Erythrocytes, production

Anemia (decreased hemoglobin and hematocrit) occurs as a result of variceal bleeding, decreased erythrocyte production, and hypersplenism. 

A decrease in erythrocyte production can be multifactorial. A deficiency in nutrients (such as iron, vitamin B12, and folic acid) is a common cause that often is easily treatable. In addition, patients with cancer and CKD are at risk for developing a hypoproductive anemia. Furthermore, patients with chronic immune-related diseases (such as rheumatoid arthritis and systemic lupus erythematosus) can develop anemia as a complication of their disease. Anemia related to these chronic inflammatory conditions is typically termed anemia of chronic disease. 

Anemia from vitamin BI2 or folic acid deficiency is treated effectively by replacing the missing nutrient. Both folic acid and vitamin B12 are essential for erythrocyte production and maturation. Replacing these factors allows for normal DNA synthesis and, consequently, normal erythropoiesis. 

Another example is uptake of the iron-containing protein, transferrin, which circulates in the blood. It binds to its receptor to form a complex that enters the cell via endocytosis. The iron is then released from the endosome for use in the cell (e.g. haemoglobin formation for erythrocyte production or cytochrome production in proliferating cells). The number of transferrin receptors in the plasma membrane increases in proliferating cells and the number in the liver is increased by cytokines during infection. This results in a lower concentration of iron in the blood which decreases the proliferation of invading pathogens (Chapters 15 and 18). 

Pharmacologic doses in women stimulate growth of facial and body hair and produce deepening of the voice, enlargement of clitoris, frontal baldness and prominent musculature. Natural androgens stimulate erythrocyte production. 

Stimulates erythrocyte production treatment of anemia in patients with kidney disease. 

Epoetin alfa, recombinant erythropoietin, is a glycoprotein that simulates erythrocyte production. Epoetin alfa is administered three times weekly subcutaneously or intravenously. Epoetin is used to treat anemia in patients with chronic renal failure, HIV infection, and patients receiving chemotherapy [104]. Development of a safe, effective nasal formulation of epoetin alfa, containing an absorption enhancer could once again improve the efficacy of epoetin alfa therapy, and reduce the number of injections required in these sensitive patient populations. 

The formed elements of blood are red blood cells, platelets, and leukocytes. Red blood cells, or erythrocytes (Figure 9.2), are flexible biconcave disk-shaped bodies whose main function is to carry oxygen to tissue bound to the hemoglobin that they contain. They are generated in the marrow of various bones by the action of stem cells. The hormone erythropoietin stimulates erythrocyte production in response to tissue needs for oxygen. Marrow stem cells also produce platelets, tiny cell fragments that contain the biochemicals necessary for blood clotting. The third kind of formed elements consists of leukocytes, which are defensive white blood cells. 

Proteins are also used clinically to treat a variety of diseases. Erythropoietin stimulates erythrocyte production in kidney dialysis and chemotherapy patients. Granulocyte stimulating factor enhances immune systems compromised by cancer treatments. Cytokines such as interferons and interleukins are used for their anti-viral and anti-tumor activities. Other proteins are used to inhibit or stimulate blood clotting. For the most part, the pharmaceutical protein industry relies on cloning native human genes and expressing and purifying their products in recombinant form. 

Epogen Procrit ) - more fully termed 1-165-erythropoetin (human clone y HEPOFL13 protein moiety -is recombinant human erythropoietin produced by genetically engineered Chinese hamster cells. It is a haematinic and regulates red blood cell production. It is used as a haemopoietic and ANTMNAEMIC in the treatment of anaemia associated with chfbnic renal failure, and also in ANTICANCER chemotherapy to stimulate erythrocyte production after treatment. 

The hormone EPO, 90% of which is produced by the kidneys, initiates and stimulates the production of RBCs. Erythropoiesis is driven by a feedback loop. The main mechanism of action of EPO is to prevent apoptosis, or programmed cell death, of erythroid precursor cells and to allow their proliferation and subsequent maturation. A decrease in tissue oxygen concentration signals the kidneys to increase the production and release of EPO into the plasma, which (1) stimulates stem cells to differentiate into proerythroblasts, (2) increases the rate of mitosis, (3) increases the release of reticulocytes from the marrow, and (4) induces Hgb formation. In normal circumstances, the RBC mass is kept at an almost constant level by EPO matching new erythrocyte production to the namral rate of loss of RBCs. Accelerated Hgb synthesis makes it possible to achieve the critical Hgb concentration necessary for RBCs to mature more rapidly, and a feedback mechanism stops further RBC nucleic acid synthesis, causing an earlier release of reticulocytes. Early appearance of large quantities of reticulocytes in the peripheral circulation (reticulocytosis) is another indication of increased RBC production. 

Erythropoietin is typical of the newer products. This protein hormone (M 51,000) stimulates erythrocyte production. People with diseases that com-... 

Human Toxicity Large amounts of CoCl2 depress erythrocyte production. May lead to death in children. Other effects include cutaneous flushing, chest pains, dermatitides, tinnitus, nausea and vomiting, nerve deafness, thyroid hyperplasia, myxedema, congestive heart failnre. See E. Beut-ler et al.. Clinical Disorders of Iron Metabolism (Grime Stratton, New York, 1963) pp 175-178. 

When the blood enzymes have been irreversibly inhibited, recovery of ChE activity depends on production of new plasma enzymes or production of new erythrocytes. Hence, complete recovery of BuChE activity that has been totally inhibited by sarin will occur in about 50 days, and recovery of the RBC-ChE, in 120 days (about 1% per day).44 In humans, after inhibition by VX, the RBC-ChE activity seems to recover spontaneously at the rate of about 0.5% to 1% per hour for a few days, but complete recovery depends on erythrocyte production.41,42... 

Low concentrations of serum inhibit polyene haemolysis [109], so that direct interaction of antibiotic with erythrocytes in vivo may not be the cause of polyene-induced haemolytic anemia observed in patients [353,354]. The survival time of red blood cells in vivo was not reduced by amphotericin B and it was suggested that haemolytic anemia following polyene therapy was the result of suppressed erythrocyte production by bone marrow [353]. 

Apiastic crisis A period during which erythrocyte production ceases. 

LEAD-INDUCED ANEMIA VIA ALTERED ERYTHROCYTE PRODUCTION AND DESTRUCTION... 

The recognition of a hemolytic or erythrocyte survival component to the anemia of Pb exposure occurred quite early in the literature, and the topic has been reviewed in past years (Angle and Mclntire, 1982 Moore, 1988 U. S. EPA 1977, 1986 Valentine and Paglia, 1980 Waldron, 1966). These earlier findings reflected the dose—response relationships for erythrocyte production and function at relatively high Pb exposures, notably for Pb workers, >40-80 pg/dl. 

TABLE 16.2 Hematological Effects of Pb in Human Populations Lead-Induced Anemia via Altered Erythrocyte Production and Destruction ... 

A lowered blood oxygen tension serves as a stimulus for erythropoiesis. Oianges are detected by the kidney, which responds by releasing erythnqXMetin, a hor mone that stimulates erythrocyte production. 

In the absence of the three accessory factors, the effect of either fraction E or H alone upon erythrocyte production was moderate. When fractions A, C and F were administered as well, a satisfactory erythrocyte response was obtained. Data taken from their paper illustrating this point are shown in Fig. 1. The administration of a combination of primary and accessory factors resulted in a rate of erythrocyte production closely approximating that produced by the intramuscular administration of an amount of commercial liver extract containing equivalent quantities of the primary and accessory factors. 

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