The blood is the transport system of the organism and thus performs important distributive functions. Considering the multitude of materials transported by the blood (e.g., nutrients, oxygen, carbon dioxide, waste products of metabolism, buffer systems, antibodies, enzymes, and hormones), its chemistry is very complex. Grossly, approximately 45% consists of the formed elements that can be separated by centrifu-gation, and of these, only 0.2% is other than erythrocytes. The 55% of removed plasma contains approximately 8% solids, of which a small portion (less than 1%) can be removed by clotting to produce defibrinated plasma, called serum. Serum contains inorganic and organic compounds, but the total solids are chiefly protein, mostly albumin, and the rest nearly all globulin. The plasma contains the protein fibrinogen, which is converted by coagulation to insoluble fibrin. The separated serum has an excess of the clotting agent thrombin.
Serum globulins can be separated by electrophoresis into a-, ¡-, and y-globulins, which contain most of the antibodies. The immunological importance of globulins is well-known. Many classes and groups of immunoglobulins are produced in response to antigens or even to a single antigen. The specificity of antibodies has been studied from various points of view, and Richards et al.73 have suggested that even though immune sera appear to be highly specific for antigen binding, individual im-munoglobulins may not only interact with several structurally diverse determinants, but may bind such diverse determinants to different sites within the combining region.
The importance of the blood coagulation process has been obvious for a long time. Coagulation mechanisms are covered in several biochemistry texts (see under "Selected Reading"), so a brief summary suffices here. The required time for blood clotting is normally 5 minutes, and any prolongation beyond 10 minutes is considered abnormal. Thrombin, the enzyme responsible for the catalysis of fibrin formation, originates from the inactive zymogen prothrom-bin; the prothrombin-thrombin transformation depends on calcium ions and thromboplastin. The fibrinogen-fibrin reaction catalyzed by thrombin involves proteolytic cleavage (partial hydrolysis), polymerization of the fibrin monomers from the preceding step, and actual clotting (hard clot formation). The final process forming the hard clot occurs in the presence of calcium ions and the enzyme fibrinase.
Thrombin, USP. Thrombin is a sterile protein substance prepared from prothrombin of bovine origin. It is used as a topical hemostatic because it can clot blood, plasma, or a solution of fibrinogen without addition of other substances. Thrombin also may initiate clotting when combined with gelatin sponge or fibrin foam.
For external use it is applied topically to the wound, as a solution containing 100 to 2,000 National Institutes of Health (NIH) units/mL in sodium chloride irrigation or sterile water for injection or as a dry powder.
Erythrocytes contain 32% to 55% hemoglobin, about 60% water, and the rest as stroma. Stroma can be obtained, after hemolysis of the corpuscles by dilution, through the process of centrifuging and consists of lecithin, cholesterol, inorganic salts, and a protein, stromatin. Hemolysis of the corpuscles, or "laking" as it is sometimes called, may be brought about by hypotonic solution, by fat solvents, by bile salts that dissolve the lecithin, by soaps or alkalies, by saponins, by immune hemolysins, and by hemolytic sera, such as those from snake venom and numerous bacterial products.
Hemoglobin (Hb) is a conjugated protein; the prosthetic group heme (hematin) and the protein (globin), which is composed of four polypeptide chains, are usually in identical pairs. The total Mr is about 66,000, including four heme molecules. The molecule has an axis of symmetry and, therefore, is composed of identical halves with an overall ellipsoid shape of the dimensions 55 X 55 X 70 A.
Iron in the heme of hemoglobin (ferrohemoglobin), is in the ferrous state and can combine reversibly with oxygen to function as a transporter of oxygen.
Hb + O2 o Oxyhemoglobin (HbO2)
In this process, the formation of a stable oxygen complex, the iron remains in the ferrous form because the heme moiety lies within a cover of hydrophobic groups of the globin. Both Hb and O2 are magnetic, whereas HbO2 is diamagnetic because the unpaired electrons in both molecules have become paired. When oxidized to the ferric state (methemoglo-bin or ferrihemoglobin), this function is lost. Carbon monoxide combines with hemoglobin to form carboxyhemoglobin (carbonmonoxyhemoglobin) to inactivate it.
The stereochemistry of the oxygenation of hemoglobin is very complex, and it has been investigated to some extent. Some evidence from x-ray crystallographic studies reveals that the conformations of the a and ft chains are altered when their heme moieties complex with oxygen, thus promoting complexation with oxygen. It is assumed that hemoglobin can exist in two forms, the relative position of the subunits in each form being different. In the deoxy form, a and ¡3 subunits are bound to each other by ionic bonds in a compact structure that is less reactive toward oxygen than is the oxy form. Some ionic bonds are cleaved in the oxy form, relaxing the conformation. The latter conformation is more reactive to oxygen.
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