Bone Marrow & Blood Formation

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Bone Marrow & 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).

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.

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.

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.

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.

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.

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

Thymus Gland
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, foreign proteins, etc.). 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
The lymph nodes are small oval or bean-shaped capsules that are strung along the a length of vessels that 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 taken from food in the intestine during digestion. They 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 arranged along the route of large blood vessels and are concentrated in areas such as the abdomen, underarms, groin, and neck. Small sacs called follicles within the lymph nodes 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 an 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).

Erythrocytes (Red Blood Cells)
The erythrocytes, or red blood cells ("corpuscles"), contain hemoglobin - a substance that is able to bind with oxygen. Oxygen from the lungs is carried by the erythrocytes to all the tissues of the body. A person who has anemia, a condition caused by too few erythrocytes in the blood, will experience symptoms such as weakness, fatigue, and shortness of breath.

Leukocytes (White Blood Cells)
There are five different types of leukocytes, or white blood cells, within the body:

  • neutrophils,
  • basophils,
  • eosinophils,
  • monocytes, and
  • lymphocytes.

These cells fight viral, bacterial, and other infections and participate in the hypersensitivity responses seen in allergic reactions.

Neutrophils, basophils, and eosinophils are granulocytes - white blood cells whose main purpose is to destroy bacteria. Granulocytes are distinguished by the small particles, or granules, that reside within each cell and contain substances to fight infections. Granulocytes undergo many stages of development before becoming mature neutrophils, basophils, or eosinophils. The more immature, myeloid series of granulocytes include cells known as myeloblasts, promyelocytes, myelocytes, metamyelocytes, band forms ("stab cells"), and polymorphonuclear leukocytes (PMNs).

If there is a "block" in the development of an individual's myelogenous (granulocytic) cell line, either chronic myelogenous leukemia (CML) or acute myelogenous leukemia (AML) may result.

Monocytes
Monocytes are medium-to-large mobile cells that can travel along the walls of the blood vessels and adhere to tissue surfaces. They contain cellular systems that consume foreign substances by surrounding and digesting of microorganisms and foreign particles or enveloping foreign substances within the plasma membrane. Monocytes originate in the bone marrow as immature monoblasts and promonocytes. Once these early cell forms develop into monocytes, they circulate in the bloodstream for about 24 hours. If the monocytes detect an area of inflammation, they move into tissues to become macrophages - larger phagocytic cells that help lymphocytes to detect foreign microorganisms and launch immune system responses.

Lymphatic tissue contains both fixed and circulating elements. Many different types of lymphatic cells interact to combat infections and recognize abnormal cells within the body. Fixed lymphoid tissue is found in the lymph nodes, spleen, thymus, tonsils and adenoids, bone marrow, and various sites within the gastrointestinal tract, respiratory system, and liver. Circulating lymphatic cells, such as the lymphocytes (nongranular leukocytes with a single nucleus) and monocyte/macrophage cells, originate from stem cells in the blood-forming tissues. The stem cells give rise to daughter cells that ultimately develop into B-cells or T-cells. Daughter T-cells migrate to the thymus, where they mature into T-cells. It is believed that daughter B-cells complete their development within the bone marrow.

B-cells combat infections by changing into plasma cells, which secrete antibodies. Plasma cell antibodies become attached to the invading germ, which is then recognized and destroyed by the blood granulocytes. T-cells are able to detect virus-infected cells within the body. They interact with macrophages to rid the body of the virus.

If there is a "block" in the development of an individual's lymphocytes, either chronic lymphocytic lymphocytic leukemia (CLL)  or acute lymphocytic leukemia (ALL) may result.

Platelets
Although platelets are classified as a type of blood cell, they are actually just pieces of megakaryocytes - bone marrow giant cells that contain a many-lobed nucleus (cell center). Platelets are the major blood-clotting elements of the body. They group together to seal off blood vessel damage caused by cuts or other traumatic injuries.

A person with a low level of platelets in the circulating blood - thrombocytopenia - may experience excessive bleeding.