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Hematology
The speciality consult is given in SOMESAN CLINIC, in the area of hematology, by Dr. TODINCA ADRIANA and Dr. POP MUNTEAN LAVINIA.

THE BLOOD

The blood is made by a liquid component, blood plasma and a solid component, represented by the figurative elements. The blood has two major functions: to transport the oxygen and carbon dioxide in the organism; and to transport nutritional molecules, where all the white cells of the blood are involved.

 

The blood plasma contains water (over 90%) where inorganic substances are soluted (especially ions) and organic substances as well (proteins, nutritional substances, metabolic compounds, hormones etc.). The sanguine plasma without the coagulation proteins is the serum. Figurative elements can be classified in: red cells or RBCs/erythrocytes, white cells (WBCs/leukocytes) and blood platelets/thrombocytes. 

ERYTHROCYTES
 
Are the most numerous figurative elements,around 4.8x106/mm³ in women and 5.5x106/mm³ in men. These values may vary depending on factors like health, age, altitude (the peruvians that like in altitudes up to 5.400m cand have 8.3x106/mm³. They are anucleated cells, in the shape of a biconcave disk. The RBCs develop in blood-poesis from erythroid cells. During the maturation process, the cells produce haemoglobin until it represents 90% or the dried cell weigh. The cells are maturated in the nearby of a macrophage that will ingest the erythrocyte's nucleus. 
The red cells are responsable with transportation of oxygen and carbon dioxide in the organism. Oxygen transportation: the emoglobin molecule is made from 4 polypeptides (two alpha chains and two beta chains), each of these are attached to a prosthesis formation, called heme groups. Each heme group contains an iron atom that will chain the oxygen molecule and will form oxyhemoglobin. The reaction is reversible. .
 
Hemoglobin  is the main compound of the erythrocyte. It's a chrome protein, made from two compounds , a protein called globin and a non protean  formation called heme. Globin is made from the association of four polypeptide chains.
From each polypeptide chain a heme molecule is attached. Due to the presence of of Fe in its molecule, heme can chain labile oxygen. The fixation reaction of o2 to Hb is not an oxidation (because it does not increase the Fe valence) but an oxygenation reaction, a reversible chain of an oxygen molecule to the bivalent Fe, this reaction results in oxyhemoglobin (HbO2) that is the main transportation form of O2 in blood. When completely saturated (oxygenated), a Hb molecule can transport 4 molecules of O2. A single erythrocyte contains about 300 000 000 Hb molecules.  Expressed in grams, Hb represents 16g in a 100 ml of blood. Each Hb gram can transport 1,34 ml of O2, so each 100ml of blood transports 20ml of O2. In the lack of Hb, the transportation capacity of blood for oxygen significantly decreases; 100ml of plasma only transports 0,2ml of O2.

Beside the oxygenated form and the reduced form, Hb can give  carbon oxide stabile compounds (CO Hb) called carboxyhemoglobin and under the action of oxydants appears the Hb derivative with trivalent Fe, called  methemoglobin. These are pathologic derivatives of Hb; they do not have the transportation function and in case their concentration increases over some limits  insufficient oxygenation of tissue appears (asphyxiation).

Hemoglobin can combine with carbon dioxide (Hb CO2), that are called carbohemoglobin or hemoglobin carbamate. This is a physiologic compound that does not affect the transportation function of O2. HbCO2 is one of the transportation forms of CO2 in lung tissue.

LEUKOCYTES (WHITE CELLS)
 
Are less than erythrocytes (4000-8000/mm3). Are nucleated cells that take part in the immune defense or the organism. Depending in the presence  or absence of cytoplasm granulation they clasify in cells without granulations (lymphocytes and monocytes) and granulocytes (cells with granulations): neutrophils, eosinophils, and basophils .
Leukocytes form is not the same.They represent an homogenous cell population. There are many types that differ in origin and morphology and in their role in the organism. Their rate expression is called leukocyte formula. In this formula, we see leukocytes with a single nucleus-mononucleated and with fragmented nucleus, polylobed-polynucleated.
The mononucleated represent 32% and the polynucleated 68% of the leukocytes. The mononucleated group contains: limphocytes, that represent  25% and  monocytes, 7%.
The leukocyte dimensions vary from 6-8µ for a small lymphocyte and 20µ in diameter for monocytes and neutrophils. Leukocytes present a complete cellular structure. They have a membrane with a remarkable plasticity. Because of it the leukocytes spread cytoplasm extensions (pseudopode), with the help of which they become mobile, can move outside the capillary vessels (diapedesis) and can englobe microbes (microphagocytosis) or cellular rests (macrophagocytosis). The granulations of the polynucleated are little bags and vesicles full with hydrolytic enzymes (lysosome) that participate in phagocytosis. In the leukocyte family plasmocytes are included, cells that come from the lymphocytes, and are specialized in producing antibodies.
 The role of leukocites is complex and different. Their main function is in participating in the defence reaction of the organism . 
 
LYMPHOCYTES
 
All the lymphocytes are produced in the bone marrow (a primary lymphoid organ). If they become immunocompetent in the bone marrow they are called B lymphocytes ( they synthetize antibodies and lymphokines) and if they become immunocompetent in the thimus (another primary lymphoid organ), they are called T lymphocytes (they only synthetize limphokines). 
T inflammatory lymphocytes that recruit macrophages and neutrophils in the place of an infection or an tissular lesion ;
T cytotoxic lymphocytes (TCL) that kill cells that are infected with viruses and (maybe) tumoral cells
T helper cells- stimulate the producing of antibodies by B lymphocytes.
 


MONOCYTES
Monocytes circulate through peripheral blood before emigrating in the tissues, where they transform in macrophage. Depending of the organ where they are located, they have specific names. So, the liver macrophages are called Kupfer cells, in the brain they are called microglial, in the bones- osteoclasts etc. The macrophages are large, phagocitary cells that englobe strange materials and cell fragments in the organism .

NEUTROPHILS
Neutrophils are blood elements that respond to chemotactic signals and leave the capillary through a complex process that implicates the cell margination (near to the blood vessels endothelium) attachment to the vessel's wall and exit through the space between the endothelial cells (process that is called diapedesis). Migration is determined by many factors: substances that are produced by microorganisms, signals sent by cells that participate in the anti inflamatory process etc. Neutrophils keep under control the bacterial populations that normally exist in the colon, oral cavity, throat. In pathologic cases, when the number of neutrophils decreases (radiations, chemotherapy, stress), these bacteria get out of control, and opportunity infections appear. .

EOSINOPHILS
The number of eosinophils is normally between 0 and 450/mm3. Their number increases in the case of some disease, especially parasitosis, and in the case of large parasites. The eosinophils granules contain cytotoxic substances, that are released over the parasite. Through these substances we see major basic protein (MBP), cationic proteins, peroxidase, B arylsulphatase, D phospholipase and histaminase. This combination is capable to destroy the parasite.

BAZOPHILS
Basophils are non phagocytic cells that, when are activated, release numerous compounds from basophile granules from their cytoplasm. They have an important role in allergic responses, especially in type I hypersensitive reactions. They are involved in the anaphylactic response. Anaphilaxys is a reaction of specific hyper sensibility, that appears in the second exposure to the same antigen. The most severe form is anaphylactic shock. A good clinical definition of anaphylactic reaction takes in count the presence of two severe manifestations: difficulty in breathing (by laryngeal edema and asthma) and hypotension. The number of basophils increases during infections also. The granules contain a series of mediators: histamine, serotonin, prostaglandine and leukotriene, with the role to increase the blood flow in the injured area. 

BLOOD PLATELETS
The platelets are cell fragments produced by the megakaryocytes and are involved in the coagulation process. In case a blood vessel is injured, blood platelets dispose in a insoluble fibrin chain, forming the blood clot.
Normally  there are 150.000-350.000/mm3. Their number is adjusted by homeostatic mechanisms (negative feedback). When the number drops under 50.000, coagulation problems appear..

BLOOD GROUPS
Now, there are 29 systems of blood groups that are recognized by ISBT-International Society of Blood Transfusion. From these systems, the most popular and important, in case of transfusion, are OAB and RHESUS (Rh). All blood groups from the 29 systems are determined by the combinations of 29 antigens on the surface or erythrocytes, and in total, there are over 400 blood groups.
The discovery of the main blood groups, the OAB blood system, was made by Landsteiner, that won the Nobel prize for medicine, in 1930.
 In OAB system, there are 4 blood groups: 0or 1, A(II), B(III) and AB(IV). These groups are determined by the presence or absence of antigen molecules, called agglutinogen. The most important agglutinogens are A, B and H. Agglutinogen H is present on type 0 erythrocytes and it's the predecessor of agglutinogen A and B. The antigen properties of these molecules are determined by the structure of carbohydrate rests attached to protein core. So, by adding a rest of N-acetyl-galactose to antigen H we obtain antigen A, and by adding a rest of galactose to antigen H we obtain antigen B.Antigen H comes from a predecessor called , by adding a rest of fucose. On the A II erythrocytes we find agglutinogen A, on BIII, agglutinogen B and on ABIV agglutinogen A and B. Agglutinogen is a natural antigen, fixated on the red cell. There are also agglutinins thar correspond to human agglutinogen. Agglutinin is a natural antibody and are found in blood serum. they are responsable for agglutination. Natural agglutinin of OAB system are alpha-anti A and beta-anti B. Agglutinin and their correspondent antibodies are not found in the blood of the same patient.

RHESUS SYSTEM (Rh)
Antigenic Rh system was discovered by Landsteiner and Wiener, in Macacus Rhesus monkey erytrocytes membrane. The system is similar to OAB system and is widely spread. There are three pairs of Rh antigens :Cc, Dd and Ee. From these, the most antigenic and the mot important is D, called Rh antigen. The antigen appears in the 6th week of life and increases in the erythroblaste, until maturity.
Rh antibodies are in the immunoglobulie class G(IgG), that can cross the placental barrier.
Different to the case of system OAB antigens and antibodies, in persons with negative Rh, the antigens on erytrocytes and the antibodies in the serum are missing. These persons can synthetize anti-Rh antibodies subsequent to a positive Rh blood transfusion, or in case orf a pregnancy with a negative Rh mother and a positive Rh baby (positive Rh father).
 

 

In OAB system, there are 4 blood groups: 0or 1, A(II), B(III) and AB(IV). These groups are determined by the presence or absence of antigen molecules, called agglutinogen. The most important agglutinogens are A, B and H. Agglutinogen H is present on type 0 erythrocytes and it's the predecessor of agglutinogen A and B. The antigen properties of these molecules are determined by the structure of carbohydrate rests attached to protein core. So, by adding a rest of N-acetyl-galactose to antigen H we obtain antigen A, and by adding a rest of galactose to antigen H we obtain antigen B.Antigen H comes from a predecessor called , by adding a rest of fucose. On the A II erythrocytes we find agglutinogen A, on BIII, agglutinogen B and on ABIV agglutinogen A and B. Agglutinogen is a natural antigen, fixated on the red cell. There are also agglutinins thar correspond to human agglutinogen. Agglutinin is a natural antibody and are found in blood serum. they are responsable for agglutination. Natural agglutinin of OAB system are alpha-anti A and beta-anti B. Agglutinin and their correspondent antibodies are not found in the blood of the same patient.

Direct application or Rh factor determination is prenatal diagnosis by amniocentesis, to find feto-maternal incompatibility. This incompatibility stand at the base of fetal erytrhroblastosis. The disease appears after an immunization of the mother with negative Rh against antigen D on the erytrocyte membrane of the fetus with positive Rh, inherited from the father. At birth, the erytrocytes caring the Rh antigen arrive in the mother's blood and she will sythetize anti-Rh antibodies. In a new pregnancy (positive Rh fetus), memory cells will synthetize anti-Rh antibodies, that arrive in the fetus's blood and determine the apparition of fetal erythroblastosis.


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Address:
Aleea Mărăşti Nr. 1
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Tel. 0751.229.475
Tel. 0362.415.521
Tel. 0362.415.535
Fax: 0362.415.540

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