Bone marrow blood cell production

Aplastic anemia—anemia due to deficient red blood cell production in the bone marrow... 

Erythropoiesis-stimulating agents Agents developed by recombinant DNA technology that have the same biologic activity as endogenous erythropoietin to stimulate erythropoiesis (red blood cell production) in the bone marrow. 

Erythropoietin A hormone primarily produced by the progenitor cells of the kidney that stimulates red blood cell production in the bone marrow. Lack of this hormone leads to anemia. 

Cherry, Yasumizu R, Toki J, et al. Production of hematopoietic stem cell-chemotactic factor by bone marrow stromal cells. Blood 1994 83(4) 964-971. 

Although the kidneys are not considered endocrine glands per se, they are involved in hormone production. Erythropoietin is a peptide hormone that stimulates red blood cell production in bone marrow. Its primary source is the kidneys. Erythropoietin is secreted in response to renal hypoxia. Chronic renal disease may impair the secretion of erythropoietin, leading to development of anemia. The kidneys also produce enzymes. The enzyme renin is part of the renin-angiotensin-aldosterone system. As will be discussed, these substances play an important role in the regulation of plasma volume and therefore blood pressure. Other renal enzymes are needed for the conversion of vitamin D into its active form, 1,25-d i hyd ro xyv itamin D3, which is involved with calcium balance. 

Patients with leukemia have a condition in which the stem cells in the bone marrow malfunction and produce an excessive number of immature white blood cells, which interfere with normal blood cell production. 

Pharmacology Erythropoietin is a glycoprotein that stimulates red blood cell production. It is produced in the kidney and stimulates the division and differentiation of erythroid progenitors in bone marrow. Hypoxia and anemia generally increase the production of erythropoietin, which in turn stimulates erythropoiesis. In patients with CRF, erythropoietin production is impaired this deficiency is the primary cause of their anemia. Epoetin alfa stimulates erythropoiesis in anemic patients on dialysis and those who do not require regular dialysis. 

Although the major physiological role of EPO is certainly to promote red blood cell production, EPO mRNA has also been detected in bone marrow macrophages, as well as some multipotential haemopoietic stem cells. Although the physiological relevance is unclear, it is possible that EPO produced by such sources may play a localized paracrine (or autocrine) role in promoting erythroid differentiation. 

Production of blood cells in bone marrow of the central axial skeleton is referred to as medullary hematopoiesis. Hematopoietic tissue in adult bone marrow is well perfused and contains fat cells (adipocytes), and various types of blood and blood precursor cells encased within a protein matrix. Fibroblast, stromal and endothelial cells within bone marrow, serve as sources of matrix proteins as well as a factory for growth factors and chemokines that regulate blood cell production and release matured cells into the circulation [2,3]. Chemokines act as signal lamps for trafficking of lymphocytes in and out of lymphoid tissues. Erythroblasts, neutrophils, lymphoblasts, macrophages, megakaryocytes, and pluripotent stem cells are also found within the calcihed lattice crisscrossing the marrow space. 

Anemia. Testosterone and similar compounds are potent stimulators of erythropoietin synthesis from the kidneys and other tissues.109 Erythropoietin, in turn, stimulates production of red blood cell synthesis in bone marrow. Human erythropoietin, however, can now be synthesized using recombinant DNA techniques. Hence, various types of anemia that occur secondary to renal disease, cancer chemotherapy, and so forth are usually treated directly with recombinant erythropoietin.109 Nonetheless, androgens may be used as an adjunct to erythropoietin and other drugs to stimulate red blood cell production in certain patients with severe or recalcitrant anemia.10... 

Long-term exposure to benzene can cause leukemia, characterized by a decrease in the number of red blood cells and an increase in the number of malfunctioning white blood cells. Metabolites of benzene may reactwith proteins and DNA in the bone marrow, altering the production of red and white blood cells. 

Hematopoiesis is the process of blood cell production that takes place in the bone marrow. Through a complex series of regulatory events, stem cells are differentiated into various types of cells, including red blood cells. Stem cell differentiation is responsive to exogenous stimuli and can be upregulated to resupply a deficient cell population. However, only a limited number of therapeutics (iron, hemin, or erythropoietin, for example) can stimulate Hb-replete red blood cell formation. Recognition of the poor bioavailability of many iron compounds or hemin compositions and the improved safety profile of a tHb relative to rmmodified Hb has renewed the interest in Hb administration as... 

Vitamin B-12 is necessary for red biood ceiis to mature prop-eriy in the bone marrow. Peopie with pernicious anemia iose their abiiity to make intrinsic factor, a substance secreted by the stomach s membrane iining that enabies vitamin B-12 to be absorbed from the intestine. Without an adequate amount of vitamin B-12, the body is unabie to synthesize DNA properiy, which affects red blood cell production. 

Any disorder or agent that injures the stem cells or prevents their proliferation can drastically affect the absolute platelet count. The minimal platelet count necessary for initial hemostasis is 50 000 mm If the platelet count falls below 20 000 mm a condition known as thrombocytopenia exists and the affected organism is extremely vulnerable to spontaneous bleeding episodes. Usually, thrombocytopenia due to marrow failure is also associated with reduced leukocyte and red blood cell production since chemicals or disorders that affect the megakaryocytes also impact other stem cells. This is typically determined by examining a peripheral smear of the blood or by a hematologist s bone marrow aspiration. 

Synthetic growth factors are being used to stimulate normal white blood cell production following cancer treatments and bone marrow transplants. 

Erythropoietin is a glycoprotein hormone that regulates red blood cell production in a feedback loop manner between kidney and bone marrow based on oxygen tension. It consists of 165 amino acids and has a molecular weight of 30,000-34,000 approximately 30% is accounted for by covalently linked carbohydrate. Erythropoietin is produced by the fetal liver and shortly after birth production switches from the liver to the kidney. In the fetus, erythropoietin functions in a paracrine-endocrine fashion because liver is the site of erythropoietin synthesis as well as ery-thropoiesis. The mechanism of this developmental switch is unclear. In the liver, erythropoietin synthesis occurs in... 

Intravenous iron therapy is an effective means to prevent iron deficiency and maintain adequate iron status for erythropoiesis. Parenteral iron improves the responsiveness to erythropoietic therapy and reduces the dose required to achieve and maintain the target Hgb/Hct. Iron administration in patients with what is known as a functional iron deficiency is more questionable. Functional iron deficiency is characterized by a low TSat (<20%) in the presence of a normal or elevated serum ferritin. In other words, there may appear to be adequate storage iron, but iron is not being carried by transferrin to the bone marrow for red blood cell production. If the Hgb is less than the target of II g/dL, under these conditions a trial of IV iron therapy may be warranted. Iron supplementation alone may improve Hgb/Hct and may... 

Anemia of chronic kidney disease— A decrease in red blood cell production caused by a deficiency in the hormone erythropoietin normally produced by progenitor cells of the kidney. As kidney function declines, less erythropoietin is available to stimulate red blood cell production (erythropoiesis) in the bone marrow. Contributing factors include iron deficiency and a shortened red blood cell lifespan. 

Over the last thirty years or so, our understanding of the complex mechanisms and interactions which regulate blood cell production has increased greatly. It is now recognized from experimental studies that cells are produced and mature within the bone marrow space from the relatively small population of pluripotent stem cells which comprise approximately 0.01-0.05% of the total nucleated marrow cell population and are established during embryogenesis (Metcalf and Moore, 1971). The two characteristic features of stem cells are that they have enormous ability to proliferate to produce more stem cells, a process known as self-renewal, and that they... 

A. Hematopoietic Syndrome. Patients who have received doses of radiation in the low to mid-lethal range will have depression of bone-marrow function with cessation of blood-cell production leading to pancytopenia. Among treated patients, deaths should be minimal. 

In contrast, there are several causes of neutrophilia (increased numbers of circulating neutrophils) that are unrelated to immune status. Neutrophilia can be part of a corticosteroid-mediated stress response (increased release of mature neutrophils from marrow and decreased egress to tissues), or an epinephrine-mediated physiologic response (demargination) due to excitement or fear. Neutrophilia can also be seen with hemorrhage or hemolysis which accelerates red blood cell production. This is thought to be due to generalized bone marrow stimulation and, in the case of hemolysis, cell destruction may result in increased demand for neutrophils (Latimer et al.,... 

Hematopoietic growth factors also have been produced in mammalian cell cultures by recombinant DNA techniques. Erythropoietin can be used in certain types of anemias to stimulate the production of red blood cells. Colony-stimulating factors (CSFs) and interleukins (ILs) can be used after bone marrow transplants and after chemotherapy to stimulate white blood cell production and decrease the risk of infection. 

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