Bone marrow is a spongy soft tissue contained inside most of the bones of the human skeleton. Sometimes it is confused with the spinal cord, but these tissues have nothing in common with each other. The spinal cord is located in the spine and performs conduction and reflex functions. The first is the transmission of nerve impulses to the brain and back, and the second, as you might guess from its name, is the organization of reflexes. But what features are inherent in the bone marrow, what it is responsible for and why it is so important for a person, we will now figure out.
What is bone marrow
The bone marrow for the hematopoietic system is the most important organ, because its main function is just the implementation of hematopoiesis, or hematopoiesis. He is directly involved in the creation of new blood cells to replace those that died, died off. In addition, the only adult tissue that contains immature cells, also known as stem cells, is the bone marrow.
There are two types of bone marrow: yellow, which is mainly represented by fat, and red – the main organ of hematopoiesis. Unlike red, yellow bone marrow does not participate in hematopoiesis.
During hematopoiesis, blood cells are formed. Hematopoiesis starts in the early embryonic period. Accordingly, there are both embryonic hematopoietic organs and those that function after birth. The organs that are responsible for hematopoiesis during the embryonic period include the yolk sac, fetal liver, spleen and bone marrow. The first hematopoietic stem cells appear in the yolk sac. This happens at the 3rd week of embryogenesis. Shortly after, from the 3rd month and before birth, the liver becomes the main hematopoietic organ of the fetus, since some of the stem cells move there. From the 4th month of embryogenesis, the formation of blood cells in the bone marrow begins. In addition, the thymus, lymph nodes and spleen are involved in hematopoiesis in the fetus. Hematopoietic stem cells are preserved in the liver and spleen, which are in a “dormant” state, which often explains the fact that foci of hematopoiesis occur outside the bone marrow. Such hematopoiesis is called extramedullary. It occurs in oncological diseases of the blood and as a result of excessive stimulation of hematopoiesis.
The volume of the bone marrow cavities in a newly born child is about 1.6 liters, of which the red bone marrow occupies almost 100% of the space. When a person grows up, hematopoiesis is centralized, while hematopoietically active tissue is preserved in the bones of the central part of the skeleton. The total volume of bone marrow in adults reaches approximately 4 liters.
The location of hematopoietic tissue in an adult is as follows: in the bones of the pelvis it is the most – 40%, in the bodies of the vertebrae it is much less – 28%, in the bones of the skull it is 13%, in the epiphyses of the tubular bones and ribs – 8%, in the sternum it is the least – only 2%. The remaining part of the bone marrow cavities is occupied by yellow bone marrow, which, as you remember, is adipose tissue. At the same time, the red and yellow bone marrow are in an equal ratio: 1:1.
Structurally, the red bone marrow is divided into: extravascular (actually, hematopoietic tissue) and vascular, which consists of wide venous vessels called sinuses. In the network of reticulin fibers inside the bone trabeculae there is a jelly-like dispersed material, which is the hematopoietic tissue.
The blood supply to the bone marrow is called perfusion. It is carried out by the main feeding artery and its small terminal arterioles. The outflow of blood occurs in this way: through the venous capillaries, blood is collected into the central venous sinus through the venous vessels. The walls of venous vessels consist of the following three layers of cells: adventitia, basement membrane and endothelium. It is in the reticulum, a thin network of connective tissue fibers formed by the processes of adventitial cells, that hematopoietic cells are located. The volume of the hematopoietic space is affected by changes in adventitial cells: the number of hematopoietic cells decreases when adventitial cells increase due to an increase in their fat content. If you look at this picture under a microscope, it looks like the transformation of red bone marrow into yellow.
At the moment when the requirements for hematopoiesis increase, adventitious cells decrease, thereby contributing to an increase in the hematopoietic component of the bone marrow.
What is the bone marrow responsible for
The main function performed by the red bone marrow is the function of hematopoiesis or hematopoiesis. It is carried out constantly and extremely intensively – more than 300 million blood cells per minute are formed in the hematopoietic organs. The function of hematopoiesis is unique in that at the right time and in the right place, a huge, but at the same time, the optimal number of blood cells of the required type is produced. The bone marrow can accelerate the production of any kind of blood cells by 5-6 times if the body needs more of them. All blood cells develop from a single parent cell. It has the morphology of a small lymphocyte and is called a multipotent hematopoietic stem cell (HSC). Its descendants are all peripheral blood cells. In the process of division and differentiation of multipotent HSC, the entire hematopoietic tissue is formed. It combines both progenitor cells and maturing and mature blood cells: erythrocytes, platelets and leukocytes, which make up human peripheral blood.
Hematopoiesis unites two large departments of hematopoiesis: lymphopoiesis and myelopoiesis.
- Myelopoiesis (or myeloid hematopoiesis). Normally, the only place where this process takes place after birth is the red bone marrow. All the shaped elements of the blood are formed there, except for lymphocytes (platelets, erythrocytes, monocytes and granulocytes), in order to then enter the peripheral blood.
- Lymphopoiesis (formation of T-lymphocytes and B-lymphocytes). After birth, it is realized in the central and peripheral lymphoid organs. The former include the red bone marrow, as well as the thymus (which retains the functions of the lymphoid organ only until puberty of the body); the latter include the lymph nodes, spleen and Peyer’s plaques of the gastrointestinal tract.
Erythrocytes, which are also called “red blood cells” – cells that do not have a nucleus, which are characterized by the shape of a biconcave disk. It is maintained in erythrocytes due to spectrin (a stabilizing membrane protein). The size of the erythrocyte normally ranges between 7.5 microns and 8.3 microns, and the life expectancy is 90-120 days. The well-known main blood groups (I, II, III, IV) are isolated based on the antigenic properties of red blood cells. The function of red blood cells is extremely important – they transport respiratory gases. The cytoplasm of the erythrocyte is filled with hemoglobin by 96%. It is a chromoprotein consisting of two parts: globin and heme. The first is protein, and the second is non–protein and is a complex of protoporphyrin IX and iron. Oxygen from the alveoli of the lungs is transported to the cells of the whole organism thanks to hemoglobin, and vice versa, from the cells to the alveoli – with the help of carbon dioxide. Normally, each hemoglobin molecule contains two pairs of identical protein chains. They are designated by the letters α and β from the Greek alphabet. Depending on the composition of these chains, there are three types of hemoglobin: embryonic, fetal and adult hemoglobin.
In peripheral blood, in addition to mature red blood cells, young red blood cells – reticulocytes can be found. These are cells without a nucleus, but contain a large number of RNA and ribosomes that have membrane receptors for transferrin. The RNA of reticulocytes continues to produce hemoglobin. At this stage, it is possible to produce hemoglobin up to 30% of the total amount in the erythrocyte. Most of them are synthesized at the prereculocyte stages of cell differentiation – 70-80% of hemoglobin. When a reticulocyte turns into a mature erythrocyte, it can no longer produce hemoglobin, as it loses RNA. In the bone marrow, the erythrocyte at the reticulocyte stage is located for one day, and then another day – in the peripheral blood.
Leukocytes, called, in turn, white blood cells, are a heterogeneous (heterogeneous) group of peripheral blood cells that contain a nucleus. They perform the function of immunity and differ in several ways. By the shape of the nucleus – segmented or rounded, by the color and nature of the cytoplasm, as well as by granularity – its presence or absence.
If there is no specific granularity, leukocytes are called agranulocytes, and if present, granulocytes. The first include lymphocytes and monocytes.
Granulocytes differ from each other by the nature of specific granularity and are of three types:
- Neutrophils (contain abundant fine pale purple (“neutrophilic”) granularity).
- Basophils (with large and non-abundant dark purple (“basophilic”) granularity).
- Eosinophils (differ in granularity, occupying the entire cytoplasm of the cell). Thanks to leukocytes, a protective function is realized in the body – immunity, which can be specific and nonspecific.
Neutrophils, monocytes and tissue macrophages are involved in one of the manifestations of nonspecific immunity (monocytes turn into them after they leave the bloodstream). They phagocytize (capture), followed by lysis (dissolution), microbes, toxins and cellular detritus (in other words, garbage). Eosinophils provide protection against parasites and are involved in allergic reactions (as are basophils).
Lymphocytes carry out reactions of specific immunity, whether innate or acquired. Specific immunity, in turn, is humoral and cellular. Humoral immunity is realized due to the synthesis of immunoglobulins of classes A, M, G, E, D by B-lymphocytes; and cellular immunity is realized with the help of diverse functions of T–lymphocytes. Acquired immunity can be formed naturally, due to various infectious diseases, or as a result of immunization of the body.
The size of leukocytes ranges from 6 microns (small lymphocytes) to 14 microns (monocytes).
Leukocytes differ from each other not only in appearance and function, but also in life expectancy. For example, the lifespan of lymphocytes varies between several hours and tens of years. Monocytes circulate in the blood for 72 hours, and then exit into the tissues, where they turn into fixed or migrating macrophages. Neutrophils are in the blood for 4-10 hours, with subsequent release into the tissues.
Platelets are the third shaped element of blood. They are equated with true cells, although they are not. In fact, these are particles of the detached cytoplasm of megakaryocytes of the bone marrow, the so-called blood plates. Platelets are characterized by aggregation (gluing) and adhesion (sticking) properties. Their participation in the mechanisms of blood clotting and fibrinolysis is determined by the presence of special biologically active substances. They also help to maintain the normal resistance and functioning of microvessels (angiotrophic function). The platelet size is 1-2 microns, and the life expectancy is 8 days
What is the yellow bone marrow responsible for
Yellow bone marrow is usually found in the diaphysis of tubular bones. It consists of reticular tissue and adipocyte cells, which contain a special pigment-lipochrome in the center of the cavity of the long bones, and outside it is surrounded by a layer of red bone marrow. Fat from adipocytes, in case of extreme necessity, for example, after prolonged fasting, the body can use as an energy source. Under normal conditions, the yellow bone marrow does not participate in hematopoiesis, but in exceptional cases, for example, after severe blood loss or acute anemia, part of the yellow bone marrow may turn red to speed up blood recovery.
The main functions of the bone marrow
The first and main task of the bone marrow is the production of blood elements, or hematopoiesis. Therefore, disorders in the process of hematopoiesis are directly related to the problems of functioning of the bone marrow. If it does not work properly, a person’s well-being may deteriorate for seemingly no apparent reason.
Insufficient bone marrow activity can cause conditions such as:
- weakness and fatigue (due to lack of hemoglobin, which is responsible for the transport of oxygen);
- fever (due to insufficient white blood cell count);
- propensity to infectious diseases (due to a decrease in white blood cells, which are necessary to fight infections);
- uneven breathing (due to a shortage of red blood cells and oxygen starvation caused by this);
- bruising or bleeding (due to platelet mass deficiency).
In addition, if we recall that it is thanks to the blood flow that all tissues and organs receive oxygen and nutrients, it becomes clear that absolutely every cell of the human body depends on the bone marrow. Also, the bone marrow is the core element of the lymphatic system. All lymphocytes originate in this tissue. And if we take into account that the immune system directly depends on the lymphatic working capacity, it turns out that without the bone marrow there would be no immunity. Most of the blood antibodies that protect the body from pathogens are synthesized in the bone marrow.
Bone marrow diseases
Regardless of what caused the damage to the tissue, especially its red part – cancer or other factors – it always poses a threat to human health and life.
Violations with such a complex name occur if stem cells multiply incorrectly. There are several types of such diseases:
- Primary myelofibrosis. It is characterized by the formation of mainly megakaryocytes and granulocytes in the bone marrow. At the end of the disease, connective tissue grows, and hematopoiesis develops outside the bone marrow.
- Polycythemia. This is a disease characterized by an absolute increase in the number of red blood cells in peripheral blood, an increase in the total volume of circulating blood, often leukocytosis, hyperthrombocytosis, enlargement of the spleen and frequent thrombosis of cerebral and coronary vessels.
- Essential thrombocytemia. Chronic myeloproliferative disease, manifested by hyperthrombocytosis (platelets above 450 × 109 / L) in combination with megakaryocytic hyperplasia of the bone marrow, in the absence of erythrocytosis, neutrophil leukocytosis.
Aplastic anemia is a disease that inhibits the hematopoietic function of the bone marrow. In other words, it loses the ability to produce the amount of blood cells necessary for the body. This happens due to damage to stem cells, which lose the ability to grow and develop into new blood cells.
Aplastic anemia can be acquired or congenital. In the first case, stem cells may lose their ability to turn into blood cells due to exposure to toxins, radiation, or after severe infectious diseases. In addition, this disease can sometimes manifest itself as a complication of some autoimmune disorders, such as lupus or rheumatoid arthritis.
Leukemia is a type of cancer in which a large number of white blood cells – leukocytes – appear in the peripheral blood. These diseases are united under a common name – hemoblastoses. There are such principles of separation of hemoblastoses:
- Depending on belonging to the department of hematopoiesis: myelopoiesis includes myeloproliferative neoplasms, and lymphopoiesis – lymphoproliferative neoplasms;
- Depending on the place of primary localization of tumor growth: leukemia (bone marrow) and hematosarcoma (outside the bone marrow);
- Depending on the aggressiveness of the course, correlating with the nature of the morphological substrate of the tumor: from immature cells (progenitor cells, blasts) or from maturing and mature cells.
Scientists find it difficult to say what exactly causes leukemia. But it is generally believed that radiation exposure, the influence of certain chemicals, as well as a number of genetic diseases increase the risk of oncological processes in the bone marrow.
Bone marrow transplantation: how, to whom and why
Bone marrow damage is life-threatening. Fortunately, red bone marrow can be restored by transplantation. Bone marrow transplantation is a method of treatment in which a patient is injected with pre–prepared bone marrow. This procedure is practically the only salvation for such complex, deadly and previously incurable diseases as lymphoma, leukemia, a complex form of anemia, malignancies of various genesis, autoimmune pathologies.
Bone marrow transplantation is, in fact, the introduction of the necessary stem cells into the patient’s body. Stem cells are found in the embryo, bone marrow, peripheral human blood, as well as in umbilical cord blood. All the listed options, except the first one, can serve as a source for transplantation. During the transplantation procedure, the collected stem cells are injected intravenously into the patient. After penetration into the bloodstream, donor hematopoietic stem particles move to the bone marrow of the patient, where, in the case of a successful procedure, they begin to produce erythrocytes, platelets and leukocytes.
It usually takes about 2-4 weeks for the transplanted material to take root. Transplantation helps the sick body to restore the ability to independently produce the necessary blood elements. This procedure is resorted to for the treatment of both oncological and other types of diseases.
Consider the types of bone marrow transplantation. Exists:
- Autologous – when the patient is injected with his own stem cells. Usually, they are withdrawn earlier during treatment, with intact bone marrow, from umbilical cord or peripheral blood, and stored frozen until the moment of transplantation, when they are thawed and injected into the patient. This type of transplantation is used after the treatment of certain cancers using high-dose chemotherapy, after which the bone marrow is destroyed.
- Syngenic – when the donor of stem cells is a person with the same set of genes – the identical twin of the patient.
- Allogeneic – when stem cells are obtained from the patient’s siblings, or a donor can be a person with whom the patient is not related, but at the same time the transplanted material is genetically as close as possible to the patient’s ownwith the patient’s cells. This type of transplantation is resorted to in the case of leukemia, severe aplastic anemia, severe complex immunodeficiency.
- Haploidentical – when stem cells are transplanted from an incompletely compatible donor. As a rule, it becomes the mother or father of the patient.
- Umbilical cord – when stem cells obtained from umbilical cord blood are transplanted. In this case, the material is frozen and stored until necessary. At the moment, there are many umbilical cord blood banks in developed countries. The advantage of this type of transplant is that the cells from this source are always very immature, which means there is no need for compatibility selection. In other words, they are suitable for everyone.
Possible risks of bone marrow transplantation
Despite the seemingly simplicity of the procedure, in fact, bone marrow transplantation is not without serious risks. After the introduction of the donor material, the patient may have a reaction called “graft versus host” (GVH). This is considered one of the most dangerous and most frequent complications after allogeneic transplantation. The essence of the reaction is that the donor bone marrow perceives the recipient’s body as an enemy and begins to work against it. The graft-versus-host reaction occurs in almost 40% of stem cell transplants. This confrontation can even lead to the death of the recipient. It is believed that the risk of a GVH reaction increases if the patient is over 30 years old. For a long time, doctors did not undertake to transplant bone marrow to people over the age of 50, the risk of mortality after the procedure is extremely high. Nowadays, doctors are less wary of the age limit.
In addition to the GVH reaction, ophthalmological, endocrine, pulmonary, neurological, musculoskeletal, immune, infectious diseases, heart failure, progression of cancer can develop as a complication for transplantation.
Erythrocytes, leukocytes, platelets and components of the lymphatic system are all produced by the bone marrow. He is rarely remembered and, as a rule, only in cases of serious diseases. The bone marrow cannot be seen or touched, and if something is wrong with it, it does not hurt. Nevertheless, it is one of the most important tissues in the body and failures in its work in many cases end in death.