Erythropoiesis is the physiological process by which the body produces red blood cells (erythrocytes).
It ensures that blood has a sufficient number of cells to transport oxygen from lungs to body’s tissues and return carbon dioxide to be exhaled
In a healthy adult, body produces approximately 2 million red blood cells every second to replace those that have reached the end of their 120-day lifespan.
Sites of Erythropoiesis
The location of red blood cell production changes throughout a person’s life:
- Early Fetus : Occurs in the yolk sac (Mesoblastic stage).
- Mid-trimester Fetus : Primarily in the liver and spleen (Hepatic stage).
- Fetus (Late) & After Birth: Transitions to the red bone marrow (Myeloid stage).
- Adults: Primarily limited to the bone marrow of the axial skeleton, such as the pelvis, vertebrae, sternum, and ribs.
Stages of Erythropoiesis
The process begins with a multipotent hematopoietic stem cell and proceeds through several distinct morphological stages.
As the cell matures, its size decreases, hemoglobin concentration increases, and the nucleus is eventually ejected.
| Stages | Key Characteristics |
| Proerythroblast | The first precursor cell with a large nucleus and no hemoglobin. |
| Basophilic Erythroblast | Intense protein synthesis; Cytoplasm stains deep blue due to high RNA content. |
| Polychromatophilic Erythroblast | Hemoglobin starts to appear, changing the staining pattern to a mix of pink and blue. |
| Orthochromatic Erythroblast | Also called a Normoblast.
Hemoglobin is abundant; the nucleus shrinks and is finally ejected. |
| Reticulocyte | An immature, anucleated cell containing a “reticulum” of ribosomal RNA.
It enters the bloodstream. |
| Erythrocyte | The fully mature, biconcave red blood cell.
It has lost all organelles and is specialized for gas transport. |
Regulation
Erythropoiesis is regulated by a negative feedback loop to maintain homeostasis.
Primary regulator is hormone erythropoietin, produced mainly by kidneys.
- When oxygen levels in the blood drop (hypoxia) due to high altitude, blood loss, or lung disease, kidneys detect the change.
- The kidneys secrete EPO into bloodstream.
- EPO travels to the bone marrow and stimulates proliferation and maturation of erythroid progenitor cells.
- The increased number of RBCs raises blood’s oxygen-carrying capacity, which inhibits further EPO release.
Essential Nutritional Factors
To build functional red blood cells, body requires specific raw materials:
- Iron: Essential for synthesis of heme group in hemoglobin.
- Vitamin B12 and Folic Acid: Necessary for DNA synthesis and cell division.
- Proteins: Required for globin chains of hemoglobin.
- Copper and Vitamin C: Assist in absorption and mobilization of iron.
Clinical Significance
Disruptions in erythropoiesis lead to various blood disorders:
- Anemia: A deficiency in RBCs or hemoglobin, often caused by iron deficiency, lack of B12 (Pernicious anemia), or kidney failure (lack of EPO).
- Polycythemia: An overproduction of RBCs, which can thicken the blood and increase the risk of clots.
Did you know? Athletes sometimes use synthetic EPO (“blood doping”) to artificially increase their red blood cell count, improving endurance by boosting oxygen delivery to muscles. This practice is banned in professional sports due to health risks and unfair advantage.