Bone Marrow Disorders

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What is bone marrow?

The bone marrow is the only site of blood production after birth. Bones are composed of both cortex and medulla. The cortex is a strong layer of compact bone and the medulla is a honeycomb of spongy bone which forms the medullary cavity and contains the bone marrow. The marrow is soft fatty tissue which can be found inside the sternum (middle of the chest), pelvis (hip bone), and femur (thigh bone). Fibrous tissue in the marrow supports haemopoietic stem cells, which are large "primitive" undifferentiated cells. The haemopoietic stem cells can differentiate (change and specialise) to become a particular type of mature cell. These include erythrocytes, granulocytes, macrophages, monocytes, mast cells, megakaryocytes and lymphoid cells. Normally, only mature cells are released from the bone marrow and enter the bloodstream.

Any condition that may cause an abnormality in the production of the haemopoietic stem cell, the haemopoietic precursor or the mature blood cells can cause a bone marrow disorder. A variety of things can go wrong, including:

  • The over production of one cell type which will affect the overall cell balance in the bone marrow. This may result in a decrease in the production of other cell types.
  • Production of abnormal cells that don't mature or function properly.
  • Cell compression caused by an overgrowth of the supporting fibrous tissue network, resulting in abnormally shaped cells and decreased numbers of cells.
  • One cell lineage that becomes predominant because the cells do not undergo cell death at a normal rate.
  • The decreased production of cells, or the rapid loss of cells because they are fragile.
  • Insufficient nutrients available to create normal red blood cells (if iron deficient red blood cells may be microcytic (cells are smaller than normal), if vitamin B12 or folate deficient red blood cells may be macrocytic (cells are larger than normal)).
  • Diseases may spread to the bone marrow, affecting cell production and maturation.

The Cells

White Blood Cells (WBCs)
White blood cells are involved in defending the body against infectious diseases and foreign materials.There are five different types of white blood cells: lymphocytes, neutrophils (also called granulocytes), eosinophils, basophils, and monocytes. Each plays a unique role in protecting the body from infection. Neutrophils and monocytes kill and digest bacteria. Eosinophils and basophils produce cytokines which regulate and adapt the immune response. Lymphocytes exist in the blood and lymphatic system. There are two main types of lymphocytes, T cells and B cells. T cells, which finish maturation in the thymus gland, help the body distinguish between itself and foreign agents. B cells produce antibodies - proteins that attach to specific antigens. The number of blood cells present in the bloodstream is often the first indicator of disease.

Red Blood Cells (RBCs)
The main function of red blood cells (RBCs) is to transport oxygen from the lungs to tissues and organs throughout the body. They are able to perform this important function due the presence of haemoglobin (a protein) present within each cell.

Platelets (Thrombocytes)
Platelets are fragments of cells called megakaryocytes. The body uses platelets in the clotting process to plug holes in leaking blood vessels and to help activate other clotting factors.

The Disorders

Leukaemia is a cancer of the blood cells that may affect any blood cell type. Usually the bone marrow produces stem cells that are allowed to mature into "adult" blood cells. However, in cases of leukaemia the affected bone marrow begins with one abnormal haemopoietic stem cell that begins to continuously replicate itself. The resulting leukaemic cells are immature blood cells that are known as blast cells. These blast cells can continually replicate but are unable to differentiate into normal functional mature blood cells. Patients with leukaemia may have frequent infections, fatigue, bleeding, bruising, anaemia, night sweats, and bone and joint pain. The spleen, which filters the blood removing old cells, may become enlarged, as may the liver and lymph nodes.

Myeloproliferative neoplasms (MPN) are a group of diseases present in the bone marrow and peripheral blood, characterised by the overproduction of abnormal myeloid precursor cells. In MPN conditions, excessive production of a cell's precursor leads to an increased number of that particular type of cell, and decreased numbers of other types of blood cell. This results in symptoms related to blood cell overproduction, shortages, and dysfunction throughout the body.

Myelodysplastic Syndrome (MDS) is a group of diseases characterised by abnormal bone marrow cell production. Frequently with MDS, cell turn over is increased as well as cell death therefore not enough normal blood cells are produced. This leads to symptoms of anaemia, infection, and excessive bleeding and bruising. MDS syndromes are classified by how the cells in the bone marrow and bloodstream look under the microscope. Over time, MDS can progress to acute myeloid leukaemia (AML).

Aplastic anaemia is associated with a loss of cell precursors (usually red blood cells) due to a defect in the stem cell producing them or due to an injury to the bone marrow environment. Some aplastic anaemias are caused by exposure to chemicals such as benzene, radiation, or certain drugs. A few are due to rare genetic abnormalities such as Fanconi's anaemia or associated with an acute viral illness such as human parvovirus. The cause is unknown in about half of the cases.

Other disorders include:

  • Plasma cell disorders, a group of conditions associated with an overproduction of one clone of a B lymphocyte and its antibody protein, including multiple myeloma, primary amyloidosis and “monoclonal gammopathy of uncertain significance” (MGUS).
  • Lymphomas and other cancers that spread into the marrow and affect cell production.
  • Anaemias caused by deficiencies (e.g. iron) and/or haemoglobinopathies that result in the production of abnormal haemoglobin.
  • Anaemias caused by a deficiency or dysfunction of the cytokine erythropoietin, a protein produced by the kidneys that stimulates RBC production.

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