Erythocytes Red blood cells

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  Red blood cells (RBC), also called erythrocytes are biconcave in shape, like a disc, and have
an 8 μm diameter in vivo and 7.2 μm on blood smears in mammals. The shape of erythrocytes
is very important for their function. They are not true cells as they do not have a nucleus. The
major function of red blood cells is to pick up oxygen from the lungs and release it into the
tissues of the body. They perform this function due to their hemoglobin content. Hemoglobin
intervenes also in: ▪ maintaining the blood pH, as a buffer system, and in ▪ the transport of CO2
from the tissues to the lungs.

           Red blood cell count
           Red blood cell count is expressed as millions of erythrocytes found in 1 μl     (1 cubic
millimeter) of blood. Normal ranges vary with sex:
           Men: 5-5.5 millions/μl blood
           Women: 4.5-5 millions/μl
           Physiologic variations of red blood cell count
       A higher red blood cell count is found in the following physiological conditions:
       -- men as compared to women
       - living at high altitude
       - during exercise
       - in the first 1-3 days of life
A lower than normal red blood cell count is found in
           - elder people
           - after a meal rich in beverages
An increase in RBC over 6-6.5 millions/ μl is called polycythemia; a decrease of RBC bellow 4
millions/ μl, associated with a decreased concentration of hemoglobin in blood,            is called
Anemia is due to either 1). decreased production of RBC in bone marrow or 2). shortened
lifespan of RBC’s.
       1.Decreased production of RBC can occur in the following conditions:
       -    bone marrow failure (radiation, toxins, replacement by a tumor)
       -    nutritional deficiencies that impair the RBC production: iron, copper, vitamin B12,
            folate, malnutrition
       -    erythropoietin deficiency (secondary to renal diseases)
       2. A decreased lifespan of RBC’s can occur in the following conditions:
       -    hemolysis (erythrocyte destruction)
       -    hemorrhage (bleeding)
In the case of hemodilution (over hydration), the RBC count will also be lower than normal.
Polycythemia is:
1. associated to diseases that cause tissue hypoxia
2. a proliferative, tumor like, disease of bone marrow, in which there is an overproduction of
RBC -polycythemia vera
In case of hemoconcentration the RBC is also higher than normal.

          Composition of RBC
          RBC are in fact sacs that carry O2. They have a cell membrane that envelopes the
cytoplasm. The cytoplasm is consisted of 64% water and 36% dry residuum. Of this dry
substance, 34% is represented by hemoglobin. This the protein that binds O2 in the lungs and
carries it to the tissues. The other 2 % are represented by other structure proteins, enzymes and
              Hemoglobin is a hemoprotein (made up of 4 subunits, identical 2 by 2. Each subunit is
called globin and consists of a polypeptidic chain and a heme group. The 4 globins form
together one hemoglobin molecule. The heme is an organic molecule, arranged in a circle, with
an iron atom in the middle. This ferrous iron (Fe2+) in the middle of each of the heme ring is the
part of the molecule of hemoglobin that can reversibly bind O2.
              Normal concentration oh hemoglobin is:
              14-16 g/dL in men
              13.5-15.5 g/dL in women
              Measurement of hemoglobin concentration in blood is useful mainly for estimating the
blood capacity of carrying O2 to the tissues.
               Types of Hb:
          -     embryonic
          -     fetal
          -     adult
          -     abnormal hemoglobin molecules (hemoglobinopathie)

Combinations of hemoglobin
               O2 binding to Hb in the lungs results in oxyhemoglobin. O2 "unloading" occurs in the
tissues to give deoxyhemoglobin (reduced Hb) which is dark red//bluish. As Hb releases O2
into the tissues, it picks up CO2. Approximately 20% of the CO2 carried in blood is bound to
amino acids of the globin portions hemoglobin.               The condition in which the level
deoxyhemoglobin in capillary blood is higher than 5 g/dl, regardless the level of
oxyhemoglobin, is called cyanosis. Hb that carries CO2 is called carbaminohemoglobin.
Carbaminohemoglobin has a darker color.
          In certain pathological conditions, hemoglobin can bind some other substances and
lose its function. Hemoglobin binds carbon monoxide (CO) to form carboxyhemoglobin. In other
cases, the iron in the heme structure can oxidize and form methemoglobin.

                                   The properties of erythrocytes
       1. Gas transport: RBC transport respiratory gases all around the body. They are carrying
O2 from the lungs to the tissues. In the tissues, O2 is released and will be used for intracellular
aerobic chemical reactions, and CO2 produced by metabolizing cells passes from the tissues
into the blood. CO2 is transported back to the lungs for removal from the body.
       2. Deformability: represents the ability of erythrocytes to change their shape as they
pass through narrow spaces, such as small capillaries. Erythrocyte deformability is important for
erythrocyte function, as this property is considered as determinant of microvascular perfusion.
       3. Selective permeability of the cell membrane: erythrocytes have a semi permeable
membrane      ,   which    explains     the   volume   variations   of   erythrocytes   exposed   to
hypertonic/hypotonic solutions.
! hemolysis = the breakage of the RBC’s membrane, causing the release of the hemoglobin and
other internal components into the surrounding fluid.
!! Hemolysis may compromise the laboratory’s test parameters
In vitro hemolysis is caused by: ▪ hypotonic fluids, ▪ exposure of blood to excessive heat or cold;
▪ shaking the blood in the test tube
In vivo hemolysis is caused by: ▪ insect/snake venom ▪hypotonic fluids ▪ antigen-antibodies
reaction, such as in transfusion reactions.
       4. Stability in suspension
       This stability of erythrocyte in suspension is the base of a laboratory test that is
frequently ordered in clinical medicine – the erythrocyte sedimentation rate.
       The erythrocyte sedimentation rate (ESR) measures the distance that erythrocytes have
fallen after 1 hour in a vertical column of anticoagulated blood.
       The test is simple and inexpensive and is used as a non-specific index of inflammation.
       Normal values: 6-8 mm in men, 10-14 mm in women
   Use of ESR:
      as a diagnostic test: ESR is increased in anemia, infection, inflammation, cancer,
       collagen diseases
       !!!! it is a non-specific test
      as a prognostic test: to monitor a person with an associated disease

       5. Antigenic property
       Blood can fall into one of different groups and types in accordance with the types of
antigens present in the cells. Red blood cell membrane contains numerous glycoprotein
molecules, that act as antigens. There are 30 common antigens and hundreds of rare antigens
on RBC membrane. The most powerful and most important are the antigens of the OAB system
and Rh system, because they are highly antigenic and can cause severe blood transfusion
reactions in case of blood incompatibility.
        OAB system
    A certain blood group in 0AB system is defined by:
       the presence of antigens (agglutinins) on RBC surface
       the presence of antibodies (agglutinins) in plasma
        There are 3 antigens in this system: A, B and H, the latter being a weak antigen. In 0AB
system there are 4 blood types: 0(I), A (II), B(II), AB(IV), according to the antigen in red blood
cells membrane. Thus, individuals classified as 0(I) group possess the H antigen in erythrocyte
membrane, those that are included in A (II) group have the A antigen in red blood cell’s
membrane, those belonging to B (III) group have the B antigen and AB (IV) have both A and B
antigen in erythrocyte membrane. In plasma there are natural occurring antibodies against A
and B antigens. Antibodies against A antigen are called anti-A or alpha and those against B
antigen are called anti-B or beta. The antibodies found in plasma of an individual are oriented
against the antigen that is not present on RBC of that person and therefore is recognized as
foreign. Thus, 0 (I) blood group possesses both anti-A (alpha) and anti-B (beta) antibodies (both
A and B antigens are missing in the blood of such a person and therefore are foreign); A (II)
group possesses anti-B (beta) antibodies, B(III) possesses anti-A (alpha) antibodies and AB(IV)
does not have antibodies. Whenever an antibody encounters the correspondent antigen, this
will cause erythrocytes to aggregate together in large clumps, this process being known as
agglutination. For this reason, antibodies are called also agglutinogens and the antibodies are
known as agglutinins.
Agglutinogens are expressed on erythrocyte membrane starting the 3rd month of the intrauterine
life and are present on the surface of almost all cells in the body. In 80% of population the
antigens of the OAB system are also present in secretions (saliva, tears, gastric and intestinal
juice, sperm), such persons being called secretors. Agglutinins occur naturally in month 3-6
after birth.
        Rh system
        A blood group in Rh system is characterized by the presence or absence of the Rh
antigen on RBC surface (spontaneous agglutinin never occur !!). In this system there are 2
blood groups: Rh positive (do have Rh antigen, about 85% of the population) and Rh negative
(do not have the Rh antigen) on erythrocyte membrane.
        When discussing the Rh system, immunization refers to formation of anti-Rh antibodies
in the blood of a Rh negative person. Whenever such a person comes into contact with Rh
positive red blood cells (containing the Rh antigen), this Rh antigen is recognized as foreign and
antibodies against it will be synthesized. The immunization occurs in Rh negative persons who
accidentally are transfused with Rh positive blood or in Rh negative mothers who carry Rh
positive child (inherited from the father).
        Other blood group systems
        Beside OAB and Rh systems, there are many other kinds of antigens on red blood cell
membrane. These groups are not significant for blood transfusions, but they are useful in
forensics, for identifying a person or for establishing fatherhood.
        The importance of blood-typing
        Blood typing is important in •blood transfusions, •for identifying a person and •for
establishing fatherhood.
Blood transfusion defines the process of transfer of blood from one person (donor) to another
(recipient). A transfusion is indicated in case the recipient’s blood concentration of hemoglobin
is less than 7 g/dL. The two bloods have to be appropriately matched; if not, the RBC will clump
and agglutinate. This can lead stop the circulation in different parts of the body. On the other
hand, hemoglobin released by destroyed erythrocytes can produce, when eliminated through
urine, acute renal failure. To be compatible, the blood groups must obey the Landsteiner
principle: the antibodies (agglutinins) in receiver plasma must not match the antigens
(agglutinogens) in donor’s blood.
To avoid the problems of group incompatibility, the serum form the recipient is tested against
the donor’s cells. If no reaction occurs, the transfusion is safe.

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