Blood formation begins in early embryogenesis and goes through several stages.
First phase – 2-3d weeks. The first blood islands appear in the mesenchyme of the yolk sac. They consist of three components:
1 – cells forming the wall of primary blood vessels – endotheliocytes.
2 – hematopoietic cells - CFU derived from central cells of the blood islands.
3 – primary erythrocytes – megaloblasts. Megaloblasts have nuclei and contain fetal hemoglobin (Hb F). Some megaloblasts loss their nuclei and become megalocytes.
The second phase (4 – 8 weeks) is called "hepatic phase" because hemopoietic islands appear in the liver and lymphatic tissues. In contrast of intravascular hemopoiesis in yolk sac in liver there is an extravascular hematopoiesis. All blood cells differentiate from CFU in the liver.
The third phase (from 12 week) of fetal hemopoiesis involves the red bone marrow and lymphatic organs – thymus, spleen, and lymph nodes.
After birth, hemopoiesis is confined to red bone marrow and lymphatic organs.
Postnatal hemopoiesis (post embryonic)
All blood cells arise from a common stem cell, which is derived from mesenchymal cell. Stem cells or the colony-forming units – CFU are pluripotential cells because they give rise to all of the blood cells.
Stem cells or CFU represent the first stage of postnatal hemopoiesis.
In the second stage CFU gives rise to two kinds of semi-stem cells.
One of them is lymphoid semi-stem cell (LSC). Other one is myeloid semi-stem cell (MSC).
These cells are particularly determined cells. They are capable to develop only into lymphocytes or only into all other blood cells. Development of blood cells from LSC is called lymphopoiesis. Development of blood cells from MSC is called myelopoiesis.
Subsequent development is possible only under the influence of special hormones, which called hemopoietins, hemopoietic factors or growth factors.
Therefore, the cells of the thirdstage are called hemopoietin-sensitive cells. Each blood cell has it's own hemopoietin.
Myeloid semi-stem cell (GEMM) forms 4 kinds of hemopoietin-sensitive cells:
Erythropoietin-sensitive cell;
Leukopoietin-sensitive cell;
Monopoietin-sensitive cell;
Thrombopoietin-sensitive cell.
Lymphoid semi-stem cell forms only T-lymphopoietin-sensitive cell or B-lymphopoietin-sensitive cell.
Therefore the potency of these cells becomes restricted. They are also called unipotential cells. All the cells pertaining to the first three stages are morphologically indistinguishable. All of them look like small lymphocyte.
The first recognisable cells constitute the forth stage of hemopoiesis. These are actively dividing cells that called blast cells. In cytoplasm of these cells appear specific organelles and enzymes.
There are six types of blast cells:
Proerythroblast or simple erythroblast;
Myeloblast;
T- lymphoblast;
B- lymphoblast;
Megakaryoblast;
Monoblast.
Thefifth stage is called cell differentiation. From this point it is useful to consider the formation of every blood cell separately.
Erythropoiesis. Proerythroblast forms basophilic erythroblast, containing large spherical nucleus and basophilic cytoplasm due to the presence of free ribosomes. Further ribosomes begin to synthesise hemoglobin.
The cytoplasm displays both eosinophilia, due to the presence of hemoglobin, and basophilia, due to the presence of the ribosomes.
That’s why these cells are called polychromatophilic erythroblasts.
At the next stage erythroblasts more and more accumulate hemoglobin and the cells become acidophilic erythroblasts.
Further nucleus is condensed, and cell will be called normoblast. This cell has a small compact nucleus and acidophilic cytoplasm.
At the next stage normoblast loses its nucleus by extruding it from the cell. Sometimes new (young) erythrocytes have thin basophilic network on the acidophilic background due to RNA remaining in the cytoplasm. Such erythrocytes are called reticulocytes.
All mature erythrocytes represent the sixth stage of erythropoiesis.
All mature erythrocytes come into blood circulation as soon as they are formed, bone marrow is not a storage site for red blood cells.
Granulopoiesis. Myeloblast forms promyelocytes, which have a large spherical nucleus and azurophilic granules in the cytoplasm.
Recognition of the neutrophil, eosinophil and basophil ones become possible only in the next stage, when specific granules appear. These cells are called neutrophilic, eosinophilic and basophilic myelocytes.
Myelocytes continue to divide and give rise to metamyelocytes. In the metamyelocyte nucleus becomes more heterochromatic and indented like horse shoe. These are young neutrophilic, eosinophilic and basophilic metamyelocytes.
Further indentation deepens. Such cell is called band cell or band neutrophilic, eosinophilic and basophilic cells.
Further nucleus becomes lobulated. Such cells are considered as mature granulocytes, also called a polymorphonuclear neutrophil, eosinophil and basophil and are the cells of the sixth stage.
Band cells are sometimes seen in the circulation along with mature granulocytes. In the normal blood band cells are account for about 0,5-2,0%.
Monocytopoiesis divides in a mitosis way and monoblast gives rise to promonocyte. Promonocyte has a large nucleus slightly indented and basophilic cytoplasm. Promonocyte is transformed into mature monocyte, which is the cell of the sixth stage.
Thrombocytopoiesis (formation of platelets). This process divides in a mitosis way and megakaryoblast gives rise to promegakaryocyte. At the next stage chromosomes are replicate but there is neither karyokinesis no cytokinesis. That's why megakaryocyte is polyploid cell. The sites of cytoplasm divided from the megakaryocytes and come into blood circulation as the platelets, which are the cells of the sixth stage.
That is platelets are membrane bounded cytoplasmic fragments.
Lymphopoiesis. T-lymphoblasts leave the marrow and travel to the thymus and to the thymus-depending zones of lymphoid organs. There T-lymphoblasts divide in a mitosis way and become mature T-cells. T-cells enter into blood circulation as long-lived small lymphocytes.
B-lymphoblasts remain in the red marrow, where complete it's differentiation. As a result the mature B-lymphocytes formed, which enter into the circulation.
Some B-lymphoblasts leave red marrow and travel to the peripheral lymphatic organs, where complete their differentiation.
Mature T- and B-lymphocytes form the cells of the sixth stage.
Connective Tissue:
Proper and specialised
(Tissues of the inner environment)
There is a big group of connective tissues in the human body, which developed from mesenchyme and have common structural and functional features. They are as follows: Blood, Lymph, Connective tissue proper (Fibrous connective tissue), Specialised connective tissue, Cartilage and Bone (Skeletal connective tissues).
