Erythrocyte deformability

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Erythrocyte deformability refers to the ability of erythrocytes (red blood cells, RBC) to change shape under a given level of applied stress, without hemolysing (rupturing). This is an important property because erythrocytes must change their shape extensively under the influence of mechanical forces in fluid flow or while passing through microcirculation. The extent and geometry of this shape change can be affected by the mechanical properties of the erythrocytes, the magnitude of the applied forces, and the orientation of erythrocytes with the applied forces. Deformability is an intrinsic cellular property of erythrocytes determined by geometric and material properties of the cell membrane, [1] although as with many measurable properties the ambient conditions may also be relevant factors in any given measurement. No other cells of mammalian organisms have deformability comparable with erythrocytes; furthermore, non-mammalian erythrocytes are not deformable to an extent comparable with mammalian erythrocytes. In human RBC there are structural support that aids resilience in RBC which include the cytoskeleton- actin and spectrin that are held together by ankyrin.

Contents

The phenomenon

Shape change of erythrocytes under applied forces (i.e., shear forces in blood flow) is reversible and the biconcave-discoid shape, which is normal for most mammals, is maintained after the removal of the deforming forces. In other words, erythrocytes behave like elastic bodies, while they also resist to shape change under deforming forces. This viscoelastic behavior of erythrocytes is determined by the following three properties: [2] 1) Geometry of erythrocytes; the biconcave-discoid shape provides an extra surface area for the cell, enabling shape change without increasing surface area. This type of shape change requires significantly smaller forces than those required for shape change with surface area expansion. 2) Cytoplasmic viscosity; reflecting the cytoplasmic hemoglobin concentration of erythrocytes. 3) Visco-elastic properties of erythrocyte membrane, mainly determined by the special membrane skeletal network of erythrocytes.[ citation needed ]

Physiological significance

Erythrocyte deformability is an important determinant of blood viscosity, hence blood flow resistance in the vascular system. [3] It affects blood flow in large blood vessels, due to the increased frictional resistance between fluid laminae under laminar flow conditions. It also affects the microcirculatory blood flow significantly, where erythrocytes are forced to pass through blood vessels with diameters smaller than their size.[ citation needed ]

Clinical significance

Erythrocyte deformability is altered under various pathophysiological conditions. Sickle-cell disease is characterized by extensive impairment in erythrocyte deformability, being dependent on the oxygen partial pressure. Erythrocyte deformability has also been demonstrated to be impaired in diabetes, peripheral vascular diseases, sepsis and a variety of other diseases. The property offers broad utility in disease diagnosis [4] (also see Measurement, below).

Stored packed red blood cells (sometimes denoted "pRBC" or "StRBC") also experience changes in membrane properties like deformability during storage and related processing, as part of a broader phenomenon known as "storage lesion." While the clinical implications are still being explored, deformability can be indicative of quality or preservation thereof for stored RBC product available for blood transfusion. [5] [6] [7] Perfusion (or perfusability) is a deformability-based metric that may offer a particularly physiologically-relevant representation of storage-induced deterioration of RBC occurring in blood banks, and the associated impacts of storage conditions/systems. [8]

Measurement

Erythocyte deformability is a measurable property, and various means for its measurement have been explored - with each having results and significance being highly particularized to the given approach employed. Accordingly, the term is somewhat loose in the sense that a given cell or sample of cells may be deemed significantly more "deformable" by one means/metric relative to another means/metric. Thus for meaningful "apples-to-apples" comparisons involving cell deformability, it is important to utilize the same qualitative approach.[ citation needed ]

Ektacytometry based on laser diffraction analysis is a commonly preferred (and a fairly direct) method for measuring deformability. [9] Another direct metric is optical tweezers, which targets individual cells. Deformability can in effect be measured indirectly, such as by how much pressure and/or time it takes cells pass through pores of a filter (i.e., filterability or filtration) [10] or perfuse through capillaries (perfusion), [11] in vitro or in vivo, having smaller diameters than the cells'. Some deformability tests may be more physiologically-relevant than others for given applications. For example, perfusion is more sensitive to relatively small changes in deformability (compared to filterability), [12] thus making it preferable for assessing RBC deformability in contexts where microcirculatory implications are of particular interest. Moreover, some tests may track how deformability itself changes as conditions change and/or as deformation is repeated.[ citation needed ]

Erythrocytes/RBC may also be tested for other (related) membrane properties, including erythrocyte fragility (osmotic or mechanical) and cell morphology. Morphology can be measured by indexes which characterize shape changes of differences among cells. Fragility testing involves subjecting a sample of cells to osmotic and/or mechanical stress(es), then ascertaining how much hemolysis results thereafter, and then characterizing susceptibility to or propensity for stress-induced hemolysis with an index or profile (which can be useful to assess cells' ability to withstand sustained or repeated stresses).[ citation needed ]

Other related red blood cell properties can include adhesion and aggregation, which along with deformability are often classed as RBC "flow properties."

Related Research Articles

Red blood cell 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 for "red" and kytos for "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.

Hemolysis Rupturing of red blood cells and release of their contents

Hemolysis or haemolysis, also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid. Hemolysis may occur in vivo or in vitro.

Blood transfusion Intravenous transference of blood products

Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but modern medical practice commonly uses only components of the blood, such as red blood cells, white blood cells, plasma, clotting factors and platelets.

Hemodynamics or haemodynamics are the dynamics of blood flow. The circulatory system is controlled by homeostatic mechanisms of autoregulation, just as hydraulic circuits are controlled by control systems. The hemodynamic response continuously monitors and adjusts to conditions in the body and its environment. Hemodynamics explains the physical laws that govern the flow of blood in the blood vessels.

A blood bank is a center where blood gathered as a result of blood donation is stored and preserved for later use in blood transfusion. The term "blood bank" typically refers to a division of a hospital where the storage of blood product occurs and where proper testing is performed. However, it sometimes refers to a collection center, and some hospitals also perform collection. Blood banking includes tasks related to blood collection, processing, testing, separation, and storage.

Hereditary spherocytosis 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.

Hemorheology, also spelled haemorheology, or blood rheology, is the study of flow properties of blood and its elements of plasma and cells. Proper tissue perfusion can occur only when blood's rheological properties are within certain levels. Alterations of these properties play significant roles in disease processes. Blood viscosity is determined by plasma viscosity, hematocrit and mechanical properties of red blood cells. Red blood cells have unique mechanical behavior, which can be discussed under the terms erythrocyte deformability and erythrocyte aggregation. Because of that, blood behaves as a non-Newtonian fluid. As such, the viscosity of blood varies with shear rate. Blood becomes less viscous at high shear rates like those experienced with increased flow such as during exercise or in peak-systole. Therefore, blood is a shear-thinning fluid. Contrarily, blood viscosity increases when shear rate goes down with increased vessel diameters or with low flow, such as downstream from an obstruction or in diastole. Blood viscosity also increases with increases in red cell aggregability.

Hemolytic anemia Medical condition

Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels or elsewhere in the human body (extravascular). This most commonly occurs within the spleen, but also can occur in the reticuloendothelial system or mechanically. Hemolytic anemia accounts for 5% of all existing anemias. It has numerous possible consequences, ranging from general symptoms to life-threatening systemic effects. The general classification of hemolytic anemia is either intrinsic or extrinsic. Treatment depends on the type and cause of the hemolytic anemia.

A Coombs test, also known as antiglobulin test (AGT), is either of two blood tests used in immunohematology. They are the direct and indirect Coombs tests. The direct Coombs test detects antibodies that are stuck to the surface of the red blood cells. Since these antibodies sometimes destroy red blood cells, a person can be anemic and this test can help clarify the condition. The indirect Coombs detects antibodies that are floating freely in the blood. These antibodies could act against certain red blood cells and the test can be done to diagnose reactions to a blood transfusion.

Blood doping is a form of doping in which the number of red blood cells in the bloodstream is boosted in order to enhance athletic performance. Because such blood cells carry oxygen from the lungs to the muscles, a higher concentration in the blood can improve an athlete's aerobic capacity (VO2 max) and endurance. Blood doping can be achieved by making the body produce more red blood cells itself using drugs, giving blood transfusions either from another person or back to the same individual, or by using blood substitutes.

Codocyte

Codocytes, also known as target cells, are red blood cells that have the appearance of a shooting target with a bullseye. In optical microscopy these cells appear to have a dark center surrounded by a white ring, followed by dark outer (peripheral) second ring containing a band of hemoglobin. However, in electron microscopy they appear very thin and bell shaped. Because of their thinness they are referred to as leptocytes. On routine smear morphology, some people like to make a distinction between leptocytes and codocytes- suggesting that in leptocytes the central spot is not completely detached from the peripheral ring, i.e. the pallor is in a C shape rather than a full ring.

Distributive shock is a medical condition in which abnormal distribution of blood flow in the smallest blood vessels results in inadequate supply of blood to the body's tissues and organs. It is one of four categories of shock, a condition where there is not enough oxygen-carrying blood to meet the metabolic needs of the cells which make up the body's tissues and organs. Distributive shock is different from the other three categories of shock in that it occurs even though the output of the heart is at or above a normal level. The most common cause is sepsis leading to a type of distributive shock called septic shock, a condition that can be fatal.

Hereditary elliptocytosis Medical condition

Hereditary elliptocytosis, also known as ovalocytosis, is an inherited blood disorder in which an abnormally large number of the person's red blood cells are elliptical rather than the typical biconcave disc shape. Such morphologically distinctive erythrocytes are sometimes referred to as elliptocytes or ovalocytes. It is one of many red-cell membrane defects. In its severe forms, this disorder predisposes to haemolytic anaemia. Although pathological in humans, elliptocytosis is normal in camelids.

Hereditary stomatocytosis Medical condition

Hereditary stomatocytosis describes a number of inherited autosomal dominant human conditions which affect the red blood cell, in which the membrane or outer coating of the cell 'leaks' sodium and potassium ions.

Rouleaux Stacks or aggregations of red blood cells

Rouleaux are stacks or aggregations of red blood cells (RBCs) that form because of the unique discoid shape of the cells in vertebrates. The flat surface of the discoid RBCs gives them a large surface area to make contact with and stick to each other; thus forming a rouleau. They occur when the plasma protein concentration is high, and, because of them, the ESR is also increased. This is a nonspecific indicator of the presence of disease.

Acquired hemolytic anemia can be divided into immune and non-immune mediated forms of hemolytic anemia.

Shu Chien, is a Chinese–American physiologist and bioengineer. His work on the fluid dynamics of blood flow has had a major impact on the diagnosis and treatment of cardiovascular diseases such as atherosclerosis. More recently, Chien's research has focused on the mechanical forces, such as pressure and flow, that regulate the behaviors of the cells in blood vessels. Chien is currently President of the Biomedical Engineering Society.

Erythrocyte aggregation

Erythrocyte aggregation is the reversible clumping of red blood cells (RBCs) under low shear forces or at stasis.

Erythrocyte fragility refers to the propensity of erythrocytes to hemolyse (rupture) under stress. It can be thought of as the degree or proportion of hemolysis that occurs when a sample of red blood cells are subjected to stress. Depending on the application as well as the kind of fragility involved, the amount of stress applied and/or the significance of the resultant hemolysis may vary.

Intravascular hemolysis describes hemolysis that happens mainly inside the vasculature. As a result, the contents of the red blood cell are released into the general circulation, leading to hemoglobinemia and increasing the risk of ensuing hyperbilirubinemia.

References

  1. ↑ Chien S (1987). "Red cell deformability and its relevance to blood flow". Annual Review of Physiology. 49: 177–192. doi:10.1146/annurev.ph.49.030187.001141. PMID   3551796.
  2. ↑ Mohandas N, Chasis JA (1993). "Red blood cell deformability, membrane material properties and shape: regulation by transmembrane, skeletal and cytosolic proteins and lipids". Seminars in Hematology. 30 (3): 171–192. PMID   8211222.
  3. ↑ Baskurt OK, Meiselman HJ (2003). "Blood rheology and hemodynamics". Seminars in Thrombosis and Hemostasis. 29 (5): 435–450. doi:10.1055/s-2003-44551. PMID   14631543.
  4. ↑ Tillmann W (1986). "[Reduced deformability of erythrocytes as a common denominator of hemolytic anemias]". Wien Med Wochenschr. 136 Spec No: 14–6. PMID   3548086.
  5. ↑ Decreased Erythrocyte Deformability After Transfusion and the Effects of Erythrocyte Storage Duration, Anesth Analg, published ahead of print February 28, 2013
  6. ↑ Journal of Blood Transfusion, Volume 2012, Article ID 102809
  7. ↑ Ann Ist Super Sanita 2007; 43(2):176-85.
  8. ↑ Transfusion. 2012 May;52(5):1010-23. Artificial microvascular network: a new tool for measuring rheologic properties of stored red blood cells. Burns JM, Yang X, Forouzan O, Sosa JM, Shevkoplyas SS.
  9. ↑ Baskurt OK; Hardeman; M.R. Uyuklu M; et al. (2009). "Comparison of three commercially available ektacytometers with different shearing geometries". Biorheology. 46 (3): 251–264. doi:10.3233/BIR-2009-0536. PMID   19581731.
  10. ↑ Advances in Hemodynamics and Hemorheology, Volume 1, edited by T.V. How
  11. ↑ Lab Chip. 2006 Jul;6(7):914-20. Direct measurement of the impact of impaired erythrocyte deformability on microvascular network perfusion in a microfluidic device. Shevkoplyas SS, Yoshida T, Gifford SC, Bitensky MW.
  12. ↑ Lab Chip. 2006 Jul;6(7):914-20. Direct measurement of the impact of impaired erythrocyte deformability on microvascular network perfusion in a microfluidic device. Shevkoplyas SS, Yoshida T, Gifford SC, Bitensky MW.
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