Nucleated red blood cell

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NRBCs are visible as larger cells with dark centers.

In mammals, a nucleated red blood cell (NRBC), also known by several other names, is a red blood cell (RBC or erythrocyte) that retains a nucleus. Normal mature mammalian RBCs have no nucleus, but progenitor cells in the erythropoietic lineage (the process of making RBCs) do. Normally, nucleated RBCs are found only in the circulation of fetuses and newborn infants.[1] After infancy, RBCs normally only contain a nucleus during the very early stages of the cell's life, and the nucleus is ejected as a normal part of cellular differentiation before the cell is released into the bloodstream. Thus, if NRBCs are seen on an adult's peripheral blood smear, it suggests that there is a very high demand for the bone marrow to produce RBCs, and immature RBCs are being released into circulation. Possible pathologic causes include anemia, myelofibrosis, thalassemia, miliary tuberculosis, cancers involving bone marrow (myelomas, leukemias, lymphomas), and in chronic hypoxemia.[2]


Several names are used for nucleated RBCs—erythroblast, normoblast, and megaloblast—with one minor variation in word sense. [3] [4] [5] [6] The name normoblast always refers to normal, healthy cells that are the immediate precursors of normal, healthy, mature (anucleate) RBCs. The name megaloblast always refers to abnormally developed precursors. Often the name erythroblast is used synonymously with normoblast, but at other times it is considered a hypernym. In the latter sense, there are two types of erythroblasts: normoblasts as cells that develop as expected, and megaloblasts as unusually large erythroblasts that are associated with illness.

Healthy development[edit]

There are four stages in the normal development of a normoblast.

A comprehensive diagram of human hematopoiesis
Illustration Description Image
Proerythroblast.png Pronormoblast
Basophilic erythroblast.png Basophilic normoblast Prorubricyte.jpg
Polychromatic erythroblast.png Polychromatic normoblast (also polychromatophilic) Rubricyte.jpg
Orthochromatic erythroblast.png Orthochromatic normoblast (also orthochromatophilic) Metarubricyte.jpg


A megaloblast is an unusually large erythroblast that can be associated with vitamin B12 deficiency (caused by pernicious anemia or dietary insufficiency), folic acid deficiency, or both (such anemias are collectively called megaloblastic anemias). This kind of anemia leads to macrocytes (abnormally large red cells) and the condition called macrocytosis. The cause of this cellular gigantism is an impairment in DNA replication that delays nuclear maturation and cell division. Because RNA and cytoplasmic elements are synthesized at a constant rate despite the cells' impaired DNA synthesis, the cells show nuclear-cytoplasmic asynchrony.

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