Mean Cell Volume (MCV)
The mean cell volume
indicates the volume of the "average" red cell in a sample. It is
expressed in femtoliters (fl; 10-15 liters). Traditionally, MCV was
a calculated parameter, derived by using the following formula:
MCV = (PCV ÷ RBC) x 10
Present-day automated hematology analyzers
provide a more accurate, direct measure of MCV,
based on the actual volume of the cell as it passes through a laser (newer laser-based hematologic analyzers) or an electronic beam. The amount of laser light scattered in a forward direction or the amplitude of pulses
created in the electronic field as the cells through the detector is equivalent to the cell volume, which is averaged based on the number of cells analyzed by the instrumen. The
instruments also "channelize" the scatter or impluses, segregating them into
channels representing relative ranges of cell size. This data is then
assembled into a cell size histogram, such as shown at right. The
histogram provides additional useful information about the characteristics
of the red cell population.
Histogram and red cell parameters from a normal canine blood sample.
Red cell populations with the MCV above the reference interval are termed
macrocytic. Conversely, red cell populations with the MCV below the reference interval are termed
Increased MCV (macrocytosis)
- Red cell clumping or agglutination: With impedance based analyzers, agglutinated RBC are detected as single large red cells, resulting in very high MCVs (> 90 fl) and low MCHCs. This occurs rarely with the newer laser-based analyzers, since the agglutinated clumps are excluded from the analysis (which may decrease the RBC count but does not affect the MCV).
- Storage-related changes: Red cells swell with storage, increasing the MCV and decreasing MCHC. This will occur quite rapidly, within 24 hours of collection particularly if the blood sample is not kept cool until analysis.
- Hyperosmolality: With the ADVIA hematology analyzer, macrocytosis can be observed in animals with severe hyperosmolality, e.g. hypernatremia. This is attributed to dehydration of red blood cells which occurs in vivo due to the hyperosmotic environment. Once these dehydrated cells are placed in an iso-osmolar diluent for counting within the analyzer, they are now actually hypertonic compared to the diluent and swell in vitro in the diluent, thus increasing the MCV and decreasing the MCHC.
- Physiologic: Breed-associated macrocytosis has been reported in Greyhounds (around 81 fl) and Miniature and Toy Poodles (up to 90 fl), without any evidence of anemia.
- Regenerative anemia: Since young red blood cells are usually larger, the MCV can be increased above reference intervals (and the MCHC decreased). These findings are less apparent with laser-based hematology analyzers. Ccats that have recovered from a recent anemia can be macrocytic, since punctate reticulocytes (which are frequently larger than normal red blood cells) can persist for up to 3 weeks in the circulation. This is called a post-regenerative macrocytosis.
- Red cell swelling due to osmotic effects/membrane abnormalities:
- Artifact (see above)
- Hereditary stomatocytosis: This inherited defect has been reported in Malamutes, Miniature Schnauzers, Pomeranians, Drentje-patrishjond and other breeds. There are breed-specific membrane defects in lipid content or the sodium/potassium pump, resulting in macrocytic and hypochromic red blood cells. Affected animals may not even be anemic.
- Defects in nuclear maturation/DNA synthesis
- Primary myelodysplasia: This is a clonal disorder, that in cats, is usually caused by FeLV.
- Folate or vitamin B12 deficiency: Both are required for DNA synthesis (thymidine and nucleoproteins). Impaired DNA synthesis delays cell division resulting in macrocytosis. These deficiencies can occur with intestinal disorders and small intestinal bacterial overgrowth (although macrocytosis is not a feature of these diseases), drugs which inhibit folate/vitamn B12 absorption or metabolism (e.g. trimethoprim sulphur, hydroxyurea) or because of other mineral deficiencies or excess, such as cobalt deficiency (primary or secondary to molybdenum excess) in ruminants. Cobalt is essential in the molecular structure of vitamin B12
- Inherited abnormalities in erythropoiesis: Congenital dyserythropoietic anemia (CDA) is an inherited defect in humans that results in macrocytosis. This has been reported in Poll Hereford cattle.
- Unknown mechanism or miscellaneous: Hyperthyroidism has been associated with macrocytosis in cats in some studies. This was attributed to thyroid hormone induced red cell production, with decreased maturation time and premature release of larger red blood cells.
Decreased MCV (microcytosis)
- Excess EDTA: EDTA is hypertonic and will cause cellular dehydration (decreasing the MCV and increasing the MCHC).
- Hyponatremia: An artifact of the ADVIA used at Cornell University is caused by a hypoosmolar environment in vivo, e.g. hyponatremia, to which erythrocytes adjust by increasing cytoplasmic water content. When put in a diluent prior to counting in the machine in vitro, osmosis results in water loss from RBCs within the analyzer, causing cell shrinkage (low MCV and high MCHC).
- Young animals: Puppies and kittens < 8-16 weeks old and calves and foals up to 1-2 months old can be microcytic and anemic. Calves and foals can remain microcytic (but not anemic) for up to 1 year of age. This is associated with low iron stores (and is called a “physiologic iron deficiency”). Neonatal alpacas can be anemic but are not microcytic.
- Breed associations: Microcytosis without anemia is found in Akitas, and possibly other Oriental breeds, such as the Shiba or Sharpeis, and Siberian Huskies
- Iron deficiency: Iron is an essential component of many enzymes in cells and is also part of the heme group in hemoglobin (which consists of a porphyrin ring containing iron ). Much of the body's iron stores are within red blood cells where iron is critical for hemoglobin synthesis. Iron deficiency could be due to inadequate intake or absorption of iron, excessive loss with external hemorrhage, or interference with iron metabolism. For more information on iron, refer to the chemistry section of this webpage.
- Lack or loss of iron: In adult animals, iron deficiency usually results from chronic exte3rnal blood loss, often gastrointestinal in origin. Young animals are predisposed to iron deficiency due to low iron intake (in milk), low body iron stores, and rapid growth rate. Iron deficiency is thought to result in microcytosis by the following hypothesized mechanism: Erythrocyte division in the bone marrow is governed by the hemoglobin concentration. Cell division stops when a critical hemoglobin concentration has been reached. Therefore, if hemoglobin production is defective (as occurs in iron deficiency), erythrocytes continue to divide until that hemoglobin concentration is reached. With each division they become successively smaller.
- Interference with iron use/uptake: Drugs, such as chloramphenicol and lead can interfere with iron uptake into hemoglobin. Nutritional deficiencies (or excesses) are an important cause of iron deficiency in animals, particularly herbivores. A deficiency of pyridoxine or copper can result in iron deficiency anemia. Pyridoxine is required for heme synthesis in red blood cells, whereas copper is an essential component of ceruloplasmin and haephestin which are required for the transfer of iron to/from macrophages and intestinal epithelial cells, respectively. An excess of some minerals, in particular zinc, can also inhibit copper absorption resulting in a secondary copper and then iron deficiency.
- Liver disease: Acquired or congenital hepatic shunts may produce microcytosis with or without anemia. The MHCH is usually normal but can be low. The microcytosis in shunting is thought to be due to altered iron metabolism from liver dysfunction and usually resolves with successful shunt closure.
- Unknown mechanisms or miscellaneous: An inherited dyserythropoietic disorder in English Springer Spaniels is associated with microcytic erythrocytes. Severe fragmentation anemias can result in microcytosis. Note, that although spherocytes in immune-mediated hemolytic anemia (IMHA) appear smaller on blood films (because they have reduced diameter), they usually have normal volumes. Therefore, microcytosis is unusual with IMHA.
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