Blood cells are produced in the hematopoietic organs, and their main hematopoietic organs are not the same during the embryonic period and at different developmental periods after birth.
Hematopoietic organs in the embryonic period 1. Mesodermal hematopoietic stage: occurs in the first 1-2 months of embryonic life. The yolk sac is the first site of hematopoiesis to appear. The mesodermal mesenchymal cells in the wall of the yolk sac are the starting base of the hematopoietic system. Initially, blood cells are generated in the blood island of the yolk sac, and the cells in the periphery of the blood island differentiate and develop into primitive blood cells.
2. Hepatopoietic stage: It occurs in the 2-5 months of embryo. The yolk sac atrophies and degenerates, and the liver takes over its hematopoietic function. It can differentiate not only primary primitive erythrocytes but also secondary primitive erythrocytes, which gradually develop and mature into erythrocytes and enter the blood through the blood sinusoids. At this time, the hematopoietic activity of the liver is very active. The spleen is also involved in hematopoiesis around the third month of life, mainly producing red blood cells, granulocytes, lymphocytes and monocytes. By the fifth month, the hematopoietic function of the spleen gradually decreases, and only lymphocytes and monocytes are produced, and this hematopoietic activity is maintained throughout life.
3.Bone marrow hematopoietic stage: This stage begins in the 4th month of embryonic life. The fetus begins to develop bone marrow hematopoietic tissues, initially producing only granulocytes, followed by red blood cells and megakaryocytes. Along with bone marrow hematopoiesis, the thymus and lymph nodes also begin to produce blood. The thymus gland produces lymphocytes and continues to do so after birth; the lymph nodes mainly produce lymphocytes and plasma cells, and are also involved in the production of red blood cells early in life.
The above three stages are intertwined with each other and are actually difficult to separate.
Bone marrow: The bone marrow is the only organ that produces red blood cells, granulocytes and megakaryocytes after birth, as well as lymphocytes and monocytes. From newborn to 4 years old, the bone marrow has an active hematopoietic function throughout the body. 5-7 years old, adipocytes begin to appear between the hematopoietic cells in the tubular bones. With age, the extent of red marrow in the tubular bone gradually decreases, fatty tissue gradually increases, and the bone marrow turns yellow, called yellow marrow. Although blood is no longer produced in the yellow marrow, it still retains potential hematopoietic function. Around 18-20 years of age, the red marrow is limited to the flat bones such as the skull, sternum, spine, and ilium, as well as the proximal ends of the humerus and femur. The red marrow accounts for about half of the total bone marrow. Later, the hematopoietic activity of the red marrow continues for life, but its activity may decrease slightly with age.
The bone marrow is observed visually as a spongy, gelatinous or fatty tissue enclosed in a hard marrow cavity. It is divided into two parts: red marrow (hematopoietic cells) and yellow marrow (fat cells). Normal adult bone marrow weighs 1,600 grams to 3,700 grams, or about 3.4% to 5.9% of body weight, with the red marrow weighing about 1,000 grams.
The bone marrow has a complex and rich vascular system. The human bone marrow relies mainly on nutrient arteries to supply capillaries throughout the marrow cavity. All the arteries of the bone marrow are accompanied by nerve bundles, nerve fibers derived from the spinal nerves, which together with the arteries enter the marrow cavity from the nutrient foramen, distribute parallel to the nutrient arteries in the marrow cavity, and terminate in smooth muscle fibers in the arterial walls. The differentiation of bone marrow hematopoietic stem cells into the red, granular and megakaryocytic lineages is related to the hematopoietic microenvironment, which may consist of blood vessels, macrophages, nerves and stroma. If considered from its function, the hematopoietic microenvironment should include all factors affecting hematopoiesis, among which vascular factors are important because all kinds of hematopoietic substances and their stimulating substances have to enter the bone marrow through blood vessels in order to create blood. There is a barrier between the site of hematopoiesis and blood circulation, namely the bone marrow blood barrier, which has the role of controlling the entry and exit of blood cells into and out of the bone marrow.
2. Thymus gland: After birth to old age, the thymus gland undergoes certain changes. After puberty, the hematopoietic activity gradually disappears and is replaced by adipose tissue.
The thymus is not only one of the important hematopoietic organs during the embryonic period, but also still has an active hematopoietic function after birth, especially in the two years after birth, the growth of glandular tissue is more rapid and hematopoietic activity is also very strong. The thymus is separated into many incomplete lobules by connective tissue. The peripheral part of the lobules is called the cortex and the central part is called the medulla. The cortex is filled with dense lymphocytes, with the most superficial layer being the more primitive lymphocytes, the middle layer being medium-sized lymphocytes, and the deeper layer being small lymphocytes. Although the adult thymus is atrophied, it is able to reproduce itself because T cells have settled in the surrounding lymphoid tissue. In addition to delivering T lymphocytes to the surrounding lymphoid tissue, the thymus also secretes thymosin by the epithelial reticulum, and stem cells are induced to differentiate and mature into immunoreactive T lymphocytes under the action of thymosin.
3. Spleen: The spleen is the largest lymphoid organ in the body, and its substance is divided into two parts: the red and white marrow. The white medulla includes the lymphatic sheath around the central artery and the splenic nodules. Around the central artery is the thymus-dependent zone of the spleen, which is mainly composed of T-lymphocytes. The splenic nodules are the lymph nodes within the spleen, which contain germinal centers and are dominated by B lymphocytes. In addition to producing lymphocytes and monocytes, the spleen also has the function of storing blood and destroying senescent red blood cells.
4.Lymphatic nodes of appendix and ileum: stem cells of bone marrow are collected here, and the proliferating stem cells can be induced to differentiate into bone marrow-dependent lymphocytes (B cells) and spread in the surrounding lymphoid organs.
5. Lymph nodes: divided into a peripheral part of the cortex and a central part of the medulla. The central part of the superficial cortical lymphoid follicles is the site of B-cell proliferation, called the germinal center or reaction center; the deep cortical layer is mainly composed of T-cells migrating from the thymus, called the thymus-dependent area; under the stimulation of antigen, T-lymphocytes can proliferate and produce a large number of sensitized small lymphocytes, which act directly on the antigen via blood flow. The medulla is mainly composed of myeloid cords (lymphatic cords) and lymphatic sinuses. The main components of myeloid cords are B lymphocytes, plasma cells and macrophages, etc.
The above (2), (3), (4) and (5) parts belong to the lymphoid organs for hematopoiesis. Lymphatic organs, divided into central lymphatic organs and peripheral lymphatic organs. The lymphoid tissue in the thymus and bone marrow is the central lymphoid organ, which is the focus of lymphatic lineage directed stem cells; the lymph nodes, spleen and other lymphoid tissues are the peripheral lymphoid organs, where differentiated T cells and B cells are located.
6, reticuloendothelial system (RES): including reticulocytes in the spleen and lymph nodes, endothelial cells covering the sinusoidal gaps in the liver, bone marrow, adrenal cortex, anterior pituitary gland, and free tissue cells in other organs. Its main cellular component is reticulocytes, which can differentiate into phagocytic reticulocytes. Monocytes in the blood, which enter the reticular tissue after generation from the medulla, are histiocytes; under certain conditions, they can be transformed into free phagocytes with phagocytic function, forming the so-called monocyte-macrophage system.
Under normal conditions, an infant born after 2 months of age will never have extramedullary hematopoiesis. In pathological states, foci of hematopoiesis can appear in tissues outside the bone marrow, such as the spleen, liver, and lymph nodes.