Bone Marrow

Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. As a result, platelets have a diameter of 2–3 μm. Nuclei are not present; however, a variety of organelles are present and aid in different platelet functions.

Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Human marrow composition changes with age. In the young, the entire bone marrow is red, as there is increased blood cell production. As age increases, there is gradual change to the yellow marrow variety. The yellow marrow can revert to red marrow when hematopoiesis is needed (e.g., anemia). The red marrow, by hematopoiesis, produces about 6 billion cells per kilogram per day. The process relies on hematopoietic cells (stem cells and progenitors) producing mature effector cells (lymphocytes, platelets, granulocytes, erythrocytes) with the aid of nonhematopoietic elements. Production is regulated by cytokines released in the bone marrow environment and feedback from target tissues. The marrow structure allows hematopoiesis to take place in the extravascular area, and after staged differentiation, blood cells are released into circulation.

Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythropoiesis starts with hematopoietic stem cells, which develop into lineage-committed progenitors and differentiate into mature RBCs. The process occurs in stages, and extrusion of the nuclei and organelles occurs prior to maturation. Thus, mature RBCs lack nuclei and have a biconcave shape. RBCs carry hemoglobin, and the shape allows efficient oxygen transport. Billions of RBCs are produced daily, as the life span is 120 days. Senescent or deformed RBCs are removed by macrophages in the spleen, liver, and bone marrow.

The myeloid lineage produces a diverse group of blood cells (leukocytes) involved in the defense of the body against foreign substances or infectious agents. Monocytes, neutrophils, eosinophils, basophils, and mast cells all arise from the common myeloid progenitor (CMP), which develops from bone marrow stem cells. However, leukocytes have different functions. Neutrophils kill invading bacteria and fungi, eosinophils increase in parasitic infections, basophils and mast cells are key to allergic response as sources of histamine, and monocytes are released from bone marrow to become macrophages in the tissues. The development in the bone marrow is regulated by different cytokines.

Trace elements are minerals required in small amounts (1–100 mg/day in adults) to carry out biologic functions. These elements act as cofactors for essential enzymes as well as being components of hormones and antioxidant molecules. Trace elements have essential roles in oxygen transport, energy metabolism, and immune responses. Iron, chromium, copper, and iodine are among these elements. Overt deficiencies in resource-rich countries are rare because of varied food supply, food fortification, and supplement use. However, deficiencies can develop in certain medical conditions. Toxicity can also occur when there is exposure to concentrations larger than those physiologically required.

Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. B and T lymphocytes play a role in adaptive immunity, and NK cells provide host defense against atypical proteins such as tumor cells. While all developmental stages begin in bone marrow, lymphocyte maturation differs. B lymphocytes and NK cells differentiate in bone marrow before migrating to secondary lymphoid organs (such as lymph nodes). T lymphocytes, however, proceed to the thymus for further maturation.