Bone marrow and blood formation

In humans, the bones are not solid, but 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 even extends into the bony canals that hold the blood vessels.

The marrow may contain fat cells, fluid, fibrous tissue, blood vessels, and hematopoietic, or blood-forming, cells. Marrow looks yellow when it holds many fat cells; it appears red when it has more blood-forming material. The marrow is the principal site for hematopoiesis (blood formation), which, after birth, occurs primarily within the bones of the legs, arms, ribs, sternum (breastbone), and vertebrae (backbones).

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Stem Cells
Many of the blood cells that populate the arteries and veins are born and mature within the bone marrow. They are derived from hematopoietic cells 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.

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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 the normal adult, production amounts to about 2.5 billion erythrocytes, 2.5 billion platelets, and 1.0 billion granulocytes (granular leukocytes) per kilogram of body weight.

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If the stem cells stop functioning because of drugs, radiation, infection, or other toxic event, they become unable to make any of the blood cells. The circulating blood will be deficient in all types of blood cells, a condition known as pancytopenia. The inside of the bone marrow will appear empty and will lack the normal quantity of cells. This stem cell disorder , which is called aplastic anemia, may be 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); such treatments are generally discouraged in adults.

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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 person 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, a disease in which bone marrow cells multiply outside of the bone marrow tissue, or myelodysplastic ("preleukemia") syndromes, are the result of marrow dysfunction in either the stem cells or progenitor cell lines.

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Spleen
The spleen is a vital organ that is 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, but these measurements vary greatly with age, nutrition, disease status, and other factors.

The spleen contains a white pulp of lymphoid tissues and a red pulp that contains red blood cells and hollow cavities called sinuses. Both red and white pulps are abundant in phagocytes, the cells that consume foreign substances within the body. The spleen manufactures lymphocytes and other immune system cells to combat infection. It is a storehouse for 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.

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Certain leukemia patients may develop splenomegaly - an enlarged spleen. In some forms of leukemia, such as chronic lymphocytic leukemia (CLL) and 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

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