Erythrocyte Deformability
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Erythrocyte deformability refers to the ability of
erythrocytes 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 "holl ...
(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 microcirculation is the circulation of the blood in the smallest blood vessels, the microvessels of the microvasculature present within organ tissues. The microvessels include terminal arterioles, metarterioles, capillaries, and venules. ...
. The extent and
geometry Geometry (; ) is, with arithmetic, one of the oldest branches of mathematics. It is concerned with properties of space such as the distance, shape, size, and relative position of figures. A mathematician who works in the field of geometry is ...
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, although as with many measurable properties the ambient conditions may also be relevant factors in any given measurement. No other cells of
mammalian Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur o ...
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 Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ov ...
and
spectrin Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. Spectrin forms pentagonal or hexagonal arrangements, forming a scaffold and playing an important role in maintenance of plasma membr ...
that are held together by ankyrin.


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 Elastic is a word often used to describe or identify certain types of elastomer, elastic used in garments or stretchable fabrics. Elastic may also refer to: Alternative name * Rubber band, ring-shaped band of rubber used to hold objects togeth ...
bodies, while they also resist to shape change under deforming forces. This viscoelastic behavior of erythrocytes is determined by the following three properties: 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 Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyt ...
concentration of erythrocytes. 3) Visco-elastic properties of erythrocyte membrane, mainly determined by the special membrane skeletal network of erythrocytes.


Physiological significance

Erythrocyte deformability is an important determinant of blood viscosity, hence blood flow resistance in the vascular system. 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.


Clinical significance

Erythrocyte deformability is altered under various
pathophysiological Pathophysiology ( physiopathology) – a convergence of pathology with physiology – is the study of the disordered physiological processes that cause, result from, or are otherwise associated with a disease or injury. Pathology is th ...
conditions.
Sickle-cell disease Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blo ...
is characterized by extensive impairment in erythrocyte deformability, being dependent on the
oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...
partial pressure. Erythrocyte deformability has also been demonstrated to be impaired in
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
, peripheral
vascular The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away f ...
diseases,
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
and a variety of other diseases. The property offers broad utility in disease diagnosis (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 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 mo ...
. 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 bank 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 department of a hospital usually within a Clinical Pathology laborat ...
s, and the associated impacts of storage conditions/systems.


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. ''Ektacytometry'' based on
laser diffraction analysis Laser diffraction analysis, also known as laser diffraction spectroscopy, is a technology that utilizes diffraction patterns of a laser beam passed through any object ranging from nanometers to millimeters in size to quickly measure geometrical dim ...
is a commonly preferred (and a fairly direct) method for measuring deformability. 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) or perfuse through capillaries (''perfusion''), ''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),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. 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.


Related erythrocyte properties

Erythrocytes/RBC may also be tested for other (related) membrane properties, including
erythrocyte fragility Erythrocyte fragility refers to the propensity of erythrocytes (red blood cells, RBC) 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 ...
(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). Other related red blood cell properties can include adhesion and aggregation, which along with deformability are often classed as RBC "flow properties."


References

{{reflist Hematology