Thomas Gregor Brodie and George Lovell Gulland

“ 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. ”

“ 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 ”

“ 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 defence against organisms and of many other functions, none of which can be affected without corresponding alterations occurring in the circulating fluid. ”

“ In chronic anaemias, regeneration always goes on side by side with destruction, and it is important to remember that the state of the blood in these conditions gives the measure, not of the amount of destruction which is taking place so much as of the amount of regeneration of which the organism is capable. ”

“ In acute anaemias, such as those associated with septicaemia, there is no doubt that blood destruction plays the principal part. But if the cause of anaemia is a chronic one, a gastric cancer, for instance, though there may possibly be an increased amount of destruction of corpuscles in some cases, and though there is often loss by haemorrhage, the cancer interferes with nutrition, the blood is impoverished and does not nourish the erythroblasts in the marrow sufficiently, and the new corpuscles which are turned out are few and poor in haemoglobin. ”

“ 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 (φάγειν, to eat) . ”

“ Again, many instances are known in which two distant tissues communicate with one another by means of chemical messengers, bodies termed hormones (ὁρμάειν, 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 animal is seen in the way in which it is employed in protecting the body should it be invaded by micro-organisms. ”

“ The 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 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 time, without requiring any very great increase in the concentration of that substance in the blood. ”

“ In order that a more active animal might be 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. ”

“ The 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. ”

“ The organisms may be injected alive in a virulent condition, or with their virulence lessened by heat or cold, by 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 ”

“ The last step in the change is the action of thrombin upon fibrinogen to form fibrin, and the clot is complete.
The intrinsic value to the animal of these changes is quite 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 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. ”

“ Severe malarial infection, syphilis, pregnancy, chronic gastro-intestinal disease, chronic gas-poisoning, are all, in different cases, known to have been causally associated with it, and it is probable that a congenital weakness of the bone-marrow has often to do with its production, as in many cases a family or hereditary history of the disease can be obtained. ”

“ 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. ”

“ 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. ”

“ 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 room temperature the first sign of clotting may not make its appearance until eight minutes after its removal from the body. ”

“ 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 platelets or 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 lime salt present, forms thrombin or fibrin-ferment. ”

“ 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 result.
Opsonic action depends on the presence of a substance, the “opsonin,” in the serum of an immunized animal, which makes the organism in question more easily taken up by the phagocytes (leucocytes) of the blood. The opsonin becomes fixed to the organisms. ”

“ In the mammal they are biconcave disks with bevelled edges, they do not contain a nucleus so that they are not cells. In the bird they are larger, ellipsoidal in shape and have a large nucleus in the centre of the cell. In reptiles and amphibia the red corpuscles are also nucleated, but the stroma portion containing the haemoglobin is arranged in a thickened annular part encircling the nucleus. ”

“ Only a part of the marrow, the so-called red marrow, is normally occupied by erythroblastic tissue, the rest of the medullary cavity of the bones being taken up by fat. If any long-continued demand for red corpuscles is made, the fat is absorbed, and its place gradually taken by red marrow. ”

“ 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 dependent on the inherent or acquired characters of the blood serum. It is a commonplace thatImmunity. ”

“ An increase is very much more frequent, and is known as leucocytosis, though in this term is usually connoted a relative increase in the proportion of the polymorphonuclear neutrophile leucocytes. Leucocytosis occurs under a great variety of conditions, normally to a slight extent during digestion, during pregnancy, and after violent exercise, and abnormally after haemorrhage, in the course of inflammations and many infective diseases, in malignant disease, in such toxic states as uraemia, and after the ingestion of nuclein and other substances. ”

“ 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. ”

“ The symptoms are those of a progressive anaemia, in which gastro-intestinal disturbance usually plays a large part, and nervous symptoms are common, and they become at last much more severe than those of any secondary anaemia. The patient may die in the first attack, but more usually, when things seem to be at their worst, improvement sets in, either spontaneously or as the result of treatment, and the patient slowly regains apparent health. ”

“ In order that it may exert this power it requires the presence of a substance normally present in the serum known as “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 ”

“ The rate of supply is of much less importance in the case of the other food substances because they are far more soluble in water, so that the supply in sufficient quantity can easily be met by a relatively slow blood flow. ”

“ In fatal cases the internal organs are found to be pale, and very often their cells contain an excessive amount of fat. In many anaemias there is a special tendency to haemorrhage. Most of the above symptoms and organic changes are directly due to diminished respiratory interchange from the loss of haemoglobin, and to its effect on the various organs involved. ”

“ These are apt, however, to be small and to contain a subnormal amount of haemoglobin, and it is only after some time that they are destroyed and their place taken by normal corpuscles. If the loss has been very great, nucleated red corpuscles may even be carried into the blood-stream. The blood possesses a great power of recovery, if time be given it, because the organ (bone-marrow) which forms so many of its elements never, in health, works at high pressure. ”

“ 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. ”

“ Bad hygienic conditions, over-fatigue, want of proper food, especially of the iron-containing proteids of meat, the strain put upon the blood and blood-forming organs by the accession of puberty and the occurrence of menstruation, all probably play a part in it. ”

“ No adequate explanation of the formation of the toxin in the immense majority of the cases, in which there is no tapeworm, has yet been given. It is certain that no organism as yet known is concerned. ”