Part 30

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 fine tubes, the lymphatics, through which excess of fluid or any solid particles present are drained away. The contained fluid acts as an intermediary 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 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 act as the vehicle for the removal of those waste products (carbonic acid, &c.) which must of 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 size are readily absorbed into the blood stream.

But in addition to fluid, the tissue spaces may at times be found to contain solid matter in the 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 special provision is made to prevent such an accident. These, therefore, are made to travel along the lymphatic channels, and so, before gaining access to the blood stream and thus to the body generally, have to run the gauntlet of the protective mechanism provided by the lymphatic glands, where in the major number of cases they are readily destroyed.

Hence we see that first and foremost we have to regard the blood as a food-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 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 overestimate, for it plays the essential role in rendering the animal immune to the attacks of invading organisms. The question of immunity is discussed elsewhere, and it is sufficient merely to indicate the 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, (1) 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 ([Greek: Phagein], to eat). Thus, by its power 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 vegetable origin.

_General Properties._--Blood is an opaque, viscid liquid of bright red 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 index than

that of the liquid in which they float. The specific gravity in man averages about 1.055. The specific gravity of the liquid portion, the plasma (Gr. [Greek: plasma], something formed or moulded, [Greek: plassein], to mould), is about 1.027, whilst that of the corpuscles amounts to 1.088. To litmus it reacts as a weak alkali.

_Blood Plasma._--The plasma is a solution in water of a varied number of substances, and as a solvent it confers on the blood its 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, urea, urates, xanthin bases, creatin and small amounts of other nitrogenous bodies, carbonic acid as carbonates, other 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 composition:--

In 1000 grms. plasma-- Water 901.51 Substances not vaporizing at 120 deg. C.-- Fibrin 8.06 Other proteins and organic substances 81.92 Inorganic substances-- Chlorine 3.536 Sulphuric acid 0.129 Phosphoric acid 0.145 Potassium 0.314 Sodium 3.410 Calcium 0.298 Magnesium 0.218 Oxygen 0.455 ----- 8.505 ----- 98.49 ------- 1000.00

_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 heating (in this instance at a temperature of 56 deg.C.), and is precipitated by 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 deg.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 part is precipitated, and this portion has been termed the eu-globulin fraction, the 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 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 glucoside character.

Serum-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 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 deg., 77 deg. and 84 deg. C. On the other hand the 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 appearance in the fluid part of the blood, or serum, as it is now called. The first of these is fibrin ferment (for its origin see section on _Clotting_ below). The other, fibrinoglobulin, possesses all the typical characteristics of the globulins and coagulates at 64 deg. C.

_Carbohydrates._--Three several carbohydrates are described as occurring in plasma, viz. glycogen, animal gum and dextrose. 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 white blood corpuscles, since some leucocytes undoubtedly contain glycogen. A small amount of carbohydrate having the formula for starch and yielding a reducing sugar on hydrolysis with acid has also been described. The constant carbohydrate constituent of plasma, however, is dextrose. This is present to the approximate amount of 0.15% in arterial blood. The amount may be much greater in the blood of the portal vein during carbohydrate absorption, and according to some observers there is less in venous than in arterial blood, but the difference is small and falls within the error of observation. The statement that when no absorption is taking place the blood of the hepatic vein is richer in dextrose than that of the portal vein (Bernard) is denied by Pavy.

_Fats._--Plasma or serum is as a rule quite clear, but after a meal rich in fats it may become quite milky owing to the presence of neutral fats in a very fine state of subdivision. This suspended fat rapidly disappears from the blood after fat absorption has ceased. To some extent it varies in composition with that of the fat absorbed, but usually consists of the glycerides of the 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 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 esters (about 0.06%).

_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, 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: ammonia as carbonate or carbamate (0.2 to 0.6%), urea (0.02 to 0.05%), creatine, creatinine, uric acid, xanthine, hypoxanthine and occasionally hippuric acid. Three ferments are also described as being present: (1) a glycolytic ferment exerting an 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, phosphates, carbonates and possibly sulphates, of sodium, potassium, calcium and magnesium. The most abundant metal is sodium and the most abundant acid is hydrochloric. These two are present in sufficient amount to form about 0.65% 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 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 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 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. [Greek: erythros], 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. [Greek: leukos], white). Lastly, there are present a large number of small 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 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. Dog 0.0073 mm. Rabbit 0.0069 mm. Cat 0.0065 mm. Goat 0.0041 mm.

The coloured corpuscles of 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:--

Pigeon 0.0147 mm. long by 0.0065 mm. wide. Frog 0.0223 " " 0.0157 " " Newt 0.0293 " " 0.0195 " " Proteus 0.0580 " " 0.0350 " " Amphiuma 0.0770 " " 0.0460 " "

Their number also varies as follows:--

Man 4,000,000 to 5,000,000 per cub. mm. Goat 9,000,000 to 10,000,000 " " Sheep 13,000,000 to 14,000,000 " " Birds 1,000,000 to 4,000,000 " " 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 nucleus, but possess a thin envelope. Their specific gravity is distinctly higher than that of the plasma (1.088), so that if clotting has been prevented, blood on standing yields a large deposit which may form as much as half the total 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 dissociation of oxyhaemoglobin occurs as the oxygen tension falls from about 40 to 20 mm. of mercury. That the oxygen forms a definite 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 band between those lines. In association with this, oxyhaemoglobin has a typical bright red colour, whereas haemoglobin is dark purple. A further striking characteristic of haemoglobin is that it contains iron in its 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 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. [Greek: istos], web, tissue). In this cleavage the iron is found in the pigment. By the use of a strong acid, it may be made to yield iron-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 liver, but whether the whole of this 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 spleen to examine the red corpuscles and to destroy or in some way to 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 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 day indicates that the destruction must be considerable, and since the number of corpuscles does not vary there must be an equivalent formation of new ones. This takes place in the red bone-marrow, where special cells are provided for their continuous 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 precursors of the blood capillaries are formed.

_White Blood Corpuscles._--These constitute the second important 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 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_;[1] 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:--

1. _The Polymorphonuclear Cell._--This possesses a nucleus of very complicated outline and a fair amount of protoplasm filled with numbers of fine granules which stain with eosin. They vary in size but are usually about 0.01 mm. in 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 0.0065 mm. in diameter. It has a large spherical nucleus with a small rim of clear protoplasm surrounding it. It forms from 15 to 40% of the number of leucocytes, and is less markedly amoeboid than the other varieties.

4. _The Hyaline_ (Gr. [Greek: hualinos], glassy, crystalline, [Greek: ualos], glass) _cell or macrocyte_ (Gr. [Greek: makros], long or large).--This is a cell similar to the last with a spherical, 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 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 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 division of specific mother cells located in that tissue. The macrocyte is believed by many to represent a further 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 diet and also, to a considerable extent, in disease.

_Platelets._--The platelets or thrombocytes (Gr. [Greek: thrombos], 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 shed or otherwise 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 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 groups, and during clotting, fibrin filaments may be observed to shoot out from these clumps.