BLOOD, PATHOLOGY OF (see also ANAEMIA). The changes in the blood in disease are probably as numerous and varied as the diseases which attack the body. The immense ma jority of these changes are, however, so subtle that they 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 asso ciated 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 (q.v.) from the attacks of bac teria or their toxins, of agglutinative action, of opsonic action, of the precipitin tests, and of haemolysis, are all largely depend ent on the inherent or acquired characters of the blood serum.
The methods at present employed in examining the blood clini cally are : the enumeration of the red and white corpuscles per cubic millimetre; the estimation of the percentage of haemo globin and of the specific gravity of the blood; the microscopic examination of freshly-drawn blood and of blood films made upon cover-glasses, fixed and stained. In special cases the alkalinity and the rapidity of coagulation may be ascertained, or the blood may be examined bacteriologically. We have no universally accepted means of estimating, during life, the total amount of blood in the body, though the method of Haldane and Lorrain Smith, in which the total oxygen capacity of the blood is estimated, and its total volume worked out from that datum, has seemed to promise important results (Town. of Physiol. vol. xxv. p. 331, 19oo).
Estimates of the total volume of blood in man vary between about -2-1-0- and 11,1,- of the body weight but no doubt it varies from time to time. After death the amount of blood sometimes seems to be increased, and sometimes, as in "pernicious anaemia," it is certainly diminished. But the high counts of red corpuscles which are occasionally reported as evi dence of plethora or increase of the total blood are really only indications of concentration of the fluid except in certain rare cases. It is necessary, therefore, in examining blood diseases, to confine ourselves to the study of the blood-unit, which is always taken as the cubic millimetre, without reference to the number of units in the body.
Though the relative proportions of the leucocytes are probably continually undergoing change even in health, especially as the result of taking food, the number of red corpuscles remains much more constant. Through the agency of some unknown mechanism, the supply of fresh red corpuscles from the bone-marrow keeps pace with the destruction of effete corpuscles, and in health each corpuscle contains a definite and constant amount of haemo globin. The disturbance of this arrangement in anaemia may be due to loss or to increased destruction of corpuscles, to the supply of a smaller number of new ones, to a diminution of the amount of haemoglobin, in the individual new corpuscles, or to a com bination of these causes.
It is most easy to illustrate this by describing what happens after a haemorrhage. If this is small, the loss is replaced by the fully-formed corpuscles held in reserve in the marrow, and there is no disturbance. If it is larger, the amount of fluid lost is first made up by fluid drawn from the tissues, so that the num ber of corpuscles is apparently diminished by dilution of the blood ; the erythroblasts, or formative red corpuscles, of the bone marrow are stimulated to proliferation, and new corpuscles are quickly thrown into the circulation. 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, nu cleated red corpuscles may even, in some cases, 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. Only a part of the marrow, the so-called red marrow, is normally occupied by erythroblastic tis sue, 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. This compensatory change is found in all chronic anaemias, no matter what their cause may be, except in some rare cases in which the marrow does not react.
It is often very difficult, especially in "secondary" anaemias, to say which of the above processes is mainly at work. 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 be an increased amount of destruction of cor puscles due to sepsis, and though there is often loss by haemor rhage, the cancer interferes with nutrition, the blood is impover ished and does not nourish the erythroblasts in the marrow suffi ciently, and the new corpuscles which are turned out are few and poor in haemoglobin. In chronic anaemias, regeneration always goes on side by side with destruction, and it is important to re member 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. The evidence of destruction has often to be sought for in other organs, or in secretions or excretions.
The number and nature of the leucocytes in the blood bears no constant or necessary relation to the number or condition of the red corpuscles, and their variations depend on entirely different conditions. The number in the cubic millimetre is usually about 7,000, but may vary in health from S,000 to ro,000. A diminution in their number is known as leucopenia, and is found in starvation, in some infective diseases, as for example in typhoid fever, in malaria and Malta fever, and in pernicious anaemia. 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 condi tions, normally to a slight extent during digestion, during preg nancy, and after violent exercise, and abnormally of ter haemor rhage, 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. It does not occur in some infective diseases, the most important of which are ty phoid fever, malaria, influenza, measles and uncomplicated tuber culosis. In all cases where it is sufficiently severe and long con tinued, the reserve space in the bone-marrow is filled up by the active proliferation of the leucocytes normally found there, and is used as a nursery for the leucocytes required in the blood. In many cases leucocytosis is known to be associated with the de fence of the organism from injurious influences, and its amount depends on the relation between the severity of the attack and the power of resistance. There may be an increase in the propor tions present in the blood of lymphocytes (lymphocytosis), and of eosinophile cells (eosinophilia). This latter change is associated specially with some forms of asthma, with certain skin diseases, and with the presence of animal parasites in the body, such as ankylostoma and filaria.
The disease in which the number of leucocytes in the blood is greatest is leucocythaemia or leucaemia. There are two main forms of this disease, in both of which there are anae mia, enlargement of the spleen and lymphatic glands, or of either of them, leucocytic hypertrophy of the bone-marrow, and de posits of leucocytes in the liver, kidney and other organs. The difference lies in the kind of leucocytes present in excess in the blood, blood-forming organs and deposits in the tissues. In the one form these are lymphocytes, which are found in health mainly in the marrow, the blood itself, the lymph glands and in the lym phatic tissue round the alimentary canal ; in the other they are the kinds of leucocytes normally found in the bone-marrow myelocytes, neutrophile, basophile, and eosinophile, and polymor phonuclear cells, also neutrophile, basophile and eosinophile. The clinical course of the two forms may differ. The first, known as lymphatic leucaemia or lymphaemia, may be acute, and prove fatal in a few weeks or even days with rapidly advancing anaemia, or may be chronic and last for one or two years or longer. The second, known as spleno-myelogenous leucaemia or myelaemia, is almost always chronic, and may last for several years. Recovery does not take place, though remissions may occur. The use of the X-rays has been found to influence the course of this disease very favourably, at least, for a time. The most recent view of the pathology of the disease is that it is due to an overgrowth of the bone-marrow leucocytes analogous in some respects to tumour growth and caused by the removal of some controlling mechanism rather than by stimulation. In course of time a lymphaemia may pass into a myelaemia. The anaemia accompanying the disease is due partly to the leucocyte overgrowth, which takes up the space in the marrow belonging of right to red corpuscle forma tion and interferes with it.
