Agglutinative action is evidence of the presence in a serum of a somewhat similar set of substances, known as “agglutinins.” When a portion of an antiserum is added to an emulsion of the corresponding organism, the organisms, if they are motile, cease to move, and in any case become gathered together into clumps. In all probability several different bodies are concerned in this process. This reaction, in its practical applications at least, may be regarded as a reaction of infection rather than of immunization as ordinarily understood, for it is found that the blood serum of patients suffering from typhoid, Malta fever, cholera, and many other bacterial diseases, agglutinates the corresponding organisms. This fact has come to be of great importance in diagnosis.
The precipitin test depends on a somewhat analogous reaction. If the serum of an animal be injected repeatedly into another animal of different species, a “precipitin” appears in the serum of the animal treated, which causes a precipitate when added to the serum of the first animal. The special importance of this fact is that it can be utilized as a method of distinguishing between human blood and that of animals, which is often of importance in medical jurisprudence.
In this summary the facts adduced are practically all biological, and are due to the extraordinary activity with which the study of bacteriology (q.v.) has been pursued in recent years. The chemistry of the blood has not hitherto been found to give information of clinical or diagnostic importance, and nothing need here be added to what is said above on the physiology of the blood. Enough has been said, however, to show the extraordinary complexity of the apparently simple blood serum.
The methods at present employed in examining the blood clinically are: the enumeration of the red and white corpuscles per cubic millimetre; the estimation of the percentage of haemoglobin 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 J.S. Haldane and J. 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 (Journ. of Physiol. vol. xxv. p. 331, 1900). 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 evidence 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.
Anaemia is often used as a generic term for all blood diseases, for in almost all of them the haemoglobin is diminished, either as a result of diminution in the number of the red corpuscles in which it is contained, or because the Anaemia. individual red corpuscles contain a smaller amount of haemoglobin than the normal. As haemoglobin is the medium of respiratory interchange, its diminution causes obvious symptoms, which are much more easily appreciated by the patient than those caused by alterations in the plasma or the leucocytes. It is customary to divide anaemias into “primary” and “secondary”: the primary are those for which no adequate cause has as yet been discovered; the secondary, those whose cause is known. Among the former are usually included chlorosis, pernicious anaemia, and sometimes the leucocythaemias; among the latter, the anaemias due to such agencies as malignant disease, malaria, chronic metallic poisoning, chronic haemorrhage, tubercle, Bright’s disease, infective processes, intestinal parasites, &c. As our knowledge advances, however, this distinction will probably be given up, for the causes of several of the primary anaemias have been discovered. For example, the anaemia due to bothriocephalus, an intestinal parasite, is clinically indistinguishable from the other forms of pernicious anaemia with which it used to be included, and leucocythaemia has been declared by Löwit, though probably erroneously, to be due to a blood parasite closely related to that of malaria. In all these conditions there is a considerable similarity in the symptoms produced and in the pathological anatomy. The general symptoms are pallor of the skin and mucous membranes, weakness and lassitude, shortness of breath, palpitation, a tendency to fainting, and usually also gastro-intestinal disturbance, headache and neuralgia. The heart is often dilated, and on auscultation the systolic murmurs associated with that condition are heard. 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. The diagnosis depends ultimately in all cases upon the examination of the blood.
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 haemoglobin. 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 combination 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 number 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, 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. 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. 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 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. 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. The evidence of destruction has often to be sought for in other organs, or in secretions or excretions.
Of the so-called primary anaemias the most common is chlorosis, an anaemia which occurs only in the female sex, between the ages of fifteen and twenty-five as a rule. Its symptoms are those caused by a diminution of haemoglobin, and though it is never directly fatal, and is extremely amenable to treatment with iron preparations, its subjects very frequently suffer from relapses at varying intervals after the first attack. Its causation is probably complex. 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. It has also been suggested that internal secretions may be concerned in stimulating the bone-marrow, and that in the female sex in particular the genital organs may act in this way. Imperfect assumption of function by these organs at puberty, caused perhaps by some of the above-mentioned conditions, might lead to sluggishness in the bone-marrow, and to the supply to the blood of the poorly-formed corpuscles deficient in haemoglobin which are characteristic of the disease. Chlorosis is the type of anaemias from imperfect blood-formation. Lorrain Smith has produced evidence to show that the total amount of haemoglobin in the body is not diminished in this disease, but that the blood-plasma is greatly increased in amount, so that the haemoglobin is diluted and the amount in each blood-unit greatly lessened.
Pernicious anaemia is a rarer disease than chlorosis, occurs usually later in life, and is distributed nearly equally between the two sexes. But it is of great importance because of its almost uniformly fatal termination, though its downward course is generally broken by temporary improvement on one or more occasions. 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. This remission may be followed by a relapse, that again by a remission, and so on, but as a rule the disease is fatal within, at the outside, two or three years.
The prime cause of the disease is not known. It seems probable indeed that the causal factors are numerous. 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 condition is now regarded as a chronic toxaemia, partly because of the clinical symptoms and pathological appearances, partly because analogous conditions can be produced experimentally by such poisons as saponin and toluylendiamin, and partly because of the facts of bothriocephalus anaemia. The site of production of the toxin, or toxins, for it is possible that several may have the same effect on the blood, is possibly not always the same, but must often be the alimentary canal, as bothriocephalus anaemia proves. Not all persons affected with this intestinal tapeworm contract the disease, but only those in whose intestines the worm is dead and decomposing or sometimes only “sick.” The expulsion of the worm puts an end to the absorption of the toxin and the patients recover. 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.