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
Greek may refer to:
Greece
Anything of, from, or related to Greece, a country in Southern Europe:
*Greeks, an ethnic group.
*Greek language, a branch of the Indo-European language family.
**Proto-Greek language, the assumed last common ancestor ...
''erythros'' for "red" and ''kytos'' for "hollow vessel", with ''-cyte'' translated as "cell" in modern usage), are the most common type of
blood cell
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 the
vertebrate
Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...
's principal means of delivering
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 wel ...
(O
2) to the body
tissues—via blood flow through the
circulatory system
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
. RBCs take up oxygen in the
lung
The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
s, or in fish the
gill
A gill () is a respiratory organ that many aquatic organisms use to extract dissolved oxygen from water and to excrete carbon dioxide. The gills of some species, such as hermit crabs, have adapted to allow respiration on land provided they are ...
s, and release it into tissues while squeezing through the body's
capillaries
A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
.
The
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
of a red blood cell is rich in
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 (erythrocyte ...
, an
iron
Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in f ...
-containing
biomolecule
A biomolecule or biological molecule is a loosely used term for molecules present in organisms that are essential to one or more typically biological processes, such as cell division, morphogenesis, or development. Biomolecules include large ...
that can bind oxygen and is responsible for the red color of the cells and the blood. Each human red blood cell contains approximately 270 million hemoglobin molecules. The
cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
is composed of
proteins
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
and
lipids
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
, and this structure provides properties essential for physiological
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
function such as
deformability and
stability
Stability may refer to:
Mathematics
*Stability theory, the study of the stability of solutions to differential equations and dynamical systems
**Asymptotic stability
**Linear stability
**Lyapunov stability
**Orbital stability
**Structural stabilit ...
of the blood cell while traversing the circulatory system and specifically the
capillary
A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
network.
In humans, mature red blood cells are flexible
biconcave disk
A biconcave disc — also referred to as a discocyte — is a geometric shape resembling an oblate spheroid with two concavities on the top and on the bottom.
Biconcave discs appear in the study of cell biology, where it is meta-stable, and ...
s. They lack a
cell nucleus
The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...
and
organelle
In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...
s, to accommodate maximum space for hemoglobin; they can be viewed as sacks of hemoglobin, with a
plasma membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
as the sack. Approximately 2.4 million new erythrocytes are produced per second in human adults.
Erich Sackmann
Erich Sackmann (born 26 November 1934) is a German experimental physicist and a pioneer of biophysics in Europe.
Career
Sackmann obtained his MSc (1961) and PhD (1964) degrees from the University of Stuttgart in the group of Theodor Förster. H ...
, ''Biological Membranes Architecture and Function.'', Handbook of Biological Physics, (ed. R.Lipowsky and E.Sackmann, vol.1, Elsevier, 1995 The cells develop in the
bone marrow
Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...
and circulate for about 100–120 days in the body before their components are recycled by
macrophage
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
s. Each circulation takes about 60 seconds (one minute).
Approximately 84% of the cells in the human body are 20–30 trillion red blood cells.
[Laura Dean]
''Blood Groups and Red Cell Antigens''
/ref> Nearly half of the blood's volume ( 40% to 45%) is red blood cells.
Packed red blood cells
Packed red blood cells, also known as packed cells, are red blood cells that have been separated for blood transfusion. The packed cells are typically used in anemia that is either causing symptoms or when the hemoglobin is less than usually 70 ...
(pRBC) are red blood cells that have been donated, processed, and stored in a 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 ...
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 ...
.
Structure
Vertebrates
The vast majority of vertebrates, including mammal
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 or ...
s and humans, have red blood cells. Red blood cells are cells present in blood to transport oxygen. The only known vertebrates without red blood cells are the crocodile icefish (family Channichthyidae
The crocodile icefish or white-blooded fish comprise a family (Channichthyidae) of notothenioid fish found in the Southern Ocean around Antarctica. They are the only known vertebrates to lack hemoglobin in their blood as adults. Icefish populatio ...
); they live in very oxygen-rich cold water and transport oxygen freely dissolved in their blood. While they no longer use hemoglobin, remnants of hemoglobin genes can be found in their genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
.
Vertebrate red blood cells consist mainly of 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 (erythrocyte ...
, a complex metalloprotein
Metalloprotein is a generic term for a protein that contains a metal ion Cofactor (biochemistry), cofactor. A large proportion of all proteins are part of this category. For instance, at least 1000 human proteins (out of ~20,000) contain zinc-bi ...
containing heme
Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver.
In biochemical terms, heme is a coordination complex "consisti ...
groups whose iron atoms temporarily bind to oxygen molecules (O2) in the lungs or gills and release them throughout the body. Oxygen can easily diffuse
Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical p ...
through the red blood cell's cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
. Hemoglobin in the red blood cells also carries some of the waste product carbon dioxide
Carbon dioxide (chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is transpar ...
back from the tissues; most waste carbon dioxide, however, is transported back to the pulmonary capillaries
A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
of the lung
The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
s as bicarbonate
In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula .
Bicarbonate serves a crucial biochemic ...
(HCO3−) dissolved in the blood plasma
Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intra ...
. Myoglobin
Myoglobin (symbol Mb or MB) is an iron- and oxygen-binding protein found in the cardiac and skeletal muscle tissue of vertebrates in general and in almost all mammals. Myoglobin is distantly related to hemoglobin. Compared to hemoglobin, myoglobi ...
, a compound related to hemoglobin, acts to store oxygen in muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
cells.
The color of red blood cells is due to the heme group of hemoglobin. The blood plasma
Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intra ...
alone is straw-colored, but the red blood cells change color depending on the state of the hemoglobin: when combined with oxygen the resulting oxyhemoglobin is scarlet, and when oxygen has been released the resulting deoxyhemoglobin is of a dark red burgundy color. However, blood can appear bluish when seen through the vessel wall and skin. Pulse oximetry
Pulse oximetry is a noninvasive method for monitoring a person's oxygen saturation. Peripheral oxygen saturation (SpO2) readings are typically within 2% accuracy (within 4% accuracy in 95% of cases) of the more accurate (and invasive) reading of ...
takes advantage of the hemoglobin color change to directly measure the arterial
An artery (plural arteries) () is a blood vessel in humans and most animals that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry oxygenated blood; the two exceptions are the pul ...
blood oxygen saturation
Oxygen saturation (symbol SO2) is a relative measure of the concentration of oxygen that is dissolved or carried in a given medium as a proportion of the maximal concentration that can be dissolved in that medium at the given temperature. It ca ...
using colorimetric
Colorimetry is "the science and technology used to quantify and describe physically the human color perception".
It is similar to spectrophotometry, but is distinguished by its interest in reducing spectra to the physical correlates of color ...
techniques. Hemoglobin also has a very high affinity for carbon monoxide
Carbon monoxide (chemical formula CO) is a colorless, poisonous, odorless, tasteless, flammable gas that is slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom connected by a triple bond. It is the simple ...
, forming carboxyhemoglobin which is a very bright red in color. Flushed, confused patients with a saturation reading of 100% on pulse oximetry are sometimes found to be suffering from carbon monoxide poisoning.
Having oxygen-carrying proteins inside specialized cells (as opposed to oxygen carriers being dissolved in body fluid) was an important step in the evolution of vertebrates as it allows for less viscous
The viscosity of a fluid is a measure of its resistance to deformation at a given rate. For liquids, it corresponds to the informal concept of "thickness": for example, syrup has a higher viscosity than water.
Viscosity quantifies the inter ...
blood, higher concentrations of oxygen, and better diffusion of oxygen from the blood to the tissues. The size of red blood cells varies widely among vertebrate species; red blood cell width is on average about 25% larger than capillary
A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
diameter, and it has been hypothesized that this improves the oxygen transfer from red blood cells to tissues.
Mammals
The red blood cells of mammal
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 or ...
s are typically shaped as biconcave disks: flattened and depressed in the center, with a dumbbell-shaped cross section, and a torus
In geometry, a torus (plural tori, colloquially donut or doughnut) is a surface of revolution generated by revolving a circle in three-dimensional space about an axis that is coplanar with the circle.
If the axis of revolution does not tou ...
-shaped rim on the edge of the disk. This shape allows for a high surface-area-to-volume (SA/V) ratio to facilitate diffusion of gases. However, there are some exceptions concerning shape in the artiodactyl
The even-toed ungulates (Artiodactyla , ) are ungulates—hoofed animals—which bear weight equally on two (an even number) of their five toes: the third and fourth. The other three toes are either present, absent, vestigial, or pointing poster ...
order (even-toed ungulates
Ungulates ( ) are members of the diverse clade Ungulata which primarily consists of large mammals with hooves. These include odd-toed ungulates such as horses, rhinoceroses, and tapirs; and even-toed ungulates such as cattle, pigs, giraffes, cam ...
including cattle, deer, and their relatives), which displays a wide variety of bizarre red blood cell morphologies: small and highly ovaloid cells in llama
The llama (; ) (''Lama glama'') is a domesticated South American camelid, widely used as a List of meat animals, meat and pack animal by Inca empire, Andean cultures since the Pre-Columbian era.
Llamas are social animals and live with othe ...
s and camels (family Camelidae
Camelids are members of the biological family Camelidae, the only currently living family in the suborder Tylopoda. The seven extant members of this group are: dromedary camels, Bactrian camels, wild Bactrian camels, llamas, alpacas, vicuñas, ...
), tiny spherical cells in mouse deer (family Tragulidae
The asterisk ( ), from Late Latin , from Ancient Greek , ''asteriskos'', "little star", is a typographical symbol. It is so called because it resembles a conventional image of a heraldic star.
Computer scientists and mathematicians often v ...
), and cells which assume fusiform, lanceolate, crescentic, and irregularly polygonal and other angular forms in red deer and wapiti (family Cervidae
Deer or true deer are hoofed ruminant mammals forming the family Cervidae. The two main groups of deer are the Cervinae, including the muntjac, the elk (wapiti), the red deer, and the fallow deer; and the Capreolinae, including the reindeer ...
). Members of this order have clearly evolved a mode of red blood cell development substantially different from the mammalian norm. Overall, mammalian red blood cells are remarkably flexible and deformable so as to squeeze through tiny capillaries
A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
, as well as to maximize their apposing surface by assuming a cigar shape, where they efficiently release their oxygen load.
Red blood cells in mammals are unique amongst vertebrates as they do not have nuclei when mature. They do have nuclei during early phases of erythropoiesis
Erythropoiesis (from Greek 'erythro' meaning "red" and 'poiesis' "to make") is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell.
It is stimulated by decrea ...
, but extrude them during development as they mature; this provides more space for hemoglobin. The red blood cells without nuclei, called reticulocytes
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 mat ...
, subsequently lose all other cellular organelle
In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...
s such as their mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
, Golgi apparatus
The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ins ...
and endoplasmic reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
.
The spleen
The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes . acts as a reservoir of red blood cells, but this effect is somewhat limited in humans. In some other mammals such as dogs and horses, the spleen sequesters large numbers of red blood cells, which are dumped into the blood during times of exertion stress, yielding a higher oxygen transport capacity.
Human
A typical human red blood cell has a disk diameter of approximately 6.2–8.2 µm and a thickness at the thickest point of 2–2.5 µm and a minimum thickness in the centre of 0.8–1 µm, being much smaller than most other human cells
There are many different types of cells in the human body.
Cells derived primarily from endoderm
Exocrine secretory epithelial cells
* Brunner's gland cell in duodenum (enzymes and alkaline mucus)
*Insulated goblet cell of respiratory and ...
. These cells have an average volume of about 90 fL with a surface area of about 136 μm2, and can swell up to a sphere shape containing 150 fL, without membrane distension.
Adult humans have roughly 20–30 trillion red blood cells at any given time, constituting approximately 70% of all cells by number. Women have about 4–5 million red blood cells per microliter (cubic millimeter) of blood and men about 5–6 million; people living at high altitudes with low oxygen tension will have more. Red blood cells are thus much more common than the other blood particles: there are about 4,000–11,000 white blood cells
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
and about 150,000–400,000 platelet
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
s per microliter.
Human red blood cells take on average 60 seconds to complete one cycle of circulation.[
The blood's red color is due to the spectral properties of the hemic iron ]ion
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conven ...
s in 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 (erythrocyte ...
. Each hemoglobin molecule carries four heme groups; hemoglobin constitutes about a third of the total cell volume. Hemoglobin is responsible for the transport of more than 98% of the oxygen in the body (the remaining oxygen is carried dissolved in the blood plasma
Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intra ...
). The red blood cells of an average adult human male store collectively about 2.5 grams of iron, representing about 65% of the total iron contained in the body.
Microstructure
Nucleus
Red blood cells in mammals ''anucleate'' when mature, meaning that they lack a cell nucleus
The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...
. In comparison, the red blood cells of other vertebrates have nuclei; the only known exceptions are salamander
Salamanders are a group of amphibians typically characterized by their lizard-like appearance, with slender bodies, blunt snouts, short limbs projecting at right angles to the body, and the presence of a tail in both larvae and adults. All ten ...
s of the genus ''Batrachoseps
''Batrachoseps'' is a genus of lungless salamanders (plethodontids) often called slender salamanders. They can be distinguished from other lungless salamanders by the four toes they have on each foot.
Their genus name ''Batracho-seps'' means "f ...
'' and fish of the genus ''Maurolicus
''Maurolicus'' is an oceanic ray-finned fish genus which belongs in the marine hatchetfish family Sternoptychidae. They are commonly known as pearlsides, but the brilliant pearlside is the related ''Argyripnus iridescens''. Occasionally, "bris ...
''.
The elimination of the nucleus in vertebrate red blood cells has been offered as an explanation for the subsequent accumulation of non-coding DNA in the genome. The argument runs as follows: Efficient gas transport requires red blood cells to pass through very narrow capillaries, and this constrains their size. In the absence of nuclear elimination, the accumulation of repeat sequences is constrained by the volume occupied by the nucleus, which increases with genome size.
Nucleated red blood cell
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 the ...
s in mammals consist of two forms: normoblasts, which are normal erythropoietic precursors to mature red blood cells, and megaloblasts, which are abnormally large precursors that occur in megaloblastic anemia
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 replication, DNA synthesis during red blood cell production. ...
s.
Membrane composition
Red blood cells are deformable, flexible, are able to adhere to other cells, and are able to interface with immune cells. Their membrane
A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. B ...
plays many roles in this. These functions are highly dependent on the membrane composition. The red blood cell membrane is composed of 3 layers: the glycocalyx
The glycocalyx, also known as the pericellular matrix, is a glycoprotein and glycolipid covering that surrounds the cell membranes of bacteria, epithelial cells, and other cells. In 1970, Martinez-Palomo discovered the cell coating in animal cells ...
on the exterior, which is rich in carbohydrates
In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or may ...
; the lipid bilayer
The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...
which contains many transmembrane protein
A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...
s, besides its lipidic main constituents; and the membrane skeleton, a structural network of proteins located on the inner surface of the lipid bilayer. Half of the membrane mass in human and most mammalian red blood cells are proteins. The other half are lipids, namely phospholipid
Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
s and cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
.
Membrane lipids
The red blood cell membrane comprises a typical lipid bilayer
The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...
, similar to what can be found in virtually all human cells. Simply put, this lipid bilayer is composed of cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
and phospholipid
Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
s in equal proportions by weight. The lipid composition is important as it defines many physical properties such as membrane permeability and fluidity. Additionally, the activity of many membrane proteins is regulated by interactions with lipids in the bilayer.
Unlike cholesterol, which is evenly distributed between the inner and outer leaflets, the 5 major phospholipids are asymmetrically disposed, as shown below:
Outer monolayer
* Phosphatidylcholine
Phosphatidylcholines (PC) are a class of phospholipids that incorporate choline as a headgroup.
They are a major component of biological membranes and can be easily obtained from a variety of readily available sources, such as egg yolk or soyb ...
(PC);
* Sphingomyelin
Sphingomyelin (SPH, ˌsfɪŋɡoˈmaɪəlɪn) is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphocholine and ceramide, or a ethano ...
(SM).
Inner monolayer
* Phosphatidylethanolamine
Phosphatidylethanolamine (PE) is a class of phospholipids found in biological membranes. They are synthesized by the addition of cytidine diphosphate-ethanolamine to diglycerides, releasing cytidine monophosphate. ''S''-Adenosyl methionine can s ...
(PE);
* Phosphoinositol
Inositol phosphates are a group of mono- to hexaphosphorylated inositols. They play crucial roles in diverse cellular functions, such as cell growth, apoptosis, cell migration, endocytosis, and cell differentiation.
The group comprises:
* inositol ...
(PI) (small amounts).
* Phosphatidylserine
Phosphatidylserine (abbreviated Ptd-L-Ser or PS) is a phospholipid and is a component of the cell membrane. It plays a key role in cell cycle signaling, specifically in relation to apoptosis. It is a key pathway for viruses to enter cells via ap ...
(PS);
This asymmetric phospholipid distribution among the bilayer is the result of the function of several energy-dependent and energy-independent phospholipid
Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
transport proteins. Proteins called "Flippase
Flippases (rarely spelled flipases) are transmembrane lipid transporter proteins located in the membrane which belong to ABC transporter or P4-type ATPase families. They are responsible for aiding the movement of phospholipid molecules between the ...
s" move phospholipids from the outer to the inner monolayer, while others called "floppase
Flippases (rarely spelled flipases) are transmembrane lipid transporter proteins located in the membrane which belong to ABC transporter or P4-type ATPase families. They are responsible for aiding the movement of phospholipid molecules between the ...
s" do the opposite operation, against a concentration gradient in an energy-dependent manner. Additionally, there are also "scramblase
Scramblase is a protein responsible for the translocation of phospholipids between the two monolayers of a lipid bilayer of a cell membrane. In humans, phospholipid scramblases (PLSCRs) constitute a family of five homologous proteins tha ...
" proteins that move phospholipids in both directions at the same time, down their concentration gradients in an energy-independent manner. There is still considerable debate ongoing regarding the identity of these membrane maintenance proteins in the red cell membrane.
The maintenance of an asymmetric phospholipid distribution in the bilayer (such as an exclusive localization of PS and PIs in the inner monolayer) is critical for the cell integrity and function due to several reasons:
* Macrophages
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
recognize and phagocytose
Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ...
red cells that expose PS at their outer surface. Thus the confinement of PS in the inner monolayer is essential if the cell is to survive its frequent encounters with macrophages of the reticuloendothelial system
In anatomy the term "reticuloendothelial system" (abbreviated RES), often associated nowadays with the mononuclear phagocyte system (MPS), was originally launched by the beginning of the 20th century to denote a system of specialised cells that eff ...
, especially in the spleen
The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes . .
* Premature destruction of thallassemic and sickle red cells has been linked to disruptions of lipid asymmetry leading to exposure of PS on the outer monolayer.
* An exposure of PS can potentiate adhesion of red cells to vascular endothelial cells, effectively preventing normal transit through the microvasculature. Thus it is important that PS is maintained only in the inner leaflet of the bilayer to ensure normal blood flow in microcirculation.
* Both PS and phosphatidylinositol 4,5-bisphosphate
Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number of ...
(PIP2) can regulate membrane mechanical function, due to their interactions with skeletal proteins such as 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 ...
and protein 4.1R. Recent studies have shown that binding of spectrin to PS promotes membrane mechanical stability. PIP2 enhances the binding of protein band 4.1R to glycophorin C
Glycophorin C (GYPC; CD236/CD236R; glycoprotein beta; glycoconnectin; PAS-2) plays a functionally important role in maintaining erythrocyte shape and regulating membrane material properties, possibly through its interaction with protein 4.1. Moreo ...
but decreases its interaction with protein band 3, and thereby may modulate the linkage of the bilayer to the membrane skeleton.
The presence of specialized structures named "lipid rafts
The plasma membranes of cells contain combinations of glycosphingolipids, cholesterol and protein receptors organised in glycolipoprotein lipid microdomains termed lipid rafts. Their existence in cellular membranes remains somewhat controversial. ...
" in the red blood cell membrane have been described by recent studies. These are structures enriched in cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
and sphingolipids
Sphingolipids are a class of lipids containing a backbone of sphingoid bases, a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological sphinx because o ...
associated with specific membrane proteins, namely flotillins, STOM
Stomatin also known as human erythrocyte integral membrane protein band 7 is a protein that in humans is encoded by the STOM gene.
Clinical significance
Stomatin is a 31 kDa integral membrane protein, named after the rare human haemolytic an ...
atins (band 7), G-proteins
G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their act ...
, and β-adrenergic receptor
The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta ...
s. Lipid rafts
The plasma membranes of cells contain combinations of glycosphingolipids, cholesterol and protein receptors organised in glycolipoprotein lipid microdomains termed lipid rafts. Their existence in cellular membranes remains somewhat controversial. ...
that have been implicated in cell signaling events in nonerythroid cells have been shown in erythroid cells to mediate β2-adregenic receptor signaling and increase cAMP
Camp may refer to:
Outdoor accommodation and recreation
* Campsite or campground, a recreational outdoor sleeping and eating site
* a temporary settlement for nomads
* Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...
levels, and thus regulating entry of malaria
Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...
l parasites into normal red cells.
Membrane proteins
The proteins of the membrane skeleton are responsible for the deformability, flexibility and durability of the red blood cell, enabling it to squeeze through capillaries less than half the diameter of the red blood cell (7–8 μm) and recovering the discoid shape as soon as these cells stop receiving compressive forces, in a similar fashion to an object made of rubber.
There are currently more than 50 known membrane proteins, which can exist in a few hundred up to a million copies per red blood cell. Approximately 25 of these membrane proteins carry the various blood group antigens, such as the A, B and Rh antigens, among many others. These membrane proteins can perform a wide diversity of functions, such as transporting ions and molecules across the red cell membrane, adhesion and interaction with other cells such as endothelial cells, as signaling receptors, as well as other currently unknown functions. The blood type
A blood type (also known as a blood group) is a classification of blood, based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrate ...
s of humans are due to variations in surface glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
s of red blood cells. Disorders of the proteins in these membranes are associated with many disorders, such as hereditary spherocytosis
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 (sp ...
, hereditary elliptocytosis
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 ...
, hereditary stomatocytosis
Hereditary stomatocytosis describes a number of inherited, mostly autosomal dominant human conditions which affect the red blood cell and create the appearance of a slit-like area of central pallor (stomatocyte) among erythrocytes on peripheral b ...
, and paroxysmal nocturnal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's innate immune system. This destructive process occu ...
.
The red blood cell membrane proteins organized according to their function:
Transport
* Band 3
Band 3 anion transport protein, also known as anion exchanger 1 (AE1) or band 3 or solute carrier family 4 member 1 (SLC4A1), is a protein that is encoded by the gene in humans.
Band 3 anion transport protein is a phylogenetically-preserved ...
– Anion transporter, also an important structural component of the red blood cell membrane, makes up to 25% of the cell membrane surface, each red cell contains approximately one million copies. Defines the Diego Blood Group;
* Aquaporin 1
Aquaporin 1 (AQP-1) is a protein that in humans is encoded by the ''AQP1'' gene.
AQP-1 is a widely expressed water channel, whose physiological function has been most thoroughly characterized in the kidney. It is found in the basolateral and api ...
– water transporter, defines the Colton Blood Group;
* Glut1
Glucose transporter 1 (or GLUT1), also known as solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1), is a uniporter protein that in humans is encoded by the ''SLC2A1'' gene. GLUT1 facilitates the transport of glucose across ...
– glucose and L-dehydroascorbic acid transporter;
* Kidd antigen protein – urea transporter;
* RHAG
Rh-associated glycoprotein (RHAG) is an ammonia transporter protein that in humans is encoded by the ''RHAG'' gene. RHAG has also recently been designated CD241 (cluster of differentiation 241). Mutations in the RHAG gene can cause stomatocytosi ...
– gas transporter, probably of carbon dioxide, defines Rh Blood Group and the associated unusual blood group phenotype Rhnull;
* Na+/K+ – ATPase;
* Ca2+ – ATPase;
* Na+ K+ 2Cl− – cotransporter;
* Na+-Cl− – cotransporter;
* Na-H exchanger;
* K-Cl – cotransporter;
* Gardos Channel.
Cell adhesion
* ICAM-4 – interacts with integrins
Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, ...
;
* BCAM – a glycoprotein that defines the Lutheran blood group and also known as Lu or laminin
Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major components of the basal lamina (one of the layers of the basement membrane), the protein network foundation for most cells and organs. The laminins ...
-binding protein.
Structural role – The following membrane proteins establish linkages with skeletal proteins and may play an important role in regulating cohesion between the lipid bilayer and membrane skeleton, likely enabling the red cell to maintain its favorable membrane surface area by preventing the membrane from collapsing (vesiculating).
* Ankyrin
Ankyrins are a family of proteins that mediate the attachment of integral membrane proteins to the spectrin-actin based membrane cytoskeleton. Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral mem ...
-based macromolecular complex – proteins linking the bilayer to the membrane skeleton through the interaction of their cytoplasmic domains with Ankyrin
Ankyrins are a family of proteins that mediate the attachment of integral membrane proteins to the spectrin-actin based membrane cytoskeleton. Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral mem ...
.
** Band 3
Band 3 anion transport protein, also known as anion exchanger 1 (AE1) or band 3 or solute carrier family 4 member 1 (SLC4A1), is a protein that is encoded by the gene in humans.
Band 3 anion transport protein is a phylogenetically-preserved ...
– also assembles various glycolytic
Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...
enzymes, the presumptive CO2 transporter, and carbonic anhydrase
The carbonic anhydrases (or carbonate dehydratases) () form a family of enzymes that catalyze the interconversion between carbon dioxide and water and the dissociated ions of carbonic acid (i.e. bicarbonate and hydrogen ions). The active site ...
into a macromolecular complex termed a "metabolon In biochemistry, a metabolon is a temporary structural-functional complex formed between sequential enzymes of a metabolic pathway, held together both by non-covalent interactions and by structural elements of the cell, such as integral membrane pro ...
," which may play a key role in regulating red cell metabolism and ion and gas transport function
Function or functionality may refer to:
Computing
* Function key, a type of key on computer keyboards
* Function model, a structured representation of processes in a system
* Function object or functor or functionoid, a concept of object-oriente ...
.
** RHAG
Rh-associated glycoprotein (RHAG) is an ammonia transporter protein that in humans is encoded by the ''RHAG'' gene. RHAG has also recently been designated CD241 (cluster of differentiation 241). Mutations in the RHAG gene can cause stomatocytosi ...
– also involved in transport, defines associated unusual blood group phenotype Rhmod.
* Protein 4.1R-based macromolecular complex – proteins interacting with Protein 4.1R.
** Protein 4.1R – weak expression of Gerbich antigens;
** Glycophorin C
Glycophorin C (GYPC; CD236/CD236R; glycoprotein beta; glycoconnectin; PAS-2) plays a functionally important role in maintaining erythrocyte shape and regulating membrane material properties, possibly through its interaction with protein 4.1. Moreo ...
and D – glycoprotein, defines Gerbich Blood Group;
** XK – defines the Kell Blood Group and the Mcleod unusual phenotype (lack of Kx antigen and greatly reduced expression of Kell antigens);
** RhD/RhCE – defines Rh Blood Group and the associated unusual blood group phenotype Rhnull;
** Duffy protein – has been proposed to be associated with chemokine
Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In additio ...
clearance;
** Adducin – interaction with band 3;
** Dematin- interaction with the Glut1 glucose transporter.
Surface electrostatic potential
The zeta potential
Zeta potential is the electrical potential at the slipping plane. This plane is the interface which separates mobile fluid from fluid that remains attached to the surface.
Zeta potential is a scientific term for electrokinetic potential in coll ...
is an electrochemical property of cell surfaces that is determined by the net electrical charge of molecules exposed at the surface of cell membranes of the cell. The normal zeta potential of the red blood cell is −15.7 millivolt
The volt (symbol: V) is the unit of electric potential, electric potential difference (voltage), and electromotive force in the International System of Units (SI). It is named after the Italian physicist Alessandro Volta (1745–1827).
Defi ...
s (mV).[Tokumasu F, Ostera GR, Amaratunga C, Fairhurst RM (2012) Modifications in erythrocyte membrane zeta potential by ''Plasmodium falciparum'' infection. Exp Parasitol] Much of this potential appears to be contributed by the exposed sialic acid Sialic acids are a class of alpha-keto acid sugars with a nine-carbon backbone.
The term "sialic acid" (from the Greek for saliva, - ''síalon'') was first introduced by Swedish biochemist Gunnar Blix in 1952. The most common member of this gr ...
residues in the membrane: their removal results in zeta potential of −6.06 mV.
Function
Role in transport
Recall that respiration
Respiration may refer to:
Biology
* Cellular respiration, the process in which nutrients are converted into useful energy in a cell
** Anaerobic respiration, cellular respiration without oxygen
** Maintenance respiration, the amount of cellul ...
, as illustrated schematically here with a unit of carbohydrate, produces about as many molecules of carbon dioxide, CO2, as it consumes of oxygen, O2.
:HCOH + O2 -> CO2 + H2O
Thus, the function of the circulatory system is as much about the transport of carbon dioxide as about the transport of oxygen.
As stated elsewhere in this article, most of the carbon dioxide in the blood is in the form of bicarbonate ion. The bicarbonate provides a critical pH buffer. Thus, unlike hemoglobin for O2 transport, there is a physiological advantage to not having a specific CO2 transporter molecule.
Red blood cells, nevertheless, play a key role in the CO2 transport process, for two reasons.
First, because, besides hemoglobin, they contain a large number of copies of the enzyme carbonic anhydrase
The carbonic anhydrases (or carbonate dehydratases) () form a family of enzymes that catalyze the interconversion between carbon dioxide and water and the dissociated ions of carbonic acid (i.e. bicarbonate and hydrogen ions). The active site ...
on the inside of their cell membrane. Carbonic anhydrase, as its name suggests, acts as a catalyst of the exchange between carbonic acid and carbon dioxide (which is the anhydride
An organic acid anhydride is an acid anhydride that is an organic compound. An acid anhydride is a compound that has two acyl groups bonded to the same oxygen atom. A common type of organic acid anhydride is a carboxylic anhydride, where the pa ...
of carbonic acid). Because it is a catalyst, it can affect many CO2 molecules, so it performs its essential role without needing as many copies as are needed for O2 transport by hemoglobin.
In the presence of this catalyst carbon dioxide and carbonic acid reach an equilibrium very rapidly, while the red cells are still moving through the capillary. Thus it is the RBC that ensures that most of the CO2 is transported as bicarbonate.
At physiological pH the equilibrium strongly favors carbonic acid, which is mostly dissociated into bicarbonate ion.
:CO2 + H2O <=>> H2CO3 <=>> HCO3- + H+
The H+ ions released by this rapid reaction within RBC, while still in the capillary, act to reduce the oxygen binding affinity of hemoglobin, the Bohr effect
The Bohr effect is a phenomenon first described in 1904 by the Danish physiologist Christian Bohr. Hemoglobin's oxygen binding affinity (see oxygen–haemoglobin dissociation curve) is inversely related both to acidity and to the concentration o ...
.
The second major contribution of RBC to carbon dioxide transport is that carbon dioxide directly reacts with globin protein components of hemoglobin to form carbaminohemoglobin
Carbaminohemoglobin (carbaminohaemoglobin BrE) (CO2Hb, also known as carbhemoglobin and carbohemoglobin) is a compound of hemoglobin and carbon dioxide, and is one of the forms in which carbon dioxide exists in the blood. Twenty-three percent of c ...
compounds.
As oxygen is released in the tissues, more CO2 binds to hemoglobin, and as oxygen binds in the lung, it displaces the hemoglobin bound CO2, this is called the Haldane effect The Haldane effect is a property of hemoglobin first described by John Scott Haldane, within which oxygenation of blood in the lungs displaces carbon dioxide from hemoglobin, increasing the removal of carbon dioxide. Consequently, oxygenated blood ...
. Despite the fact that only a small amount of the CO2 in blood is bound to hemoglobin in venous blood, a greater proportion of the change in CO2 content between venous and arterial blood comes from the change in this bound CO2. That is, there is always an abundance of bicarbonate in blood, both venous and arterial, because of its aforementioned role as a pH buffer.
In summary, carbon dioxide produced by cellular respiration diffuses very rapidly to areas of lower concentration, specifically into nearby capillaries.
When it diffuses into a RBC, CO2 is rapidly converted by the carbonic anhydrase found on the inside of the RBC membrane into bicarbonate ion. The bicarbonate ions in turn leave the RBC in exchange for chloride ions
The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride salts ...
from the plasma, facilitated by the band 3 anion transport protein
Band 3 anion transport protein, also known as anion exchanger 1 (AE1) or band 3 or solute carrier family 4 member 1 (SLC4A1), is a protein that is encoded by the gene in humans.
Band 3 anion transport protein is a phylogenetically-preserved ...
colocated in the RBC membrane. The bicarbonate ion does not diffuse back out of the capillary, but is carried to the lung. In the lung the lower partial pressure
In a mixture of gases, each constituent gas has a partial pressure which is the notional pressure of that constituent gas as if it alone occupied the entire volume of the original mixture at the same temperature. The total pressure of an ideal gas ...
of carbon dioxide in the alveoli causes carbon dioxide to diffuse rapidly from the capillary into the alveoli. The carbonic anhydrase in the red cells keeps the bicarbonate ion in equilibrium with carbon dioxide. So as carbon dioxide leaves the capillary, and CO2 is displaced by O2 on hemoglobin, sufficient bicarbonate ion converts rapidly to carbon dioxide to maintain the equilibrium.
Secondary functions
When red blood cells undergo shear stress in constricted vessels, they release ATP, which causes the vessel walls to relax and dilate so as to promote normal blood flow.
When their hemoglobin molecules are deoxygenated, red blood cells release S-Nitrosothiol
In organic chemistry, ''S''-nitrosothiols, also known as thionitrites, are organic compounds or functional groups containing a nitroso group attached to the sulfur atom of a thiol. ''S''-Nitrosothiols have the general formula , where ''R'' denot ...
s, which also act to dilate blood vessels, thus directing more blood to areas of the body depleted of oxygen.
Red blood cells can also synthesize nitric oxide
Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its che ...
enzymatically, using L-arginine
Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...
as substrate, as do endothelial cell
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...
s. Exposure of red blood cells to physiological levels of shear stress activates nitric oxide synthase
Nitric oxide synthases () (NOSs) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule. It helps modulate vascular tone, insulin secretion, airway tone, and perista ...
and export of nitric oxide, which may contribute to the regulation of vascular tonus.
Red blood cells can also produce hydrogen sulfide
Hydrogen sulfide is a chemical compound with the formula . It is a colorless chalcogen-hydride gas, and is poisonous, corrosive, and flammable, with trace amounts in ambient atmosphere having a characteristic foul odor of rotten eggs. The unde ...
, a signalling gas that acts to relax vessel walls. It is believed that the cardioprotective effects of garlic are due to red blood cells converting its sulfur compounds into hydrogen sulfide.
Red blood cells also play a part in the body's immune response
An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
: when lysed by pathogens such as bacteria, their hemoglobin releases free radical
A daughter category of ''Ageing'', this category deals only with the biological aspects of ageing.
Ageing
Ailments of unknown cause
Biogerontology
Biological processes
Causes of death
Cellular processes
Gerontology
Life extension
Metabo ...
s, which break down the pathogen's cell wall and membrane, killing it.
Cellular processes
As a result of not containing mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
, red blood cells use none of the oxygen they transport; instead they produce the energy carrier ATP by the glycolysis
Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...
of glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
and lactic acid fermentation
Lactic acid fermentation is a metabolic process by which glucose or other six-carbon sugars (also, disaccharides of six-carbon sugars, e.g. sucrose or lactose) are converted into cellular energy and the metabolite lactate, which is lactic acid ...
on the resulting pyruvate
Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell.
Pyruvic aci ...
. Furthermore, the pentose phosphate pathway
The pentose phosphate pathway (also called the phosphogluconate pathway and the hexose monophosphate shunt and the HMP Shunt) is a metabolic pathway parallel to glycolysis. It generates NADPH and pentoses (5-carbon sugars) as well as ribose 5-pho ...
plays an important role in red blood cells; see glucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase deficiency (G6PDD), which is the most common enzyme deficiency worldwide, is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who are affected have no symptoms. ...
for more information.
As red blood cells contain no nucleus, protein biosynthesis
Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critical ...
is currently assumed to be absent in these cells.
Because of the lack of nuclei and organelles, mature red blood cells do not contain DNA and cannot synthesize any RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
, and consequently cannot divide and have limited repair capabilities. The inability to carry out protein synthesis
Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...
means that no virus can evolve to target mammalian red blood cells. However, infection with parvovirus
Parvoviruses are a family of animal viruses that constitute the family ''Parvoviridae''. They have linear, single-stranded DNA (ssDNA) genomes that typically contain two genes encoding for a replication initiator protein, called NS1, and the pr ...
es (such as human parvovirus B19
Primate erythroparvovirus 1, generally referred to as B19 virus (B19V), parvovirus B19 or sometimes erythrovirus B19, is the first (and until 2005 the only) known human virus in the family ''Parvoviridae'', genus ''Erythroparvovirus''; it measur ...
) can affect erythroid precursors while they still have DNA, as recognized by the presence of giant pronormoblast
A proerythroblast (or rubriblast, or pronormoblast) is the earliest of four stages in development of the normoblast.
In histology, it is very difficult to distinguish it from the other "-blast" cells (lymphoblast, myeloblast, monoblast, and mega ...
s with viral particles and inclusion bodies
Inclusion bodies are aggregates of specific types of protein found in neurons, a number of tissue cells including red blood cells, bacteria, viruses, and plants. Inclusion bodies of aggregations of multiple proteins are also found in muscle cells ...
, thus temporarily depleting the blood of reticulocytes and causing anemia
Anemia or anaemia (British English) 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. When anemia comes on slowly, th ...
.
Life cycle
Human red blood cells are produced through a process named erythropoiesis
Erythropoiesis (from Greek 'erythro' meaning "red" and 'poiesis' "to make") is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell.
It is stimulated by decrea ...
, developing from committed stem cells to mature red blood cells in about 7 days. When matured, in a healthy individual these cells live in blood circulation for about 100 to 120 days (and 80 to 90 days in a full term infant). At the end of their lifespan, they are removed from circulation. In many chronic diseases, the lifespan of the red blood cells is reduced.
Creation
Erythropoiesis is the process by which new red blood cells are produced; it lasts about 7 days. Through this process red blood cells are continuously produced in the red bone marrow
Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...
of large bones. (In the embryo, the liver is the main site of red blood cell production.) The production can be stimulated by the hormone erythropoietin (EPO), synthesised by the kidney. Just before and after leaving the bone marrow, the developing cells are known as reticulocytes; these constitute about 1% of circulating red blood cells.
Functional lifetime
The functional lifetime of a red blood cell is about 100–120 days, during which time the red blood cells are continually moved by the blood flow push (in arteries), pull (in veins) and a combination of the two as they squeeze through microvessels such as capillaries. They are also recycled in the bone marrow.
Senescence
The aging red blood cell undergoes changes in its plasma membrane, making it susceptible to selective recognition by macrophage
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
s and subsequent phagocytosis in the mononuclear phagocyte system (spleen
The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes . , liver and lymph nodes), thus removing old and defective cells and continually purging the blood. This process is termed eryptosis, red blood cell programmed death. This process normally occurs at the same rate of production by erythropoiesis, balancing the total circulating red blood cell count. Eryptosis is increased in a wide variety of diseases including sepsis, haemolytic uremic syndrome, malaria
Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...
, sickle cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase deficiency (G6PDD), which is the most common enzyme deficiency worldwide, is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who are affected have no symptoms. ...
, phosphate depletion, iron deficiency and Wilson's disease. Eryptosis can be elicited by osmotic shock, oxidative stress, and energy depletion, as well as by a wide variety of endogenous mediators and xenobiotics. Excessive eryptosis is observed in red blood cells lacking the cGMP-dependent protein kinase type I or the AMP-activated protein kinase AMPK. Enzyme inhibitor, Inhibitors of eryptosis include erythropoietin, nitric oxide
Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its che ...
, catecholamines and high concentrations of urea.
Much of the resulting breakdown products are recirculated in the body. The heme constituent of hemoglobin are broken down into iron (Fe3+) and biliverdin. The biliverdin is reduced to bilirubin, which is released into the plasma and recirculated to the liver bound to albumin. The iron is released into the plasma to be recirculated by a carrier protein called transferrin. Almost all red blood cells are removed in this manner from the circulation before they are old enough to Hemolysis, hemolyze. Hemolyzed hemoglobin is bound to a protein in plasma called haptoglobin, which is not excreted by the kidney.
Clinical significance
Disease
Blood diseases involving the red blood cells include:
* Anemias (or anaemias) are diseases characterized by low oxygen transport capacity of the blood, because of low red cell count or some abnormality of the red blood cells or the hemoglobin.
:* Iron deficiency anemia is the most common anemia; it occurs when the dietary intake or absorption of iron is insufficient, and hemoglobin, which contains iron, cannot be formed.
:* Pernicious anemia is an autoimmune disease wherein the body lacks intrinsic factor, required to absorb vitamin B12, vitamin B12 from food. Vitamin B12 is needed for the production of red blood cells and hemoglobin.
:* Sickle-cell disease is a genetic disease that results in abnormal hemoglobin molecules. When these release their oxygen load in the tissues, they become insoluble, leading to mis-shaped red blood cells. These sickle shaped red cells are less deformable and Blood Viscoelasticity, viscoelastic, meaning that they have become rigid and can cause blood vessel blockage, pain, strokes, and other tissue damage.
:* Thalassemia is a genetic disease that results in the production of an abnormal ratio of hemoglobin subunits.
:*Hereditary spherocytosis syndromes are a group of inherited disorders characterized by defects in the red blood cell's cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
, causing the cells to be small, sphere-shaped, and fragile instead of donut-shaped and flexible. These abnormal red blood cells are destroyed by the spleen
The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes . . Several other hereditary disorders of the red blood cell membrane are known.
:* Aplastic anemia is caused by the inability of the bone marrow
Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...
to produce blood cells.
:* Pure red cell aplasia is caused by the inability of the bone marrow to produce only red blood cells.
* Hemolysis is the general term for excessive breakdown of red blood cells. It can have several causes and can result in hemolytic anemia.
:* The malaria
Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...
parasite spends part of its life-cycle in red blood cells, feeds on their hemoglobin and then breaks them apart, causing fever. Both sickle-cell disease and thalassemia are more common in malaria areas, because these mutations convey some protection against the parasite.
* Polycythemias (or erythrocytoses) are diseases characterized by a surplus of red blood cells. The increased viscosity of the blood can cause a number of symptoms.
:* In polycythemia vera the increased number of red blood cells results from an abnormality in the bone marrow.
* Several microangiopathy, microangiopathic diseases, including disseminated intravascular coagulation and thrombotic microangiopathies, present with pathognomonic (diagnostic) red blood cell fragments called schistocytes. These pathologies generate fibrin strands that sever red blood cells as they try to move past a thrombus.
Transfusion
Red blood cells may be given as part of a 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 ...
. Blood may be blood donation, donated from another person, or stored by the recipient at an earlier date. Donated blood usually requires screening (medicine), screening to ensure that donors do not contain risk factors for the presence of blood-borne diseases, or will not suffer themselves by giving blood. Blood is usually collected and tested for common or serious blood-borne diseases including Hepatitis B, Hepatitis C and HIV. The blood type
A blood type (also known as a blood group) is a classification of blood, based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrate ...
(A, B, AB, or O) or the blood product is identified and matched with the recipient's blood to minimise the likelihood of acute hemolytic transfusion reaction, a type of transfusion reaction. This relates to the presence of antigens on the cell's surface. After this process, the blood is stored, and within a short duration is used. Blood can be given as a whole product or the red blood cells separated as packed red blood cells.
Blood is often transfused when there is known anaemia, active bleeding, or when there is an expectation of serious blood loss, such as prior to an operation. Before blood is given, a small sample of the recipient's blood is tested with the transfusion in a process known as cross-matching.
In 2008 it was reported that human embryonic stem cells had been successfully coaxed into becoming red blood cells in the lab. The difficult step was to induce the cells to eject their nucleus; this was achieved by growing the cells on stromal cells from the bone marrow. It is hoped that these artificial red blood cells can eventually be used for blood transfusions.
A human trial is conducted in 2022, using blood cultured from stem cells obtained from donor blood.
Tests
Several blood tests involve red blood cells. These include a ''RBC count'' (the number of red blood cells per volume of blood), calculation of the hematocrit (percentage of blood volume occupied by red blood cells), and the erythrocyte sedimentation rate. The blood type
A blood type (also known as a blood group) is a classification of blood, based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrate ...
needs to be determined to prepare for a 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 ...
or an organ transplantation.
Many diseases involving red blood cells are diagnosed with a blood film (or peripheral blood smear), where a thin layer of blood is smeared on a microscope slide. This may reveal poikilocytosis, which are variations in red blood cell shape. When red blood cells sometimes occur as a stack, flat side next to flat side. This is known as ''rouleaux formation'', and it occurs more often if the levels of certain serum proteins are elevated, as for instance during inflammation.
Separation and blood doping
Red blood cells can be obtained from whole blood by centrifugation, which separates the cells from the blood plasma
Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intra ...
in a process known as blood fractionation. Packed red blood cells
Packed red blood cells, also known as packed cells, are red blood cells that have been separated for blood transfusion. The packed cells are typically used in anemia that is either causing symptoms or when the hemoglobin is less than usually 70 ...
, which are made in this way from whole blood with the plasma removed, are used in transfusion medicine. During blood donation, plasma donation, the red blood cells are pumped back into the body right away and only the plasma is collected.
Some athletes have tried to improve their performance by blood doping: first about 1 litre of their blood is extracted, then the red blood cells are isolated, frozen and stored, to be reinjected shortly before the competition. (Red blood cells can be conserved for 5 weeks at , or over 10 years using cryoprotectants) This practice is hard to detect but may endanger the human cardiovascular system which is not equipped to deal with blood of the resulting higher viscosity. Another method of blood doping involves injection with erythropoietin to stimulate production of red blood cells. Both practices are banned by the World Anti-Doping Agency.
History
The first person to describe red blood cells was the young Dutch biologist Jan Swammerdam, who had used an early microscope in 1658 to study the blood of a frog. Unaware of this work, Anton van Leeuwenhoek provided another microscopic description in 1674, this time providing a more precise description of red blood cells, even approximating their size, "25,000 times smaller than a fine grain of sand".
In the 1740s, Vincenzo Menghini in Bologna was able to demonstrate the presence of iron by passing magnets over the powder or ash remaining from heated red blood cells.
In 1901, Karl Landsteiner published his discovery of the three main ABO blood group system, blood groups—A, B, and C (which he later renamed to O). Landsteiner described the regular patterns in which reactions occurred when blood serum, serum was mixed with red blood cells, thus identifying compatible and conflicting combinations between these blood groups. A year later Alfred von Decastello and Adriano Sturli, two colleagues of Landsteiner, identified a fourth blood group—AB.
In 1959, by use of X-ray crystallography, Dr. Max Perutz was able to unravel the Hemoglobin#Structure of heme, structure of hemoglobin, the red blood cell protein that carries oxygen.
The oldest intact red blood cells ever discovered were found in Ötzi the Iceman, a natural mummy of a man who died around 3255 BCE. These cells were discovered in May 2012.
See also
* Altitude training
* Blood substitute
* Red blood cell indices
* Serum (blood)
* Er blood group collection
References
External links
''Blood Groups and Red Cell Antigens''
by Laura Dean. Searchable and downloadable online textbook in the public domain.
Database of vertebrate erythrocyte sizes
Red Gold
Public Broadcasting Service, PBS site containing facts and history
{{DEFAULTSORT:Red Blood Cell
Human cells
Blood cells
Respiration
1658 in science
Microscopic discoveries by Antonie van Leeuwenhoek