoiesis is the production of platelets, which play a key role in primary hemostasis, coagulation, and inflammation.
• Thrombopoietin (Tpo) is the main regulator of thrombopoiesis and is primarily synthesized in the liver.
• Tpo is produced at a constant rate; when platelet mass is low, more Tpo is free in plasma, stimulating thrombopoiesis

Platelet Formation

• The precursor megakaryoblast differentiates from the megakaryocyte CFU. The intermediate megakaryocytes contain an irregularly lobed nucleus (endomitosis).

Erythroid Series

• The maturation of red blood cells (RBCs), forming small, anucleate, biconcave blood cells.
• The regulator of erythropoiesis is erythropoietin (EPO), a hormone produced by the kidneys in response to low oxygen levels (hypoxia).
• EPO stimulates the bone marrow to increase red blood cell production
• Includes stages proerythroblast, basophilic erythroblast, polychromatophilic erythroblast, orthochromatic erythroblast, reticulocyte, and erythrocyte.

Monocytes

• Differentiates from granulocyte-macrophage precursor cells (GM-CFU), toward the monoblast lineage which gives rise to monocytes.
• GM-CFU directs cells to the monoblast lineage where M-CSF receptor is specific to monocyte series.
• Precursor cells of monocytes and lymphocytes do not exhibit specific cytoplasmic granules or nuclear segmentation.
• Monoblasts is structurally similar to myeloblasts, with large and basophilic nuclei.

Test your knowledge on hematopoiesis and the processes involved in blood cell production during fetal development and adulthood. This quiz covers key concepts such as the primary sites of blood cell production, the functions of stem cells, and the types of cells involved in the formation of blood components.