Bone marrow reserve

Age-related reductions in bone marrow reserve can render the elderly patient more susceptible to anemia that is caused by multiple minor and often unrecognized diseases (e.g., nutritional deficiencies) that negatively affect erythropoiesis. 

The GFR can be measured most precisely using the 51Cr-EDTA clearance method, but for everyday practice the determination based on nomograms using serum creatinine values provides an adequately accurate estimate. It should be emphasized, however, that the myelotoxicity is also influenced by the general condition of the patient, especially by the extent of bone marrow reserve. Therefore, even when using an AUC-based administration scheme the seriousness of myelotoxicity cannot be accurately predicted. 

In anemia of critical illness, the mechanism for RBC replenishment and homeostasis is altered by, for example, blood loss or cytokines, which can blunt the erythropoietic response and inhibit RBC production. Age-related reductions in bone marrow reserve can render the elderly patient more snsceptible to anemia that is cansed by multiple minor and often nnrecognized diseases (e.g., nntritional deficiencies) that negatively affect erythropoiesis. 

Although the extent of leukopenia is not related to cumulative anthracycline dose, patients who have received extensive prior chemotherapy develop more severe leukopenia, possibly because of diminished bone marrow reserve (24). There was a strong correlation between dose and both leukocyte nadirs and platelet nadirs in 287 patients who received single-agent epirubicin 40, 60, 90, or 135 mg/m every 3 weeks (56). Myelosuppression correlates with exposure to epirubicin, as reflected by the plasma AUC (57). 

Bone marrow suppression is a recognized toxic effect of flucytosine anemia, leukopenia, and thrombocytopenia occur in about 5% of cases. The hematological effects are dose-related and occur after prolonged high blood concentrations of flucytosine (over 100 pg/ml). Hematotoxicity is seen more often in the presence of renal insufficiency and hence during the use of flucytosine in combination with amphotericin. If bone marrow reserve has already been depleted by underlying disease or by medications, the risk of hematotoxicity increases. 

The antipsychotic agents are known to precipitate proteins and may coprecipitate polynucleotides so they can no longer participate in nucleic acid synthesis. Chlorpromazme also increases the loss of macromolecules from the intracellular pools that are essential for cellular replication. When the hone marrow from a patient with phenothiazine-induced agranulocytosis is examined, it initially appears to have no cellularity (aplastic), hut over time it becomes hyperplastic. It is believed that toxic effects of the phenothiazines are not seen in all patients taking the medications because the majority of patients have enough bone marrow reserve to overcome the toxic effects. ... 

Although rare, acute hemolytic anemia can occur. This may reflect an immune reaction or may be due to glucose-6-phosphate dehydrogenase deficiency. Agranulocytosis occurs in -0.1% of patients who receive sulfadiazine and also can occur with other sulfonamides. Although neutropenia may persist for weeks or months after sulfonamide is withdrawn, most patients recover spontaneously with supportive care. Pancytopenia with complete suppression of bone-marrow activity is extremely rare. It probably results from a direct myelotoxic effect and may be fatal. Reversible suppression of the bone marrow is quite common in patients with limited bone marrow reserve (e.g., patients with AIDS or those receiving myelosuppressive chemotherapy). 

The versatility of immunophenotypic analysis has enhanced its usefulness. Immunophenotyping can be performed on a variety of specimens including cryop-reserved tissue sections, routinely preserved tissue sections, cells in suspension, tissue-touch preparations ( touch preps ), fine-needle aspiration smears, cytology thin preps and smears, as well as bone marrow aspirate smears. With the evolution of medical science and technical ability the number and types of antigens that can be detected in each type of preparation have greatly increased. Furthermore, as an additional result of these technical and scientific advances, immunophenotyping, particularly of routinely fixed tissue sections, can be performed reliably in many laboratories. 

Serum folate below 7 nmol per L or erythrocyte folate below 320 nmol per L indicates negative folate balance and early depletion of body reserves. At this stage, the first bone marrow changes are detectable. 

Felbamate is currently reserved for patients who are refractory to other drugs after careful consideration of the benefitrharm balance. In some countries the indication has been restricted to refractory Lennox-Gastaut syndrome. It is wise to avoid felbamate in patients with previous blood dyscrasias or autoimmune disorders, especially lupus erythematosus. Before they start to take it, patients should be informed about the potential risks and early symptoms of bone-marrow toxicity, such as bruisability, petechiae, fever of unknown origin, weakness, and fatigue. Hematology tests should be performed at baseline and during treatment, and dose escalation should be slow. 

The minerals in bones are completely replaced about every seven years, being deposited and withdrawn many times, just like money in a bank account. The body is designed so that minerals and trace elements that play key roles in body activities have a backup reserve in case of emergency. Extra iron, if needed, is stored in the liver, spleen, and bone marrow as ferritin, an iron-phosphorus protein. Sodium reserves are in the bones, stomach walls, and joints.The liver stores a year s supply of vitamin B)2 in case of temporary deficiency in the diet. Fat tissue in the body is also an energy fuel reserve. The body is prepared to deal with short-term deficiencies of most essential nutrients. 

Most of the body s neutrophils and neutrophilic precursors reside in the bone marrow (approximately 9 billion cells) in contrast to the circulation (approximately 700 million). Similarly, only 1% of the eosinophils in the body are found in peripheral blood, whereas the skin, lungs, and gastrointestinal tract are the preferred sites of residence. There is no marrow reserve pool of monocytes. Neutrophil development in the bone marrow begins with the stem cell and proceeds through intermediate precursors, such as the myeloblast, promyelocyte, myelocyte, and metamyelocyte. 

Because it is extremely toxic to bone marrow, its use is reserved for life-threatening infections where no other antibiotic is effective. 

Mollin and Ross believe that only when depletion of tissues has become extreme do serum B12 levels fall below the lowest limit of the normal range and megaloblasts appear in the bone marrow. They estimate that months or even years would elapse before tissue reserves would be restored to normal on the dosage regimes indicated above. 

Nonpregnant women—It has been established that there are many healthy, nonanemic, young women who have negligible amounts of iron stores (the liver, bone marrow, and spleen may contain some unused iron which may be drawn upon to meet physiological requirements). These women have no reserves to meet increased needs due to such events as blood loss, pregnancy, and other stresses. Furthermore, some women who use the contraceptive pill may become depleted of folic acid and, therefore, have increased susceptibility to megaloblastic anemia (hormones present in oral contraceptives reduce the utilization of dietary folic acid). 

The human body contains only about 0.004% iron, or only 3 to 4 g in an adult. About 70% of the iron is present in the hemoglobin, the pigment of the red blood cells. Most of the rest (about 30%) is present as a reserve store in the liver, spleen, and bone marrow. Despite the very small amount in the body, iron is one of the most important elements in nutrition and of fundamental importance to life. It is a component of hemoglobin, myoglobin (muscle hemoglobin), the cytochromes, catalase, and peroxidase. As part of these heme complexes and metalloenzymes, it serves important functions in oxygen transport and cellular respiration. 

About 70% of the iron is present in the hemoglobin, the pigment of the red blood celb. The other 30% is present as a reserve store in the 9ver, spleen, and bone marrow... 

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