Reticulocyte

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Reticulocyte
Polychromatic erythrocyte.png
Reticulocytes
Erythrocyte.png
Erythrocytes (mature cells)
Details
Gives rise to Red blood cells
Location Bone marrow (most), blood (some)
Identifiers
Latin reticulocytus
MeSH D012156
TH H2.00.04.1.01007
FMA 66785
Anatomical terms of microanatomy

Reticulocytes are immature red blood cells (RBCs). In the process of erythropoiesis (red blood cell formation), 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.

Contents

Clinical significance

To accurately measure reticulocyte counts, automated counters use a combination of laser excitation, detectors and a fluorescent dye that marks RNA and DNA (such as titan yellow or polymethine). [1]

Reticulocytes appear slightly bluer than other red cells when looked at with the normal Romanowsky stain. Reticulocytes are also relatively large, a characteristic that is described by the mean corpuscular volume.

Supravital stain of a smear of human blood from a patient with hemolytic anemia. The reticulocytes are the cells with the dark blue dots and curved linear structures (reticulum) in the cytoplasm. Reticulocytes Human Blood Supravital Stain.jpg
Supravital stain of a smear of human blood from a patient with hemolytic anemia. The reticulocytes are the cells with the dark blue dots and curved linear structures (reticulum) in the cytoplasm.

The normal fraction of reticulocytes in the blood depends on the clinical situation but is usually 0.5% to 2.5% in adults and 2% to 6% in infants. A reticulocyte percentage that is higher than "normal" can be a sign of anemia, but this depends on the health of a person's bone marrow. Calculating the reticulocyte production index is an important step in understanding whether or not the reticulocyte count is appropriate to the situation. This is often a more important question than whether the percentage is in the normal range; for instance, if someone is anemic but has a reticulocyte percentage of only 1%, the bone marrow is likely not producing new blood cells at a rate that will correct the anemia.

Immature reticulocyte fraction (IRF)

Reticulocytes at less mature levels can be detected by having higher intensity fluorescence regions. An increased immature reticulocyte fraction (IRF), specifically an IRF more than or equal to 0.23, together with an increased absolute reticulocyte count, generally indicates an adequate erythroid response to anemia. [2] An IRF of more than 0.23 but a subnormal or normal absolute reticulocyte count (with a corresponding reticulocyte production index of less than or equal to 2) is seen in for example acute infection, iron deficiency anemia, human immunodeficiency virus infection, sickle disease with crisis, pregnancy, and myelodysplastic syndrome. [2] An IRF of less than 0.23 is seen in diseases that lead to decreased erythropoietic activity, predominantly chronic renal insufficiency. [2]

Development

The development begins with the expulsion of the normoblast nucleus, and is followed by loss of organelles and remodeling of the plasma membrane, giving rise to an erythrocyte. [3]

Research

Reticulocytes are a valuable tool for biologists who study protein translation. Reticulocytes are unusual among cells in that they contain all of the machinery necessary to translate proteins but lack a nucleus. Since a cell's nucleus contains many components that make studying translation difficult, these cells are quite useful. Scientists can collect reticulocytes from animals such as rabbits and extract the mRNA and translation enzymes to study protein translation in a cell-free, in vitro system, allowing greater control over the environment in which proteins are being synthesized. [4] [5]

Related Research Articles

<span class="mw-page-title-main">Red blood cell</span> Oxygen-delivering blood cell and the most common type of blood cell

Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek erythros 'red' and kytos 'hollow vessel', with -cyte translated as 'cell' in modern usage), are the most common type of blood cell and the vertebrate's principal means of delivering oxygen (O2) to the body tissues—via blood flow through the circulatory system. RBCs take up oxygen in the lungs, or in fish the gills, and release it into tissues while squeezing through the body's capillaries.

<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">Complete blood count</span> Routine laboratory test of blood cells

A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cells and platelets, the concentration of hemoglobin, and the hematocrit. The red blood cell indices, which indicate the average size and hemoglobin content of red blood cells, are also reported, and a white blood cell differential, which counts the different types of white blood cells, may be included.

<span class="mw-page-title-main">Lymphocyte</span> Subtype of white blood cell

A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells, B cells, and Innate lymphoid cells (ILCs), of which natural killer cells are an important subtype. They are the main type of cell found in lymph, which prompted the name "lymphocyte". Lymphocytes make up between 18% and 42% of circulating white blood cells.

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

Fanconi anemia (FA) is a rare, AR, genetic disease resulting in impaired response to DNA damage in the FA/BRCA pathway. Although it is a very rare disorder, study of this and other bone marrow failure syndromes has improved scientific understanding of the mechanisms of normal bone marrow function and development of cancer. Among those affected, the majority develop cancer, most often acute myelogenous leukemia (AML), MDS, and liver tumors. 90% develop aplastic anemia by age 40. About 60–75% have congenital defects, commonly short stature, abnormalities of the skin, arms, head, eyes, kidneys, and ears, and developmental disabilities. Around 75% have some form of endocrine problem, with varying degrees of severity. 60% of FA is FANC-A, 16q24.3, which has later onset bone marrow failure.

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

Hereditary spherocytosis (HS) is a congenital hemolytic disorder, wherein a genetic mutation coding for a structural membrane protein phenotype leads to a spherical shaping of erythrocytic cellular morphology. As erythrocytes are sphere-shaped (spherocytosis), rather than the normal biconcave disk-shaped, their morphology interferes with these cells' abilities to be flexible during circulation throughout the entirety of the body - arteries, arterioles, capillaries, venules, veins, and organs. This difference in shape also makes the red blood cells more prone to rupture under osmotic and/or mechanical stress. Cells with these dysfunctional proteins are degraded in the spleen, which leads to a shortage of erythrocytes resulting in hemolytic anemia.

<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">Pyruvate kinase deficiency</span> Medical condition

Pyruvate kinase deficiency is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells. Both autosomal dominant and recessive inheritance have been observed with the disorder; classically, and more commonly, the inheritance is autosomal recessive. Pyruvate kinase deficiency is the second most common cause of enzyme-deficient hemolytic anemia, following G6PD deficiency.

<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.

<span class="mw-page-title-main">Left shift (medicine)</span>

Left shift or blood shift is an increase in the number of immature cell types among the blood cells in a sample of blood. Many clinical mentions of left shift refer to the white blood cell lineage, particularly neutrophil-precursor band cells, thus signifying bandemia. Less commonly, left shift may also refer to a similar phenomenon in the red blood cell lineage in severe anemia, when increased reticulocytes and immature erythrocyte-precursor cells appear in the peripheral circulation.

<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.

The reticulocyte production index (RPI), also called a corrected reticulocyte count (CRC), is a calculated value used in the diagnosis of anemia. This calculation is necessary because the raw reticulocyte count is misleading in anemic patients. The problem arises because the reticulocyte count is not really a count but rather a percentage: it reports the number of reticulocytes as a percentage of the number of red blood cells. In anemia, the patient's red blood cells are depleted, creating an erroneously elevated reticulocyte count.

The term macrocytic is from Greek words meaning "large cell". A macrocytic class of anemia is an anemia in which the red blood cells (erythrocytes) are larger than their normal volume. The normal erythrocyte volume in humans is about 80 to 100 femtoliters. In metric terms the size is given in equivalent cubic micrometers. The condition of having erythrocytes which are too large, is called macrocytosis. In contrast, in microcytic anemia, the erythrocytes are smaller than normal.

Red blood cell indices are blood tests that provide information about the hemoglobin content and size of red blood cells. Abnormal values indicate the presence of anemia and which type of anemia it is.

<span class="mw-page-title-main">Pappenheimer bodies</span> Abnormal iron deposits in red blood cells

Pappenheimer bodies are abnormal basophilic granules of iron found inside red blood cells on routine blood stain. They are a type of inclusion body composed of ferritin aggregates, or mitochondria or phagosomes containing aggregated ferritin. They appear as dense, blue-purple granules within the red blood cell and there are usually only one or two, located in the cell periphery. They stain on a Romanowsky stain because clumps of ribosomes are co‐precipitated with the iron‐containing organelles.

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">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.

<span class="mw-page-title-main">Nucleated red blood cell</span> Red blood cell with a cell nucleus

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. 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.

<span class="mw-page-title-main">White blood cell differential</span> Blood test

A white blood cell differential is a medical laboratory test that provides information about the types and amounts of white blood cells in a person's blood. The test, which is usually ordered as part of a complete blood count (CBC), measures the amounts of the five normal white blood cell types – neutrophils, lymphocytes, monocytes, eosinophils and basophils – as well as abnormal cell types if they are present. These results are reported as percentages and absolute values, and compared against reference ranges to determine whether the values are normal, low, or high. Changes in the amounts of white blood cells can aid in the diagnosis of many health conditions, including viral, bacterial, and parasitic infections and blood disorders such as leukemia.

References

  1. Davis BH, Bigelow NC (1994). "Reticulocyte analysis and reticulocute maturity index". In Darzynkiewicz Z, Crissman HA (eds.). Flow cytometry. Methods in Cell Biology. Vol. 42. San Diego: Academic Press. pp. 263–74. ISBN   0-12-203052-4.
  2. 1 2 3 Chang CC, Kass L (1997). "Clinical significance of immature reticulocyte fraction determined by automated reticulocyte counting". Am J Clin Pathol. 108 (1): 69–73. doi: 10.1093/ajcp/108.1.69 . PMID   9208980.
  3. Moras, Martina; Lefevre, Sophie D.; Ostuni, Mariano A. (December 19, 2017). "From Erythroblasts to Mature Red Blood Cells: Organelle Clearance in Mammals". Front. Physiol. 8: 1076. doi: 10.3389/fphys.2017.01076 . PMC   5742207 . PMID   29311991.
  4. "The Basics: In Vitro Translation - US".
  5. Woodward, William R.; Ivey, Joel L.; Herbert, Edward (1974). "[67a] Protein synthesis with rabbit reticulocyte preparations". Nucleic Acids and Protein Synthesis Part F. Methods in Enzymology. Vol. 30. pp.  724–731. doi:10.1016/0076-6879(74)30069-9. ISBN   9780121818937. PMID   4853925.