The M:E ratio is sensitive to hematologic factors that may impair red blood cell life span, inhibit overall production, or cause dramatic increases in a particular cell line. Each of these conditions reflects bone marrow dynamics through alterations of the M:E ratio. Many observations in the peripheral smear can be traced back to the pathophysiologic events at the level of bone marrow. A perfect example of this is the response of the bone marrow to anemia. As anemia develops and becomes more severe, the patient becomes symptomatic, and the kidney senses hypoxia secondary to a decreased hemoglobin level. Tissue hypoxia stimulates an increased release of erythropoietin (EPO), a red blood cell-stimulating hormone, from the kidney. EPO travels through the circulation and binds with a receptor on the youngest of bone marrow precursor cells, the pronormoblast. Bone marrow has the capacity to expand production 6-8 times in response to an anemic event. Consequently, the bone marrow delivers reticulocytes and nucleated red blood cells to the peripheral circulation prematurely if the kidney senses hypoxic stress. What is observed in the peripheral blood smear is polychromasia (stress reticulocytes, large polychromatophilic red blood cells) and nucleated red blood cells. Both of these cell types indicate that the bone marrow is regenerating in response to an event, a dynamic that represents the harmony between bone marrow and peripheral circulation.
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