Blood Formation
Erythropoiesis is the process by which red blood cells (erythrocytes) are formed.
Location and Timing of Erythropoiesis
- Early Stages: In the early embryo, blood cells originate in the yolk sac mesoderm.
- Second Trimester: Hemopoiesis (blood cell formation) primarily occurs in the developing liver during the second trimester, with the spleen playing a minor role.
- Third Trimester Onward: As skeletal elements ossify and bone marrow develops within their medullary cavities, bone marrow becomes the primary site of hemopoiesis during the third trimester and throughout adulthood.
Stem Cells and Differentiation
- Pluripotent Stem Cells: All blood cells, including erythrocytes, arise from a single type of pluripotent stem cell located in the bone marrow. These stem cells have the capacity to self-renew and give rise to all blood cell lineages.
- Lineage Commitment: The pluripotent stem cells produce two main lineages of progenitor cells:
- Lymphoid cells: These cells differentiate into lymphocytes.
- Myeloid cells: These cells give rise to granulocytes, monocytes, erythrocytes, and megakaryocytes (which produce platelets).
Erythropoiesis: A Multi-Step Process
- 1. Proerythroblast: This is the first recognisable progenitor cell in the erythroid lineage. It is a large cell with loose chromatin, prominent nucleoli, and basophilic cytoplasm due to the abundance of ribosomes synthesising haemoglobin.
- 2. Basophilic Erythroblast: The basophilic erythroblast has even more intensely basophilic cytoplasm and a condensed nucleus.
- 3. Polychromatophilic Erythroblast: As the cell volume reduces and ribosomes decrease, areas of the cytoplasm begin to be filled with haemoglobin, leading to a mix of basophilic and acidophilic staining.
- 4. Orthochromatophilic Erythroblast (Normoblast): In this stage, the nucleus becomes highly condensed (pyknotic) and the cytoplasm is uniformly acidophilic due to the high concentration of haemoglobin.
- 5. Reticulocyte: The orthochromatophilic erythroblast ejects its nucleus, which is then phagocytosed by macrophages. The remaining cell, called a reticulocyte, still contains a few ribosomes that can be visualised with special staining techniques. Reticulocytes are released into the bloodstream.
- 6. Mature Erythrocyte: Reticulocytes mature into erythrocytes within a few days. The mature erythrocyte is a non-nucleated, biconcave disc packed with haemoglobin for oxygen transport.
Regulation of Erythropoiesis
- Erythropoietin (EPO): Erythropoiesis is primarily regulated by erythropoietin, a glycoprotein hormone produced by cells in the kidneys.
- Stimulus for EPO Production: EPO production is stimulated by low blood oxygen levels (hypoxia).
- Action of EPO: EPO acts on erythroid progenitor and precursor cells, stimulating their proliferation and differentiation and promoting haemoglobin synthesis.