Nucleated red blood cell

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A human peripheral blood smear; NRBCs are visible as larger cells with dark centers. Nucleated red cells.jpg
A human peripheral blood smear; NRBCs are visible as larger cells with dark centers.

A nucleated red blood cell (NRBC), also known by several other names, is a red blood cell that contains a cell nucleus. Almost all vertebrate organisms have hemoglobin-containing cells in their blood, and with the exception of mammals, all of these red blood cells are nucleated. [1] In mammals, NRBCs occur in normal development as precursors to mature red blood cells in erythropoiesis, the process by which the body produces red blood cells.

Contents

NRBCs are normally found in the bone marrow of humans of all ages and in the blood of fetuses and newborn infants. [2] [3] After infancy, RBCs normally contain a nucleus only 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. The presence of circulating NRBCs in adults occurs in situations of hematopoietic stress such as severe infection, massive hemorrhage, marrow infiltration, or extramedullary hematopoiesis. [4] That is, if NRBCs are identified on an adult's complete blood count or 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. [5]

Nomenclature

Normocyte, Giemsa stain Normocyte.jpg
Normocyte, Giemsa stain

Several names are used for nucleated RBCs—erythroblast, normoblast, and megaloblast—with one minor variation in word sense. [6] [7] [8] [9] 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

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

IllustrationDescriptionImage
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

Pathogenesis

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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See also

Related Research Articles

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A blood cell, also called a hematopoietic cell, hemocyte, or hematocyte, is a cell produced through hematopoiesis and found mainly in the blood. Major types of blood cells include red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes). Together, these three kinds of blood cells add up to a total 45% of the blood tissue by volume, with the remaining 55% of the volume composed of plasma, the liquid component of blood.

<span class="mw-page-title-main">Anemia</span> Medical condition

Anemia or anaemia is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. The name is derived from Ancient Greek: ἀναιμία anaimia, meaning 'lack of blood', from ἀν- an-, 'not' and αἷμα haima, 'blood'. When anemia comes on slowly, the symptoms are often vague, such as tiredness, weakness, shortness of breath, headaches, and a reduced ability to exercise. When anemia is acute, symptoms may include confusion, feeling like one is going to pass out, loss of consciousness, and increased thirst. Anemia must be significant before a person becomes noticeably pale. Symptoms of anemia depend on how quickly hemoglobin decreases. Additional symptoms may occur depending on the underlying cause. Preoperative anemia can increase the risk of needing a blood transfusion following surgery. Anemia can be temporary or long term and can range from mild to severe.

<span class="mw-page-title-main">Myelodysplastic syndrome</span> Diverse collection of blood-related cancers

A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may include fatigue, shortness of breath, bleeding disorders, anemia, or frequent infections. Some types may develop into acute myeloid leukemia.

<span class="mw-page-title-main">Reticulocyte</span> Blood cells

Reticulocytes are immature red blood cells (RBCs). In the process of erythropoiesis, reticulocytes develop and mature in the bone marrow and then circulate for about a day in the blood stream before developing into mature red blood cells. Like mature red blood cells, in mammals, reticulocytes do not have a cell nucleus. They are called reticulocytes because of a reticular (mesh-like) network of ribosomal RNA that becomes visible under a microscope with certain stains such as new methylene blue and Romanowsky stain.

<span class="mw-page-title-main">Erythropoiesis</span> Process which produces red blood cells

Erythropoiesis is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell.

<span class="mw-page-title-main">Megaloblastic anemia</span> Medical condition

Megaloblastic anemia is a type of macrocytic anemia. An anemia is a red blood cell defect that can lead to an undersupply of oxygen. Megaloblastic anemia results from inhibition of DNA synthesis during red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis (M) stage. This leads to continuing cell growth without division, which presents as macrocytosis. Megaloblastic anemia has a rather slow onset, especially when compared to that of other anemias. The defect in red cell DNA synthesis is most often due to hypovitaminosis, specifically vitamin B12 deficiency or folate deficiency. Loss of micronutrients may also be a cause.

Primary myelofibrosis (PMF) is a rare bone marrow blood cancer. It is classified by the World Health Organization (WHO) as a type of myeloproliferative neoplasm, a group of cancers in which there is growth of abnormal cells in the bone marrow. This is most often associated with a somatic mutation in the JAK2, CALR, or MPL gene markers. In PMF, the healthy marrow is replaced by scar tissue (fibrosis), resulting in a lack of production of normal blood cells. Symptoms include anemia, increased infection and an enlarged spleen (splenomegaly).

<span class="mw-page-title-main">Microcytic anemia</span> Medical condition

Microcytic anaemia is any of several types of anemia characterized by smaller than normal red blood cells. The normal mean corpuscular volume is approximately 80–100 fL. When the MCV is <80 fL, the red cells are described as microcytic and when >100 fL, macrocytic. The MCV is the average red blood cell size.

<span class="mw-page-title-main">Myeloblast</span>

The myeloblast is a unipotent stem cell which differentiates into the effectors of the granulocyte series. It is found in the bone marrow. Stimulation of myeloblasts by G-CSF and other cytokines triggers maturation, differentiation, proliferation and cell survival.

<span class="mw-page-title-main">Sideroblastic anemia</span> Medical condition

Sideroblastic anemia, or sideroachrestic anemia, is a form of anemia in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells (erythrocytes). In sideroblastic anemia, the body has iron available but cannot incorporate it into hemoglobin, which red blood cells need in order to transport oxygen efficiently. The disorder may be caused either by a genetic disorder or indirectly as part of myelodysplastic syndrome, which can develop into hematological malignancies.

<span class="mw-page-title-main">Proerythroblast</span>

A proerythroblast is the earliest of four stages in development of the normoblast.

<span class="mw-page-title-main">Extramedullary hematopoiesis</span> Medical condition

Extramedullary hematopoiesis refers to hematopoiesis occurring outside of the medulla of the bone. It can be physiologic or pathologic.

Myelophthisic anemia is a severe type of anemia found in some people with diseases that affect the bone marrow. Myelophthisis refers to the displacement of hemopoietic bone-marrow tissue by fibrosis, tumors, or granulomas. The word comes from the roots myelo-, which refers to bone marrow, and phthysis, shrinkage or atrophy.

<span class="mw-page-title-main">Promyelocyte</span>

A promyelocyte is a granulocyte precursor, developing from the myeloblast and developing into the myelocyte. Promyelocytes measure 12-20 microns in diameter. The nucleus of a promyelocyte is approximately the same size as a myeloblast but their cytoplasm is much more abundant. They also have less prominent nucleoli than myeloblasts and their chromatin is more coarse and clumped. The cytoplasm is basophilic and contains primary red/purple granules.

Microcytosis or microcythemia is a condition in which red blood cells are unusually small as measured by their mean corpuscular volume.

Normocytic anemia is a type of anemia and is a common issue that occurs for men and women typically over 85 years old. Its prevalence increases with age, reaching 44 percent in men older than 85 years. The most common type of normocytic anemia is anemia of chronic disease.

<span class="mw-page-title-main">White blood cell</span> Type of cells of the immunological system

White blood cells, also called leukocytes or leucocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. White blood cells include three main subtypes; granulocytes, lymphocytes and monocytes.

<span class="mw-page-title-main">Polychromasia</span> Medical condition

Polychromasia is a disorder where there is an abnormally high number of immature red blood cells found in the bloodstream as a result of being prematurely released from the bone marrow during blood formation These cells are often shades of grayish-blue. Polychromasia is usually a sign of bone marrow stress as well as immature red blood cells. 3 types are recognized, with types 1 and 2 being referred to as 'young red blood cells' and type 3 as 'old red blood cells'. Giemsa stain is used to distinguish all three types of blood smears. The young cells will generally stain gray or blue in the cytoplasm. These young red blood cells are commonly called reticulocytes. All polychromatophilic cells are reticulocytes, however, not all reticulocytes are polychromatophilic. In the old blood cells, the cytoplasm either stains a light orange or does not stain at all.

Congenital dyserythropoietic anemia type IV has been described with typical morphologic features of CDA II but a negative acidified-serum test.

References

  1. Hartenstein, V (2006). "Blood cells and blood cell development in the animal kingdom" (PDF). Annu Rev Cell Dev Biol. 22: 677–712. doi:10.1146/annurev.cellbio.22.010605.093317. PMID   16824014 . Retrieved October 28, 2016.
  2. Greer, JP; Arber, DA; Glader, BE; List, AF; Means, RM; Rodgers, GM (19 November 2018). "Chapter 1: Examination of the Blood and Bone Marrow, sec. "Nucleated Red Blood Cell Counts"". Wintrobe's Clinical Hematology (14th ed.). Wolters Kluwer Health. ISBN   978-1-4963-6713-6.
  3. Kottke-Marchant, K; Davis, B (6 June 2012). Laboratory Hematology Practice. John Wiley & Sons. p. 294. ISBN   978-1-4443-9857-1.
  4. Shehata, Amira M.F. (2020-09-30). "Clinical significance of nucleated red blood cell count in pediatric patients with transfusion-dependent beta thalassemia". Menoufia Medical Journal. 33 (3): 949–955.
  5. Blood Smear: Details on RBCs, WBCs
  6. " Erythroblast " at Dorland's Medical Dictionary
  7. " Normoblast " at Dorland's Medical Dictionary
  8. " Megaloblast " at Dorland's Medical Dictionary
  9. Normoblasts at the U.S. National Library of Medicine Medical Subject Headings (MeSH)