Hematopoiesis is the production of all the blood cells including RBCs, WBCs and platelets. Bone marrow is the major site of hematopoiesis. As the RBCs and platelets have a limited life span they need to be replaced continuously. Pluripotent stem cell, called the hematopoietic stem cell is the main type of cell which differentiates into all the blood cell lines.
Haematopoietic stem cells (HSCs) are located in the medulla of the bone marrow. They have the ability to differentiate into all of the mature blood cell types and tissues. Along with differentiation these cells also renew themselves.
As they proliferate, one of the daughter cells remain as HSC. This is called asymmetric division. Other daughter cells include myeloid and lymphoid progenitor cells, which follow the other differentiation pathways, but cannot renew themselves. This is one of the main processes in the body.
Sites of Hematopoiesis
Initially, blood formation occurs in clusters which are aggregated in the yolk sac, called the blood islands. Later this process starts in the spleen, liver and lymph nodes. With growth and development of bone marrow, the whole process is shifted to the marrow.
Still the maturation, activation, and some proliferation of the lymphoid cells occur in the spleen, thymus, and lymph nodes later in life. In children, this process occurs in the long bones such as the femur and tibia while in adults it occurs in the pelvis, cranium, vertebrae, and sternum. In some cases the extra-medullary sites also start the process of hematopoiesis again later in life. This process is called extra-medullary hematopoiesis.
Various blood cell lines are:
- Erythroid cells: These include red blood cells, which carry oxygen. Premature RBCs or reticulocytes and mature RBCs or erythrocytes are released into the blood. The reticulocyte count is used clinically to estimate the rate of erythropoiesis in the body.
- Lymphocytes: These are the major constituents of body’s immune system. They have common lymphoid progenitors. The lymphoid lineage includes T-cells, B-cells and NK cells (natural killer cells) and their production is called lymphopoiesis.
- Myelocytes: The myeloid progenitor cells differentiate further under the influence of cytokines and growth factors like CSF-colony stimulating factors. These consist of granulocytes, megakaryocytes and macrophages. They are derived from a common myeloid progenitor. They play a major role in the process of innate immunity, adaptive immunity, and blood clotting. Production of these cells is called myelopoiesis.
- Granulopoiesis (or granulocytopoiesis) is the differentiation or production of granulocytes.
- Megakaryocytopoiesis is the production of megakaryocytes.
Erythropoiesis is the production of RBCs. Decreased oxygen in the blood stimulates the production of erythropoietin in the kidneys, which promotes the process of erythropoiesis in the bone marrow. It initially occurs in the liver in the newborns; later with the maturation of bone marrow till the seventh month of life, erythropoiesis starts in the bone marrow.
The following stages of development occur within the bone marrow:
Initially, hemocytoblast, which is the multipotent hematopoietic stem cell, becomes a unipotent stem cell, which later differentiates into a pronormoblast, also called pro-erythroblast. These precursor erythrocytes further differentiate into a basophilic cell named early normoblast (also called erythroblast), then into an intermediate normoblast, and later into late normoblast.
At this stage, the nucleus is expelled before the cell becomes a reticulocyte. These cells are released into the circulation. These precursor erythrocytes are about 1% of the total RBCs. Reticulocytes after 1-2 days are converted into erythrocytes.
Proerythroblasts have mild basophilia and are of size 12-20 um in diameter. Basophilic erythroblast have strong basophilia and are of 10-15 um in diameter. Polychromatophilic erythroblasts are smaller, 12-20 um in diameter.
The process of thrombocyte production is called thrombopoiesis. Platelets are fragmentations of special cells called megakaryocytes. A single megakaryocyte can give rise to thousands of thrombocytes. Like erythropoietin, thrombopoietin stimulates megakaryopoiesis.
Megakaryopoiesis is the megakaryocyte maturation and differentiation. Intracellular signalling on stimulation of thrombopoietin promotes megakaryocyte growth and maturation. It also enhances membrane stability and promotes platelet granule formation. The cytoplasm of the megakaryocytes defines regions which fragment into mature platelets. This last step of pro-platelet process and platelet formation is independent of thrombopoietin.
The main output of this process is a neutrophil. It starts with a myeloblast which differentiates into a neutrophilic promyelocyte. These promyelocyte are relatively larger cells with purple-staining azurophilic granules (this is why they are called granulocytes).
Promyelocytes differentiate into myelocytes. Presence of small specific or secondary granules is specific for myelocytes. The number of specific granules per cell is increased during this stage while the number of azurophilic granules per cell decreases. As a result, cytoplasmic basophilia is gradually lost. The production of granule stops till the end of the myelocyte stage.
In the later stages, the reduction in cell size and a change in nuclear shape occur. When the nucleus becomes flattened and the chromatin is condensed, the cell is called a metamyelocyte. When the nucleus becomes horseshoe-shaped, it is called a band cell. The cell is considered a mature neutrophil when the nucleus becomes segmented into lobes.