1.1-Hematopoiesis

Hematopoiesis: Erythropoiesis Overview

  • Erythropoiesis is the process through which red blood cells (RBCs) are produced from bone marrow precursors.

  • Key stages include: Rubriblast, Prorubricyte, Rubricyte, Metarubricyte, Reticulocyte, and Mature RBC.

Rubriblast (Proerythroblast)

  • Duration in Bone Marrow: Stays for about 24 hours.

  • Maturation: Takes 5-7 days for a rubriblast to mature into an RBC; involves 3-5 mitotic divisions.

  • Size: Approximately 17-25 µm. Identification relies on cytoplasmic and nuclear characteristics rather than size.

  • Cytoplasmic Appearance: Basophilic (blue) as hemoglobin begins to develop.

  • Nuclear Characteristics: Round to oval nucleus with 1-2 visible nucleoli, fine chromatin material evenly distributed.

  • N:C Ratio: High ratio of 8:1 that decreases as maturation occurs.

  • Cell Division: Divides once to produce two prorubricytes.

Prorubricyte (Basophilic Erythroblast)

  • Consensus Nomenclature: Prorubricyte (Rubri), Basophilic Erythroblast (Erlich), Basophilic Normoblast (Normo).

  • Size: 15-17 µm.

  • Cytoplasmic Color: Blue with potential deeper hue upon staining.

  • Nuclear Characteristics: Chromatin begins to condense with visible clumps at the nuclear periphery; no visible nucleoli.

  • N:C Ratio: Approximately 6:1.

  • Division: Each prorubricyte divides twice to produce 8 rubricytes.

Rubricyte (Polychromatophilic Erythroblast)

  • Duration in Bone Marrow: About 30 hours.

  • Size: 12-15 µm.

  • Cytoplasm: Reddish-blue (polychromatophilic) indicating developed hemoglobin.

  • Nuclear Characteristics: Moderately compact chromatin.

  • N:C Ratio: 4:1 indicating a maturation phase.

  • Division: Undergoes one division leading to 16 metarubricytes.

Metarubricyte (Orthochromatophilic Erythroblast)

  • Duration in Bone Marrow: Approximately 48 hours.

  • Size: 8-12 µm.

  • Cytoplasm: Red-blue-grayish appearance; advanced hemoglobin development.

  • Nuclear Characteristics: Highly compact chromatin; last stage with a nucleus.

  • N:C Ratio: 1:2, reflecting near maturity.

  • Division: Does not divide further; nucleus eventually extruded as a pyrenocyte.

Reticulocyte (Polychromatophilic Normocyte)

  • Nomenclature: Polychromatophilic Erythrocyte (Erlich), Polychromatophilic Normocyte (Normo).

  • Size: 8-12 µm, slightly larger than mature RBCs.

  • Cytoplasm: Purple-red-blue (polychromasia) due to ongoing hemoglobin synthesis; no central pallor.

  • Nuclear Characteristics: Karyorrhexis indicative of nuclear death; high chromatin density.

  • Heme Biosynthesis: Occurs throughout the maturation process with mitochondria and ribosomes present in reticulocytes.

  • Duration in Bone Marrow: About 2 days, remaining adherent to the marrow due to fibronectin.

  • Circulation Duration: 24 hours before maturation into a fully functional RBC.

Erythropoiesis Regulation

  • EPO Involvement: Stimulates early release of reticulocytes in response to hypoxia; increases reticulocyte count in anemia, leading to reticulocytosis.

  • Reticulocyte Count: Normal adult range is 0.5-1.5%; elevated in hypoxia.

  • MCV: Average volume measured to indicate size of RBC. Macrocytosis and microcytosis conditions referenced based on the MCV readings.

Apoptosis in Erythropoiesis

  • Cell Cycle Regulation: EPO prevents programmed cell death in immature RBC precursors to support hematopoiesis.

  • Fas Ligand Mechanism: Immature cells show interaction where FasL from mature RBCs can lead to apoptosis in immature precursors when EPO is low.

Mature Red Blood Cell (Erythrocyte)

  • Nomenclature: Normocyte (Normo).

  • Size: 6-8 µm, with central pallor not exceeding 1/3 of the cell diameter.

  • Cytoplasm Color: Red due to full hemoglobin content; absence of inclusions or basophilia.

  • Lifespan: Approximately 120 days before undergoing senescence and recycling.

Red Blood Cell Morphology and Indices

  • MCV and MCHC Classifications:

    • <80 fL: Microcytic; associated with iron deficiency;

    • 80-100 fL: Normocytic; reflective of several possible anemia types;

    • 100 fL: Macrocytic; indicative of megaloblastic anemia or chronic liver disease.

  • Conditions Related to RBC Indices: Detailed analysis of specific anemias based on indices provides insights into pathophysiological states.

Questions for Review

  1. Identify the most mature normoblast among provided options.

  2. Determine the characteristic of late rubricyte.

  3. Understand relations of EPO effects concerning normoblastic divisions.