Bone Marrow & Blood Formation
Bones are not solid, but instead are made up of two distinct regions. The outer, weight-bearing area is hard, compact, and calcium-based. It surrounds a lattice-work of fibrous bone known as cancellous tissue.The inner region, or marrow, which is one of the largest organs of the body, is located within the bones. It fills the shafts of the long bones, the trabeculae (spaces within cancellous tissue), and extends into the bony canals that hold the blood vessels.
Bone marrow may contain fat cells, fluid, fibrous tissue, blood vessels, and blood-forming (hematopoietic) cells. Marrow appears yellow in color when it holds many fat cells and red when it has more blood-forming material. The marrow is the principal site for blood formation (hematopoiesis), which occurs primarily in the bones of the legs, arms, ribs, breastbone (sternum), and spine (vertebrae).
Many of the blood cells that comprise the bloodstream within the arteries and veins are born and mature within the bone marrow. They are derived from hematopoietic cells that are called stem cells. Stem cells within the bone marrow continuously divide to form new cells.
Some of the new cells remain unchanged as stem cells and have a lifelong capacity for self-renewal. These cells are called pluripotential cells. Other, unipotential stem cells have a limited capacity for self-renewal. Also known as progenitor cells, unipotential cells become committed to forming only one type of blood cell line—erythrocytes (red blood cells), leukocytes (white blood cells), or platelets.
Colonies of progenitor cells provide offspring of increasing differentiation (maturity). They react to specific compounds known as poietins. Poietins stimulate the progenitor cells until they transform into the appropriate young blood cell known as a "blast" cell.
Although stem cells are few in number—composing no more than 3% to 5% of all cells in the marrow—they are the only cells capable of producing the progenitor cells that eventually form all of the blood elements. The number of blood cells produced every day is enormous. In adults, blood cell production amounts to about 2.5 billion erythrocytes, 2.5 billion platelets, and 1.0 billion granulocytes (granular leukocytes) per kilogram of body weight.
If the stem cells stop functioning (e.g., because of drugs, radiation, infection, or other toxic event), they become unable to make any of the blood cells and the circulating blood becomes deficient in all types of blood cells (condition known as pancytopenia). The inside of the bone marrow appears empty and lacks the normal quantity of cells. This stem cell disorder, which is called aplastic anemia, is treated by bone marrow transplant or immunosuppressive medications. In rare circumstances, children with aplastic anemia may respond to therapy with steroids or androgens (male sex hormones); however, such treatments generally are discouraged in adults.
Progenitor cells also may die or lose the ability to function due to drugs, radiation, infection, or other toxic event. Depending on which progenitor cells cease to work, the patient may develop pure red cell aplasia (lack of red blood cells), megakaryocytic aplasia (absence of platelets) or leukopenia (low white blood cell count).
Other types of bone marrow abnormalities, such as myeloproliferative disorder (disease in which bone marrow cells multiply outside of the bone marrow tissue) and myelodysplastic ("preleukemia") syndromes, are the result of marrow dysfunction in either the stem cells or progenitor cell lines.
The spleen is a vital organ located on the left side of the body under the lower rib cage. It is a "ductless gland" that is closely associated with the circulatory system. The adult spleen, which holds the largest collection of blood-filtering lymphatic tissue in the body, is roughly 5 inches long and weighs about 5 to 7 ounces. These measurements vary with age, nutrition, disease status, and other factors.
The spleen contains a white pulp of lymphoid tissues, a red pulp that contains red blood cells, and hollow cavities called sinuses. Both red and white pulps are abundant in phagocytes (cells that consume foreign substances within the body). The spleen manufactures lymphocytes and other immune system cells to combat infection. It stores healthy blood cells, and its lymphatic tissue filters out old and damaged blood cells, microorganisms, and cell waste. In case of bone marrow malfunction, the spleen may assume the role of blood cell formation.
Certain leukemia patients may develop an enlarged spleen (splenomegaly). In some forms of leukemia (e.g., chronic lymphocytic leukemia [CLL], hairy cell leukemia [HCL]), splenectomy (removal of the spleen) may be an effective form of treatment. Splenectomy is one of many therapeutic options for HCL.
The thymus gland is, to some extent, an "age-dependent" organ. It functions to create T lymphocytes (T-cells) in the developing fetus, attains its full size after a child is 2 years of age, and then shrinks to a nearly undetectable size by puberty (adolescence).
The thymus is located in front of the heart. It has two lobes and contains thymocytes (immature lymphocytes), epithelial cells (cells that cover the internal and external body surfaces, including the lining of blood vessels, etc.), and macrophages (large cells that ingest microorganisms and other foreign substances.
T-cells primarily are responsible for cell-mediated immunity and immune system regulation. Within the thymus, immature pre-T-cells develop and are able to recognize antigens (substances capable of starting a specific immune system response; e.g., bacteria, viruses, foreign proteins). The immature pre-T-cells then migrate to other lymphoid tissues, such as the spleen and lymph nodes, where they mature and undergo additional differentiation. Although the thymus shrinks with age, it continues to aid immune system function throughout a person's lifetime.
Lymph nodes are small oval or bean-shaped capsules that are located along the a length of large blood vessels and channel lymph and chyle on the way back to the blood. Lymph is the transparent, slightly yellow, liquid that is collected from the body's tissues, and chyle is the milky fluid removed from food in the intestine during digestion. Lymph nodes contain collections of lymphocytes (specialized white blood cells; nongranular leukocytes; plasma cells (antibody-releasing cells), and macrophages (large cells that ingest foreign substances and help lymphocytes to launch immune system responses).
The lymph nodes are concentrated in areas such as the abdomen, underarms, groin, and neck. Small sacs within the lymph nodes (called folllicles) contain B lymphocytes (B-cells). T-cells deep within the lymph nodes play a role in the induction of B-cell responses. B-cells eventually mature into plasma cells that produce antigen-specific antibody, which is an immune system chemical that is directed against a specific foreign substance.
During infection, the lymph nodes increase in size, especially in infants and children. They return to normal after the infection has passed. Occasionally, a lymph node that appears permanently enlarged may reflect a cancerous condition. For example, in rare instances, leukemia that has spread outside of the bone marrow may cause enlargement of a lymph nodes(s).