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See also:ANATOMY AND See also:PHYSIOLOGY In all living organisms, except the most See also:minute, only a mini-mum number of cells can come into immediate contact with the See also:general See also:world, whence is to be See also:drawn the See also:food See also:supply for the whole organism . Hence those cells—and they are by far the most numerous—which do not See also:lie on the food-absorbing See also:surface, must gain their nutriment by some indirect means . Further,each living See also:cell produces See also:waste products whose See also:accumulation would speedily prove injurious to the cell, hence they must be constantly removed from its immediate neighbourhood and indeed from the organism as a whole . In this instance again, only a few cells can lie on a surface whence such materials can be directly discharged to the exterior . Hence the See also:main number of the cells of the organism must depend upon some mechanism by which the waste products can be carried away from them to that See also:group of cells whose See also:duty it is to modify them, or See also:discharge them from the See also:body . These two ends are attained by the aid of a circulating fluid, a fluid which is constantly flowing past every cell of the body . From it the cells See also:extract the food materials they require for their sustenance, and into it they discharge the waste materials resulting from their activity . This circulating See also:medium is the See also:blood . Whilst undoubtedly the two functions of this circulating fluid above given are the more prominent, there are yet others of See also:great importance . For instance, it is known that many tissues as a result of their activity produce certain chemical substances which are of essential importance to the See also:life of other See also:tissue cells . These substances—See also:internal secretions as they are termed —are carried to the second tissue by the blood stream . Again, many instances are known in which two distant tissues communicate with one another by means of chemical messengers, bodies termed hormones (opµaety, to stir up), which are produced by one group of cells, and sent to the other group to excite them to activity . Here, also, the path by which such messengers travel is the blood stream . A further and most important manner in which the circulating fluid is utilized in the life of an See also:animal is seen in the way in which it is employed in protecting the body should it be invaded by micro-organisms . Hence it is clear that the blood is of the most vital importance to the healthy life of the body . But the fact that it is See also:present as a circulating medium exposes the animal to a great danger, viz. that it may be lost should any See also:vessel carrying it become ruptured . This is constantly liable to happen, but to minimize as far as possible any such loss, the blood is endowed with the See also:peculiar See also:property of clotting, i.e. of setting to a solid or stiff jelly by means of which the orifices of the torn vessels become plugged and the bleeding stayed . The performance of these essential functions depends upon the See also:maintenance of a continuous flow past all tissue cells, and this is attained by the circulatory mechanism, consisting of a central See also:pump, the See also:heart, and a See also:system of ramifying tubes, the See also:arteries, through which the blood is forced from the heart to every tissue (see VASCULAR SYSTEM) . A second set of tubes, the See also:veins, collects the blood and returns it to the heart . In many invertebrates the circulating fluid is actually poured into the tissue spaces from the open terminals of the arteries . From these spaces it is in turn drained away by the veins . Such a system is termed a haemolymph system and the circulating fluid the haemolymph . Here the essential point gained is that the fluid is brought into See also:direct contact with the tissue cells . In all vertebrates, the ends of the arteries are See also:united to the commencements of the veins by a plexus of extremely minute tubes, the capillaries, consequently the blood is always retained within closed tubes and never comes into contact with the tissue cells . It is while passing through the capillaries that the blood performs its See also:work; here the blood stream is at its slowest and is brought nearest to the tissue cell, only being separated from it by the extremely thin See also:wall of the capillary and by an equally thin layer of fluid . Through this narrow barrier the interchanges between cell and blood take See also:place . The See also:advantage gained in the vertebrate animal by retaining the blood in a closed system of tubes lies in the great diminution of resistance to the flow of blood, and the consequent great increase in See also:rate of flow past the tissue cells . Hence any food stuffs which can travel quickly through the capillary wall to the tissue cell outside can be supplied in proportionately greater quantity within a given See also:time, without requiring any very great increase in the concentration of that substance in the blood . Conversely, any highly diffusible substance may be withdrawn from the tissues by the blood at a similarly increased See also:pace . These conditions are more peculiarly of importance for the supply of See also:oxygen and the removal of carbonic See also:acid—especially for the former, because the amount of it which can be carried by the blood is small . But as the rate at which a tissue lives, i.e. its activity, depends upon the rate of its chemical reactions, and as these are fundamentally oxidative, the more rapidly oxygen is carried to a tissue the more rapidly it can live, and the greater the amount of work it can perform within a given time . The rate of supply is of much less importance in the See also:case of the other food substances because they are far more soluble in See also:water, so that the supply in sufficient quantity can easily be met by a relatively slow blood flow . Hence we find that the See also:gradual See also:evolution of the animal See also:kingdom goes See also:hand in hand with the gradual development of a greater oxygen-carrying capacity of the blood and an increase in the rate of its flow . In the groundwork of a tissue are a number of spaces—the tissue spaces . They are filled with fluid and intercommunicate freely, finally connecting with a number of See also:fine tubes, the lymphatics, through which excess of fluid or any solid particles present are drained away . The contained fluid acts as an interrnediary between the blood and the cell; from it, the cell takes its various food stuffs, these having in the first instance been derived from the blood, and into it the cell discharges its waste products . On the course of the lymphatics a number of typical structures, the lymphatic glands, are placed, and the See also:lymph has to pass through these structures where any deleterious products are retained, and the fluid thus purified is drained away by further lymphatics and finally returned to the blood . Thus there is a second stream of fluid from the tissues, but one vastly slower than that of the blood . The flow is too slow for it to See also:act as the vehicle for the removal of those waste products (carbonic acid, &c.) which must of See also:necessity be removed quickly . These must be removed by the blood . The same is true for the main number of other waste products, which, however, being of small molecular See also:size are readily absorbed into the blood stream . But in addition to fluid, the tissue spaces may at times be found to contain solid See also:matter in the See also:form of particles, which may represent the debris of destroyed cells, or which are, as is quite commonly the case, micro-organisms . Apparently such material cannot be removed from a tissue by absorption into the blood stream—indeed in the case of living organisms such an absorption would in many instances rapidly prove fatal, and See also:special See also:provision is made to prevent such an See also:accident . These, therefore, are made to travel along the lymphatic channels, and so, before gaining See also:access to the blood stream and thus to the body generally, have to run the See also:gauntlet of the protective mechanism provided by the lymphatic glands, where in the See also:major number of cases they are readily destroyed . Hence we see that first and foremost we have to regard the blood as a food-See also:carrier to all the cells of the body; in the second place as the vehicle carrying away most if not all the waste products; in a third direction, it is acting as a means for transmitting chemical substances manufactured in one tissue to distant cells of the body for whose See also:nutrition or excitation they may be essential; and in addition to these important functions there is yet another whose value it is almost impossible to over-estimate, for it plays the essential role in rendering the animal immune to the attacks of invading organisms . The question of See also:immunity is discussed elsewhere, and it is sufficient merely to indicate the See also:chief means by which the blood subserves this essential protective mechanism . Should living organisms find their way into the surface cells or within the tissue spaces, the body fights them in a number of ways . (I) It may produce one or more chemical substances capable of neutralizing the toxic material produced by the organism . (2) It may produce chemical substances which act as poisons to the micro-organism, either paralysing it or actually killing it . Or (3) the organism may be attacked and taken up into the body of wandering cells, e.g. certain of the leucocytes, and then digested by them . Such cells are therefore called phagocytes (4aryecv, to eat) . Thus, by itspower of reacting in these ways the body has become capable of withstanding the attacks of many different varieties of micro-organisms, of both animal and See also:vegetable origin . General Properties.—Blood is an opaque, viscid liquid of See also:bright red See also:colour possessing a distinct and characteristic odour,. especially when warm . Its opacity is due to the presence of a very large number of solid particles, the blood corpuscles, having a higher refractive See also:index than that of the liquid in which they See also:float . The specific gravity in See also:man averages about 1•oS5 . The specific gravity of the liquid portion, the plasma (Gr. irMavµa, something formed or moulded, srA& ro av, to See also:mould), is about 1.027, whilst that of the corpuscles amounts to r•o88 . To See also:litmus it reacts as a weak See also:alkali . Blood Plasma.—The plasma is a See also:solution in water of a varied number of substances, and as a solvent it confers on the blood its See also:power of acting as a carrier of food stuffs and waste products . One important food substance, oxygen, is, however, only partly carried in solution, being mainly combined with haemoglobin in the red corpuscles . The food stuffs carried by the plasma are proteins, carbohydrates, salts and water . The main waste products dissolved in it are ammonium carbonate, See also:urea, urates, xanthin bases, creatin and small amounts of other nitrogenous bodies, carbonic acid as See also:carbonates, other See also:carbon compounds such as cholesterin, lecithin and a number of other substances . Thus, if we take mammalian blood as a type, the plasma would have the following approximate See also:composition: In Ioo0 grms. plasma Water 901.51 Substances not vaporizing at I2o° C . ' See also:Fibrin . . 8•o6 Other proteins and organic substances 81.92 Inorganic substances See also:Chlorine . 3.536 Sulphuric acid . 0.129 Phosphoric acid . 0'145 See also:Potassium . 0•314 See also:Sodium . 3.410 See also:Calcium . 0.298 See also:Magnesium 0.218 Oxygen . 0'455 _ 8.505 98'49 See also:I000.00 Proteins.—The proteins of the blood plasma belong to the two classes of the albumins and the globulins . The globulins present are named fibrinogen and serum-globulin; as its name implies, the chief physiological property of fibrinogen is that it can give rise to fibrin, the solid substance formed when blood clots . It possesses the typical properties of a globulin, i.e. it coagulates on See also:heating (in this instance at a temperature of 56° C.), and is precipitated by See also:half saturating its solution with ammonium sulphate . It differs from other globulins in that it is less soluble . It is only present in very small quantities, 0.4% . The other globulin, serum-globulin, is not coagulated until 75° C. is reached, and we now know that it is in reality a mixture of several proteins, but so far these have not been completely separated from one another and obtained in a pure form . On dialysing a solution of serum-globulin a See also:part is precipitated, and this portion has been termed the eu-globulin fraction, the See also:remainder being known, in contradistinction, as the pseudo-globulin . Again, on diluting a solution and adding a small amount of acetic acid a precipitate is formed which in some respects differs from the remainder of the globulin present . Whether in these two instances we are dealing with approximately pure substances is extremely doubtful . A further important point in connexion with the See also:chemistry of the globulins is that dextrose may be found among their decomposition products, i.e. that a part of it, or possibly the whole, possesses a See also:glucoside See also:character . Serum-See also:albumin gives all the typical colour and precipitation reactions of the albumins . If plasma be weakly acidified with sulphuric acid, then treated with crystals of ammonium sulphate until a slight precipitate forms, filtered and the filtrate allowed to evaporate very slowly, typical crystals of serum-albumin may form . According to many it is a See also:uniform and specific substance, but others hold the view that it consists of at least three distinct substances, as shown by the fact that if a solution be gradually heated coagulation will occur at three different temperatures, viz. at 73° 77° and 84° C . On the other hand the See also:close agreement between different analyses of even the amorphous preparations points to there being but one serum-albumin .
When blood clots two new proteins make their See also:appearance in the fluid part of the blood, or serum, as it is now called
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The first of these is fibrin ferment (for its origin see See also:section on Clotting below)
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The other, fibrinoglobulin, possesses all the typical characteristics of the globulins and coagulates at 64° C
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Carbohydrates.—Three several carbohydrates are described as occurring in plasma, viz. glycogen, animal See also:gum and dextrose
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If glycogen is present in solution in the plasma it is there in very small quantities only, and has probably arisen from the destruction of the See also: To some extent it varies in composition with that of the fat absorbed, but usually consists of the glycerides of the See also:common fatty acids—palmitic, stearic and oleic . In addition, there is a small amount of fatty acid in solution in the plasma . As to the form in which this occurs there is some uncertainty . It is possibly present as a See also:soap or even as a neutral fat, since a little can be dissolved in plasma, the solvent substance being probably protein or cholesterin . Fatty acids also appear to be present to some extent combined with cholesterin forming cholesterin See also:esters (about o.o6%) . Other Organic Compounds.—In addition to the substances above described, belonging to the three main classes of food stuffs, there are still other organic bodies present in plasma in small amounts, which for convenience we may classify as non-nitrogenous and nitrogenous . Among the former may be mentioned lactic acid, See also:glycerin, a lipochrome, and probably many other substances of a similar type whose separation has not yet been effected . The non-protein nitrogenous constituents consist of the following: See also:ammonia as carbonate or carbamate (0.2 to o.6%), urea (0.02 to 0.05%), creatine, ce. atinine, uric acid, xanthine, hypoxanthine and occasionally hippuric acid . Three ferments are also described as being present: (r) a glycolytic ferment exerting an See also:action upon dextrose; (2) a lipase or fat-splitting ferment; and (3) a diastase capable of converting starch into sugar . Salts.—The saline constituents of plasma comprise chlorides, See also:phosphates, carbonates and possibly sulphates, of sodium, potassium, calcium and magnesium . The most abundant See also:metal is sodium and the mist abundant acid is hydrochloric . These two are present in sufficient amount to form about o.65% of sodium chloride . The phosphate is present to about 0.02% . Sulphuric acid is always present if the blood has been calcined for the purposes of the See also:analysis, and may then be present to about 0'013% . This is, however, probably produced during the destruction of the protein, since it has been shown that no sulphate can be removed from normal plasma by See also:dialysis . The amount of potassium present (0.03 %) is less than one-tenth of that of the sodium, and the quantities of calcium and magnesium are even less . Formed Elements.—When viewed under the See also:microscope the main number of these are seen to be small yellow bodies of very uniform size, size and shape varying, however, in different animals . When observed in bulk they have a red colour, their presence in fact giving the typical colour to blood . These are the red blood corpuscles or erythrocytes (Gr. pvOpbs, red) . Mingled with them in the blood are a smaller number of corpuscles which possess no colour and have therefore been called white blood corpuscles or leucocytes (Gr . X euicbs, white) . Lastly, there are present a large number of small See also:lens-shaped structures, less in number than the red corpuscles, and much more difficult to distinguish . These are known as blood platelets . Red Corpuscles.—These are present in very large See also:numbers and, under normal conditions, all possess exactly the same appearance . With rare exceptions their shape is that of a biconcave disk with bevelled edges, the size varying somewhat in different animals, as is seen in the following table which gives their diameters: Man 0.•0075 mm . See also:Dog 0.0073 mm . See also:Rabbit . 0.0069 mm . See also:Cat 0.0065 mm . See also:Goat 0.0041 mm . The coloured corpuscles of See also:amphibia as well as of nearly all vertebrates below mammals are biconvex and elliptical . The following are the dimensions of some of the more common: See also:Pigeon . 0.0147 mm. See also:long by 0.0065 mm. wide . See also:Frog 0.0223 0.0157 See also:Newt 0.0293 0.0195 See also:Proteus . . 0.0580 „ 0.0350 Amphiuma . 0.0770 0.0460 „ Goat 9,000,000 to 10,000,000 See also:Sheep 13,000,000 to 14,000,000 Birds . 1,000,000 to 4,000,000 See also:Fish 250,000 to 2,000,000 Frog . 500,000 per cub. mm . Proteus 36,000 „ In mammals they are apparently homogeneous in structure, have no See also:nucleus, but possess a thin envelope . Their specific gravity is distinctly higher than that of the plasma (r•o88), so that if clotting has been prevented, blood on See also:standing yields a large See also:deposit which may form as much as half the See also:total See also:volume of the blood . Chemical Composition.—On destruction the red corpuscles yield two chief proteins, haemoglobin and a nucleo-protein, and a number of other substances similar to those usually obtained on the break-down of any cellular tissue, such for instance as lecithin, cholesterin and inorganic salts . The most important protein is the haemoglobin . To it the corpuscle owes its distinctive property of acting as an oxygen carrier, for it possesses the power of combining chemically with oxygen and of yielding up that same oxygen whenever there is a decrease in the concentration of the oxygen in the solvent . Thus in a given solution of haemoglobin the amount of it which is combined with oxygen depends absolutely on the oxygen concentration . The greatest See also:dissociation of oxyhaemoglobin occurs as the oxygen tension falls from about 40 to 20 mm. of See also:mercury . That the oxygen forms a definite See also:compound with the haemoglobin is proved by the fact that haemoglobin thoroughly saturated with oxygen (oxyhaemoglobin) has a definite absorption spectrum showing two bands between the D and E lines, whilst haemoglobin from which the oxygen has been completely removed only gives one See also:band between those lines . In association with this, oxyhaemoglobin has a typical bright red colour, whereas haemoglobin is dark See also:purple . A further striking characteristic of haemoglobin is that it contains See also:iron in its See also:molecule . The amount present, though small bears a perfectly definite quantitative relation to the amount of oxygen with which the haemoglobin is capable of combining (two atoms of oxygen to one of iron) . One See also:gram of haemoglobin crystals can combine with 1.34 cc. of oxygen . On destruction with an acid or alkali, haemoglobin yields a pigment portion, haematin, and a protein portion, globin, the latter belonging to the group of the histones (Gr. ivrbs, See also:web, tissue) . Their number also varies as follows: Man . 4,000,000 to 5,000,000 per cub. mm . „ 77 In this cleavage the iron is found in the pigment . By the use of a strong acid, it may be made to yield iron-See also:free pigment, the remainder of the molecule being much further decomposed . Destruction and Formation.—In the performance of their work the corpuscles gradually deteriorate . They are then destroyed, chiefly in the See also:liver, but whether the whole of this See also:process is effected by the liver alone is not decided . It is proved, however, that the destruction of the haemoglobin is entirely effected there . It was for a long time considered to be one of the functions of the See also:spleen to examine the red corpuscles and to destroy or in some way to See also:mark those no longer fitted for the performance of their work . It is proved that the destruction of the haemoglobin is entirely effected in the liver, since both the main cleavage products may be traced to this See also:organ, which discharges the pigmentary portion as the bile pigment, but retains the iron-protein moiety at any rate for a time . The amount of bile pigment eliminated during the See also:day indicates that the destruction must be consider-able, and since the number of corpuscles does not vary there must be an See also:equivalent formation of new ones . This takes place in the red See also:bone-marrow, where special cells are provided for their continuous See also:production . In embryonic life their formation is effected in another way . Certain mesodermic cells, resembling those of the connective tissue, collect masses of haemoglobin, and from these elaborate red blood corpuscles which thus come to lie in the fluid part of the cell . By a canalization of the branches of these cells which unite with branches of other cells the pre-cursors of the blood capillaries are formed . White Blood Corpuscles.—These constitute the second import-See also:ant group of formed elements in the blood, and number about 12,000 to 20,000 per cubic mm . They are typical wandering cells carried to all parts of the body by the blood stream, but often leave that stream and gain the tissue spaces by passing through the capillary wall . They exist in many varieties and were first classified according as, under the microscope, they presented a granular appearance or appeared clear . The cells were also distinguished from one another according as they possessed fine or coarse granules . The granules are confined to the See also:protoplasm of the cell, and it has been shown that they differ chemically, because their staining properties vary . Thus, some granules select an acid stain, and the cells containing them are then designated acidophile or eosinophile; l other granules select a basic stain and are called basophile, while yet others prefer a neutral stain (neutrophile) . In human blood the following varieties of leucocytes may be distinguished: r . The Polymorphonuclear Cell.—This possesses a nucleus of very complicated outline and a See also:fair amount of protoplasm filled with numbers of fine granules which stain with eosin . They vary in size but are usually about o•or mm. in See also:diameter . They are highly amoeboid and phagocytic, and form about 70% of the total number of leucocytes . 2 . The Coarsely Granular Eosinophile Cell.—These large cells contain a number of well-defined granules which stain deeply with acid dyes . The nucleus is crescentic . The cells amount to about 2 % of the total number of leucocytes, though the proportion varies considerably . They are actively amoeboid . 3 . The Lymphocyte.—This is the smallest leucocyte, being only about o•oo65 mm. in diameter . It has a large spherical nucleus with a small rim of clear protoplasm surrounding it . It forms from r 5 to 40 % of the number of leucocytes, and is less markedly amoeboid than the other varieties . 4 . The Hyaline (Gr. vaAcuos, glassy, crystalline, &\m, See also:glass) cell or macrocyte (Gr . ,uaKpos, long or large).—This is a cell similar to the last with a spherical, See also:oval or indented nucleus, but it has much more protoplasm . It constitutes about 4 % of all the leucocytes and is highly amoeboid and phagocytic . 5 . The Basophile Cell.—This possesses a spherical nucleus and the protoplasm contains a small number of granules staining i The suffix -phile, See also:Greek c5 Xe?v, to love, prefer, is in scientific terminology frequently applied to substances that exhibit such preference for particular stains or reagents, the names of which form the first part of the word.deeply with basic dyes . It is rarely found in the blood of adults except in certain diseases . Functions.—These cells act as scavengers or as destroyers of living organisms that may have gained access to the tissue spaces . They See also:play an important part in the chemical processes underlying the phenomena of immunity, and some at least are of importance in starting the process of clotting . They are constantly suffering destruction in the performance of their work . Many, too, are lost to the body by their passage through the different mucous surfaces . Their origin is still obscure in many points . The lymphocytes are derived from lymphoid tissue, wherever it exists in the different parts of the body . The polymorphonuclear and eosinophile cells are derived from the bone-marrow, each by See also:division of specific See also:mother cells located in that tissue . The macrocyte is believed by many to represent a further See also:stage in the development of the lymphocyte . Their rate of formation may be influenced by a variety of conditions—for instance, they are found to vary in number according to the See also:diet and also, to a considerable extent, in disease . Platelets.—The platelets or thrombocytes (Gr . Bpoµf3os, See also:clot) are the third class of formed elements occurring in mammalian blood . There are still, however, many observers who consider that platelets are not present in the normal circulating blood, but only make their appearance after it has been See also:shed or other-See also:wise injured . They are minute lens-shaped structures, and may amount to as many as 800,000 per cubic mm . Under certain conditions, examination has shown that they are protoplasmic and amoeboid, and that each one contains a central body of different staining properties from the remainder of the structure . This has been regarded by some as a nucleus . On being brought into contact with a See also:foreign surface they adhere to it firmly, very rapidly passing through a number of phases resulting ultimately in the formation of granular debris . In shed blood they tend to collect into See also:groups, and during clotting, fibrin filaments may be observed to shoot out from these clumps . See also:Variations in the Blood of different Animals.—If we contrast the blood of different animals of the vertebrate class we find striking See also:differences both in microscopic appearances and in chemical properties . In the first place, the corpuscles vary in amount and in See also:kind . Thus, whilst in a mammal the corpuscles form 40 to 50 % of the total volume of the blood, in the See also:lower vertebrates the volume is much less, e.g. in frogs as See also:low as 25 % and in fishes even lower . The deficiency is chiefly in the red corpuscles, the ratio of white to red increasing as we examine the blood from animals lower in the See also:scale . The corpuscles themselves are also found to vary, especially the red ones . In the mammal they are biconcave disks with bevelled edges, they do not contain a nucleus so that they are not cells . In the See also:bird they are larger, ellipsoidal in shape and have a large nucleus in the centre of the cell . In See also:reptiles and amphibia the red corpuscles are also nucleated, but the stroma portion containing the haemoglobin is arranged in a thickened See also:annular part encircling the nucleus . When seen from the See also:flat they are oval in section . In fishes the corpuscles show very much the same structure . A further very significant difference to be observed between the bloods of different vertebrates is in the amount of haemoglobin they contain; thus in the lower classes, fishes and amphibia, not only is the number of red corpuscles small but the amount of haemoglobin each corpuscle contains is relatively low . The concentration of the haemoglobin in the corpuscles attains its maximum in the mammal and the bird . Since the haemoglobin is practically the same from whatever animal it is obtained and can only combine with the same amount of oxygen, the oxygen-capacity of the blood of any vertebrate is in direct proportion to the amount of haemoglobin it contains . Therefore we see that as we ascend the scale in the vertebrate See also:series the oxygen-carrying capacity of the blood rises . This increase was a natural preliminary See also:condition for the progress of evolution . In See also:order that a more active animal might be See also:developed the main essential was that the chemical processes of the cell should be carried out more rapidly, . and as these processes are fundamentally oxidative, increased activity entails an increased rate of supply of oxygen . This latter has been brought about in the animal kingdom in two ways, first by an increase in the concentration of the haemoglobin of the blood effected by an increase both in the number of corpuscles and in the amount of haemoglobin contained in each, and secondly by an increase in the rate at which the blood has been made to pass through the tissues . In the lower vertebrates the blood pressure is low and the haemoglobin content of the blood is low, consequently both rate of blood-flow and oxygen-content are low . In contrast with this, in higher vertebrates the blood pressure is high and the haemoglobin content of the blood is high, consequently both rate of blood-flow and oxygen-content are high . We must See also:associate with this important step in evolution the means employed for the more rapid absorption of oxygen and for its increased rate of discharge to the tissues, the most important features of which are a diminution in the size of the corpuscle and the attainment of its ,peculiar shape, both resulting in the production of a relatively enormous corpuscular surface in a unit volume of blood . Variations are also found in the white corpuscles as well as in the red, but these differences are not so striking and lie chiefly in unimportant details of structure of individual cells . Enormous variations are to be found in different See also:species of mammals, but the cells generally conform to the types of secreting cells or phagocytes . The platelets also differ in the different species . In the frog, for instance, many are spindle-shaped and contain a nucleus-like structure . Birds' blood is stated to contain no platelets . The variations in number of these bodies have not been satisfactorily ascertained on See also:account of the difficulties involved in any See also:attempt to preserve them and to render them visible under the microscope . Differences are also found in the chemical composition of the plasma . The chief variation is in the amount of protein present, which attains its maximum concentration in birds and mammals, while in reptiles, amphibia and fishes it is much less . The bloods of the latter two classes are much more watery than that of the mammal . Moreover, it has been proved that there are specific differences in the chemical nature of the various proteins present even between different varieties of mammals . Thus the ratio of the globulin fraction to the albumin fraction may vary considerably, and again, one or other of the proteins may be quite specific for the animal from which it is derived . Clotting.—If a See also:sample of blood be withdrawn from an animal, within a See also:short time it undergoes a series of changes and becomes converted into a stiff jelly . It is said to clot . If the process is watched it is seen to start first from the surfaces where it is in contact with any foreign body; thence it extends through the blood until the whole See also:mass sets solid . A short time elapses before this process commences—a time dependent upon two chief conditions, viz. the temperature at which the blood is kept and the extent of foreign surface with which it is brought into contact . Thus in a mammal the blood clots most quickly at a temperature a little above body temperature, while if the blood be cooled quickly the clotting is considerably delayed and in the case of some animals altogether prevented . For example, human blood kept at body temperature clots in three minutes, while if allowed to cool to See also:room temperature the first sign of clotting may not make its appearance until eight minutes after its removal from the body . The process of clotting is also considerably accelerated by making the blood flow in a thin stream over a wide surface . The full completion of the process occupies some time if the blood be kept quiet, but ultimately the whole mass of the blood becomes converted into a solid . At this stage the containing vessel may be inverted without any drop of fluid escaping . A short time after this stage has been reached drops of a yellow fluid appear upon the surface and, increasing in size and number, run together to form a layer of fluid separated from the clot . This fluid is termed serum; its appearance is due to the contraction of the clot, which thus squeezes out the fluid from between its solid constituents . Contraction continues for about twenty-four See also:hours, at the end of which time a large quantity (one-third or more of the total volume) of serum may havebeen separated . The clot contracts uniformly, thus preserving throughout the same general shape as that of the vessel in which the blood has been collected . Finally the clot swims freely in the serum which it has expressed . The cause of the clot formation has been found to be the precipitation of a solid from the liquid plasma of the blood . This solid is in the form of very minute threads and hence is termed fibrin . The threads See also:traverse the mass of blood in every possible direction, interlacing and thus confining in their meshes all the solid elements of the blood . Soon after their deposition they begin to See also:contract, and as the meshwork they form is very minute they carry with them all the corpuscles of the blood, These with the fibrin form the shrunken clot . If the rate at which blood clots be retarded either by cooling or by some other process the corpuscles may have time to See also:settle, partially or completely, in which case distinct layers may form . The lowermost of these contains chiefly the red corpuscles, the second layer may be See also:grey owing to the high percentage of leucocytes present, while a third, marked by opalescence only, may be very rich in platelets . Above these a clear layer of fluid may be found . This is plasma . The formation of these layers depends solely upon the rate of sedimentation of these elements, the rate depending partly upon differences in specific gravity, and partly upon the tendency the corpuscles have to run into clumps . See also:Horse's blood offers one of the best instances of the clumping of red corpuscles, and in this animal sedimentation of the red corpuscles is most rapid . If now such a sedimented blood is allowed to clot the process is found to start in the See also:middle two layers, i.e. in those containing the white corpuscles and platelets . From these layers it spreads through the See also:rest of the liquid, being most retarded, however, in the red corpuscle layer, and particularly so if the sedimentation has been very See also:complete . Not only does the clotting process start from the layers containing the leucocytes and platelets, but in them it also proceeds more quickly . These observations clearly indicate that the clotting process is initiated by some See also:change starting from these elements . The See also:object of the clotting of the blood is quite clear . It is to prevent, as far as possible, any loss of blood when there is an injury to an animal's vessels . The shed blood becomes converted into a solid, and this, extending into the interior of the ruptured vessel, forms a plug and thus arrests the bleeding . It is found that clotting is especially accelerated whenever the blood touches a foreign tissue, for instance, the See also:outer layers of a torn blood-vessel wall, muscle tissue, &c., i.e. in exactly those conditions in which rapid clotting becomes of the greatest importance . Yet another very pregnant fact in connexion with clotting is that if an animal be bled rapidly and the blood collected in successive samples it is found that those collected last clot most quickly . Hence the more excessive the See also:haemorrhage in any case, the greater becomes the onset of the natural cure for the bleeding, viz. clotting . When we begin to inquire into the nature of clotting we have to determine in the first place whence the fibrin is derived . It has long been known that two chemical substances at least are requisite for its production . Thus certain fluids are known, e.g. some samples of hydrocele or pericardial fluid, which will not clot spontaneously, but will clot rapidly when a small quantity of serum or of an old blood-clot is added to it . The constituent substance which is present in the first-named fluids is known as fibrinogen, and that present in the serum or the clot is known as fibrin-ferment or thrombin . Fibrinogen is present in living blood dissolved in the plasma; it is also present in such fluids as hydrocele or pericardial effusions, which, though capable of clotting, do not clot spontaneously . Thrombin, on the other hand, does not exist in living blood, but only makes its appearance there after blood is shed . It is not yet certain what is the nature of the final reaction between fibrinogen and thrombin . The possibilities are, that thrombin may act—(r) by acting upon fibrinogen, which it in some way converts into fibrin, (2) by uniting with fibrinogen to form fibrin, or (3) by yielding part of itself to the fibrinogen which thus becomes converted into fibrin . The experimental study of the rate of fibrin formation, when different strengths of thrombin solutions are allowed to act upon a fibrinogen solution, leads us to the probable conclusion that the first of these three possibilities is the correct one, and that thrombin therefore exerts a true ferment action upon fibrinogen . It is known that in the reaction, in addition to the formation of fibrin, yet another protein makes its appearance . This is known as fibrinoglobulin, and apparently it arises from the fibrinogen, so that the change would be one of cleavage into fibrin and fibrinoglobulin . It is very noteworthy that although the amount of fibrin formed during the clotting appears very bulky, yet the actual See also:weight is extremely small, not more than o•4 grms. from Too cc. of blood . Having ascertained that the clotting is due to the action of thrombin upon fibrinogen, we now see that the next step to be explained is the origin of thrombin . It has been shown that the final step in its formation consists in the See also:combination of another substance, termed prothrombin, with calcium . Any soluble calcium See also:salt is found to be effective in this respect, and conversely the removal of soluble calcium (e.g. by sodium oxalate) will prevent the formation of thrombin and therefore of clotting . In the next place it can be proved that prothrombin does not exist as such in circulating blood, so that the problem becomes an inquiry as to the origin of prothrombin . Experiment has shown that in its turn prothrombin arises from yet another precursor, which is named thrombogen, and that thrombogen also is not to be found in circulating blood but only makes its appearance after the blood is shed . The See also:conversion of thrombogen into prothrombin has been proved to be due to the action of a second ferment which has been named thrombokinase, and this latter is again absent from living blood . Hence the question arises, whence are derived thrombogen and thrombokinase ? In the study of this question it has been found that if the blood of birds be collected direct from an artery through a perfectly clean cannula into a clean and dust-free glass vessel, it does not clot spontaneously . The plasma collected from such blood is found to contain thrombogen but no thrombokinase . A some-what similar plasma may be prepared from a mammal's blood by See also:collecting samples of blood from an artery into vessels which have been thoroughly coated with See also:paraffin, though in this instance thrombogen may be absent as well as thrombokinase . If plasma containing thrombogen but no thrombokinase be treated with a saline extract of any tissues it will soon clot . The saline extract contains thrombokinase . This ferment can therefore be derived from most tissues, including also the white blood corpuscles and the platelets . Thrombogen is produced from the leucocytes, but it is not yet certain whether it is also formed from the platelets . The See also:discovery of the origin of the thrombokinase from tissue cells explains a fact that has long been known, namely, that if in collecting blood, it is allowed to flow over cut tissues, clotting is most markedly accelerated . The fact that birds' blood if very carefully collected will not clot spontaneously tends to prove that thrombokinase is not derived from the leucocytes, and makes probable its origin from the platelets, for it is known that birds' blood apparently does not contain platelets, at any rate in the form in which they are found in mammalian blood . When examining the general properties of platelets, See also:attention was drawn to the remarkably rapid manner in which they undergo change on coming into contact with a foreign surface . It is apparently the actual contact which initiates these changes, changes which are fundamentally chemical in character, resulting in the production of thrombokinase and possibly also of thrombogen . Thus as our knowledge at present stands the following statement gives a recapitulated account of the changes which constitute the many phases of clotting . When blood escapes from a blood-vessel it comes into contact with a foreign surface, either a tissue or the damaged walls of the cut vessel . Very speedily this contact results in the discharge of thrombogen and thrombokinase, the former from the white blood corpuscles and also possibly from the platelets, the latter from the plateletsor from the tissue with which the blood comes in contact . The interaction of these two bodies next results in the formation of prothrombin, which, combining with the calcium of any soluble See also:lime salt present, forms thrombin or fibrin-ferment . The last step in the change is the action of thrombin upon fibrinogen to form fibrin, and the clot is complete . The See also:intrinsic value to the animal of these changes is quite See also:plain . The power of clotting and thus stopping haemorrhage is of essential importance, and yet this clotting must not occur within the living blood-vessels, or it would speedily result in See also:death . That the tissues should be able to accelerate the process is of very obvious value . That the inner lining of the blood-vessels does not act as a foreign tissue is possibly due to the extreme smoothness of their surface . Further, an animal must always be exposed to a possible danger in the absorption of some thrombin from a mass of clotted blood still retained within the body, and we know that if a quantity of active ferment be injected into the blood-stream intravascular clotting does result . Under all usual conditions this is obviated, the protective mechanism being of a twofold character . First, it is found that thrombin becomes converted very quickly into an inactive modification . Serum, for instance, very quickly loses its power of inducing clotting in fibrinogen solutions . Secondly, the body has been found to possess the power of making a substance, antithrombin, which can combine with thrombin forming a substance which is quite inactive as far as clotting is concerned . Finally, there is See also:evidence that normal blood contains a small quantity of this substance, antithrombin, and that under certain conditions the amount present may be enormously increased . (T . G . BR.) See also:Pathology of the Blood . The changes in the blood in disease are probably as numerous and varied as the diseases which attack the body, for the blood is not only the medium of respiration, but also of nutrition, of See also:defence against organisms and of many other functions, none of which can be affected without corresponding alterations occurring in the circulating fluid . The immense See also:majority of these changes are, however, so subtle that they See also:escape detection by our present methods . But in certain directions, notably in regard to the relations with micro-organisms, changes in the blood-plasma can be made out, though they are not associated in all cases with changes in the formed elements which float in it, nor with any obvious microscopical or chemical alterations . The phenomena of immunity to the attacks of bacteria or their toxins, of agglutinative action, of opsonic action, of the precipitin tests, and of haemolysis, are all largely Immunity dependent on the inherent or acquired characters of the blood serum . It is a See also:commonplace that different See also:people vary in their susceptibility to the attacks of different organisms, and different species of animals also vary greatly . This " natural immunity " is due partly to the power possessed by the leucocytes or white blood corpuscles of taking into their bodies and digesting or holding in an inert state organisms which reach the blood—See also:phagocytosis,—partly to certain bodies in the blood serum which have a bactericidal action, or whose presence enables the phagocytes to See also:deal more easily with the organisms . This natural immunity can be heightened when it exists, or an artificial immunity can be produced in various ways . Doses of organisms or their toxins can be injected on one or several occasions, and provided that the lethal dose be not reached, in most cases an increased power of resistance is produced . The organisms may be injected alive in a virulent condition, or with their virulence lessened by See also:heat or See also:cold, by See also:antiseptics, by cultivation in the presence of oxygen, or by passage through other animals, or they may first be killed, or their toxins alone injected . The method chosen in each case depends on the organism dealt with . The result of this treatment is that in the animal treated protective substances appear in the serum, and these substances can be transferred to the serum of another animal or of man; in other words the active immunity of the experimental animal can be translated into the passive immunity of man . According to the nature of the substances injected into the former, its serum may be antitoxic, if it has been immunized against any particular toxin, or See also:anti-bacterial, if against an organism . See also:Familiar examples of these are, of the former See also:diphtheria antitoxin, of the latter anti-See also:plague and anti-typhoid sera . An antitoxin exerts its effects by actual combination with the respective toxin, the combination being inert . It is probable that the ultimate source of the antitoxin is to be found in the living cells of the tissues and that it passes from them into the blood . The action of an antibacterial serum depends on the presence in it of a substance known as " immune-body," which has a special See also:affinity and power of combining with the bacterium used . In order that it may exert this power it requires the presence of a substance normally present in the serum known as " See also:complement." The development of these " anti-bodies," though ,it has been studied mainly in connexion with bacteria and their toxins, is not confined to their action, but can be demonstrated in regard to many other substances, such as ferments, tissue cells, red corpuscles, &c . In some animals, for example, the blood serum has the power of dissolving the red corpuscles of an animal of different species; e.g. the See also:guinea-See also:pig's serum is " haemolytic " to the red corpuscles of the ox . This haemolytic power (haemolysis) can be increased by repeated injections of red corpuscles from the other animal, in this case also, as in the bacterial case, by the production and action of immune-body and complement . The antiserum produced in the case of the red corpuscles may sometimes, if injected into the first animal, whose red corpuscles were used, cause extensive destruction of its red corpuscles, with haemoglobinuria, and sometimes a fatal |