A mature red blood cell, also known as an erythrocyte, is a specialized blood cell primarily responsible for transporting oxygen from the lungs to the body’s tissues and carrying carbon dioxide back to the lungs. In its mature form, this cell is unique among human cells because it lacks a nucleus and most other organelles, which allows it to maximize space for hemoglobin, the protein that binds oxygen. A nucleated red blood cell (NRBC) represents an immature stage of a red blood cell that still retains its nucleus.
The Nucleus: A Key Difference
The presence or absence of a nucleus is a defining characteristic distinguishing immature from mature red blood cells. Red blood cell production, called erythropoiesis, begins in the bone marrow from hematopoietic stem cells. These stem cells differentiate through several stages, including proerythroblasts, erythroblasts, and normoblasts, all of which contain a nucleus.
During the final stages of maturation, the red blood cell precursor expels its nucleus in a process called enucleation. This nuclear extrusion allows the cell to become biconcave and flexible, enabling it to navigate narrow capillaries and optimize oxygen transport. After enucleation, the reticulocyte matures into a fully functional erythrocyte, losing any remaining organelles before entering the bloodstream.
Where Nucleated Red Blood Cells Belong
Nucleated red blood cells are a normal finding in specific physiological contexts. They are found within the bone marrow, where red blood cells are continuously produced and mature. Their presence in the bone marrow indicates the ongoing process of erythropoiesis, as these are the precursor cells before they fully develop and extrude their nuclei.
Additionally, NRBCs are a normal component of the peripheral blood in fetuses and newborns. During fetal development, the liver and then the bone marrow produce red blood cells, and the oxygen demands and production mechanisms differ from those in adults. In healthy term newborns, NRBCs are present at birth and usually disappear from circulation within the first few days to weeks of life.
Why They Appear in Peripheral Blood
The appearance of nucleated red blood cells in adult peripheral blood indicates underlying medical conditions. Their presence suggests bone marrow stress or damage, prompting premature release of these immature cells into circulation. This occurs with increased demand for red blood cell production or a disruption of the normal bone marrow environment.
Common reasons for NRBCs in adult blood include severe anemia, where the body attempts to compensate for a low red blood cell count by accelerating red blood cell production and releasing immature forms. Conditions causing chronic or acute oxygen deprivation (hypoxia), such as severe lung illness or heart failure, can also stimulate NRBC release to enhance oxygen-carrying capacity. Massive blood loss or rapid destruction of red blood cells (hemolysis) similarly triggers an urgent demand for new red blood cells, leading to NRBCs.
Bone marrow disorders are another cause of circulating NRBCs. These include conditions where the bone marrow’s structure or function is compromised, such as myelofibrosis (a rare blood cancer that causes scarring in the bone marrow), or certain types of leukemia and myelodysplastic syndromes.
In these instances, the normal maturation process is disrupted, or the bone marrow’s barrier to the bloodstream is compromised, allowing immature cells to escape. The presence of NRBCs in adult peripheral blood can signal a serious condition and may prompt further diagnostic testing to identify the root cause.