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.
This toxaemia affects the marrow and through it the blood, the gastro-intestinal apparatus and the nervous system, especially the spinal cord, in different proportions in different cases. The effect upon the marrow is to alter the type of red corpuscle formation, causing a reversion to the embryonic condition, in which the nucleated red corpuscles are large (megaloblasts), and the corpuscles in the blood formed from them are also large, are apparently ill suited to the needs of the adult, and easily break down, as the deposits of iron in the liver, spleen, kidneys and marrow prove. Whether this reversion is due to an exhaustion of the normal process or to an inhibition of it is not definitely known. The result is that the circulating red corpuscles are enormously diminished; it is usual to find 1,000,000 or less in the cubic millimetre instead of the normal 5,000,000. Though the haemoglobin is of course absolutely diminished, it is always, in severe cases, present in relatively higher percentage than the red corpuscles, because the average red corpuscle is larger and contains more haemoglobin than the normal. The large nucleated red corpuscles (megaloblasts) with which the marrow is crowded, often appear in the blood.
Other anaemias, such as those known as lymphadenoma, or Hodgkin’s disease, splenic anaemia, chloroma, leucanaemia and the anaemia pseudo-leucaemica of children, need not be described here, as they are either rare or their occurrence or nature is still too much under discussion.
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 7000, but mayLeucocytosis. vary in health from 5000 to 10,000. 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.
